Robert M. Brosh Jr., Ph.D.
Laboratory of Molecular Gerontology
251 Bayview Boulevard
Baltimore, MD 21224
Roles of DNA Helicases in Genomic Stability: Genetic mutations in a class of molecular motor proteins known as helicases are linked to a growing number of human disorders, indicating that these enzymes have vitally important roles during replication, DNA repair, recombination and transcription. My research team believes that defining the biochemical and cellular functions of helicases will help us understand molecular defects associated with chromosomal variability. The focus of our group is genetic diseases frequently associated with premature aging, cancer, and/or mitochondrial dysfunction arising from mutations in genes encoding DNA helicases that operate uniquely in pathways of DNA repair and the replication stress response. A special topic of interest is the application of small molecules to modulate helicase activity as a tool to assign specific helicase functions in vivo and potential development of therapeutic strategies.
Dr. Robert Brosh received his B.S. in chemistry from Bethany College in 1985, M.S. in biochemistry from Texas A & M University in 1988, and Ph.D. in biology from the University of North Carolina at Chapel Hill in 1996. He did postdoctoral work at NIH before assuming his present position as a Principal Investigator in the Laboratory of Molecular Gerontology, NIA in 2000. Dr. Brosh's group is engaged in biomedical studies of DNA repair diseases. His research program also investigates the emerging importance of helicases in other facets of biology including cellular metabolism and inflammation.
Bharti SK, Sommers JA, Awate S, Bellani MA, Khan I, Bradley L, King GA, Seol Y, Vidhyasagar V, Wu Y, Abe T, Kobayashi K, Shin-Ya K, Kitao H, Wold MS, Branzei D, Neuman KC, Brosh RM Jr. A minimal threshold of FANCJ helicase activity is required for its response to replication stress or double-strand break repair. Nucleic Acids Res. 2018;46(12):6238-6256.
Khan I, Crouch JD, Bharti SK, Sommers JA, Carney SM, Yakubovskaya E, Garcia-Diaz M, Trakselis MA, Brosh RM Jr. Biochemical Characterization of the Human Mitochondrial Replicative Twinkle Helicase: SUBSTRATE SPECIFICITY, DNA BRANCH MIGRATION, AND ABILITY TO OVERCOME BLOCKADES TO DNA UNWINDING. J Biol Chem. 2016;291(27):14324-39.
Banerjee T, Sommers JA, Huang J, Seidman MM, Brosh RM Jr. Catalytic strand separation by RECQ1 is required for RPA-mediated response to replication stress. Curr Biol. 2015;25(21):2830-2838.
Brosh RM Jr. DNA helicases involved in DNA repair and their roles in cancer. Nat Rev Cancer. 2013;13(8):542-58.
Aggarwal M, Sommers JA, Shoemaker RH, Brosh RM Jr. Inhibition of helicase activity by a small molecule impairs Werner syndrome helicase (WRN) function in the cellular response to DNA damage or replication stress. Proc Natl Acad Sci U S A. 2011;108(4):1525-30.
Related Scientific Focus Areas
Genetics and Genomics
Molecular Biology and Biochemistry
This page was last updated on February 14th, 2019