Keywords
Last Name

Anurag Singh, PhD

TitleAssistant Professor
InstitutionBoston University School of Medicine
DepartmentPharmacology & Experimental Therapeutics
Address72 E. Concord St Silvio Conte (K)
Boston MA 02118
Phone(617) 638-4175
ORCID ORCID Icon0000-0003-4705-8683
 Research Expertise & Professional Interests
Dr. Singh’s 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 exploiting the various lineage-specific KRAS dependency signatures to reveal mechanisms by which oncogenic KRAS maintains tumor cell survival in a context-dependent manner. In colon cancer, Dr. Singh has identified the TGF-b activated kinase as a component of a Wnt-driven proinflammatory signaling network that promotes tumor cell survival in KRAS dependent colon cancer cells. In lung and pancreatic cancers, Dr. Singh’s lab is studying the molecular basis for the relationship between the developmental epithelial-mesenchymal transition (EMT) program and KRAS oncogene dependency, as well as a role for non-coding microRNAs in mediating this relationship. The lab uses computational methods to derive genomic profiles in cancer cell lines and human primary tumors. These profiles reveal differentially expressed gene modules that can be built into systems-level signaling network models of KRAS-driven tumor cell survival signaling. Components of these network models are functionally validated and tested by cell and molecular methodologies using cancer cell lines in vitro as well as xenografted tumors in mice.


Dr. Singh has expertise in:

1. Cell biology – mammalian cell culture, cell based assays, drug-dose response assays, luciferase reporter assays, immunofluorescence, laser confocal microscopy.

2. Functional genomics – cDNA microarray gene expression analyses, shRNA/RNAi assays, miRNA assays.

3. Molecular biology – PCR, qPCR, Northern blotting, cloning, Gateway cloning, mutagenesis, inducible gene expression (Tet system or ER fusion proteins).

4. Biochemistry – in vitro enzymatic/kinase assays, fluorescence-based small GTPase assays (GEFs/GAPs), IP and pull-down assays, signaling pathway analysis, Western blotting.

5. Mouse tumor models – transgenic mice and xenografted subcutaneous human tumors in immuno-compromised mice. In vivo pharmacology, IP drug delivery. Immunohistocytochemistry.

6. Research interests include:
a) signal transduction pathways in cancer progression, specifically the RAS signaling network.
b) identification of oncogenic kinases such as TAK1.
c) signaling network crosstalk e.g. RAS-Wnt.

 Self-Described Keywords
  • APC
  • Colon cancer
  • KRAS
  • Lung cancer
  • Melanoma
  • NRAS
  • Pancreatic cancer
  • RAS
  • TAK1
  • Wnt
 Publications
Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
List All   |   Timeline
  1. 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.
    View in: PubMed
  2. 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.
    View in: PubMed
  3. 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.
    View in: PubMed
  4. 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.
    View in: PubMed
  5. Folaron M, Kalmuk J, Lockwood J, Frangou C, Vokes J, Turowski SG, Merzianu M, Rigual NR, Sullivan-Nasca M, Kuriakose MA, Hicks WL, Singh AK, Seshadri M. Vascular priming enhances chemotherapeutic efficacy against head and neck cancer. Oral Oncol. 2013 Sep; 49(9):893-902. PMID: 23890930.
    View in: PubMed
  6. 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.
    View in: PubMed
  7. 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. PMID: 22341439.
    View in: PubMed
  8. 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. PMID: 21985784.
    View in: PubMed
  9. 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; 5(11).
  10. 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. PMID: 20531305.
    View in: PubMed
  11. Singh A, Settleman J. Oncogenic K-ras "addiction" and synthetic lethality. Cell Cycle. 2009 Sep 1; 8(17):2676-7. PMID: 19690457.
    View in: PubMed
  12. 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. PMID: 19477428.
    View in: PubMed
  13. 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(21):6867-76. PMID: 18980981.
    View in: PubMed
  14. 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. 2008 Jun 15; 68(12):4853-61. PMID: 18559533.
    View in: PubMed
  15. Campbell PM, Singh A, Williams FJ, Frantz K, Ulkü AS, Kelley GG, Der CJ. Genetic and pharmacologic dissection of Ras effector utilization in oncogenesis. Methods Enzymol. 2006; 407:195-217. PMID: 16757325.
    View in: PubMed
  16. 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. PMID: 15516977.
    View in: PubMed
  17. 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; 44(10):1963-75.
Anurag's Networks
Click the "See All" links for more information and interactive visualizations!
Concepts
_
BU Co-Authors
_
Similar BU People
_
Same Department