2005 Department Based Research 

Department of Anesthesiology Department of Biomedical Informatics Department of Emergency Medicine Department of Family Medicine Department of Internal Medicine Department of Molecular and Cellular Biochemistry Department of Molecular Virology, Immunology and Medical Genetics Department of Neurological Surgery Department of Neurology Department of Neuroscience Department of Obstetrics and Gynecology Department of Ophthalmology

Department of Orthopaedics Department of Otolaryngology Department of Pathology Department of Pediatrics Department of Pharmacology Department of Physical Medicine and Rehabilitation Department of Physiology and Cell Biology Department of Psychiatry & OSU Harding Hospital Department of Radiation Medicine Department of Radiology Department of Surgery School of Biomedical Science

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DEPARTMENT OF ANESTHESIOLOGY                    
Daniel Sedmak, MD, Interim Chair
Anesthesiology has 45 faculty members with research interests in cardiovascular, gastrointestinal and neural diseases and processes. It collaborates with 15 departments, divisions or institutes involved in biomedical and patient-oriented research, and in animal or genomic models of heart failure, hypertension, wound healing, diabetic vasculopathies, aging, spinal cord injury, neural plasticity, mechanosensitivity, inflammatory bowel diseases, irritable bowel syndrome and atherosclerosis. Clinical studies complement these efforts for ischemic spinal cord injury studies in thoracic aortic aneurysm patients, heart-failure studies with 3-D echocardiography and finite element analysis, cardio/bio-impedance studies, computer modeling of cardiopulmonary interactions, functional magnetic resonance imaging of pain path-ways and anesthesia, and studies in obese patients with Roux-en-Y surgeries. Studies are funded by the National Institutes of Health (NIH), Federation of Anesthesia and Education Research, Davis/Bremer Medical Research Endowment, Strategic Initiative Grants or industry grants. Several NIH grants are pending, and two have been funded as principal investigator (PI) or co-PI by Anesthesiology faculty. Studies resulted in 22 peer-reviewed publications in 2005.

Ongoing Research Programs

• A number of faculty members are conducting cardiovascular research. One investigation is on heart failure and β-adrenergic receptor dysfunction in a microinfarction-induced ovine model of chronic heart failure. More recently this is being done in collaboration with investigators at Columbus Children’s Heart Institute. Surgery is often a treatment for cardiovascular disease.
  
  
• Genomic modeling is a powerful approach to studying mechanisms of disease. Investigators in Anesthesiology, in collaboration with Neuroscience or the OSU Davis Heart and Lung Research Institute, are using transgenic mouse models to study diverse events including wound healing, receptor function or dysfunction, diabetic vascular disease, hypertension, atherosclerosis and heart failure. Anesthesiology has also invented a myocardial electrical impedance (MEI) device for real-time assessment of graft viability. The device can deter-mine graft viability before the end of surgery, thus avoiding serious cardiovascular complications and improving patient safety and recovery.
  
  
• The department is developing expertise in the latest imaging techniques for clinical investigations. Robert Small, MD, and collaborators are applying functional magnetic resonance imaging (fMRI) to study brain activation caused by pain and in response to anesthesia. This was published in Anesthesiology in2004. Nadia Nathan, MD, in collaboration with Cardiology, developed a system for fully automated import of cardiac data (e.g. geometry, pressure and elasticity components) to an industry standard finite-element modeling tool (Abaqus). The tool that incorporates 3-D echocardiography geometry data has three main features: (1) quality management of cardiac interventions by providing cardiac data quantification; (2) a display of finite elements that allows individual visualization suitable for training and analysis; and (3) individual simulation of interventions suitable for surgical planning and training, as well as education.
  
  
• Hamdy Elsayed-Awad, MD, and an interdisciplinary team are using a large animal model and genomic models to study ischemic spinal cord injury in patients undergoing surgery to repair a thoracoabdominal aortic aneurysm (TAAA). Spinal cord injury leading to paraplegia is a devastating complication in TAAA. Studies are focused on the cellular and molecular mechanisms of ischemic spinal cord injury. The potential exists for testing new therapeutic interventions to protect the spinal cord.
  
  
• Studies supported by the National Institutes of Health, National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) are investigating the function and dysfunction of the gastrointestinal nervous system, the so-called enteric nervous system. It regulates motility, secretion and vasomotor functions of the gut. Dysfunction can lead to diarrhea, constipation, dysmotility or irritable bowel syndrome.
  

Research Accomplishments of 2005

• A team led by Mark Gerhardt, MD, PhD, was the first to develop and publish an ovine model of chronic ischemic heart failure (CHF). Their most important contribution of 2005 was a publication in the Journal of Cardiac Failure, the first study published to investigate the use of partial Left Ventricular Assist Device (LVAD) support in a CHF model. New studies with John Bauer, PhD, at Children’s Hospital are unraveling molecular signaling mechanisms during progressive ventricular remodeling in CHF. Studies are funded by the Foundation for Anesthesia Education and Research. Another award is pending through the National Heart, Lung and Blood Institute.
  
  
• Myocardial Electrical Impedance (MEI) research has been ongoing for 15 years. In the history of MEI, the OSU interdisciplinary MEI group is the only one that has measured MEI clinically on heart surgery patients in the operating room with both IRB and FDA approval. The human MEI study was supported by a Strategic Initiative Grant. More than 40 heart surgery patients were measured through 2005.
  
  
• Studies of cardiovascular diseases using genomic models are progressing. Manipulations that cause activation of the rac1 gene, leading to overproduction of superoxide free radicals, promote wound healing (Surgery, 2005). Hamdy Hassanain, PhD, has four pending grants from the National Institutes of Health (NIH) and is co-principal investigator on two funded NIH grants. An interdisciplinary Strategic Initiative Grant supported a study to develop a transgenic mouse model with overexpression of C-reactive protein (CRP) to study the cause-effect relationship in vascular disease and atherosclerosis. Researchers have evidence that they can induce much higher circulating CRP levels in transgenic mice compared to age-matched controls. This and other studies are establishing the CRP phenotype for future studies on peripheral vascular disease and atherosclerosis.
  
  
• A recent study by Hamdy Elsayed-Awad, MD, examined kinetic profiles of biomarkers in central and peripheral compartments of patients undergoing surgical repair of an aortic aneurysm. This study established a clinical paradigm for distinguishing between surgical trauma and ischemic/reperfusion periods following aortic cross clamp in thoracoabdominal aortic aneurysm (TAAA) patients. An important related discovery is the involvement of T cells and heat-shock protein in the injury and paraplegia in an animal model. In a recent case, specific T-cell clones were identified in a TAAA patient with ischemia/reperfusion injury leading to paraplegia.
  
  
• Fievos Christofi, PhD, has a new grant from the National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) in collaboration with faculty in Neuroscience (Helen Cooke, PhD) and the OSU Davis Heart and Lung Research Institute (Arturo Cardounel, PhD, and Hamdy Hassanain, PhD) for a study focusing on therapeutic applications of purine-receptor agonists in inflammatory bowel diseases. Early findings have promising implications for patients with inflammatory bowel disease. Another discovery is that the cAMP signaling pathway may be involved in sensory neuron hypersensitivity that occurs after infection with a human nematode pathogen Trichinella spiralis, with implications for irritable bowel syndrome. Yun Xia, MD, is collaborating with Jackie Wood, PhD, and others in the OSU Department of Physiology & Cell Biology to study neuroimmune communication in the gastro-intestinal tract. His studies are funded through an NIDDK K08 Clinical Investigator Training Grant and a Davis/Bremer grant. Findings relate to sites of neuropeptides and receptors that may be involved in gut inflammatory responses.
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DEPARTMENT OF BIOMEDICAL INFORMATICS  (BMI)
Joel Saltz, MD, PhD, Chair
The National Library of Medicine defines biomedical informatics as the intersection of informational and computing sciences with an application domain in health care and biomedicine. The Department of Biomedical Informatics (BMI) is a collaboration of high-end and Grid-computing scientists, image analysis/computer vision specialists and systems biologists/bioinformaticians who address problems intersecting computer science and biomedical and scientific research. Researchers apply distributed and parallel computing techniques to data retrieval and integration, imaging, simulation, medical informatics and computational biology. They also develop middleware and optimizations to enable Grid computing in the biological, medical and physical sciences. Over the past year, BMI received nine awards from federal agencies with total funding exceeding $1.7 million, in addition to ongoing support of more than $1 million.

Ongoing Research Programs

• High-end, data-intensive and grid-computing research – Faculty and staff researchers of the multiscale computing area develop middleware technology and techniques to enable management, sharing and manipulation of data at multiple scales across heterogeneous, dynamic collections of storage and computation systems. Some application areas include:
  – large-scale collaborative biomedical clinical studies
  – analysis of gene expression and functional imaging information
  – imaging, analysis and simulation of oil reservoirs and data-driven control of oil production
  – analysis of satellite data
  – analysis of multi-resolution, multiple-grid simulation datasets
  
  
• Image analysis/computer vision – The imaging research group focuses on microscopic and radiologic image analysis, computer vision, machine learning, medical imaging, hybrid system identification with applications in video segmentation, generalized principal component analysis, geometric theories of computer vision, and symmetry-based recognition and matching.
  
  
• Systems biology/bioinformatics – The systems biology/bioinformatics group focuses on bioinformatic analysis of gene regulation involving chromatin, transcription factor (TF) interactions with DNA, promoter analysis and other related topics. Another line of investigation is the development of computational and evolutionary sciences in a comparative genomics context, including the development of novel phylogenetic methods to correlate genotypes and phenotypes and to find diagnostic polymorphisms among organisms. Recently, this group has begun to study molecular changes associated with zoonoses and pandemics from a whole-genome perspective with particular emphasis on coronaviruses (SARS) and influenza (avian and other influenza strains).
  

Research Accomplishments of 2005

• caBIG - caGrid 0.5 middleware development – The multiscale computing laboratory (Joel Saltz, MD, PhD; Umit Catalyurek, PhD; Tahsin Kurc, PhD; Scott Oster, MS; Shannon Hastings, MS; Stephen Langella, MS) developed and released caGrid 0.5 in September 2005. The cancer Biomedical Informatics Grid, or caBIG™, is a voluntary, virtual informatics infrastructure that connects data, research tools, scientists and organizations to leverage their strengths and expertise with common standards and shared tools. The current test bed architecture of caBIG™ is dubbed caGrid. The software embodiment and corresponding documentation of this architecture constitute the caGrid 0.5 release. caGrid 0.5 is the first test-bed release of the grid infrastructure to support the caBIG™ community. The caGrid 0.5 software release contains tools for creating and deploying caBIG™-compliant grid services to the caGrid 0.5 infrastructure. The software infrastructure is designed to satisfy the use of case requirements from various caBIG™ Domain Workspaces. caGrid 0.5 is providing the infrastructure for caBIG™ applications. BMI is also leading the next phase of the development, caGrid 1.0, during 2006.
  
  
• Grid computer-assisted detection application – This group (Joel Saltz, MD, PhD; Metin Gurcan, PhD; Ashish Sharma, PhD; Tony Pan, MS) developed GridCAD, a grid-enabled application that exposes Computer Aided Detection (CAD) algorithms as grid services. This provides remote execution of multiple, geographically dispersed CAD systems using image databases at different locations. GridCAD fosters collaboration through secure sharing of CT image data and CAD algorithms for research and clinical studies. To be scalable, secure, open-source and platform-independent, it uses open-source caGrid middleware (the core Grid software infrastructure of caBIG) and OSU Mobius software. GridCAD allows remote image databases to be queried and previewed. It also enables a selected set of CAD algorithms to be run on the queried images. Once CAD results (marked locations on images) are available, users can view full resolution images overlaid with CAD results. This reduces processing time and the algorithm development cycle via remote compute resource recruitment and CAD compute farms. Since it provides remote CAD execution, there is reduced data transfer and no need to transmit PHI. A GridCAD testbed was demonstrated at the 2005 meeting of the Radiological Society of North America. This work will play a role in grid-based activities of the caBIG In Vivo Imaging Workspace and the Testbed Special Interest Group.
  
  
• Virtual mouse placenta: successful tissue segmentation image modeling and representation – Microscopic imaging is a tool to characterize phenotype (e.g., morphology and behavior) change caused by genotype manipulation such as mutation and gene knockout. Kun Huang, PhD, with Gustavo Leone, PhD, used high-resolution microscopic imaging to study the morphological change in mouse placenta induced by retinoblastoma (Rb) gene knockout. To assess this change, they segmented each microscopic image into regions corresponding to tissue types. Due to the complex structure of these tissues and the large variation among the more than 2,000 images, they designed a Bayesian-supervised segmentation method that uses image features of all levels and applied this method to the entire data set. The high variation of the microscopic images necessitated using image features at all levels (including pixel color, texture, RBC count, nuclei size and vacuole count) rather than classic color- and texture-based segmentation algorithms. The algorithm is scalable to the large image data set and resulted in  segmentation of the 2,000 images, which will be used for further phenotype analysis.
  
  
• Image modeling is critical for analyzing and compressing complex images with different textures (e.g., different types of tissues). Tim Huang, PhD, in collaboration with Yi Ma, PhD, at the University of Illinois, used a new technique called generalized principal component analysis to model images and image sequences using hybrid linear models. In their approach, regions in the images with different textures are modeled by different linear models. This leads to a more effective representation of images than current image compression standards such as JPEG and JPEG2000. Results were presented at the International Conference on Computer Vision (ICCV) in October 2005. This approach was extended to model image sequences and segment high-resolution ultrasound image sequences. It was also presented at the ICCV’s Dynamical Vision Workshop.
  
  
• Bioinformatics –  A group led by Ilya Ioschikhes, PhD, (including Naum Gershenzon, PhD, Li Wang, PhD, and Amutha Ramaswamy, PhD) proposed a refined algorithm for mapping putative binding sites for transcription factors (TFs) – proteins regulating gene transcription. Position-weight matrices (PWMs) are used to find TF binding sites in DNA sequences. Most PWMs provide a low level of sensitivity and specificity. This group presented a new computational algorithm that improves the PWMs. They then applied the proposed technique to the PWMs of the GC-box, the binding site for Sp1. Comparison of old and new PWMs showed that the latter increase both sensitivity and specificity. The majority of commonly used PWMs are the 4-row mononucleotide matrices, although 16-row dinucleotide matrices are more informative. The algorithm determines the 16-row matrices, and preliminary results show that such matrices provide better results than 4-row matrices. The team also obtained refined PWMs for other promoter elements, in particular for the TATA-box, ETS-1, and more, that required modification of the algorithm. The respective projects involved collaboration with Gary Stormo, PhD, an expert in TF mapping from Washington University in St. Louis, and Michael Ostrowski, PhD (then in the OSU Department of Molecular Genetics).
  
  
• Other research accomplishments by the Ioschikhes group include: structural dynamic modeling of single nucleosomes and their short arrays by Normal Mode Analysis (in collaboration with Ivet Bahar, PhD, at the University of Pittsburgh); discovery of synergy of human Pol II core promoter elements by statistical sequence analysis; study of the Downstream Core Element (with researchers from the University of Medicine and Dentistry of New Jersey); development of software for promoter analysis, etc. Results were published in the journals Proteins, Bioinformatics, Mol Cell Bio, Appl Bioinformatics, and Proc 5th IEEE Int Symp Bioinf Bioeng.
  

Division of Anatomy                                        
Kenneth Jones, PhD, Director
The Division of Anatomy has nine full-time faculty with a teaching mission that served more than 2,300 undergraduate, graduate and professional students in 2004-2005. Required and elective courses are offered in human anatomy, embryology, histology, neuroanatomy and radiological anatomy. Workshops in anatomy are offered as continuing professional education to physical therapists, occupational therapists, athletic trainers, paramedics and emergency medical technicians. The faculty’s interests lie in three principal areas: the biomechanical effects of trauma, applied neuroanatomy and the development of medical education technologies. The Division hired one faculty member in September 2005 to replace Julia Guy, PhD, and assist in teaching a large undergraduate enrollment. In scholarship, David Clark, PhD, published the 2nd Edition of his textbook, The Brain and Behavior, and Guy published the 3rd Edition of her text, Learning Human Anatomy, and of her computer program, AnatLab.

Ongoing Research Programs

• Kenneth Jones, PhD, and John Bolte, PhD, expanded the Division’s portfolio in biotrauma with contracts from industrial and federal funding sources.
  
  
• John Bolte, PhD, organized the first of what is to be an annual Injury Biomechanics Symposium that was attended by more than 80 representatives from 17 universities and three foreign countries. The Second Annual Biomechanics of Injury Symposium was held in May 2006.
  
  
• David Clark, PhD, studied a novel treatment of attention deficit  hyperactivity disorder in children that involves stimulation of the vestibular system (NIH).
  

Research Accomplishments of 2005
Research funding support for the Division of Anatomy totaled $903,251 in 2005. The projects included:

• An ongoing NIH grant to David Clark, PhD, for trials on stimulating the vestibulocochlear nerve to treat attention deficit hyperactivity disorder.
  
  
• Two contracts from the National Highway and Transportation Safety Administration for basic research that will lead to improving the biofidelity of anthropomorphic test devices were awarded to Kenneth Jones, PhD, and John Bolte, PhD.
  
  
• A contract from Nissan Motors for human factor tests of a new automobile seat design was awarded to John Bolte, PhD and Kenneth Jones, PhD.
  
  
• Julia Guy, PhD, published the third edition of Anatlab: The Anatomy Lab. This interactive multimedia CD supplements the undergraduate laboratory experience and is used by a number of colleges and universities in the United States and Canada. 
  
  
• Thomas Hayes, PhD, earned  the OSU College of Medicine’s Distinguished Educator (Basic Science) Award.
  
  
• John Chidley, MS, PT, earned an Excellence in Teaching Award from the Department of Bioinformatics and the College of Medicine.
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DEPARTMENT OF EMERGENCY MEDICINE
Douglas Rund, MD, Chair
The Department of Emergency Medicine includes 30 faculty, 38 residents, one research fellow, a research nurse coordinator, a research technician and support staff. Department research has focused on the laboratory and the development of clinical-based studies. Established in 1990, this academic department has shown steady growth.

Ongoing Research Programs

• The Laboratory Research Program, directed by Mark Angelos, MD, is based in the OSU Davis Heart and Lung Research Institute and is focused on cardiac reperfusion.
  
  
• Michael Sayre, MD’s Resuscitation Research Program mission is to increase survival from sudden cardiac arrest in central Ohio and beyond by developing and researching innovative and diagnostic treatment strategies.
  
  
• Robert Guthrie, MD, operates a Clinical Trials Research Program evaluating new drugs for the long-term care of patients with hypertension, cholesterol disorders and diabetes.
  

Research Accomplishments of 2005

• Seven research abstracts were presented at the Society of Academic Emergency Medicine’s national scientific meeting in May 2005 in New York City. Two abstracts were presented at The American Heart Association’s Scientific Sessions in November 2005 in Dallas, Texas.
  
  
• Mark Brauner, DO, first-year resident in Emergency Medicine, received Best Presentation and Young Investigator Award at The International Conference on Electron Paramagnetic Resonance Spectroscopy and Imaging of Biological Systems in Columbus.
  
  
• The Department established an undergraduate Research Associate Program with the hospital volunteer office. Director Jeff Caterino, MD, and coordinator Carol Schneider, RN, began Winter Quarter 2004/2005 orienting OSU undergraduates to screen and enroll patients in approved clinical trials in the Emergency Department. In its first year, the program has increased the numbers of enrolled subjects and provided students interested in medicine with experience interacting with patients, nurses and physicians.
  
  
• Terry Vanden Hoek, MD, associate professor at University of Chicago Hospitals, presented “New Life for the Treatment of Sudden Death” at Emergency Medicine’s 3rd Annual Spring Research Day. His talk was followed by presentations from department senior residents, fellows and faculty.
  
  
• Recognizing the need for a collaborative forum for clinical research personnel at OSU, Carol Schneider, RN, research coordinator, established OSU Clinical Research Professionals (OCRP). At monthly meetings, research coordinators and other research personnel hear presentations related to clinical research at OSU from representatives of departments and research offices. Attendees share their own research knowledge gained over years of working in clinical trials.
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DEPARTMENT OF FAMILY MEDICINE     
Mary Jo Welker, MD, Chair
The Department of Family Medicine provides quality health care based on the family practice model of teaching, pursuing cutting-edge research and scholarship, and providing service through personal, professional and political efforts. The Department fosters, facilitates and reports collaborative inter-disciplinary research directed toward optimizing health. Central to these efforts is the Ohio State Primary Care Research Institute, a collaboration including faculty from the Division of General Internal Medicine and the Division of Ambulatory Pediatrics plus numerous other departments at OSU. Family Medicine’s collective laboratory is the 29-site Ohio State Primary Care Practice-Based Research Network, which includes all of Franklin County and serves some 140,000 patients. Outside funding for research projects increases annually.

Ongoing Research Programs 

• The Ohio Center of Excellence for Bioterrorism Preparedness and Response is a two-year federally funded grant to establish a collaborative, inter-disciplinary and multi-institutional effort to prepare curricula in bioterrorism preparedness and responsiveness that can be integrated into medicine, nursing, public health and allied health.
  
  
• Academic Administrative Units in Primary Care is a three-year federally funded grant that is helping the Ohio State Primary Care Research Institute expand research in cancer, diabetes, genetics and cardiopulmonary conditions.
  
  
• Collaborative Pharmacotherapy Management of type 2 diabetes mellitus is a Davis/Bremer-supported grant initiative that introduces evidence-based, collaborative pharmacotherapy management (CPM) into the chronic care of adult family medicine patients with type 2 diabetes. 
  
  
• Funded initially by Columbus Compact Corporation and subsequently by the Ohio Board of Regents, Ohio TeleHELP: The Ohio TeleHealth, Education, and Linkage Program supports planning, implementation and study of telehealth initiatives throughout Ohio. 
  
  
• A study titled Using B-Type Natriuretic Peptide as a Screen for Asymptomatic Heart Failure in Hypertensive Patients with Either Ischemic Heart Disease and/or Diabetes examines the association between plasma b-type natriuretic peptide (BNP) levels and ventricular function in a group of ambulatory patients of ages 65 years or older who have a history of hypertension with either ischemic heart disease and/or diabetes mellitus, but no history and/or symptoms suggesting heart failure. This study is funded by the Crisafi-Monte Primary Care Cardiopulmonary Grant Program.

Research Accomplishments of 2005  

• Doug Post, PhD, received a National Institutes of Health (NIH) grant for his project titled “Patient-Centered Communication During Chemotherapy.” This two-year, $299,000 project will: develop a patient-centered communication intervention for breast cancer patients undergoing chemotherapy; examine patient reactions to the intervention; and evaluate the intervention’s effects on pain, depression and fatigue symptoms over time.
  
  
• Post is also co-investigator for two other NIH-funded projects. One is “Efficacy of Web-Based Training in Skin Cancer Triage,” a five-year initiative through a subcontract from Brown University that evaluates a Web-based education curriculum in skin cancer detection for primary care physicians. The other is “Reducing Cervical Cancer in Appalachia,” a five-year project based on the OSU Comprehensive Cancer Center’s aim to increase Pap smear screening among Ohio Appalachian women, identify factors related to tobacco use and cessation intervention among those women, and determine social, behavioral and biological variables that raise the risk of abnormal Pap smears.
  
  
• Randy Wexler, MD, was awarded a grant for his project, “Cognitive Behavioral Therapy - Techniques and Lifestyle Changes: Reducing Systolic Blood Pressure,” a study testing the hypothesis that patients can be taught to implement Lifestyle Behavioral Changes (LBCs - restricting dietary sodium, engaging in aerobic physical activities, and moderating alcohol intake) augmented with Cognitive Behavioral Therapy-Techniques (CBT-T) in the time frame of a routine primary care office visit. Wexler and colleagues will conduct a prospective randomized clinical trial comparing LBCs augmented by CBT-T to usual care in treating hypertension in the primary care setting.
  
  
• In a related study, Wexler is developing a profile of hypertensive patients seen in the OSU Primary Care Network. This project, “Reducing Systolic Blood Pressure: Using the Transtheoretical Model to Develop Hypertension Readiness to Change Profiles,” will allow him to develop and test behavioral interventions based on patient needs and willingness to reduce blood pressure. 
  
  
• Doug Knutson, MD, completed a major grant project, “Ohio State’s Four-Year Family Medicine Curriculum: C.A.S.E. (Comprehensive Active Student Education),” and is extending his work through a similar grant project: “Teaching to the CORE: Using Core Competencies Without Losing Core Values.”  In the former project, Knutson and his team developed educational initiatives emphasizing a patient-centered focus for disease management and prevention in response to national goals and health priorities. The latter project will enhance medical school curriculum at OSU, focusing on core competencies while creating an environment enabling students to retrain in altruism and service.
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DEPARTMENT OF INTERNAL MEDICINE
Michael Grever, MD, Chair
The Department of Internal Medicine comprises 12 divisions, each dedicated to innovations in patient care, research and education. Following are research highlights from 2005:

Division of Cardiovascular Medicine                     
William Abraham, MD, Director
The Cardiovascular Clinical Research Unit (CCRU), in partnership with patients, healthcare professionals and researchers, provides leadership in conducting clinical trials that investigate new cardiovascular drug and device therapies. By linking the OSU Ross Heart Hospital and the OSU Davis Heart and Lung Research Institute, the CCRU helps clinical researchers and basic scientists work together to improve patient care and outcomes. The CCRU manages more than 50 clinical research projects, including investigator-initiated single-site studies, NIH-sponsored multi-site trials, and industry-sponsored trials. Studies span a number of research areas: heart failure, interventional cardiology, electrophysiology, cardiac imaging, cardiac genotyping and pulmonary hypertension. Investigators and research staff identify patients who may be candidates for specific protocols, then follow them closely throughout the studies, often for several years. Results from these clinical studies form the basis for standard-of-care practices and identify additional questions for translational and basic research. 

Ongoing Research Programs

• Heart failure and a controlled trial investigating outcomes of exercise training (HF-ACTION); PI: William Abraham, MD
  
  
• Hemodynamically guided home self-therapy in severe heart failure patients (Homeostasis II); PI: Garrie Haas, MD
  
  
• Safety and tolerability of IV PST 2744 in adults with chronic heart failure: A phase I/II study (PST 2744); PI: Garrie Haas, MD
  
  
• Chronicle offers management to patients with advanced signs and symptoms of heart failure: An implantable hemodynamic monitoring system (COMPASS); PI: William Abraham, MD
  
  
• Trial to Assess Chelation Therapy (TACT); PI: Raymond Magorien, MD
  

Research Accomplishments of 2005

• The Cardiovascular Clinical Research Unit (CCRU) continued to evolve as a model for clinical research at OSU Medical Center and as a national leader in conducting clinical research on new cardiovascular drug and device therapies. Regarding the former, Director Garrie Haas, MD, and Manager Deanna Golden-Kreutz, PhD, are participating with Hospital Revenue Cycle Management in structuring a formalized hospital billing process for clinical research, with Information Warehouse in the development of clinical research databases, and with Human Resources in restructuring research personnel descriptions. CCRU staff have been recognized by the HF-Action and TACT trials for excellence in protocol and medication compliance, respectively.

On the national level, the Division has had a number of accomplishments that place OSU as a key participant in cardiovascular device and drug research:

• The nation’s first permanent device for monitoring and treating congestive heart failure was implanted using a minimally invasive cardiac catheterization procedure at the OSU Ross Heart Hospital. This investigational cardiac device, called the HeartPod (Savacor, Inc.), allows patients to monitor and make changes to their treatment regimen, if needed, based on specifications pre-set by their physician. The device is being tested for functionality and efficacy. OSU is also the nation’s highest enrolling site for the HeartPod (n=5). Garrie Hass, MD, is the local principal investigator. Charles Bush, MD, medical director of the OSU Ross Heart Hospital, and Charles Love, MD, director of the EP Lab, conduct the implants. William Abraham, MD, is the national principal investigator. 
  
  
• Ohio’s first investigational elastic mesh net (Paracor Medical, Inc.) was implanted during a minimally invasive cardiothoracic procedure performed at the OSU Ross Heart Hospital. The device, made from a metal alloy and coated with silicone, is designed to retain an engineered shape and, by applying gentle pressure to the heart’s walls, researchers hope that it will prevent enlargement and weakening that is common in congestive heart failure. William Abraham, MD, is principal investigator. Benjamin Sun, MD, a co-investigator and chief of Cardiothoracic Surgery, implanted the device. 
  
  
• OSU was also one of only four sites in the nation to test the investigational drug PST 2744, a derivative of androstenedione (Sigma Tau Healthscience SPA). While chemically unrelated to cardiac glycosides or phosphodiesterase inhibitors, PST 2744 inhibits the sodium/potassium ATPase pump, stimulates the sarcoplasmic reticulum calcium pump (SERCA) and reduces angiotensin I and II plasma levels. The clinical tolerability, safety and effectiveness of the drug, administered as an infusion, in improving the pumping activity of the heart were studied in chronic heart failure patients. OSU was the highest enrolling site in the United States. Garrie Haas, MD, was principal investigator. 
  
  
• OSU participated in a study assessing the three-month safety and efficacy of ultrafiltration using CHF Solution’s System 100 in the reduction of fluid overload in patients hospitalized with acute decompensated heart failure. Ultrafiltration was compared to traditional IV diuretic treatment. Garrie Haas, MD, was principal investigator. OSU’s involvement with the study has led to additional funding from CHF Solutions to study the effect of ultrafiltration on heart rate variability. Philip Binkley, MD, is principal investigator.
  

Division of Dermatology                  
Mark Bechtel, MD, Director
Mark Bechtel, MD, became Division director in 2005. Dermatology is working with the Division of Hematology and Oncology on cutaneous lymphoma and cutaneous oncology, focusing on comprehensive clinical management, clinical trials and oncologic genetic research. A cutaneous oncology facility is being designed to provide increased surgical space for Mohs surgery and collaboration between Dermatology and Hematology and Oncology.

Ongoing Research Programs and Accomplishments of 2005

• A complex Medical Dermatology Clinic was established for Dermatology residents, focusing on evaluation/management of patients with autoimmune bullous diseases, collagen vascular diseases and severe psoriasis.
  
  
• Mark Bechtel, MD, was recognized in the 2005-2006 Best Doctors in America. He serves on the American Academy of Dermatology’s Guidelines and Standards of Care Task Force.
  
  
• David Lambert, MD, is collaborating with Ronald Glaser, PhD, in an NIH-funded study on the effects of stress on basal cell carcinoma. Lambert also is collaborating with Amanda Tolland, PhD, in studying molecular genetics of squamous cell carcinoma.
  

Division of Endocrinology, Diabetes and Metabolism        
Kwame Osei, MD, Director
The Division of Endocrinology, Diabetes and Metabolism continues to excel in research, teaching and patient care. The Endocrinology specialty at the Ohio State University Hospital was cited for the 12th time among the Best Divisions in Hormonal Disorders by U.S. News & World Report (1993-98 and 2000-2005). In coming years, the Division will expand its accomplishments through research in diabetes, islet cell transplantation, osteoporosis and bone diseases, thyroid cancer and benign thyroid-pituitary disorders.

Ongoing Research Programs

• Thyroid Cancer Program at the OSU Martha Morehouse Medical Plaza (Matthew Ringel, MD)
  
  
• Non-human primate experimental model of islet cell transplantation (Elizabeth Diakoff, MD)
  
  
• Diabetes Research Center (Kwame Osei, MD)
  
  
• Women’s Health Initiative (WHI) and Osteoarthritis Initiative (OAI) (Rebecca Jackson, MD)
  

Research Accomplishments of 2005

• In conjunction with the OSU Comprehensive Cancer Center – James Cancer Hospital and Solove Research Institute, the Division has established the Thyroid Cancer Program at the OSU Martha Morehouse Medical Plaza. This program aims to: 1) define the molecular basis of thyroid cancer growth and metastasis;  2) develop chemotherapies as an adjunct for radioiodine and thyroxine therapy; and 3) develop a translational research program in thyroid cancer at OSU Medical Center.
  
  
• The Division, in conjunction with the Division of Transplantation, has established a Non-Human Primate Experimental Model of Islet Cell Transplantation (ICTP). The success of this program has become the backbone of the human ICTP initiative. Objectives are to develop therapies to ensure longstanding islet cell functional survival in humans by immunoprotection and to promote islet cell growth and anti-apoptosis.
  
  
• The College of Medicine’s Executive Committee approved a business plan to establish a Diabetes Research Center, which will devise therapeutic strategies for: 1) maintaining functional ICTP and PAT; 2) diabetes and cardiovascular disease, and 3) prevention of type 2 diabetes. A Community Diabetes Program also will be developed.
  
  
• The Division supports two prestigious NIH Centers: the Women’s Health Initiative (WHI) and the Osteoarthritis Initiative (OAI). Given the strengths of these centers, the Division has recruited new faculty in bone epidemiology.
  

Division of General Internal Medicine             
Robert Murden, MD, Director
The Division of General Internal Medicine provides high-quantity, high-quality patient care with a focus on medical education and research. The Division receives more than 50,000 outpatient visits and almost 3,000 inpatient visits yearly. Seven faculty were named in Best Doctors in America®, five were listed among Columbus Monthly’s top 250 doctors in central Ohio, and 10 were cited for excellence on one of those lists. The Division’s clinical care and education in geriatrics were ranked 31st in the nation by U.S. News and World Report. Clinical research within the Division focuses on perioperative care, hypertension and point-of-service testing for diabetes, hyperlipidemia and anti-coagulation management. In General Internal Medicine, research in dictation is as strong a focus as clinical research. Educational research focuses for medical students include geriatrics, professionalism, faculty development, physical diagnosis, and healing as an art. Faculty also research the use of decision-making aids by physicians.

Ongoing Research Programs

• Point of service testing in diabetes and anti-coagulation management – Mark Wurster, MD
  
  
• Faculty development of community-based primary care preceptors in underserved communities – Cynthia Ledford, MD
  
  
• Comparison of medical student and volunteer senior partner expectator for a regional senior partner experience in medical school – Robert Murden, MD
  

Research Accomplishments of 2005

• Continued production of history taking and physical exam cases for educational CDs by Cynthia Kreger, MD. These are used in several classes at OSU and sold nationwide.
  
  
• The faculty development proposal by Cynthia Ledford, MD, was funded for more than $200,000, the largest grant ever obtained by a principal investigator in the Division of General Internal Medicine.
  
  
• Almost half of the faculty was involved in research projects in 2005, the highest participation ever.
  

Division of Hematology and Oncology                 
Michael Caligiuri, MD, Director
Research focuses on developing drug therapies for treating solid tumor and hematologic malignancies, and on cancer prevention through nutrition and natural products. The Division’s annual direct peer-reviewed funding increased to more than $12.3 million in 2005. Notable awards include a V Foundation – American Association for Cancer Research grant for Miguel Villalona, MD, and a Specialized Centers of Research (SCOR) grant from the Leukemia & Lymphoma Society for John Byrd, MD. Investigators oversee more than 130 clinical protocols, and several received grants for clinical trials on anticancer therapies. Byrd was awarded two NCI grants to predict the response of chemoimmunotherapy and epigenetic therapy in chronic lymphocytic leukemia (CLL). Thomas Lin, MD, PhD, received two NCI awards to study a novel dosing schedule for flavopiridol in CLL and for a phase I study of the AKT inhibitor in 17-AAG in CLL. Sherif Farag, MD, PhD, received an NCI grant to study mTOR inhibition as a therapeutic target in myelomas. Manisha Shah, MD, is principal investigator for a study using Celebrex to treat metastatic differentiated thyroid cancer.

Ongoing Research Programs

• Innate immunity: elucidation and modulation for cancer therapy program project grant. This program applies basic biology related to the innate immune system to cancer therapy with an emphasis on antibody therapy in hematologic malignancy – Michael Caligiuri, MD
  
  
• Phase I trials of anti-cancer agents. This program performs early drug development in solid and hematologic tumors with performance of detailed pharmacokinetic and pharmacodynamic studies – Michael Grever, MD
  
  
• Experimental therapeutics in chronic lymphocytic leukemia (CLL). This SCOR grant is designed to create new and improve current therapies for CLL – John Byrd, MD
  
  
• Leuteal adjuvant oophorectomy in Vietnamese breast cancer – Richard Love, MD
  
  
• Prevention of esophageal cancer with berries – Gary Stoner, PhD
  

Research Accomplishments of 2005

• John Byrd, MD, was awarded a five-year, $6.25 million SCOR grant from the Leukemia and Lymphoma Society to develop new and improve current therapies for chronic lymphocytic leukemia.
  
  
• Miguel Villalona, MD, received a V Foundation – AACR Grant in Translational Research to identify genetically based racial differences that may help predict response to lung cancer treatment.
  
  
• The chemoprevention program, led by Gary Stoner, PhD, realized the effective translation of lab research to bedside care with a clinical trial using black raspberries in the form of oral gels, lozenges and freeze-dried preparations to inhibit the development of oral, esophageal and colon cancers.
  

Division of Human Genetics                               
Albert de la Chapelle, MD, PhD, Interim Director
The Division of Human Genetics (HG) serves as a single platform for translational and clinical research, clinical activities, and education and outreach. The Division’s goals are to enhance OSU Medical Center as a leader in gene discovery/characterization and molecular epidemiology, to set standards for the clinical management of patients with genetic predisposition, and to set guidelines for society regarding the research and clinical use of genetic information. Clinical responsibilities are to provide genetic counseling to patients and families, and expert consultations to physicians and other professionals. HG not only provides medical genetics care to residents of central Ohio and surrounding states, but also gives patients and physicians in the community free access to HG research protocols. HG coordinates clinical-genomic databases, specimen repositories and the use of both in-house and referral diagnostic facilities to support clinical research in human genetics.

Ongoing Research Programs

• Columbus-area hereditary nonpolyposis colon cancer (HNPCC) study – Albert de la Chapelle, MD, PhD
  
  
• Variants in high risk breast cancer genes and contribution to cancer risk – Amanda Toland, PhD
  
  
• Frequency and clinical spectrum of germline PTEN mutations in a population-based series of incident breast cancer cases in central Ohio – Charles Shapiro, MD
  
  
• Funny polyps study – Albert de la Chapelle, MD, PhD
  
  
• Cancer family history public health campaign/Jameslink – Kimberly Kelly, PhD
  

Research Accomplishments of 2005

• Columbus-area HNPCC (hereditary nonpolyposis colon cancer) study – Albert de la Chapelle, MD, PhD.  Funded by a grant from the National Cancer Institute and by Ohio Biomedical Research and Technology Transfer grants, this is a case series of unselected colorectal and endometrial cancer patients who are being screened for Lynch syndrome – the most common heritable colon cancer syndrome caused by germline mutations in a series of mismatch repair genes. This is the largest series of colorectal cancer patients (1,066) to receive complete genetic testing for Lynch syndrome. Findings showed that 2.3 percent of all colorectal cancer patients (1 of  45) has Lynch syndrome (NEJM 2005). Similar frequencies of Lynch syndrome were found in endometrial cancer patients (Cancer Research 2006). Also, these studies proved the efficacy of screening for Lynch syndrome by using immunohistochemistry for the four mismatch repair proteins in all newly diagnosed colorectal cancers in the Pathology Department. This is leading to a change in clinical practices around the nation and world. 
  
  
• Funny polyps study – Albert de la Chapelle, MD, PhD. This study, previously led by Charis Eng, MD, PhD, includes a heterogeneous group of patients with at least five colon polyps, one of which has to have hyperplastic histology. Pathology of all polyps was re-reviewed by study pathologist Joe Willis from Case Western Reserve University for verification. Germline DNA from the patients was tested for mutations in a number of genes known to lead to polyposis when mutated. The findings were published this year and were surprising in the number and type of gene mutations identified (JAMA 2005).
  
  
• Comparative genotype-phenotype correlations in Cowden syndrome (CS) and Bannayan-Ruvalcaba-Riley syndrome (BRR) – Charis Eng, MD, PhD. The Eng lab tested patients with atypical features of Cowden syndrome or Bannayan-Ruvalcaba-Riley syndrome for germline PTEN mutations for several years. The notable finding in 2005 involved the frequency of PTEN mutations in a series of children with macrocephaly and autistic behavior (J Med Genet 2005). As a result of this publication, pediatric geneticists should consider PTEN mutations in the differential diagnosis for patients presenting with these features. Clinical genetic testing of the PTEN gene in the OSU Molecular Pathology Laboratory on a fee-for-service basis is increasing (from 120 cases in 2005 to a projected 160 cases in 2006). 
  

Division of Immunology                                        
Ronald Whisler, MD, Director
The Division of Immunology makes advances in academic excellence and research while serving the University and the community in the clinical setting. The Division’s publications and peer-reviewed grants demonstrate considerable strength. Examples include National Institutes of Health (NIH)-supported studies of Fc receptors by Clark Anderson, MD, and the NIH-funded Osteoarthritis Initiative led by principal investigator (PI) Rebecca Jackson, MD, and co-PIs Kevin Hackshaw, MD, and Ronald Whisler, MD. The Division also has been active with clinical investigations into more efficacious treatment regimens for rheumatoid arthritis, sarcoidosis, spondyloarthropathies and other connective tissue disorders. Plans are in place to increase teaching and research opportunities by adding more clinician investigators.

Ongoing Research Programs and Research Accomplishments of 2005

• How FcRn prolongs IgG lifespan – Clark Anderson, MD
  
  
• FcRn binds and transports albumin – Clark Anderson, MD
  
  
• Clinical centers for the Osteoarthritis Initiative – Kevin Hackshaw, MD, and Ronald Whisler, MD, co-principal investigators
  
  
• Abatacept in rheumatoid arthritis – Kevin Hackshaw, MD (clinical)
  

Division of Infectious Diseases       
Larry Schlesinger, MD, Director
The Division of Infectious Diseases increased its research portfolio and strengthened ties with other University researchers and academic institutions in 2005. Division faculty submitted 27 grants. Research included $2.26 million from the National Institutes of Health (NIH), the Health Resources and Services Administration, and the Department of Health and Human Services to support studies for patients with HIV/AIDS. The Division’s NIH-awarded AIDS Clinical Trials Unit (ACTU) was ranked 17th among the top 25 research awards across the University. The Center for Microbial Interface Biology (CMIB) continued development of new multidisciplinary research programs to explore fundamental questions in infectious diseases, pathogenesis and bioterrorism. New research awards for the CMIB totaled $3.65 million. A new BSL-3 facility on West Campus will open in 2006, providing research space for continued work on tuberculosis and other aerosol pathogens. The Biomedical Research Tower, scheduled to open in December 2006, will also provide the CMIB with additional BSL II-III research space.

Ongoing Research Programs

• Adult AIDS Clinical Trials Unit – Susan Koletar, MD
  
  
• AIDS Education and Training Center – Michael Para, MD
  
  
• TB and innate immune regulation of lung macro-phages – Larry Schlesinger, MD
  
  
• Planning regional centers of excellence – Larry Schlesinger, MD
  
  
• CD8 T cells and immunity to tuberculosis in old mice – Joanne Turner, PhD
  

Research Accomplishments of 2005

• The OSU AIDS Clinical Trials Unit (ACTU) helps advance AIDS care via clinical research on the pathogenesis, prevention, course and treatment of HIV infection and its associated complications through affiliation with the national and inter-national organization, the AIDS Clinical Trials Group (ACTG). By serving in leadership roles for protocol development and administrative functioning of the group, OSU participates in the design and implementation of clinical trials that seek to 1) optimize clinical management of HIV and related complications, 2) evaluate agents with novel mechanisms or improved toxicity profiles for the treatment of HIV and/or for major co-pathogens (such as tuberculosis and hepatitis), 3) evaluate the safety, immunogenicity, and efficacy of multiple candidate HIV vaccines and adjuvants, 4) develop means of reducing HIV transmission, and 5) minimize the risk of vertical transmission by maximizing care of HIV-infected women during their child-bearing years. Principal Investigator (PI) Susan Koletar, MD, participates in both the scientific research and the management of the ACTG as a member of several committees. Co-PI Michael Para, MD, also chairs a protocol committee, and David Wininger, MD, serves on the metabolic committee. In 2005, ACTU investigators published eight manuscripts and presented abstracts at national meetings.
  
  
• AIDS Education and Training Center (AETC) – The Pennsylvania Mid-Atlantic AIDS Education and Training Center, funded by the Health Resources and Services Administration, has a local performance site based in the Infectious Diseases Division at OSU (Michael Para, MD, PI). Targeting physicians and other healthcare professionals, this training center updates clinical practices and expands the capacity to provide HIV care to an underserved patient population in Ohio. The Center has met its training goals for the past two years. Its grant was refunded for five years in 2005.
  
  
• Center for Microbial Interface Biology (CMIB) – In 2005 the CMIB grew to nearly 40 personnel. Four faculty members had direct appointments in the CMIB, and there were approximately 20 investigator participants from throughout the OSU campus. Research funding for CMIB members totaled $2.79 million, with another $3.16 million in review.The second year of the P-RCE (Planning Regional Centers of Excellence) ID biodefense grant was completed. A program project grant and developmental funds were submitted to the Great Lakes Regional Center of Excellence in Biodefense and Emerging Infectious Diseases Research. The CMIB is a centerpiece for collaborations with units/departments across the University. Several program project grants and a training grant have been awarded or submitted with these units, including a Third Frontier application for a Wright Center of Innovation in conjunction with the OSU College of Food, Agricultural and Environmental Sciences. A Provost Targeted Investment Initiative proposal on infectious diseases public health preparedness has been submitted in conjunction with the OSU School of Public Health and the OSU colleges of Veterinary Medicine, Biological Science, Pharmacy, and Food, Agricultural and Environmental Sciences. CMIB-appointed faculty in 2005 had 10 papers published or accepted, along with numerous published abstracts and invited lectureships.
  
  
• American Heart Association – Brad McGwire, MD, PhD, received an American Heart Association grant to study the protozoan parasite Trypanosoma cruzi, the agent of South American trypanosomiasis and a leading cause of heart failure in Latin America. Genes encoding the surface metalloproteases (gp63) of this parasite are structurally related to those found in other protozoa such as Leishmania. In Leishmania, gp63 is an important virulence factor that has been well characterized at the genetic, biochemical and cell biologic levels. McGwire’s laboratory has begun the biochemical characterization of gp63s in T. cruzi (TcGP63). These studies will provide information on TcGP63s and help in understanding the role of these proteases in the biology of T. cruzi and how they may contribute to heart failure in patients.

Division of Nephrology
Brad Rovin, MD, Director
U.S. News & World Report ranked the OSU Division of Nephrology 28th among American Hospitals for treating kidney diseases – the fourth consecutive year that the Division was ranked among the top 50. The Division added three faculty members: Christopher Valentine, MD, who trained at Ohio State; Jon Von Visger, MD, PhD, from Harvard University; and Uday Nori, MD, from Indiana University. The Nephrology Program Project in SLE nephritis entered its fifth year. Investigators collaborating on this project (Lee Hebert, MD, Brad Rovin, MD, Dan Birmingham, PhD, and Chack-Yung Yu, PhD) have published 39 papers and review articles on lupus nephritis and are participating in three clinical trials of novel therapeutics for treating SLE. Clinical trials run by Anil Agarwal, Nabil Haddad, Lee Hebert, Dan Spetie and Ganesh Shidham, MDs, account for more than $785,000 in research funding.

Ongoing Research Programs

• The Nephrology Program in systemic lupus erythematous (SLE) nephritis comprises three projects: an NIH Program Project to study clinical and environ-mental risk factors for SLE nephritis; an exploratory grant to determine the applicability of urine proteomics in the diagnosis and management of SLE Nephritis; and participation in clinical trials of novel SLE therapeutics – Brad Rovin, MD, Lee Hebert, MD, and Dan Birmingham, PhD
  
  
• The African-American study of hypertension and kidney disease – Lee Hebert, MD
  
  
• The role of homocysteine in cognitive dysfunction and cardiovascular outcomes in kidney transplant patients – Todd Pesavento, MD
  
  
• The efficacy and safety of an oral calcimimetic agent in the secondary hyperparathyroidism of chronic kidney disease – Anil Agarwal, MD
  
  
• The use of mycophenolate in IgA Nephropathy and focal segmental glomerulosclerosis – Dan Spetie, MD, and Ganesh Shidham, MD.
  

Research Accomplishments of 2005

• The SLE Program has accumulated one of the largest and most detailed databases in patients with recurrently active lupus. This database is used to study genetic and environmental variables associated with renal SLE flare. Several studies have been completed using the SLE database:
  
  
  • Urine proteomic studies showed that an unexpected protein may play a role in SLE nephritis. This protein, adiponectin, is a cytokine made by fat cells. It is increased in patients with SLE and kidney disease. Adiponectin appears to influence inflammation and in this way may be relevant to SLE nephritis.
    
    
  • The transcription factor NRF2 was found to regulate the expression of the proinflammatory chemokine IL-8 by stabilizing messenger RNA. Previously, NRF2 was known to regulate only cytoprotective genes.
    
    
  • An erythrocyte complement receptor (E-CR1) known to bind circulating immune complexes in SLE patients was shown to be “consumed” in a process that protects the kidney from damage during SLE disease flare. This finding has led to proposed clinical trials to increase E-CR1 levels through erythropoietin therapy, with the intent of  providing renal protection in the SLE patient.
    
    
  • Stress has been thought of as a trigger of disease flare in SLE patients, but this had never been rigorously tested until OSU researchers found that variability in stress levels, rather than the overall stress level, is a predictor of flare. Furthermore, the pro-flare effect of stress variability is influenced by polymorphisms in receptors for serotonin (5-HTT and 5HT1A). 

Division of Pulmonary, Allergy, Critical Care and Sleep Medicine
Clay Marsh, MD, Director
Building along specialty-based product lines to “create the future of medicine to improve people’s lives,” the Division is evolving to achieve the promise of personalized health care focusing on translational research. Progress is evidenced by recognition in U.S. News & World Report as the 19th best respiratory program in the country. Also, 10 faculty were recognized among Best Doctors in America®; they constituted the entire list of those recognized in central Ohio in Pulmonary and Critical Care Medicine. New initiatives, current research and ongoing projects include:

• Critical Care named one of six Signature Programs by OSU Medical Center
  
  
• A new 14-bed Sleep Medicine Center at OSU East Hospital
  
  
• A pulmonary interventional procedural program
  
  
• Personalized health care in critical care and lung cancer programs
  
  
• Sleep disorder breathing and heart failure at the OSU Ross Heart Hospital
  
  
• Translational program in mononuclear phagocyte-mediated inflammation and lung disease
  
  
• Interdisciplinary program in mitochondria biology
  
  
• Process-based research and health outcomes in critical care and lung disease
  
  
• Translational research in acute lung injury in the Intensive Care Unit
  
  
• Expansion of the clinical lung transplant program, as well as the role of the humoral immune system in transplant complications
  
  
• A translational program in interstitial and fibrotic lung disease
  
  
• A lung volume reduction surgery program, pulmonary rehabilitation and exploring the origins of chronic onstructive pulmonary disease
  
  
• Creation of an Asthma Research Center
  
  
• A translational research program in pulmonary hypertension
  
  
• Antibody-directed therapies in cancer and response of cells to immune complexes
  
  
• Role of caspases on cellular survival as it applies to cancer and inflammation
  
  
• Ischemia and metabolic function in heart and lung disease
  
  
• Measurement of reactive oxygen species
  
  
• A program in lipid signaling in cells
  
  
• Role of inflammatory cells in lung complications of bone marrow transplantation
  
  
• Decision-making analysis in clinical medicine to practice more efficient medicine

Ongoing Research Programs

• Fibrosis, remodeling and lung injury – Clay Marsh, MD; Philip Diaz, MD; Daren Knoell, PhD; and John Mastronarde, MD
  
  
• Innate immune system function – Mark Wewers, MD; Susheela Tridandapani, PhD; and Karen Wood, MD
  
  
• Mitochondria biology and critical care disease – Douglas Pfeiffer, PhD; Elliott Crouser, MD; Naeem Ali, MD; and Ruairi Fahy, MD
  
  
• Process-based research and decision making – James O’Brien, MD; Scott Aberegg, MD; and Stephen Hoffmann, MD
  
  
• Redox biology of the lung and muscle – Thomas Clanton, PhD; Ulysses Magalang, MD; Valery Khramtsov, PhD; and Narasimham Parinandi, PhD
  

Research Accomplishments of 2005

• Establishment of mitochondria biology program
  
  
• Named cornerstone program in fibrosis, remodeling and immune function by the OSU Davis Heart and Lung Research Institute
  
  
• Named a Signature Program in Critical Care Medicine at OSU Medical Center
  
  
• Seven faculty with K grants from National Institutes of Health
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DEPARTMENT OF MOLECULAR AND CELLULAR BIOCHEMISTRY
Russ Hille, PhD, Interim Chair
The Department of Molecular and Cellular Biochemistry encompasses research programs that advance understanding of the molecular basis of biological processes and disease states in humans and model organisms. Research projects span a range of topics, from genetic studies of human motor neuron diseases to the reaction mechanism of enzymes in various (patho)physiological processes. Each research project is relevant to one or more of the identified “Signature Programs” of OSU Medical Center, including Critical Care (Douglas Pfeiffer, PhD; Patrice Hamel, PhD), Heart (Tsonwin Hai, PhD; Hamel; Russ Hille, PhD; Kamal Mehta, PhD; Pfeiffer), Cancer (Hai; Samson Jacob, PhD; Mark Parthun, PhD; Saïd Sif, PhD; Scott Walsh, PhD; Lai-Chu Wu, PhD), and Neurosciences (Arthur Burghes, PhD; Hille; Jeff Kuret, PhD; Jiyan Ma, PhD; Jill Rafael-Fortney, PhD; Sung Ok Yoon, PhD). 

Ongoing Research Programs

• Research in the laboratory of Charles Bell, PhD, focuses on the structural biology of protein-protein and protein-nucleic acid interactions involved in homologous recombination DNA-repair processes, particularly the DNA strand-exchange proteins RecA from E. coli and Rad51 of yeast and humans, and other molecules that interact with RecA and Rad51 (such as the tumor-suppressor proteins BRCA1, BRCA2 and p53).
  
  
• The main focus of the laboratory of Arthur Burghes, PhD, is the molecular understanding of genetic neuromuscular disorders, in particular spinal muscular atrophy, an autosomal recessive disorder characterized by destruction of motor neurons in the anteriorhorn of the spinal cord. The Burghes laboratory also is developing gene therapy methods for treatment of Duchenne Muscular Dystrophy (DMD), a muscle-wasting disorder caused by mutations in the large dystrophin gene. Researchers are interested in developing strategies that allow adeno-associated virus to be used for gene therapy of DMD.
  
  
• The laboratory of Russ Hille, PhD, studies reaction mechanisms of oxidoreductase enzymes – particularly those possessing molybdenum or flavin in their active sites – and biological electron transfer, utilizing a variety of methods including kinetic, spectroscopic, mutagenic and computational studies to gain further insight into the basic elements of catalysis.
  
  
• Samson Jacob, PhD, has research interests in: metallothionein gene expression in response to toxic heavy metals (cadmium, mercury, etc.) oxidative damage (e.g., by stress or UV radiation); protein transcription factors that modulate ribosomal RNA (rRNA) gene transcription, including the role of three proteins directly involved in this process that have been discovered in his laboratory; and the role of epigenetic DNA methylation in cancer.
  
  
• Mark Parthun, PhD, studies mechanisms by which chromatin structure is formed and regulated, using S. cerevisiae as a model system. Researchers are examining the roles of proteins involved in histone acetylation and other epigenetic forms of post-translational modification.

Research Accomplishments of 2005

• Bell Laboratory – Carcinoma of the prostate is the most commonly diagnosed cancer in men. The current pharmacological treatment of choice for progressive androgen-dependent prostate cancer is the nonsteroidal antiandrogen, bicalutamide, either as monotherapy or with adjuvant castration or luteinizing hormone-releasing hormone super agonists to block the synthesis of endogenous testosterone. Researchers reported the first X-ray crystal structure of the mutant W741L androgen receptor (AR) ligand-binding domain in complex with the inducer R-bicalutamide at 1.8-angstrom resolution. The mutation confers agonist activity to bicalutamide and is likely involved in bicalutamide withdrawal syndrome. The structure demonstrates that the B ring of R-bicalutamide in the W741L mutant is accommodated at the location of the indole ring of Trp-741 in the WT AR. This work provides a structural rationale for development of new antiandrogens and selective AR modulators.
  
  
• Burghes Laboratory – Spinal muscular atrophy (SMA) is an autosomal recessive disorder caused by reduced levels of the survival motor neuron (SMN) protein as a result of loss or mutation of the SMN1 gene. SMN is encoded by two genes, SMN1 and SMN2, which differ by a single nucleotide in exon 7. As a result, the majority of the transcript from SMN2 lacks exon 7 (SMN-7). Researchers created transgenic SMN-7 mice, crossed them onto a severe SMA background and found that the SMN-7 is not detrimental; rather, it extends survival of SMA mice from 5.2 to 13.3 days. Unlike mice with selective deletion of SMN exon 7 in muscle, these mice with a small amount of full-length SMN (FL-SMN) did not show a dystrophic phenotype. SMN and SMN- 7 can associate with each other. Researchers suggest this association stabilizes SMN-7 protein turnover and ameliorates the SMA phenotype by increasing the amount of oligomeric SMN. These results will facilitate testing of therapies and indicate the importance of considering co-complexes of SMN and SMN-7 when analyzing SMN function.
  
  
• Hille Laboratory – Researchers performed X-ray absorption studies on the oxidized molybdenum center of xanthine oxidase at pH 6 and 10. Results indicate that the active site has one terminal oxygen ligand (Mo = O), two thiolate ligands (Mo-S), one terminal sulfido ligand (Mo = S) and one Mo-OH. EXAFS analysis shows that the Mo-OH bond shortens from 1.97 angstrom at pH 6 to 1.75 angstrom at pH 10, which is consistent with the generation of an Mo-O- moiety. This provides convincing structural evidence that the catalytic oxygen donor at the oxidized active site of xanthine oxidase is Mo-OH rather than the Mo-OH2 ligation previously suggested by X-ray crystallography and supports a mechanism initiated by base-assisted nucleophilic attack of the substrate by Mo-OH.
  
  
• Jacob Laboratory – To elucidate the role of epi-genetic reprogramming in cell- or tissue-specific differentiation, researchers explored the role of DNA methyltransferases (Dnmts) in the nerve growth factor (NGF)-induced differentiation of PC12 (pheochromocytoma) cells into neuronal cells. The mRNA and protein levels of de novo methyltransferase Dnmt3b increased, whereas those of Dnmt3a and Dnmt1 decreased during NGF-induced neurite outgrowth. Dnmt3b localized in the nucleus, as well as in the growing neurites. When the expression of Dnmt3b was inhibited by antisense or small interfering RNA, PC12 cells continued to proliferate and failed to generate neurites. Cells depleted of Dnmt3b were unable to exit the cell cycle even after six days of NGF treatment. This failure in differentiation correlated with significant attenuation in tyrosine phosphorylation of TrkA (a marker for NGF-induced differentiation) and reduced the expression of neuronal markers. Data indicate a novel role of Dnmt3b in neuronal differentiation.
  
  
• Parthun Laboratory – The acetylation of the NH2-terminal tail of histone H4 by type B histone acetyltransferases (HATs) is involved in chromatin assembly. Histone H4 associated with a nuclear type B HAT complex contains modifications in its globular core domain as well. In particular, acetylation was found at lysine 91. A mutation that alters this residue, which lies in the interface between histone H3/H4 tetramers and H2A/H2B dimers, confers phenotypes consistent with defects in chromatin assembly, such as sensitivity to DNA-damaging agents and derepression and alteration of silent chromatin structure. These results indicate an important role for histone modifications outside the NH2-tail domains in chromatin assembly, DNA repair and transcriptional silencing.
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DEPARTMENT OF MOLECULAR VIROLOGY,
IMMUNOLOGY AND MEDICAL GENETICS              
Carlo Croce, MD, Chair
Molecular Virology, Immunology and Medical Genetics (MVIMG) reorganized in 2004 with Carlo Croce, MD, as chair. Its mission is to foster outstanding research in the molecular genetics of human disease. MVIMG is closely aligned with OSU’s Human Cancer Genetics Program, which Croce also directs. Since 2004 the department has recruited Richard Fishel, Joanna Groden and Kay Huebner, PhDs, as full professors, and Samir Acharya, Louise Fong, Jonathon Godbout, Helen Pace, Yuri Pekarski, Christoph Schmutte and Amanda Toland, PhDs, as assistant professors. Fishel, Groden and Huebner are internationally recognized in DNA repair, cancer genetics and mouse models of human cancer. Acharya, Fong, Godbout, Pace, Pekarski, Schmutte and Toland add to departmental expertise on the role of DNA repair and genomic instability in carcinogenesis, mouse models of cancer, neuroimmunology, structural biology, tumor-suppressor gene identification and function, and functional genomics and proteomics. Nearly 65 percent of MVIMG faculty maintain multiple grant awards.

Ongoing Research Programs

• Fundamental mechanisms of bacterial and viral pathogenesis
  
  
• Immunology and immunogenetics
  
  
• DNA repair and genomic stability
  
  
• Molecular genetics of cancer
  
  
• Studies within each of these areas range from biophysical analysis to clinical translation.
  

Research Accomplishments of 2005

• Discovery of microRNA (miRNA) signatures in the pathogenesis of B-cell chronic lymphocytic leukemia and papillary thyroid carcinoma
  
  
• Identification of the human mutation that causes hereditary juvenile cobalamin deficiency
  
  
• Identification of a genetic risk factor for prostate cancer in African-American men
  
  
• Discovery of a method for assessing promoter methylation leading to cancer, and identification of a new tumor-suppressor gene
  
  
• Determination of a genetic pathway that controls the oncogeneic potential of the common chronic lymphocytic leukemia (CLL) translocation BCR/ABL through c-myc overproduction
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DEPARTMENT OF NEUROLOGICAL SURGERY          
E. Antonio Chiocca, MD, PhD, Chair
Neurological Surgery’s growth and accomplishments were recognized by U.S. News & World Report, which ranked this program 24th in the nation. Three neurosurgeons – Louis Caragine, Jr., MD; Mario Ammirati, MD; and Atom Sarkar, MD – joined E. Antonio Chiocca, MD, PhD, John McGregor, MD, and Carole Miller, MD, to double the faculty. The newcomers use their respective subspecialty expertise to direct programs in: endovascular, minimally inva-sive neurosurgery; skull base surgery; and nanomedicine. Faculty performed 836 neurosurgeries in 2005. Balveen Kaur, PhD, joined Yoshinaga Saeki, MD, PhD, and Sean Lawler, PhD, as research faculty in the Dardinger Laboratory for Neuro-Oncology and Neurosciences. Kaur’s group is examining the microenvironment of gliomas and novel mechanisms to develop therapeutic strategies that augment existing treatments. Faculty participated in four clinical trials, received research funding exceeding $1 million and authored 18 publications. Physicians and researchers were recognized with appointments, awards and endowments.

Ongoing Research Programs
Dardinger Laboratory for Neuro-Oncology and Neurosciences –  The strictly research faculty include Yoshinaga Saeki, MD, PhD, chief of the Dardinger Laboratory; Balveen Kaur, PhD; and Sean Lawler, PhD. Atom Sarkar, PhD, will do research in nanomedicine, and E. Antonio Chiocca, MD, PhD, will retain his activities as co-director of the Dardinger Laboratory for Neuro-Oncology and Neurosciences.

• Saeki’s laboratory team is interested in developing therapeutic strategies for neurological, neoplastic and genetic disorders. Three ongoing projects employ multidisciplinary research techniques. The first involves development and applications of herpes simplex virus (HSV)-based amplicon vectors, or high-capacity plasmid-based vectors with full HSV infection machinery, for gene therapy and neuroscience research. The second involves the development and applications of engineered oncolytic HSV vectors for cancer therapy. The third involves studying the roles of G protein-coupled receptors that upregulate cAMP signaling in the axonal outgrowth of neurons and neuronal differentiation of neural progenitor cells.
  
  
• Kaur’s laboratory team attempts to understand changes in the microenvironment of gliomas, the most common primary tumor of the central nervous system. The goal is to devise better treatments, including use of oncolytic viruses (OVs) and other techniques either alone or in combination with OVs to augment existing treatment modalities. Treatment with OVs employs genetically engineered viruses with deletion of some of their viral genes, which enables selective replication of the OVs only in rapidly dividing cancer cells. Kaur’s laboratory is also investigating novel mechanisms to disrupt tumor-induced changes in vascular biology to develop therapeutic strategies that may be used alone or in combination with oncolytic viruses to augment existing treatment modalities.
  
  
• Lawler’s laboratory team is studying cell-signaling mechanisms in disorders of the central nervous system (cancer and neurodegeneration) to develop novel therapeutic approaches. Using a three-dimensional cell culture system, they are studying the migration and invasion of glioma cells, a major challenge in brain tumor therapy. They have identified small-molecule drugs that block invasion and are testing these in animal glioma models. They also have identified novel genes that may be important in migration and invasion. In addition, Lawler’s team is examining the role of the microtubule-associated protein, tau, in neurodegeneration to explore a potential link between amyloid and tau, which may be critical in the progression of Alzheimer’s disease.
  

Research Accomplishments of 2005

• Research publications centered on the use of oncolytic viruses for brain tumor models. Three publications in Cancer Research detailed the engineering of two new oncolytic viruses with remarkable efficacy against gliomas in animal models and the effects of immune responses on this efficacy.
  
  
• Yoshinaga Saeki, MD, PhD, continued his inter-institutional collaborations, which were recognized by several co-authorships, most notably in Science in December 2004.
  
  
• Funding of departmental research exceeded $1 million, including direct and indirect grant awards from the National Institutes of Health (NIH); funding had increased to about $1.5 million by June 2006. E. Antonio Chiocca, MD, PhD, was also awarded a National Gene Vector Laboratories (NGVL) grant from the NIH to obtain GMP-grade oncolytic virus for a toxicity and clinical trial.
  
  
• The Department enrolled four patients in a phase III clinical trial testing the infusion by convection of a cytotoxin against malignant glioblastoma. This trial was closed at the end of the year, and results are pending.
  
  
• A phase I clinical trial of gene immunotherapy against newly diagnosed malignant glioma opened in 2005. OSU is the primary site for this trial, which has also opened at Methodist Neuroscience in Houston, Texas, and will include participation by the University of Pennsylvania in Philadelphia and Massachusetts General Hospital in Charlestown. 
  
  
• The Department continued its participation in clinical trials of blood-brain barrier disruption for brain tumors. 
  
  
• The Department is participating in a phase II trial program for neuro-oncology.
  
  
• Departmental faculty, residents and postdoctoral fellows received many recognitions during the year, including:
  
  
  • Louis Caragine, Jr., MD, PhD, was appointed as liaison for the Young Neurosurgeons Committee of the American Association of Neurological Surgeons (AANS) to their Education and Maintenance of Certification Committee (EMCC). He also was appointed as the AANS liaison to the Council of State Neurosurgical Societies (CSNS), and he became a diplomate of the American Board of Neurological Surgery, Inc.
    
    
  • E. Antonio Chiocca, MD, PhD, was elected to the American Academy of Neurological Surgeons (AANS) at its 67th annual meeting. AANS has only 100 members, all elected by the membership. Chiocca also was elected to the editorial board of the Journal of Neurosurgery, joining only 16 others with this distinction.
    
    
  • Jennifer Cutter, PhD, postdoctoral fellow, was the first recipient of the Jeffrey Thomas Hayden Foundation Endowed Fellowship, awarded as part of a $250,000 endowment to The Ohio State University over a three-year period:  The Jeffrey Thomas Hayden Foundation Endowed Fellowship Fund in Pediatric Brain Tumor at The Ohio State University Arthur G. James Cancer Hospital and Richard J. Solove Research Institute. 
    
    
  • Balveen Kaur, PhD, received the Late-breaking Abstract Award at the meeting of the European Association for NeuroOncology (EANO) in Edinburgh, Scotland for “Vasculostatin is an extra-cellular proteolytic fragment of Brain Angio-genesis Inhibitor 1 that functions as a potent inhibitor of glioma growth and angiogenesis.”
    
    
  • Kazuhiko Kurozumi, MD, PhD, postdoctoral researcher, received the Journal of Gene Medicine Japanese Society of Gene Therapy (JSGT) Young Investigator Award for 2005 at the 11th annual meeting of the JSGT in Tokyo for “Cytokine gene-modified mesenchymal stem cells promote functional recovery and reduce infarct size in the rat middle cerebral artery occlusion model.”
    
    
  • Carole Miller, MD, received the “Local Legends” Award of the American Medical Women’s Association (AMWA). Nominated by U.S. Rep. Deborah Pryce, Miller was recognized for her pioneering efforts in neurosurgery and her ongoing commitment to the practice of medicine. 
    
    
  • Yoshinaga Saeki, MD, PhD, was invited to become a member of the National Institute of Neurological Disorders and Stroke (NINDS) Neurological Science and Disorders B (NSD-B) study section. This committee reviews grant applications supporting basic and translational bio-medical research related to neurological disorders.
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DEPARTMENT OF NEUROLOGY       
Michael Racke, MD, Chair
The mission of the Department of Neurology is to provide the highest quality neurologic patient care while performing basic, clinical and translational research with the goal of developing a better understanding of neurologic disease and formulating better treatments for these disorders. Another aspect of the mission is to disseminate this clinical and research knowledge by educating students, residents, fellows and colleagues both at Ohio State and in the community. The Department comprises nine sub-specialty divisions: Neuro-Oncology; Neuromuscular Disease; Epilepsy; Clinical Neurophysiology; Cerebrovascular Disease; Neuro-Ophthalmology/Neuro-Otology; Cognitive Disorders; Movement Disorders; and General Neurology.

Ongoing Research Programs
Research focuses on a range of neurological disorders, with a consistent theme of improving developmental therapeutics for these diseases. A testament to the breadth and depth of the research effort is indicated by the fact that, for the Department of Neurology, the OSU Research Foundation lists 140 grants funded for a total of $10.24 million for 2005.

Research Accomplishments of 2005

• The Cognitive Neurology Division had an impressive record of achievement, with ongoing funded studies dealing with dementia, autism, drug abuse and cognitive neuroscience.
  
  
  • One project aimed at developing a screening test to be administered in general medicine and family practice clinics to detect impairments needing referral for evaluation for Alzheimer’s disease.
    
    
  • Research also included use of the high-powered 8 Tesla MRI to detect early pathological changes in Alzheimer’s and changes in brain function during cognitive tasks using functional MRI. An important result of this work was to be included in a National Institute for Aging project entitled “The Alzheimer’s Disease Neuro-Imaging Initiative.” This is a multicenter investigation of neuro-imaging techniques and their application to Alzheimer’s; it is funded at the national level for $60 million.
    
    
  • Research is also ongoing into pharmacological treatments for Alzheimer’s in both the behavioral and cognitive spheres. In a program funded by the National Institute of Neurological Disorders and Stroke, investigations were begun into cognitive difficulties experienced by individuals with autism and the influence of pharmacological treatment on those difficulties. A focus in this work has been the role of cognitive flexibility, which is impaired in autism, and the noradrenergic system, which is known to influence cognitive flexibility. The goal of all this research is to refine optimal pharmacological therapy for autism.
    
    
  • Similarly, National Institute on Drug Abuse-funded work in 2005 focused on drug abuse, including investigation of cognitive difficulties experienced with cocaine withdrawal and the influence of pharmacological treatment on these cognitive difficulties.
    
    
• Jerry Mendell, MD, and his team in the Neuromuscular Division continued to develop a therapy for several types of muscular dystrophy. Through NIH-funded grants, Mendell has focused particularly on approaches to gene therapy in Duchenne and limb-girdle forms of dystrophy. In addition, he and colleagues are exploring pharmacologic options for treating these diseases. This work has continued with his move to Columbus Children’s Hospital. Other members of the Neuromuscular Division are doing translational clinical trials in spinal muscular atrophy, using agents screened in vitro and tested in an animal model developed at OSU by Arthur Burghes, PhD.
  
  
• The Cerebrovascular Disease Division, headed by Andrew Slivka, MD, is committed to clinical research on acute stroke treatment and secondary prevention that will impact patient care. This Division also has a database of patients treated acutely with thrombolytic therapy, and work has focused on finding predictors of favorable and poor clinical outcomes. Through 2005, the Division is involved in four NIH-sponsored trials. One examines the genetics of stroke. Another determines the optimal medical management of small subcortical strokes (lacunes). A pharmaceutical-sponsored study is comparing two newer anti-platelet agents for secondary stroke prevention. This study examines screening methods for determining which stroke patients will benefit from a novel thrombolytic therapy and for dramatically increasing the time window for treatment.
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DEPARTMENT OF NEUROSCIENCE              
Michael Beattie, PhD, Chair
The Department of Neuroscience (DNS) was formed in 1999 in a reorganization of the basic sciences that created the School of Biomedical Sciences. The Department has grown from 10 to 22 full-time faculty, with many joint/courtesy appointments by members in other departments and colleges. The Department’s mission is to provide a home for research and teaching in the neurosciences. The DNS is closely aligned with the new Neurobiology of Disease Institute (NBDI) and the Neuroscience Graduate Program (NGSP).

Ongoing Research Programs

• Molecular genetic studies of nervous system development
  
  
• Preclinical testing of neuroprotective agents and neural transplantation
  
  
• Studying a model of spinal muscular atrophy in the zebrafish
  
  
• Examining basic mechanisms of cytoskeletal trans-port in axons
  
  
• Studying basic cellular signaling mechanisms in the context of synaptic plasticity and the generation of epilepsy
  
  
• Probing the molecular basis for circadian rhythms in the brain and retina
  
  
• Investigating the role of stem/progenitor cells in repair of the spinal cord and retina
  
  
• Examining basic aspects of membrane channels that control neural activity
  

Research Accomplishments of 2005

• Important advances were made in understanding the role of progenitor cells in development and repair of the retina and spinal cord.
  
  
• A new research team began work on visual neurobiology under the direction of Stuart Mangel, PhD. Two new junior DNS members began work in the Center for Molecular Neurobiology.
  
  
• The department was ranked ninth in the nation for NIH research funding of neuroscience departments.
  
  
• The spinal cord injury group continued its NIH-sponsored research-training program. A peer-reviewed citation analysis of spinal cord injury research (Furla and Fehlings, J Neurotrauma 2006; 23:156) ranked Ohio State and members of the DNS first in the world for “citation classics.”
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DEPARTMENT OF OBSTETRICS AND GYNECOLOGY       
Larry Copeland, MD, Chair
This Department has several Divisions that contribute to basic or clinical research. The Division of General Obstetrics and Gynecology conducts clinical research, most of which is industry-supported and focused on hormonal therapies for pregnancy prevention and managing menopause. The Division of Gynecologic Oncology conducts clinical trials, predominantly through the Gynecologic Oncology Group, as well as industry-supported drug development trials. Most of these focus on preventing and treating ovarian, endometrial and cervical cancer. Basic research pertains to identifying molecular targets associated with gynecologic malignancies. The Division of Maternal-Fetal Medicine focuses mainly on clinical and basic research for preventing pre-term labor. This Division also participates in the National Institute of Child Health and Human Development’s Network of Maternal-Fetal Medicine Units in clinical trials related to fetal growth, diabetes in pregnancy and preventing pre-eclampsia. Research in the Division of Reproductive Biology and Vaccine Research focuses on developing and applying peptide vaccines.

Research Accomplishments of 2005  

• The Division of Gynecologic Oncology continued as a leading participant in the Gynecologic Oncology Group, the premiere clinical trials group in this field. The Division maintains accrual within the top three study centers in the United States. Advances in the past year include studies to improve survival in ovarian cancer with the use of intraperitoneal chemotherapy, and the prevention of cervical cancer with the use of vaccines.
  
  
• The Division of Maternal-Fetal Medicine continued participation in clinical trials of the Multicenter Network of the Maternal-Fetal Medicine units (funded by the National Institute of Child Health and Human Development). Focus areas included evaluating vaginal births after cesarean section (VBAC). Additional research was directed at perinatal outcomes in women with preterm rupture of membranes.
  
  
• The Division of Maternal-Fetal Medicine also continued a basic research program directed by Douglas Kniss, PhD, and William Ackerman, MD, in mechanisms of preterm labor and regulation of  the cyclooxygenase cascade. 
  
  
• The Division of Reproductive Biology and Vaccine Research continued studies relating to the use of conformational peptides in developing vaccines for treating ovarian cancer. This research is directed by Pravin Kaumaya, PhD, in association with David Cohn, MD.
  
  
• The Gynecologic Oncology Division continued to conduct basic and clinical research in the management and prognostic factors associated with endo-metrial adenocarcinoma.
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DEPARTMENT OF OPHTHALMOLOGY
Thomas Mauger, MD, Chair
The Department of Ophthalmology (William H. Havener Eye Institute at the Ohio State University Hospital Clinic – Cramblett Hall) is engaged in basic and clinical eye research. Current projects run the gamut from ocular disease caused by corneal dysfunction to neurophthalmology. Collaborations exist with Biomedical Engineering, Human Genetics and Veterinary Sciences. Basic research studies include evaluation of corneal epithelial healing mechanisms, biomechanics of the eye with ocular surgery and disease, the genetic basis of ocular tumors, the study of cerebral spinal fluid flow and the development of intracranial hypertension. The Department has expanded its involvement in clinical trials, including National Institutes of Health (NIH)-supported trials in glaucoma and age-related macular degeneration, as well as studies in intracranial hypertension, amblyopia and conjunctivitis.

Ongoing Research Programs

• Evaluation of the utility of intraoperative topography to optimize corneal shape during penetrating keratoplasty – Richard Lembach, MD
  
  
• A study of micropulsed and low fluence diode laser-tissue interaction with cultured human trabecular meshwork cell monolayers – Cynthia Roberts, PhD

Research Accomplishments of 2005

• Ultrasound characterization of ocular biomechanical properties for glaucoma screening – Jun Liu, PhD
  
  
• Topographic analysis for CLEK – Cynthia Roberts, PhD
  
  
• Participation in an Ocular Hypertension Treatment Study, funded by the National Eye Institute: National Institutes of Health, has resulted in dramatic changes in the management of glaucoma throughout the country and the world. This will lead to a significant decline in blindness.
  
  
• The meantime study opens a new area of research and potential treatment of glaucoma: neuroprotection.
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DEPARTMENT OF ORTHOPAEDICS               
Christopher Kaeding, MD, Interim Chair
Research in the Department of Orthopaedics focused on the engineering aspects of musculoskeletal conditions. The Orthopaedic BioMaterials Laboratory investigates the development and application of engineering materials to hard-tissue problems and the biomechanics of implantable fixation devices. The Ergonomics Laboratory explores causes and prevention of spinal and industrial injuries. Both of these research thrusts are conducted in collaboration with colleagues in the OSU colleges of Dentistry, Engineering, Medicine and Veterinary Medicine. Recently, Gary Bos, MD, and Joel Mayerson, MD, both of the Division of Oncology, have begun research in collaboration with Carl Morrison, MD, DVM, of the Department of Pathology, on genetic identification of tumor markers as a tool for predicting severity and prognosis. Clinical research has expanded and includes studies in sports medicine, musculoskeletal trauma and spine. With the continuing expansion of clinical faculty in Orthopaedics and associated departments, new avenues of research are being developed. 

Ongoing Research Programs

• An ongoing research program under the direction of Steve Lavender, PhD, seeks to quantify and model the biomechanics of the lumbar spine during push-pull industrial tasks to better understand the etiology (and thus give insight into the prevention) of low back pain.
  
  
• Alan Litsky, MD, ScD, leads a biomaterials research program developing and testing materials for orthopaedic, dental and veterinary applications. A novel technique to determine the source of polyethylene wear debris in total joint arthroplasties is being developed and quantified.
  
  
• Joel Mayerson, MD, is a pioneer in the application of expandable total femoral implants designed to keep up with the growth of pediatric bone tumor patients.
  
  
• Christopher Kaeding, MD, is a co-investigator in the first large, multi-institutional, prospective study of functional outcomes following anterior cruciate ligament reconstruction.
  
  
• Laura Pheiffer, MD, directs several projects quantifying the biomechanics of fracture fixation devices.
  
  
• Josue Gabriel, PhD, leads a study exploring the use of dynamic analysis modeling to predict injury to spinal structures.
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DEPARTMENT OF OTOLARYNGOLOGY
D. Bradley Welling, MD, PhD, Chair
The Department of Otolaryngology - Head and Neck Surgery at The Ohio State University is a national leader in this discipline and in treating human communication disorders. Excelling in patient care, research and education, the Department was recognized as having the highest patient-satisfaction rate at OSU Medical Center this past year, and its residents achieved the second-highest score in the country on the national in-service examination. Two new major grants were awarded to members of the Department as noted below. The Department is undergoing a period of rapid growth supported by the dean of the College of Medicine and by the Medical Center.

Ongoing Research Programs

• D. Bradley Welling, MD, PhD, received a $1.62 million R01 grant from the National Institutes of Health (NIH) for “Phenotypic Determinants of Vestibular Schwannomas.”
  
  
• Gregory Wiet, MD, received a $1.87 million R01 grant for development and testing of an otologic surgical simulator from the NIH, National Institute on Deafness and Other Communication Disorders.
  

Research Accomplishments of 2005

• The “Phenotypic Determinants of Vestibular Schwannomas”
  
  
• Dr. Wiet’s $1.87 million R01 grant for development and testing of an otologic surgical simulator from the NIH/NIDCD
  
  
• Ongoing research by Thomas DeMaria, PhD, in immunization with recombinant Streptococcus pneumoniae neuraminidase against potential  nasopharyngeal colonization
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DEPARTMENT OF PATHOLOGY    
Sanford Barsky, MD, Chair
The Department of Pathology conducts clinical, transitional and basic research focusing on five major areas: tissue banking, the Cooperative Human Tissue Network, cancer immunology, viral pathogenesis and lymphohematopoietic cell production. Department Chair Sanford Barsky, MD, is dedicated to expanding research efforts. 

Ongoing Research Programs and Accomplishments of 2005

• Cooperative Human Tissue Network – Scott Jewell, PhD, and Nilsa Ramirez, MD
  
  
• Cooperative tissue bank of HIV-positive malignancies – Leona Ayers, MD
  
  
• Cancer & Leukemia Group B – Saul Suster, MD
  
  
• Cancer immunology – Yang Liu, PhD, and Pan Zheng, MD, PhD
  
  
• Viral Pathogenesis – Joanne Trgovcich, PhD; James Van Brocklyn, PhD; and W. James Waldman, PhD
  
  
• Development of human lymphohematopoietic cell production system, awarding of phase II – Larry Lasky, MD
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DEPARTMENT OF PEDIATRICS                    
Michael Brady, MD, Interim Chair 
Faculty in the Department of Pediatrics participate in a variety of pediatric research initiatives at Columbus Children’s Research Institute and Columbus Children’s Hospital. Columbus Children’s Research Institute is ranked among the top 10 nationally in National Institutes of Health funding to freestanding children’s hospitals. Research is overseen by 11 Centers of Emphasis and traditional clinical divisions as described below:
Center for Biobehavioral Health – social and behavioral outcomes of chronic illnesses; Center for Cardiovascular Medicine – mechanism-based cardiovascular research on cardiomyopathies and endothelial biology; Center for Cell and Vascular Biology – cellular physiology, molecular biology and developmental biology; Center for Childhood Cancer – molecular pathology, biology and genomics of childhood cancer; Center for Developmental Pharmacology and Toxicology – free-radical biology, toxicology, safety and efficacy of therapeutic agents; Center for Gene Therapy – adeno-associated viral vectors for prevention and treatment of pediatric diseases, especially neuromuscular disorders; Center for Injury Research and Policy – childhood injury research and public policy relevant to childhood injury;