Lutter, van Oers selected to receive High Impact/High Risk support

By Deborah Wormser

Dr. Michael Lutter, Assistant Professor of Psychiatry, and Dr. Nicolai S.C. van Oers, Associate Professor of Immunology, have received UT Southwestern High Impact/High Risk Grants for daring work that could lead to a better understanding of the genetics of three common psychiatric conditions or a new way to battle tuberculosis.

Dr. Lutter is investigating a large family in which multiple members have anorexia nervosa, bulimia and/or obsessive compulsive disorder, in an attempt to find genetic links to those conditions.

His study is based on a cohort first encountered more than a decade ago by Howard Hughes Medical Institute Investigator Dr. Helen Hobbs, Director of the McDermott Center for Human Growth and Development, and Dr. David Waller, Professor of Psychiatry. The grant will allow Dr. Lutter to extend the collection of data to create a much more robust sample for genetic analysis.

“Family studies have established that eating disorders and obsessive compulsive disorder are highly heritable, but so far no genes have been identified,” he said, adding that finding a large family in which members of multiple generations have been affected increases both the likelihood that a genetic abnormality contributes to these conditions and the chances of finding one if it exists.

“I think there is a high probability that he will make a discovery that may have therapeutic implications for a mechanistically poorly understood and potentially deadly disorder,” said Dr. Hobbs, who is also a Professor of Internal Medicine and Molecular Genetics.

Dr. van Oers, who also holds appointments in Microbiology and Pediatrics, will attempt to build on a striking finding he recently made regarding the bacterium that causes tuberculosis.

He developed a research program characterizing microRNAs, very short pieces of RNA that contain small amounts of genetic material, in people with primary immunodeficiency diseases. These microRNAs are produced in cells that contain a nucleus, which are called eukaryotic cells and are found in higher organisms such as plants and animals. He then asked whether simpler prokaryotic cells that lack any nucleus—specifically those of Myobacterium tuberculosis (Mtb)—might also contain microRNAs.

Working with Office of Global Health researcher Dr. Tawanda Gumbo, Associate Professor of Internal Medicine, and Dr. Eric J. Hansen, Professor of Microbiology and an expert in microbial pathogenesis, Dr. van Oers used genetic deep sequencing technology to report the first discovery of microRNA-like sequences in prokaryotic cells.

These prokaryotic microRNAs are expressed in infected mammalian cells, which suggests a possible new high-impact approach to combating and controlling tuberculosis, said Dr. Edward Wakeland, Chair of Immunology.

“The findings need to be replicated several times and the deep sequencing procedures are costly. However, the possible ramifications of this study are profound given that one-third of the human population is infected with Mycobacterium tuberculosis,” said Dr. Wakeland.

He added that this work exemplifies the importance of the High Impact/High Risk program, which emphasizes work that has the potential to greatly influence the science or practice of medicine but carries a substantial risk of failure. Grant recipients receive support for a year to test a hypothesis and determine whether the idea has promise.

With the latest approvals, 34 faculty members have received grants through the program since it was established in 2001.

Dr. Wakeland holds the Edwin L. Cox Distinguished Chair in Immunology and Genetics and is Director of the Walter M. and Helen D. Bader Center for Research on Arthritis and Autoimmune Diseases, the Harold C. Simmons Arthritis Research Center and the Genomics Core at UT Southwestern.