Department of Molecular and Cellular Biochemistry   

Michael Ostrowski, PhD, Chair

Molecular and Cellular Biochemistry (MCB) research is focused on advancing basic understanding of the biochemical and molecular mechanisms underlying normal cellular processes and disease states in humans, and on translating these findings into multidisciplinary studies to benefit patients. These focuses are exemplified by two translational National Cancer Institute (NCI) program project grants for which MCB faculty serve as principal investigators. These grants include faculty in clinical and basic science departments from four colleges at Ohio State and at Nationwide Children’s Hospital. All faculty in the Department are associated with Medical Center Signature Programs, including Cancer, Heart and Neurosciences. These programs contain more faculty participation from MCB scientists than from any other basic science departments in the School of Biomedical Sciences.

• Epigenetic Mechanisms Governing the Transcriptional Regulation of Gene Expression – Samson Jacob, PhD, heads a multidisciplinary team funded by an $11.84 million NCI program project grant that includes MCB faculty members Mark Parthun, PhD, and Saïd Sif, PhD. The project combines basic studies into mechanisms of epigenetic regulation of gene expression in leukemia cells and translational studies using strategies that target epigenetic changes occurring in human leukemia.
• Genetic Analysis of the Tumor Microenvironment – Michael Ostrowski, PhD, heads a multidisciplinary team that includes members of seven departments and four colleges at Ohio State in efforts to define genes that act from cells other than the tumor cells in breast cancer progression. The team is supported by an $8.6 million NCI program project grant and from funding provided in 2007 from the Department of Defense Breast Cancer Program and the Komen Breast Cancer Foundation.
• Molecular Mechanisms Underlying Neuromuscular Diseases and Spinal Cord Injury – MCB has a strong focus on neuromuscular disease and spinal cord injury, with seven faculty members working in this area of research. Of note are studies that combine basic and translational science; one led by Arthur Burghes, PhD, and Sung-Ok Yoon, PhD, on spinal cord injury, and another led by Jill Rafael-Fortney, PhD, on heart defects in muscular dystrophy patients. Stephen Kolb, MD, PhD, is a new faculty member with a joint appointment in Neurology and MCB who performs translational work on spinal muscular dystrophy.
• Mitochondrial Biology and Dysfunction in Human Disease – Douglas Pfeiffer, PhD, heads the multidisciplinary Working Group on Mitochondrial Biology (http://www.biosci.ohio-state.edu/imb/). With plans to launch this effort into a Mito- chondrial Institute in the near future, the group consists of 34 members representing six colleges at Ohio State. The group sponsors monthly meetings and a seminar series, interactions that have led to submission of several collaborative grant applications.
• Molecular Genetics of the Regulation of RNA Processing, Transport and Stability – Daniel Schoenberg, PhD, directs the campuswide RNA Group, composed of 21 faculty members from four colleges at Ohio State (http://rna.osu.edu). These faculty account for a substantial percentage of the high-impact papers published by medical scientists at Ohio State and are among the most well-funded faculty in the life sciences.
• Structural Biology – MCB is the home of structural biology in Ohio State’s College of Medicine and has on its faculty the only two X-ray crystallographers in the college: Charles Bell, PhD, and Scott Walsh, PhD. These investigators explore the atomic structure of such important biological molecules as the androgen receptor and cytokine receptors – work that is critical for designing drugs to treat heart disease, cancer andneuromuscular disorders. MCB will hire additional faculty in this area in the coming year.

• The lab team of Daniel Schoenberg, PhD, published work demonstrating a link between the action of the src oncogene and messenger RNA decay. This work, published in the journal Molecular Cell, demonstrates that the src oncogene, a tyrosine kinase, can directly regulate messenger RNA decay by regulating the activity of a ribonuclease, PMR1, previously iscovered by the Schoenberg group. Since PMR1 is also a target of estrogen action, this raises the possibility of a mechanism linking the src oncogene and estrogen in human breast cancer.
• Saïd Sif, PhD, led a team of investigators, including MCB faculty member Samson Jacob, PhD, and Robert Baiocchi, MD, PhD, John Bryd, MD, and Michael Grever, MD, of the Department of Internal Medicine, in a study that revealed a mechanism for how epigenetic gene silencing is controlled in human leukemia. They demonstrated that the arginine methyl transferase PRMT5 is aberrantly expressed in leukemia cells because microRNAs known as mir92b and mir96 are downregulated, leading to epigenetic changes mediated by PRMT5 that silence anticancer genes and allow tumor cells to grow. Their work indicates that overexpression of these microRNAs might provide an effective way to treat certain human leukemias.
•  A collaborative study involving the lab of Samson Jacob, PhD, and Tushar Patel, MD, of the Department of Internal Medicine, uncovered a mechanism that has translational implications for hepatocellular carcinoma, a leading cancer killer worldwide for which effective treatments are lacking. These scientists showed that a specific microRNA targets a key tumor-suppressor gene, PTEN, in hepatocellular carcinoma cells. This microRNA thus provides an attractive molecular target for the development of new therapies to target this type of cancer.
• Work by Sung Ok Yoon, PhD, defines two pathways involved in the death of nerve cells resulting from spinal cord injury. The JNK pathway increases neural cell death while the PIN1 pathway protects against cell death following spinal cord injury through their action on Mcl-1, a critical regulator of cell apoptosis. This work provides potential targets for developing therapies to prevent cell death, thus perhaps limiting paralysis associated with spinal cord injury.
• Charles Bell, PhD, collaborated in a study with James Dalton, PhD, of the College of Pharmacy, that may improve drugs for treating prostate cancer. This group used X-ray crystallography to determine the three-dimensional structure of the androgen receptor in complex with a drug currently used in the treatment of prostate cancer, Cyproterone acetate (CPA). Solving this structure provides new insight at the atomic level into androgen receptor-CPA interactions and will allow the development of more specific drugs targeted to the androgen receptor without the side effects caused by CPA interfering with other steroid receptors.