Education:
Post Doc: Genetic Epidemiology; Translational Genomics Research Institute; 2003-2005
PhD; George Washington University; 2003
Research Interests:
Despite decades of research, metastatic cutaneous malignant melanoma (CMM) remains an incurable disease, demonstrating a median survival time of 9 months with a 5-year survival rate of about 5%. Detection of the disease in its earliest form is perhaps our best form of cure. Further characterization of the genetic factors involved in cutaneous melanoma etiology will form the basis for understanding which individuals within susceptible populations are most at risk, how that risk can be modified, and how that knowledge might lead to targeted surveillance and recognition of disease at early stages, when treatment strategies are maximally beneficial. Our laboratory is focused on the identification of novel genes predisposing to melanoma, as well as other cancers, using family-based linkage, candidate gene, and genome-wide association approaches.
Given the dismal response and survival rate for patients with metastatic melanoma, there is clearly a critical need for improved therapies for the treatment of metastatic melanoma. Our group is utilizing a high-throughput functional genomics approach to systematically screen thousands of gene knockdown events using RNAi to discover genes that mediate sensitivity or resistance of melanoma cells to temozolomide and other therapeutic agents. Our goals include the identification of candidate genes that will enable the development of new markers for differentially predicting patients who will show a favorable clinical response and the in vitro and in vivo evaluation of molecularly-informed TMZ-combination therapies for the treatment of metastatic melanoma.
PubMed Link:
Search PubMed
for a complete listing of Dr. Brown's publications
Selected Publications:
- Brown KM, MacGregor S, Montgomery GW, Craig DW, Zhao Z, Iyadurai K, Henders A, Homer N, Campbell M, 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, Newton-Bishop J, 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. Nature Genetics, 2008, 40(7):838-40.
- Cloughesy TF, Yoshimoto K, Nghiemphu P, Brown K, Dang J, Zhu S, Hsueh T, Chen Y, Wang W, Youngkin D, Liau L, Martin N, Becker D, Bergsneider M, Lai A, Green R, Oglesby T, Koleto M, Trent J, Horvath S, Mischel PS, Mellinghoff IK, Sawyers CL. Antitumor Activity of Rapamycin in a Phase I Trial for Patients with Recurrent PTEN-Deficient Glioblastoma. PLoS Med, 2008, 5(1):e8.
- Coon KD, Valla J, Szelinger S, Schneider LE, Niedzielko TL, Brown KM, Pearson JV, Halperin R, Dunckley T, Papassotiropoulos A, Caselli RJ, Reiman EM, & Stephan DA. Quantitation of heteroplasmy of mtDNA sequence variants identified in a population of AD patients and controls by array-based resequencing. Mitochondrion, 2006, 6(4):194-210.
- Seftor EA, Brown KM, Chin L Kirschmann DA, Wheaton WW, Protopopov A, Feng B, Balagurunathan Y, Trent JM, Nickloff BJ, Seftor REB, Hendrix MJC. Epigenetic Transdifferentiation of Normal Melanocytes By a Metastatic Melanoma Microenvironment. Cancer Research, 2005, 65: 10164-69.
- Mintz MB, Sowers R, Brown KM, Hilmer SC, Mazza B, Huvos AG, Meyers PA, LaFleur B, McDonough WS, Henry MM, Ramsey KE, Antonescu CR, Wen A, Healey JH, Daluski A, Berens ME, MacDonald TJ, Hoffman EP, Gorlick R, & Stephan DA. Osteoclastogenesis and extracellular matrix remodeling are associated with chemotherapy resistance in pediatric osteosarcoma. Cancer Research, 2005, 65:1748-54.
- Walker GJ, Indsto JO, Sood R, Faruque MU, Hu P, Pollock PM, Duray P, Holland EA, Brown K, Kefford RF, Trent JM, Mann GJ, & Hayward NK. Deletion mapping suggests that the 1p22 melanoma susceptibility gene is a tumor suppressor localized to a 9-Mb interval. Genes Chromosomes Cancer, 2004; 41:56-64.
- Brown KM, Khatua S, Peterson K, Lawlor C, Santi M, LaFleur B, Dressman D, Stephan DA, & MacDonald TJ. Differential expression of the hypoxia-inducible factor (HIF) pathway in childhood astyrocytomas identified by microarray profiling of angiogenesis-associated genes. Cancer Research, 2003, 63:1865-1870.
- Brown KM, MacDonald TJ, LaFleur B, Peterson K, Lawlor C, Chen Y, Packer R, Cogen P, & Stephan DA. Expression profiling of medulloblastoma: PDGFRA and the RAS/MAPK pathway as therapeutic targets for metastatic disease. Nature Genetics, 2001; 29: 143-152.
- Brown KM, Laitinen PJ, Piippo K, Swan H, Devaney JM, Brahmbhatt B, Donarum EA, Marino M, Tiso N, Viitasalo M, Toivonen L, Stephan DA, & Kontula K. Mutations of the cardiac ryanodine receptor (RyR2) gene in familial polymorphic ventricular tachycardia. Circulation, 2001; 103: 485-90.
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