Dr. Singh has expertise in cancer biology, functional genomics and cancer pharmacology. His laboratory studies deregulated signal transduction networks that contribute to the pathophysiology of lung, pancreatic and colon cancers. Adenocarcinomas that arise in these tissues frequently harbor mutations in the KRAS oncogene or components of the KRAS signaling pathway, such as BRAF or PI3K. The core KRAS signaling pathway has been very well characterized but the precise mechanisms governing tumor maintenance in KRAS mutant cancers remain to be fully elucidated. Through comparative whole genome expression profiling, Dr. Singh has previously shown that KRAS mutant cancers can be classified into discrete molecular subtypes based on a phenotypic dichotomy of KRAS oncogene “addiction” or dependency. He derived tissue or lineage-specific KRAS dependency gene expression signatures that reflect differing modes of KRAS-mediated signal transduction in lung versus pancreatic versus colon cancers. Therefore, Dr. Singh hypothesizes that context-specificity is critical in the analysis of KRAS signaling networks.
Current research in the Singh lab is focused on delineating mechanisms of oncogene dependency in a broader context. Preliminary results indicate that triple-negative breast cancer (TNBC) cells are KRAS-dependent. Based on this, TNBC KRAS dependency signatures will be derived to reveal candidate therapeutic targets for TNBC treatment. In melanoma, the NRAS oncogene (related to KRAS) is mutated in 20-30% of cases. NRAS dependency in melanoma is strongly correlated with expression and activation of the melanocyte lineage transcription factor and oncogene, MITF. Efforts are underway to understand MITF-mediated transcriptional mechanisms that control NRAS-dependency, with the overarching goal of identifying combination therapeutic approaches to treat NRAS mutant melenoma.
- University of North Carolina at Chapel Hill, PhD
- Stony Brook University, BS
- GMS PM730
- GMS PM802
- Published on 9/12/2017
Mehta AK, Hua K, Whipple W, Nguyen MT, Liu CT, Haybaeck J, Weidhaas J, Settleman J, Singh A. Regulation of autophagy, NF-?B signaling, and cell viability by miR-124 in KRAS mutant mesenchymal-like NSCLC cells. Sci Signal. 2017 Sep 12; 10(496). PMID: 28900044.
- Published on 9/11/2017
Grant TJ, Mehta AK, Gupta A, Sharif AAD, Arora KS, Deshpande V, Ting DT, Bardeesy N, Ganem NJ, Hergovich A, Singh A. STK38L kinase ablation promotes loss of cell viability in a subset of KRAS-dependent pancreatic cancer cell lines. Oncotarget. 2017 Oct 03; 8(45):78556-78572. PMID: 29108249.
- Published on 10/15/2016
Grant TJ, Hua K, Singh A. Molecular Pathogenesis of Pancreatic Cancer. Prog Mol Biol Transl Sci. 2016; 144:241-275. PMID: 27865459.
- Published on 9/21/2016
McNew KL, Whipple WJ, Mehta AK, Grant TJ, Ray L, Kenny C, Singh A. MEK and TAK1 Regulate Apoptosis in Colon Cancer Cells with KRAS-Dependent Activation of Proinflammatory Signaling. Mol Cancer Res. 2016 Dec; 14(12):1204-1216. PMID: 27655129.
- Published on 2/15/2016
Anderson NM, Li D, Peng HL, Laroche FJ, Mansour MR, Gjini E, Aioub M, Helman DJ, Roderick JE, Cheng T, Harrold I, Samaha Y, Meng L, Amsterdam A, Neuberg DS, Denton TT, Sanda T, Kelliher MA, Singh A, Look AT, Feng H. The TCA cycle transferase DLST is important for MYC-mediated leukemogenesis. Leukemia. 2016 Jun; 30(6):1365-74. PMID: 26876595.
- Published on 1/1/2016
Grant, T., Hua, K., Singh A. Progress in Molecular Biology and Translational Science. Molecular Pathogenesis of Pancreatic Cancer. Elsevier Press. 2016; 144:214-275.
- Published on 4/9/2015
Anurag Singh. Systems biology of cancer. Chapter 27. Deregulated signaling networks in lung cancer. Cambridge University Press. Cambridge UK. 2015; N/A(N/A):421-443.
- Published on 2/12/2015
Javaid S, Zhang J, Smolen GA, Yu M, Wittner BS, Singh A, Arora KS, Madden MW, Desai R, Zubrowski MJ, Schott BJ, Ting DT, Stott SL, Toner M, Maheswaran S, Shioda T, Ramaswamy S, Haber DA. MAPK7 Regulates EMT Features and Modulates the Generation of CTCs. Mol Cancer Res. 2015 May; 13(5):934-43. PMID: 25678598.
- Published on 3/19/2014
Wang M, Kern AM, Hülskötter M, Greninger P, Singh A, Pan Y, Chowdhury D, Krause M, Baumann M, Benes CH, Efstathiou JA, Settleman J, Willers H. EGFR-mediated chromatin condensation protects KRAS-mutant cancer cells against ionizing radiation. Cancer Res. 2014 May 15; 74(10):2825-34. PMID: 24648348.
- Published on 12/13/2012
Corcoran RB, Cheng KA, Hata AN, Faber AC, Ebi H, Coffee EM, Greninger P, Brown RD, Godfrey JT, Cohoon TJ, Song Y, Lifshits E, Hung KE, Shioda T, Dias-Santagata D, Singh A, Settleman J, Benes CH, Mino-Kenudson M, Wong KK, Engelman JA. Synthetic lethal interaction of combined BCL-XL and MEK inhibition promotes tumor regressions in KRAS mutant cancer models. Cancer Cell. 2013 Jan 14; 23(1):121-8. PMID: 23245996.
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