Robert M. Brosh Jr., Ph.D.

Senior Investigator

Translational Gerontology Branch

NIA

251 Bayview Boulevard
Suite 100
Baltimore, MD 21224

410-558-8578

broshr@mail.nih.gov

Research Topics

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.

Biography

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.

Selected Publications

  1. Awate S, Sommers JA, Datta A, Nayak S, Bellani MA, Yang O, Dunn CA, Nicolae CM, Moldovan GL, Seidman MM, Cantor SB, Brosh RM. FANCJ compensates for RAP80 deficiency and suppresses genomic instability induced by interstrand cross-links. Nucleic Acids Res. 2020;48(16):9161-9180.

  2. Butler TJ, Estep KN, Sommers JA, Maul RW, Moore AZ, Bandinelli S, Cucca F, Tuke MA, Wood AR, Bharti SK, Bogenhagen DF, Yakubovskaya E, Garcia-Diaz M, Guilliam TA, Byrd AK, Raney KD, Doherty AJ, Ferrucci L, Schlessinger D, Ding J, Brosh RM. Mitochondrial genetic variation is enriched in G-quadruplex regions that stall DNA synthesis in vitro. Hum Mol Genet. 2020;29(8):1292-1309.

  3. 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.

  4. Brosh RM Jr. DNA helicases involved in DNA repair and their roles in cancer. Nat Rev Cancer. 2013;13(8):542-58.

  5. 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.


This page was last updated on September 13th, 2021