Genomics and Cancer Biology

Understanding the Role of Genetic Variants in Human Disease

Harry Ostrer, M.D.

Harry Ostrer, MD

Professor, Department of Pathology

Professor, Department of Pediatrics


View Profile

Genetic differences play an important role in normal human development and disease. These differences can also play a role in the progression of disease and in individual responses to therapy. The laboratory of Harry Ostrer, MD, uses modern genomics to elucidate the roles of human genetic variation in these processes.

Dr. Ostrer and his team have developed functional variant assays to understand the phenotypic effects of genetic variants.

Genetic variation in human populations. The Ostrer Laboratory has characterized genetic variation in a number of human populations (Hispanics and Latinos, Jewish HapMap Project) to understand the origins and migrations of these populations. Currently, the investigators are exploring the role of natural selection in the formation of some of these populations in order to understand their disease susceptibilities. A key feature of this work is translating new findings into clinical practice to promote personalized medicine.

Human developmental disorders. Dr. Ostrer and his colleagues study the genetic basis of rare genetic disorders, notably disorders found in isolated populations and disorders of sex development, to identify both the mutational basis and the molecular mechanisms. Recently, they identified mutations in genes in the MAP kinase pathway in abnormal testicular development and now are investigating the roles of members of this pathway in normal testicular development.

Cancer genetics and genomics. The Ostrer Laboratory has explored the roles of low- and high-penetrance variants in risk of human cancers, and has developed models for predicting risk. Through genome-wide association studies, the investigators have identified common variants that increase the risk of adverse outcomes (erectile dysfunction, urinary dysfunction, proctitis) for men treated with radiation therapy for prostate cancer. The investigators have developed a molecular signature based on acquired somatic copy-number alterations that is highly predictive of risk of metastasis and may account for the increased risk among African-American men. A similar model is being developed for breast cancer.