Anurag Singh, PhD
Assistant Professor
Boston University School of Medicine
Dept of Pharmacology & Experimental Therapeutics

PhD, University of North Carolina at Chapel Hill



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.

2015-2018 Melanoma Research Alliance: Young Investigator Award
2013-2014 American Lung Association: Lung Cancer Discovery Award
2010-2015 NIH/NCI: Howard Temin Award/K99/R00


Molecular determinants of NRAS oncogene dependency in melanoma
05/01/2015 - 04/30/2018 (PI)
Melanoma Research Alliance


Defining lineage-specific determinants of K-Ras addiction in human cancers
06/01/2012 - 05/31/2016 (PI)
NIH/National Cancer Institute
5R00CA149169-05

Identifying a KRAS Regulated Micro-RNA Signaling Network in Lung Cancer
07/01/2013 - 12/31/2015 (PI)
American Lung Association


Institutional Research Grant
01/01/2012 - 12/31/2015 (PI of Sub-Project / SP)
PI: Avrum Spira, MD
American Cancer Society - MA Division





Yr Title Project-Sub Proj Pubs
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.

  1. 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).View Related Profiles. PMID: 28900044; DOI: 10.1126/scisignal.aam6291;.
  2. Grant T.J., Mehta A.K., Gupta, A., Sharif, A.A.D., Arora, K.S., Deshpande, V., Ting, D.T., Bardeesy, N., Ganem, N.J., Hergowich A., Singh A. STK38L kinase ablation promotes loss of cell viability in a subset of KRAS-dependent pancreatic cancer cell lines. Oncotarget. 2017; 8(45):78556-78572.
  3. 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.
  4. 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; PMCID: PMC4889531; DOI: 10.1038/leu.2016.26;.
  5. Grant, T., Hua, K., Singh A. Progress in Molecular Biology and Translational Science. Molecular Pathogenesis of Pancreatic Cancer. Elsevier Press. 2016; 144:214-275.
  6. 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.
  7. 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; PMCID: PMC4433453; DOI: 10.1158/1541-7786.MCR-14-0604;.
  8. 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; DOI: 10.1158/0008-5472.CAN-13-3157;.
  9. 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; PMCID: PMC3667614; DOI: 10.1016/j.ccr.2012.11.007;.
  10. 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; PMCID: PMC3291475; DOI: 10.1016/j.cell.2011.12.033;.
Showing 10 of 21 results. Show More

This graph shows the total number of publications by year, by first, middle/unknown, or last author.

Bar chart showing 21 publications over 12 distinct years, with a maximum of 3 publications in 2008 and 2016

YearPublications
20031
20041
20061
20083
20092
20102
20111
20122
20141
20152
20163
20172
In addition to these self-described keywords below, a list of MeSH based concepts is available here.

APC
Colon cancer
KRAS
Lung cancer
Melanoma
NRAS
Pancreatic cancer
RAS
TAK1
Wnt
Signal Transduction Pathways
Gastrointestinal Cancer

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