UT Health San Antonio biochemist Patrick Sung, D.Phil., one of the world’s leading experts on BRCA1 and BRCA2 cancer biology, has just received a highly competitive National Cancer Institute (NCI) Outstanding Investigator Award.
Dr. Sung is the first faculty member in UT Health San Antonio history to capture this prestigious NCI award, which is bestowed only upon researchers with august track records, elite-level scientific impact, and ascending career trajectories and research goals. The award, which began Sept. 9, will provide $6.1 million through 2026.
Dr. Sung joined UT Health San Antonio in 2019 from Yale, where he was a professor of molecular biophysics and biochemistry, therapeutic radiology and epidemiology. A $6 million grant from the Cancer Prevention and Research Institute of Texas (CPRIT) supported his recruitment.
BRCA1 and BRCA2 are tumor suppressor genes. When these genes are mutated, the loss of function leads to cancer. Primarily known for increasing risk of breast cancer in women, BRCA1 and BRCA2 mutations also are associated with ovarian cancer, prostate and breast cancer in men, and a childhood cancer called neuroblastoma. A related gene is associated with aggressive pancreatic cancer.
“This NCI award is given to the top cancer researchers in the U.S.A., and we are proud that it has come to Dr. Sung and South Texas,” said Robert A. Hromas, M.D., professor and dean of the Joe R. and Teresa Lozano Long School of Medicine at UT Health San Antonio. “Dr. Sung is an expert in the molecular mechanisms by which BRCA1 and BRCA2 mutations give rise to cancers, which could lead to new ways to treat them and possibly prevent their occurrence in the first place.”
Unique body of work
The Sung laboratory conquered a major technical challenge over several years—a feat that eluded all other labs worldwide. Using unique insect cell culture systems, the scientists were able to prompt the BRCA1 and BRCA2 genes to make their proteins. “These are very elaborate human BRCA proteins expressed in insect cells,” Dr. Sung said. “Now that this technical hurdle is overcome, we are poised to figure out how these tumor suppressor proteins function.”
“Very few groups in the world are able to conduct the type of investigations that Dr. Sung’s group is doing,” said William L. Henrich, M.D., MACP, president of UT Health San Antonio.
Like mechanics taking an engine apart and putting it back together, Dr. Sung and his colleagues are analyzing the sequence of events that occur when a BRCA mutation leads to cancer initiation and progression. The key factor is a loss of DNA repair capacity.
DNA, short for deoxyribonucleic acid, is a double-stranded molecule in all cells that contains the instructions for every process that sustains life—cell division, respiration and energy production, to name only a few. DNA repair is needed because genetic and environmental factors (such as harmful chemicals and sun exposure) damage DNA on a continual basis. Cells must constantly repair their DNA.
During cell division, the BRCA genes prompt cells to use the most accurate repair pathway to preserve our genetic blueprint.
In the absence of this protective effect of BRCA, cells revert to a less-efficient pathway, which allows the introduction of errors, genetic mutations and, ultimately, cancers.
“We know things happen, but exactly how they happen is what we want to discover,” Dr. Sung said.
It’s a complex undertaking, to say the least.
“Hundreds of BRCA mutations have been reported,” Dr. Sung said. “It’s not possible for us to go and look at every single one of them, but because of the work that we have done in the past, we can cherry-pick a few. Based on what we know about what BRCA does, we can say, ‘I think the mutation could affect this,’ and then we can carry out the necessary work to validate the hypothesis.”
Display of trust by the NCI
The NCI grant is for basic investigation to understand BRCA biology.
“The NCI Outstanding Investigator Award encourages risk taking,” Dr. Sung said. “Recipients don’t actually have to tell the reviewing panel what they want to do exactly. It provides freedom for an established investigator to come up with really provocative ideas—paths of inquiry where the chances of being wrong are actually quite high, but also where, if we are right, the impact will be tremendous.”
Dr. Sung said he is “humbled and honored to have received an award with this level of trust from the National Cancer Institute.”
In July, the Gray Foundation of New York announced grants to seven multidisciplinary teams including UT Health San Antonio. The focus is drug resistance in BRCA-deficient tumors. Dr. Sung is the principal investigator on a $3.75 million award that includes collaborators at the Dana-Farber Cancer Institute and the University of Pennsylvania.
Dr. Sung occupies the Robert A. Welch Distinguished Chair in Chemistry and is a professor in the Department of Biochemistry and Structural Biology at UT Health San Antonio. He also serves as associate dean for research in the Long School of Medicine, and leads a new research program in genetic integrity at the Mays Cancer Center, home to UT Health San Antonio MD Anderson Cancer Center.
Dr. Sung was born and raised in Hong Kong. He earned a Bachelor of Science degree at the University of Liverpool in 1981 and a Doctor of Philosophy degree at the University of Oxford in 1985, both in biochemistry. He then completed eight years of postdoctoral fellowship training at the University of Rochester in upstate New York.
His initial faculty appointment was at The University of Texas Medical Branch at Galveston. In 1997 he moved to UT Health San Antonio as associate professor, and ultimately was promoted to professor and the Zachry Distinguished Professor of Molecular Medicine. From 2001 to 2003, he was co-director of a National Cancer Institute-funded training program in DNA repair at the university.
He left UT Health San Antonio in 2003 to join the Department of Molecular Biophysics and Biochemistry at Yale University. From 2009 to 2015, Dr. Sung served two three-year terms as chair of the department, which includes several National Academy of Sciences members and a Nobel laureate.
Dr. Sung’s decision to leave the Northeast and return to South Texas was three-pronged, he said. He and his wife wanted to come back to San Antonio, the leadership of UT Health San Antonio is top-tier, and the level of investigation at the university is outstanding. “We have good science, amazing people and we love San Antonio,” he said. “I was very sincere when I told Dr. Hromas, this was our first choice at the get-go.”
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