Kevin Brown, Ph.D.
Laboratory of Translational Genomics
8717 GROVEMONT CIRCLE
GAITHERSBURG MD 20877
Discovery of Germline Cancer Susceptibility Genes
My research is focused on identifying the genetic contributions and functional pathways associated with cancer risk with a primary focus on melanoma. While early-stage melanoma is largely curable via surgical resection, late-stage melanoma remains nearly incurable despite decades of research. Much of the effort in my laboratory is directed towards better understanding the genetic factors contributing to melanoma risk, with a goal of ultimately facilitating prevention and early-detection efforts in at-risk individuals. We are actively involved in ongoing melanoma GWAS efforts within DCEG, and as members of the International Melanoma Genetics Consortium (GenoMEL) , we collaborate on melanoma GWAS meta-analyses. We also work with GenoMEL member groups to better understand the genetics of melanoma susceptibility in melanoma-prone families using whole-genome and -exome sequencing approaches. Lastly, we are actively involved in ongoing renal cell cancer GWAS at the NCI, as well as meta-analyses with international teams working in the same area.
Functional Characterization of Cancer Susceptibility Loci
Beyond susceptibility gene/locus discovery, a major focus of our laboratory is in the functional characterization of such loci. While significant strides have been made towards cataloging loci involved in cancer risk, elucidation of how risk variants influence susceptibility remains a significant challenge, with progress in this area lagging far behind. Our approach focuses both on better understanding the molecular consequences of specific risk variants on gene regulation and function, and on the phenotypic effects of allele-specific gene functions. Work in the laboratory involves fine-mapping of risk associated regions, targeted and genome-wide expression analysis, gene regulation and epigenetic work, and bioinformatic analysis of large genomic datasets.
Current projects in the laboratory include a large-scale study of the influences of germline genetic variation on both gene regulation and cellular phenotypes in melanocytes and melanoma cells, functional genomic screens to identify genes that mediate phenotypes associated with early stage tumor progression, large-scale reporter screens to identify risk-associated genetic variants conferring allele-specific gene regulatory potential, and directed analyses applied to specific susceptibility regions and genes, presently including chromosome bands 5p15.33 (TERT-CLPTM1L), 1q21.3 (multi-gene), 1q21.3 (PARP1), 22q13.1 (PLA2G6), 16q12.2 (FTO), MITF, and members of the shelterin complex.
Dr. Brown received a Ph.D. in genetics from the George Washington University in Washington, D.C., in 2003. He conducted his postdoctoral training in the Laboratory of Dr. Jeffrey Trent at the Translational Genomic Research Institute (TGen) in Phoenix, Arizona. He subsequently went on to direct his own research program at TGen as an investigator from 2005 to 2010, and served as an adjunct professor in basic medical sciences at the Mayo Clinic Cancer Center, the University of Arizona College of Medicine, and Arizona State University from 2008 to 2010. His work at TGen involved the application of whole-genome familial linkage, candidate gene, and genome-wide association study (GWAS) approaches to identify genetic variants associated with melanoma susceptibility. In 2010, Dr. Brown joined the Laboratory of Translational Genomics (LTG) in the Division of Cancer Epidemiology and Genetics (DCEG) as a tenure-track investigator. His research focuses on the genetic underpinnings of melanoma susceptibility.
Skibola CF, Bracci PM, Halperin E, Conde L, Craig DW, Agana L, Iyadurai K, Becker N, Brooks-Wilson A, Curry JD, Spinelli JJ, Holly EA, Riby J, Zhang L, Nieters A, Smith MT, Brown KM. Genetic variants at 6p21.33 are associated with susceptibility to follicular lymphoma. Nat Genet. 2009;41(8):873-5.
Brown KM, Macgregor S, Montgomery GW, Craig DW, Zhao ZZ, Iyadurai K, Henders AK, Homer N, Campbell MJ, Stark M, Thomas S, Schmid H, Holland EA, Gillanders EM, Duffy DL, Maskiell JA, Jetann J, Ferguson M, Stephan DA, Cust AE, Whiteman D, Green A, Olsson H, Puig S, Ghiorzo P, Hansson J, Demenais F, Goldstein AM, Gruis NA, Elder DE, Bishop JN, Kefford RF, Giles GG, Armstrong BK, Aitken JF, Hopper JL, Martin NG, Trent JM, Mann GJ, Hayward NK. Common sequence variants on 20q11.22 confer melanoma susceptibility. Nat Genet. 2008;40(7):838-40.
Stark MS, Woods SL, Gartside MG, Bonazzi VF, Dutton-Regester K, Aoude LG, Chow D, Sereduk C, Niemi NM, Tang N, Ellis JJ, Reid J, Zismann V, Tyagi S, Muzny D, Newsham I, Wu Y, Palmer JM, Pollak T, Youngkin D, Brooks BR, Lanagan C, Schmidt CW, Kobe B, MacKeigan JP, Yin H, Brown KM, Gibbs R, Trent J, Hayward NK. Frequent somatic mutations in MAP3K5 and MAP3K9 in metastatic melanoma identified by exome sequencing. Nat Genet. 2011;44(2):165-9.
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This page was last updated on January 19th, 2017