Newly Discovered Gene Tied to Heart & Eye Development

M.D./Ph.D. student wins national honors while pursuing molecular research

Raegan Hunt’s final year in The University of Texas Medical School at Houston class of 2006 has been typical in many ways.

Raegan Hunt

There was the last set of required clerkships in internal medicine, surgery, neurology and family practice, and five clinical electives. There was the choice of residency. She chose to specialize in pediatrics and will continue her training at the Johns Hopkins School of Medicine.

Finally, there were laboratory experiments to perform and a major genetic discovery to write up for publication.

As an M.D./Ph.D. student, Hunt completed her work for the UT Graduate School of Biomedical Sciences at Houston (GSBS), carving out time to write her dissertation about a previously uncharacterized gene that encodes a protein essential for normal cardiac and retinal development.

The discovery helped her win a $10,000 scholarship from P.E.O. International, one of 85 awards granted from among 772 nominees across the United States and Canada.

She subsequently was designated by the P.E.O. Board of Directors as the 2005-06 Jane G. Hines Endowed P.E.O. Scholar. Fewer than 20 P.E.O. Scholars are honored with the distinction of a named and endowed award. P.E.O. Scholar awards are competitively awarded to recognize excellence by women pursuing advanced graduate research in all fields of study.

Hunt’s faculty mentor, C. S. Raman, Ph.D., assistant professor of biochemistry and molecular biology, expects to submit their research paper to a major journal.

“She’s the best student I’ve ever come across,” Raman said. “Raegan is extremely intelligent, independent, conscientious and highly motivated. I’ve seen a lot of graduate students, and it would be tough to beat Raegan for her ability to persist and persevere.”

Raman’s lab focuses on two disparate fields of research – vascular biology and immune deficiency. Based on a lead obtained in vascular biology, Hunt began to work on a predicted, hypothetical gene in the human genome.

Gene’s Surprising Function

Subsequent research showed that the gene had a surprising new function in vertebrates. High levels of gene expression in heart and fetal tissues hinted that it might be involved in heart development or physiology.

Collaborating with researchers at the University of California-San Francisco, Hunt depleted the gene product in the zebra fish model, a system well-established for the study of genes involved in heart development. The genetically altered fish died by embryonic day 6 and demonstrated severely disorganized eyes and undeveloped, dysfunctional hearts.

“We found abnormal apoptosis (cell death) in the manipulated zebra fish embryos with high numbers of apoptotic cells concentrated in tissues where the gene is highly expressed under normal conditions: the heart, eyes and brain,” Hunt said. The research team is pursuing the structural and molecular basis for the serious consequences of depleting the gene during embryonic development.

Hunt also has participated in two other research projects: (a) using x-ray crystallography to characterize the structural biology of neuronal nitric oxide synthase and (b) discovery of novel functions of prostaglandins.

Information from the former project could prove useful for the development of targeted stroke therapies. The grant proposal to the National Institute of Neurological Disorders and Stroke was one of the nation’s highest scoring predoctoral research proposals, earning Hunt a Ruth L. Kirschstein Individual National Research Service Award in 2003.

Excited about Medicine, Science

Hunt said that she became excited about medicine and science in high school, “after being in the classes of some remarkable teachers.”

As an undergraduate at Texas A&M University, she studied radiological health and nuclear engineering, completed a pre-medical curriculum, and served as a volunteer emergency medical technician-paramedic for the university. Her interest in biomedical science was confirmed through positive experiences in summer research programs at the UT M. D. Anderson Cancer Center facility in Smithville and the UT Health Science Center at San Antonio.

She was attracted to the UT Health Science Center at Houston by the outstanding faculty, clinical facilities and research opportunities of the Medical School and the Texas Medical Center.

“I wanted to work toward understanding the molecular basis of disease with the goal of being able to help develop better treatment options for patients,” she said. During her first year of medical school, she co-enrolled in the GSBS through the M.D./Ph.D. program.

“Raegan is a fabulous student. She epitomizes exactly what we want in an M.D./Ph.D. student. Based on research experience that she had prior to entering the program, she knew that she wanted both degrees to prepare herself for a career as a physician-scientist. She has excelled in both medical school and graduate school, and I predict that she will have a very successful career,” said M.D./Ph.D. Program Director Dianna Milewicz, M.D., Ph.D., professor and director of medical genetics and holder of the President George Bush Chair in Cardiovascular Medicine.

By Scott Merville, Public Affairs