Internationally known biochemist building world-class genome repair program
Mays Cancer Center Annual Report
With the return of a world-acclaimed biochemist who is an international leader in understanding the cause of breast and ovarian cancers, the inevitable is happening at the Mays Cancer Center: The development of a nationally recognized genome repair program which will ultimately lead to the discovery of new therapeutics to treat different cancer types.
“Nationally speaking, we have become one of the top institutions when it comes to genome repair,” says Patrick Sung, D.Phil., the Robert A. Welch Distinguished Chair in Chemistry and a scientific program leader for Cancer Development and Progression at the cancer center.
Building this program along with the opportunity to work with Robert Hromas, M.D., FACP, dean of the Long School of Medicine, were key reasons for Dr. Sung’s return to San Antonio in January 2019.
In order to comprehend the importance of genome repair research, it is necessary to understand that cancer is often caused by faulty DNA repair. With the appearance of genetic mutation or changes to the genome, a tumor will invariably become more aggressive and begin to metastasize, explains Dr. Sung, professor of biochemistry and structural biology and associate dean for research for the medical school.
Additionally, many tumors which are ordinarily sensitive to certain cancer drugs become resistant to treatment because of mutations and instability of the genome; new drugs must be found to treat them. Yet, ultimately, they become resistant once more.
“It just becomes a vicious cycle of good response and then reverts to resistance,” Dr. Sung says. “That’s why understanding genome repair is necessary in order for us to effectively target the genome repair deficiency of tumors.”
major focus in genome repair begins with understanding how cells eliminate breaks in DNA. All types of lesions may occur in DNA, and they may all lead to genome instability, but one of Dr. Sung’s major strengths is understanding the mechanism that underlies the ability of cells to eliminate DNA breaks.
“At UT Health San Antonio, we have great strength in understanding how DNA repair works,” Dr. Sung says. “A lot of our research focus is on this. In particular, we are focusing on a group of tumor suppressor genes with functions in genome break repair. The two most famous tumor suppressor genes in this regard are BRCA1 and BRCA2.”
Since millions of people worldwide carry these mutations, which are linked to breast and ovarian cancer, the impact of his research is great.
With a long history of genome repair research spanning more than 20 years, UT Health is reaffirming and expanding its role in the field today by recruiting researchers with expertise in various areas of genome repair and cancer biology.
“We want to build upon our strengths. We have excellent funding; we have excellent scientists. We are in the process of conducting more strategic recruitment in this particular area,” he explains.
Two of these new recruits are Sandeep Burma, Ph.D., professor of neurosurgery and of biochemistry and structural biology and the Mays Family Foundation Distinguished Chair in Oncology; and Weixing “Wilson” Zhao, Ph.D., assistant professor of biochemistry and structural biology and a member of the Greehey Children’s Cancer Research Institute.
Each brings important research and expertise to the genome repair program. Dr. Burma’s research focuses on DNA repair and therapy resistance in glioblastoma. Dr. Zhao’s research focuses on investigating the BRCA1/2 tumor suppressor networks in various related biological processes.
“We have a significant distance to go in terms of building a really impactful program with all different types of expertise,” Dr. Sung says. “I am not a structural biologist like some of my colleagues; I am a biochemist. Even though we are working on related problems, my approach is different. It will take a comprehensive, holistic approach to understand genome repair in cancer biology. It is important to build a program that is multi-faceted.”
Areas of recruitment include chemists with drug development expertise; physician scientists who know how to put a clinical trial together; structural biologists to look at how the chemical compounds work; and partners who may provide tumor tissues to study and test new treatments and drugs.
“In the next 10 years or so, we should be able to paint a broad picture of why when one of the BRCA genes malfunctions, DNA repair becomes impaired at the mechanistic level,” Dr. Sung says. “It entails a lot of effort. We have a long way to go, not because we haven’t been working hard, but because the field is still at the fledgling stage. We are in the discovery phase. This is a very exciting phase. Genome repair is front and center, and the cornerstone to understanding tumor biology.”
While the genome repair program at the cancer center continues to gain notoriety, Dr. Sung and his colleagues work diligently toward their ultimate goal of providing additional and alternative treatments to future cancer patients.
A patent on the MiR-584-5p technology has been filed with Dr. Rao and Nourhan Abdelfattah, Ph.D., first author on the paper, listed as inventors. Dr. Abdelfattah completed her doctoral work in the Rao laboratory and is a postdoctoral fellow at the Houston Methodist Research Institute.
A second patent with Dr. Rao as inventor was issued by the U.S. Patent and Trademark Office. Multiple commercialization business models are under review, including a possible start-up company, according to the Office of Technology Commercialization at UT Health San Antonio.
Dr. Rao’s research has been supported by the National Cancer Institute, the William and Ella Owens Medical Research Foundation of San Antonio, the Cancer Prevention and Research Institute of Texas, and the Max and Minnie Tomerlin Voelcker Fund.
