Yu-Hua Tseng, Ph.D.
Dr. Tseng is an Assistant Investigator in the Section on Integrative Physiology and Metabolism at Joslin as well as an Assistant Professor of Medicine at Harvard Medical School. She received her doctorate in Developmental Biology and Cellular and Molecular Biology from the University of Wisconsin at Madison and completed postdoctoral training in the Section on Cellular and Molecular Physiology at Joslin under C. Ronald Kahn, M.D. Dr. Tseng was a recipient of the Individual National Research Service Award from the National Institutes of Health and was a 2005 Eleanor and Miles Shore Scholar in Medicine at Harvard Medical School.
Obesity is an epidemic health problem worldwide, which results from an imbalance between energy intake and energy expenditure. Adipose tissue plays an important role in obesity, insulin resistance and diabetes. Two functionally different types of fat are present in mammals: white adipose tissue, which is the primary site of energy storage, and brown adipose tissue, which is specific to thermogenic energy expenditure. Increasing the relative proportion and function of brown fat therefore may increase whole body energy expenditure, preventing the development of obesity. In an effort to combat obesity and its related diseases, Yu-Hua Tseng, Ph.D., investigates factors that underlie the divergent differentiation fates and functions of these two adipose cell types.
Both brown and white adipocytes are the final products of a developmental pathway that begins with mesenchymal stem cells. When triggered by appropriate developmental cues, the multipotent precursor cells become committed to the adipocyte lineage but do not yet express markers of mature adipocytes. These committed cells are called preadipocytes. Preadipocytes then undergo differentiation upon hormonal stimulation and become mature fat cells. Using a combination of DNA chips and cell biological approaches, Dr. Tseng and Joslin colleagues in the laboratory of C. Ronald Kahn, M.D., have discovered that gene expression signatures in brown preadipocytes can be used as a surrogate to predict the outcome of differentiation. Given the calorie-burning function of brown fat cells, understanding the genes and mechanisms governing their differentiation as revealed from this study may assist in the development of therapeutic agents to combat obesity.
More recently, Dr. Tseng has discovered an additional pathway for promoting the development of brown adipocytes based on a family of growth/differentiation factors called bone morphogenic proteins (BMPs). First noted for their role in bone formation, these proteins also influence embryonic development of the heart, central nervous system and other organs. Dr. Tseng has found that certain BMPs specifically promote brown, but not white, fat differentiation and are involved in regulation of whole body energy homeostasis. The clinical relevance of this discovery to human obesity is still under investigation. Dr. Tseng is currently dissecting the molecular mechanisms that underlie these effects of BMPs in multiple systems, including cultured murine and human cells, clinical samples of human adipose tissue and mouse models with tissue-specific defects in BMP signaling. The role of BMPs in other organs and tissues has been studied extensively, but Dr. Tseng is one of the first to look at their role in brown adipocyte development and function.
Tseng YH, Butte AJ, Kokkotou E, Yechoor VK, Taniguchi CM, Kriauciunas KM, Cypess AL, Niinobe M, Yoshikawa K, Patti ME, Kahn CR. Prediction of preadipocyte differentiation by gene expression reveals role of insulin receptor substrates and necdin. Nat Cell Biol 7:601-611, 2005.
Gunton JE, Kulkarni RN, Yim S, Okada T, Hawthorne WJ, Tseng YH, Roberson RS, Ricordi C, O’Connell PJ, Gonzalez FJ, Kahn CR. Loss of ARNT/HIF1b mediates altered gene expression and pancreatic-islet dysfunction in human type 2 diabetes. Cell 122:337-349, 2005.
Cohen SE, Tseng YH, Michael MD, Kahn CR. The effects of insulin-sensitizing agents in mice with hepatic insulin resistance. Diabetologia 47:407-411, 2004.
Tseng YH, Kriauciunas KM, Kokkotou E, Kahn CR. Differential roles of insulin receptor substrates in brown adipocyte differentiation. Mol Cell Biol 24:1918-1929, 2004.
Tseng YH, Ueki K, Kriauciunas KM, Kahn CR. Differential roles of insulin receptor substrates in the anti-apoptotic function of insulin-like growth factor-1 and insulin. J Biol Chem 277:31601-31611, 2002.
Tseng YH, Vicent D, Zhu J, Niu Y, Adeyinka A, Moyers JS, Watson PH , Kahn CR. Regulation of growth and tumorigenicity of breast cancer cells by the low molecular weight GTPase Rad and NM23. Cancer Res 61:2071-2079, 2001.
Zhu J, Tseng YH, Kantor JD, Rhodes CJ, Zetter BR, Moyers JS, Khan CR. Interaction of the Ras-related protein associated with diabetes Rad and the putative tumor metastasis suppressor NM23 provides a novel mechanism of GTPase regulation. ProcNatl Acad Sci U S A 96:14911-14918, 1999.