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New study of mutant gene causing thyroid cancer planned at the University of Michigan


$1.7M NIH grant funds research into the oncogene’s effect on fatty acid metabolism

Ronald Koenig, MD, PhD
Ronald Koenig, MD, PhD

ANN ARBOR, Mich.(March 8, 2011) — Ronald J. Koenig, M.D., Ph.D., professor of internal medicine in the Division of Metabolism, Endocrinology & Diabetes at the University of Michigan Medical School and program director of the Medical School’s Medical Scientist Training Program, has received a new grant to study the role of an “oncogene” in the development and progression of thyroid cancer.

The study will receive $1,717,289 over five years from the National Institutes of Health (NIH).

The research project is called “Pax8-PPARgamma regulation of transcription and metabolism.” The grant will allow Dr. Koenig to study changes in the metabolism of lipids (fatty acids) in a type of thyroid cancer and to understand the importance of these alterations, which may ultimately yield approaches to treatment.

An “oncogene” is a gene that causes the transformation of normal cells into cancerous tumor cells. The oncogene under study, known as “Pax8-PPARgamma fusion protein” (or PPFP for short), is created by a mutation that fuses two genes that are normally not connected. “An interesting characteristic of the PPFP oncogene is that half of it is comprised of PPARgamma ‑‑ a protein that plays a central role in regulating glucose (blood sugar) metabolism, lipid metabolism, and insulin sensitivity,” says Dr. Koenig.

Drugs that bind to PPARgamma, known as thiazolidinediones (TZDs), are commonly used to treat diabetes. As a novel investigative feature of this study, Dr. Koenig will assess the effects of TZD drugs on this cancer-causing gene to see if the drug makes the cancer worse or better, and why.

This grant builds upon previous work that Dr. Koenig has done on PPFP. For this study, he is working in collaboration with Thomas Giordano, M.D., Ph.D., professor in the Department of Pathology.

Dr. Koenig is recognized as a world leader in the field of thyroid cancer research. After receiving his B.S. summa cum laude from Yale University, he earned his Ph.D. in biochemistry and his M.D. at Cornell Medical College, New York City. Dr. Koenig’s internship and residency in internal medicine were at Harvard Medical School and Brigham and Women's Hospital in Boston, where he later held a fellowship in endocrinology and metabolism. He has been at the University of Michigan since 1988.

Along with his rigorous research, clinical, and teaching duties, Dr. Koenig is the chair of the NIH Molecular and Cellular Endocrinology study section, and serves as a reviewer for important medical journals such as Thyroid, Endocrinology, and Journal of Clinical Investigation. He has also served many roles with the American Thyroid Association and has been an invited guest lecturer and visiting professor at universities and conferences all over the world, most recently at the 14th International Thyroid Congress in Paris, France, in September 2010.