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Jeffrey Zigman, MD, PhD

Dr. Jeffrey Zigman recently spoke at the FPWR Research conference in Austin. A two-time recipient of funding from FPWR, Dr. Zigman studies the hormone ghrelin, also known as the “hunger hormone.” Ghrelin levels are higher than normal in individuals with PWS, and Dr. Zigman is trying to understand exactly what role this hormone plays in PWS. We recently sat down with Dr. Zigman for a Skype chat, and learned more about his background, his work on PWS, and his life outside the lab.

Dr. Zigman traces his interest in science back to his childhood. He remembers feeling completely fascinated by a Time Magazine cover story on genetic engineering that he read in 7th grade, around the same time that he did a report for science class on interferons, proteins that the body’s cells produce to defend against viruses. At this point, he had a strong interest in plants, fungi, and science fiction, and was already thinking about a career in scientific research. In college at Cornell University, after a somewhat disappointing experience working with peas in a plant lab, Dr. Zigman spotted a poster about MD/PhD programs, and started thinking about doing basic research in medicine, which would have a direct benefit on humankind. Dr. Zigman was also diagnosed with Type I diabetes while in college, so the opportunity to enroll in an MD/PhD program and study insulin secretion was personally very meaningful to him. He completed his MD/PhD at the University of Chicago, studying G-proteins expressed in the pancreas, under the supervision of Professor Donald Steiner (one of the discoverers of proinsulin, a protein from which insulin is produced). Dr Zigman stayed at U. Chicago for his residency in internal medicine, where he started to appreciate how widespread problems with eating and obesity are, and the importance of the connection between hormones and the brain in understanding hunger and eating. He moved to Beth Israel Deaconess Medical Center in Boston for a fellowship on Endocrinology, Diabetes and Metabolism, where he began to develop his research on the hormone, ghrelin. Since 2006, Dr. Zigman has been on the faculty at University of Texas Southwestern Medical Center, where, as an endocrinologist, he also runs a clinic for patients with thyroid nodules and cancer.

A significant fraction of Dr. Zigman’s research is directed towards understanding how hormones and the brain interact to control feeding. To this end, he has been studying ghrelin for many years. Ghrelin, a hormone primarily released in the stomach, appears to play an important role in telling our brains that we’re hungry. Experiments have shown that ghrelin stimulates appetite and causes animals to start eating, motivates them to seek and obtain food treats, helps them learn how to effectively find food, and enhances the ability of visual cues to stimulate hunger. Given that multiple studies have shown that ghrelin levels are significantly elevated in individuals with PWS, ghrelin may play a role in one of the most difficult aspects of PWS — namely, excessive hunger, or “hyperphagia.”

With previous support from FPWR back in 2007, Dr. Zigman studied mice that were conditioned to favor environments containing special food treats, as opposed to environments with more generic nourishment. The data generated with this initial FPWR-funded study were critical for obtaining support from the National Institute of Health for a more comprehensive research program. With his current FPWR funding, Dr. Zigman is using genetically-engineered mice with the PWS-related SNORD116 gene deleted to serve as a proxy for PWS in humans, and studying the behavior of these mice in various specialized feeding situations. Some mice are additionally being bred to be insensitive to the effects of ghrelin — i.e., they lack ghrelin receptors. Comparison of the mice with and without ghrelin receptors will test the importance of ghrelin in controlling behaviors related to food seeking. Dr. Zigman is also hoping to test the intriguing possibility that ghrelin actually plays a therapeutic role in PWS. Indeed, ghrelin prevents hypoglycemia (i.e., low blood sugar), it’s an anti-depressant, and it can decrease anxiety. Given that hypoglycemia, depression and anxiety are all common issues associated with PWS, perhaps ghrelin levels are elevated to prevent these issues from being even more serious in individuals with PWS. The results of this research may indicate therapies in which a substance akin to ghrelin is given to patients to enhance its positive PWS-related effects. On the other hand, if the most important aspect of ghrelin in PWS is its role in stimulating self-destructive eating habits, potential therapies may include drugs that block the effects of ghrelin. In addition to addressing the *how* of ghrelin and PWS, Dr. Zigman hopes to understand *why* ghrelin levels are elevated in PWS. We look forward to many exciting results on ghrelin from his group.

Given that Dr. Zigman doesn’t treat PWS patients in his clinic, it has been especially meaningful for him to meet PWS families at the two FPWR conferences he has attended. There’s a big difference between measuring the behavior of mice in feeding studies, and hearing about the daily experiences of people living with PWS. Indeed, attending FPWR conferences has truly solidified Dr. Zigman’s passion for studying PWS, and advancing basic research so that effective therapies can be developed.

When he’s not in the lab or treating patients, Dr. Zigman enjoys spending time with his dog, Bubba, and gardening. One of his particular current hobbies is growing fruit trees from the seeds of fruit he eats. You can see that his childhood interest in plants lives on!