Anurag Singh, Ph.D.

IMGP3095

Assistant Professor of Pharmacology and Medicine, Division of Hematology and Medical Oncology and Member, The Cancer Center

Department of Pharmacology

Ph.D.: The University of North Carolina at Chapel Hill, NC; Pharmacology

Principal Investigator: Laboratory of Cancer Pharmacogenomics

Research Interests

Dr. Singh’s lab studies global mechanisms underlying oncogene-driven cancer progression. We use state of the art technologies, including gene expression profiling and RNAi-based screening. Subsequently, through application of functional genomics and systems pharmacology we identify novel oncogenic signaling networks that can be exploited for therapeutic target identification and validation. Current research in the lab seeks to identify KRAS-regulated signaling networks and to use this information to provide detailed mechanistic insight into KRAS-driven tumor progression. We are also interested in contextual variability in these networks based on tissue lineage and genetic background. Through this approach, we have identified a number of attractive candidate therapeutic targets that can be antagonized to promote cancer cell death in a context-dependent manner, such as the kinase TAK1 in colon cancers. Since effective pharmacological targeting of the mutant KRAS protein has proven challenging, a key translational goal is to identify clinically efficacious small molecule inhibitors against critical nodes in oncogenic KRAS signaling networks to provide benefit for patients with highly aggressive KRAS-driven cancers.

 

Selected Publications

Singh A, Sweeney MF, Yu M, Burger A, Greninger P, Benes C, Haber DA, Settleman J. TAK1 inhibition promotes apoptosis in KRAS-dependent colon cancers. Cell 2012 Feb 17;148(4):639-50. PMC3291475. Abstract:.

Ebi H, Corcoran RB, Singh A, Chen Z, Song Y, Lifshits E, Ryan DP, Meyerhardt JA, Benes C, Settleman J, Wong KK, Cantley LC, Engelman JA. Receptor tyrosine kinases exert dominant control over PI3K signaling in human KRAS mutant colorectal cancers. J. Clin Invest. 2011 Nov; 121(11):4311-21. PMC3204842. Full article .

Singh A, Settleman J. EMT, cancer stem cells and drug resistance: an emerging axis of evil in the war on cancer. Oncogene. 2010 Aug 26; 29(34):4741-51. PMC3176718. Full Article: .

Singh A, Boyer JL, Der CJ, Zohn IE. Transformation by a nucleotide-activated P2Y receptor is mediated by activation of Galphai, Galphaq and Rho-dependent signaling pathways. J Mol Signal. 2010 Jul 23;5(11). PMC2917412. Full article: .

Singh A, Settleman J. Oncogenic K-ras “addiction” and synthetic lethality. Cell Cycle. 2009 Sep 1;8(17):2676-7. Full Article: .

Singh A, Greninger P, Rhodes D, Koopman L, Violette S, Bardeesy N, Settleman J. A gene expression signature associated with “K-Ras addiction” reveals regulators of EMT and tumor cell survival. Cancer Cell. 2009 Jun 2;15(6):489-500. PMC 2743093. Full article: .

Chin TM, Quinlan MP,Singh A, Sequist LV, Lynch TJ, Haber DA, Sharma SV, Settleman J. Reduced Erlotinib sensitivity of epidermal growth factor receptor-mutant non-small cell lung cancer following cisplatin exposure: a cell culture model of second-line erlotinib treatment. Clin Cancer Res. 2008 Nov 1;14(22):6867-76. PMC2710881. Full article: .

Montagut C, Sharma SV, Shioda T, McDermott U, Ulman M, Ulkus LE, Dias-Santagata D, Stubbs H, Lee DY, Singh A, Drew L, Haber DA, Settleman J. Elevated CRAF as a potential mechanism of acquired resistance to BRAF inhibition in melanoma. Cancer Res . 2087 Jun 15;68(12):4853-61. PMC2692356. Full article: .

Campbell PM, Singh A, Williams FJ, Frantz K, Ulk├╝ AS, Kelley GG, Der CJ. Genetic and pharmacologic dissection of Ras effector utilization in oncogenesis. Methods Enzymol. 2006; 407:195-217. Abstract: .

Singh A, Karnoub AE, Palmby TR, Lengyel E, Sondek J, Der CJ. Rac1b, a tumor associated, constitutively active Rac1 splice variant, promotes cellular transformation. Oncogene . 2004 Dec 16;23(58):9369-80. Abstract: .

Luquain C, Singh A, Wang L, Natarajan V, Morris AJ.Role of phospholipase D in agonist-stimulated lysophosphatidic acid synthesis by ovarian cancer cells. J Lipid Res . 2003 Oct;44(10):1963-75. Full Article: .

Publication Search via PubMed

Contact

Office: The Cancer Center, Boston University School of Medicine, 72 East Concord Street, K-712B, Boston, MA 02118
Office Phone: 617-638-4175
Office Fax: 617-638-4176
Lab Phone: 617-638-4189
Email: asingh3@bu.edu