Senior Research Scientist, Informatics Program
Boston Children's Hospital
Assistant Professor of Pediatrics
Harvard Medical School
Genomic instability, the ability of tumor cells to accumulate gene mutations over multiple cell divisions, is one of the central driving mechanisms of cancer. DNA repair pathway alterations are a major contributor to this process. In fact, the specific type of DNA repair pathway alteration in a given cancer has a profound impact on the biology of the tumor and may also determine the efficacy of a particular therapy. Therefore, developing reliable methods that determine the types of DNA repair pathway alteration in a tumor will have a significant impact on selecting the most effective therapy in breast cancer.
The development of next generation sequencing technology has allowed the detection of distinct mutational “signatures”, collections of genetic changes that define the biology of a tumor. One of the major goals of Dr. Szallasi’s BCRF project is to create a cellular model system that mimics these mutational signatures towards the goal of designing more effective treatments. His laboratory has assembled a panel of cell lines that contain mutations in a variety of DNA repair pathway genes that are often mutated in breast cancer. They will grow the cells for many generations (cell divisions) in order to accumulate characteristic mutational signatures, thus mimicking the processes that lead to genomic instability in a human tumor. They will then use next generation sequencing to identify gene changes that occurred over time and compare this to genomic data from breast cancer patients and correlate this information with clinical outcomes. The investigators believe these mutational signatures may provide important information to aid in selecting the most effective therapy for breast cancer.
Dr. Szallasi received his Doctor of Medicine degree from the University of Medicine in Debrecen, Hungary, in 1988. He did postdoctoral research in molecular pharmacology of cancer at the National Cancer Institute. As a faculty member, first at the Uniformed Services University of Health Sciences and currently at Boston Children's Hospital and Harvard Medical School, he has become active in the high throughput analysis of breast cancer. He has published over 100 peer-reviewed articles, mainly on the molecular pharmacology and high throughput analysis of cancer.
Dr. Szallasi's group is interested in the application of high throughput measurements for cancer research. They implemented several methods that increased the reliability of microarray and next generation sequencing measurements. They are also interested in approaches that combine genomic scale measurements in a manner that describe essential cancer biology in a robust fashion. Dr. Szallasi is currently developing methods that determine and quantify specific DNA repair pathway aberrations in human tumor biopsies. This work led to a DNA aberration profile-based method that predicts response to platinum-based therapy with high accuracy, and which is currently in the final stages of comprehensive clinical validation.