Clay Marsh, MD 

Directed by Clay Marsh, MD, the Division of Pulmonary, Critical Care and Sleep Medicine at Ohio State conducts or is involved with clinical trials in asthma, adult respiratory distress syndrome, emphysema and HIV-associated lung disease.

The Division is one of 18 participants in the National Emphysema Treatment Trial. It also studies multi-organ failure, acute and chronic lung injury and the role of cytokines and oxidant injury, mitochondrial dysfunction, and monocytes and macrophages in health and disease. The Division collaborates with the OSU Division of Cardiovascular Medicine on studies in the OSU Davis Heart and Lung Research Institute.

Marsh’s research centers on the roles of monocytes and macrophages in regulating inflammation and organ repair. He is also investigating the cause and regulation of fibrosis in lung disease and transplant, and the role of growth factors in angiogenesis (blood vessel formation), with an eye toward eventually regulating those processes in cancer and wound repair.

Marsh led a study published in a December 2004 issue of the journal Immunity that identified a new biological pathway for angiogenesis involving blood monocytes and macrophages. This discovery, he says, may give physicians a new way to intervene in many illnesses, including heart and lung disease and cancer, as well as in wound healing and organ transplantation.

“Angiogenesis is a normal function of the body, but it’s not always helpful,” he explains. “For example, while the process is critical to normal embryonic development and beneficial to wound healing and recovery from heart disease, it can be harmful when it creates new feeder lines that help cancerous tumors grow.”

The OSU researchers say angiogenesis appears to be manageable by stimulating monocytes – a type of white blood cell in the immune system – with high doses of a naturally occurring growth factor in the body called GM-CSF (granulocyte-macrophage colony stimulating factor). GM-CSF stimulates monocytes to produce soluble receptors for VEGF (vascular endothelial growth factor), which is the substance tumors secrete to signal nearby blood vessels to build connectors to them.

The tumor’s production of VEGF is the key driver of blood vessel formation, explains Marsh, senior author for the study. However, he says, soluble VEGF receptors produced by the stimulated monocytes act like sponges, soaking up all of the available VEGF, so the signal to build new blood vessels never gets through. “In essence, we think we may have found a new way to block angiogenesis,” he adds.

Dr. Marsh’s co-investigators include: Naeem Ali, MD; Michael Caligiuri, MD; Andrea Doseff, PhD; Nick Flavahan, PhD;  Periannan Kuppusamy, PhD; Jim O’Brien, MD; Mike Ostrowski, PhD; Narasimham Parinandi, PhD; Wolfgang Sadee, Dr.rer.nat; Susheela Tridandapani, PhD; and Mark Wewers, MD. His lab team includes: Melissa Hunter, PhD; Tim Eubank, PhD; Chris Baran, PhD; Yijie Wang, MS; Judy Opalek, PhD; Ryan Roberts, MD/PhD candidate; Jennifer Curry, PhD candidate; Christine Montague, PhD; Xiaokui Mo, PhD; Christie Newland and Jennifer Schroer.