Our DNA is constantly exposed to agents that can cause damage to them. In addition whenever cells divide, errors can form. These errors, called mutations, can lead to the changes in the function of critical genes that are necessary for guarding our genomes against further abnormalities, which can lead to cancer. Certain patients inherit mutations in some of these critical genes, predisposing them to cancer. Two particular genes, BRCA1 and BRCA2, have been shown to be mutated often in patients with ovarian cancer. What we have recently found is that, because of the important role these genes play in repairing damaged DNA, loss of these critical genes causes these cancers to rely on alternative methods of repairing DNA. These alternative repair methods become really important in these cells compared to normal cells because, unlike normal cells, these cancer cells have inactivated their primary repair methods, making them potentially vulnerable to drugs that can inhibit these backup repair programs. In this work, we aim to understand how these major and minor repair pathways interact with each other. First, we want to understand how DNA abnormalities arise in cells with mutations in these DNA repair genes. We also aim to demonstrate that targeting these backup pathways is a viable means of treating cancers that lack or have mutations in certain genes that are important for repairing DNA.
Dr. Richard Adeyemi, DVM, PhD is an Assistant Professor in the Division of Basic Sciences at the Fred Hutchinson Cancer Center. He obtained his Doctor of Veterinary Medicine degree with distinctions at the University of Ibadan. He then moved to the United States for graduate school in Molecular Microbiology, joining the virology lab of Dr. David Pintel at the University of Missouri. In Dr. Pintel’s lab, Dr. Adeyemi studied virus-host interactions and discovered a previously unknown cellular antiviral response that, following infection with small DNA viruses, is hijacked to promote viral replication. For his postdoc, Dr Adeyemi joined the Genetics lab of Dr Stephen Elledge at Harvard Medical School. As a Life Sciences Research Foundation (LSRF) postdoctoral fellow, Dr. Adeyemi made use of genome-scale high-throughput CRISPR screening approaches to discover the compendium of cellular genes that are essential for responding to replication stress. In particular, Dr. Adeyemi discovered Protexin, a novel complex that is involved in maintaining the integrity of cellular rDNA following DNA damage during replication. He also studied synthetic lethal pathways that modulate BRCA mutant cancer cells. At the Hutch, Dr. Adeyemi is making use of genomics, computational and molecular biology tools to further characterize the molecular mechanisms by which cells deal with replication stress and to discover novel cellular vulnerabilities that can be targeted for therapy in ovarian cancers.