Three scientists win High Impact/High Risk grants

By Deborah Wormser

Three faculty members have received grants from the UT Southwestern High Impact/High Risk Program for research that might contribute to the development of a vaccine against tuberculosis, reduce hospital-acquired infections and increase the accuracy of next-generation DNA sequencing.

The grants, which provide support for a year in order to test hypotheses and determine whether ideas have merit, were given to Dr. Michael Shiloh, Dr. Anthony Michael and Dr. Zbyszek Otwinowski to fund work that has the potential to greatly influence the science or practice of medicine, but also carries a substantial risk of failure.

three scientists high risk grants

The latest researchers selected to receive funding under the High Impact/High Risk Program are (left to right) Dr. Anthony Michael, Dr. Zbyszek Otwinowski, and Dr. Michael Shiloh. 

Dr. Shiloh, Assistant Professor of Internal Medicine and Microbiology, will pursue a novel approach in developing a vaccine against tuberculosis, which contributed to an estimated 1.4 million deaths in 2010, according to the World Health Organization.

The Centers for Disease Control and Prevention has noted that the TB vaccine currently in use does not always protect against TB, hence the search for a new strategy.

“A successful vaccine against Mycobacterium tuberculosis would be a major and dramatic step forward in improving global health,” said Dr. Mark Swancutt, Associate Professor of Internal Medicine and Interim Chief of the Division of Infectious Diseases.

“If Dr. Shiloh’s proof-of-principal experiments are validated, there would be direct bench-to-bedside implications of his work that would have a major impact on the global burden of tuberculosis,” Dr. Swancutt said.

Dr. Michael, Associate Professor of Pharmacology, will use his grant to target the problem of hospital-acquired infections by studying ways to interfere with the formation of biofilms on medical devices such as catheters. Such biofilms cause the pathogenic bacteria that grow on medical devices to become much more resistant to antibiotics than free-living varieties, he said.

He is testing a hypothesis that chemical compounds called polyamines are needed by those bacteria to make biofilms, and he will test whether blocking uptake of a specific polyamine can keep microorganisms from congregating in those biofilms.

“Tony’s proposal touches on many aspects of interest to our department, including genomic analysis for identifying chemotherapeutic targets and consequent drug-discovery efforts,” said Dr. David Mangelsdorf, Chairman of Pharmacology, in nominating Dr. Michael for the award.

Dr. Otwinowski, Professor of Biochemistry, was nominated by Dr. Steven L. McKnight, Chairman of Biochemistry, for work that could greatly improve genetic sequencing of mutations that result from DNA damage or replication errors that occur after birth and are implicated in aging and the development of cancer.

“I will apply a novel experimental method combined with an associated data analysis that I hypothesize will provide unbiased and robust estimates of the acquired mutation levels in any part of an organism,” Dr. Otwinowski said.

With the latest approvals, 37 faculty members have received grants through the High Impact, High Risk program, which was established in 2001.


Dr. Mangelsdorf holds the Raymond and Ellen Willie Distinguished Chair in Molecular Neuropharmacology in Honor of Harold B. Crasilneck, Ph.D., and the Distinguished Chair in Pharmacology.

Dr. McKnight holds the Sam G. Winstead and F. Andrew Bell Distinguished Chair in Biochemistry and the Distinguished Chair in Basic Biomedical Research.