About Student Research
Yeng Her (2011-present)
Understanding cancer caused by defects in energy metabolism
Born in a refugee camp in Cambodia, Yeng Her escaped with his family to the United States, where he went on to receive his undergraduate degree in chemistry from the University of Wisconsin at Madison. Following two years of post-baccalaureate research experience in Dr. Mahers lab, Yeng was accepted into Mayo Clinic’s M.D./Ph.D. Medical Scientist Training Program (MSTP). For the Ph.D. portion of his work, Yeng is studying familial paraganglioma (PGL). This rare tumor is particularly intriguing because it can run in families.
Predisposition to PGL is due to inheritance of surprising mutations - errors in the nuclear genes that encode subunits of the mitochondrial succinate dehydrogenase (SDH) complex, part of the tricarboxylic acid (TCA) cycle of oxidative energy metabolism. It is surprising to biochemists that defects in this step of energy metabolism can cause cancer.
Because the TCA cycle is crucial for generating ATP, mutations that break the TCA cycle drastically reduce the ability of a cell to generate useful energy from blood nutrients. This is hardly the type of change that might be expected to initiate cancer. Nonetheless, SDH mutations inherited from a parent set the stage for random and accidental loss of the remaining healthy SDH gene copy in somatic cells. When the remaining healthy SDH gene is lost from a neuroendocrine cell (part of the involuntary nervous system), a PGL tumor results. Some PGL tumors secrete dangerous hormones, and some of the tumors become metastatic and lethal. It remains unknown why SDH mutations cause PGL; and why only neuroendocrine cells are at risk for tumorigenesis.
Yeng is studying novel PGL tumor cell lines and other cell models originally developed by Deb Evans, a former student in Dr. Maher's lab. In collaboration with Mayo Clinic clinicians and other researchers, rare PGL tumors are being grown in culture and in immunodeficient mice. Other human cells have also been genetically engineered to create SDH deficiency. These tools allow Yeng to test hypotheses about how loss of SDH creates an imbalance of metabolite molecules that confuses neuroendocrine cells into growing out of control. This research has the potential to create smarter rational approaches to managing PGL tumors in patients.
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