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Ajay Singh, Ph.D.

Assistant Professor of Oncologic Sciences

Office:
USA Mitchell Cancer Institute
1660 Springhill Avenue
Mobile, AL. 36604
(251) 445-9843
(251) 460-6994 fax
asingh@usouthal.edu

Research Interests:
-Identification of novel gene targets in cancer development and understanding the mechanisms of their action
-Developing novel approaches for cancer therapy and chemo-prevention

Honors and Awards:
-Department of Biotechnology (DBT) fellowship, Govt. of India (1992-94)
-Junior/Senior Research Fellowships by University grant commission (UGC) and Council of Scientific and Industrial Research (CSIR), Govt. of India (1994-2001)
-Dr. J. S. Pruthi Award by Indian Society of Spices, Calicut, India (2002)
-Outstanding Performance Award, University of Nebraska Medical Center, Omaha, Nebraska (2004, 2005, 2007)
-Invited faculty, Indian Society of Oncology Continuing Medical Education, Sushila Tiwari Memorial Cancer Research Institute, HIHT University, Dehradun, Uttarakhand, India (2008)
-Invited to serve as Guest Editor of a Special Issue “MicroRNAs in Health and Disease” of Molecular and cellular Pharmacology Journal (2011)

Education:
-Ph.D., Life Science, Devi Ahilya University, India. (2002)
-M.S., Biotechnology, Aligarh M. University, India. (1994)
-B.S., Zoology (Honors), Aligarh M. University, India. (1992)

Professional Appointments:
-Member, USA Mitchell Cancer Institute, 2009-present
-Assistant Professor, USA Biochemistry and Molecular Biology, 2010
-Member, Biomedical Research Training Program, UNMC (2006-2009)
-Member, Graduate Faculty, UNMC (2006-2009)
-Assistant Professor, Biochemistry and Molecular Biology, UNMC (2006-2009)

Service:
Scientific Reviewer: US Department of Defense (DOD)
Scientific Reviewer: Prostate Cancer Research Program (2009-present)
Scientific Reviewer: Lung Cancer Research Program (2009)
Scientific Reviewer: Breast Cancer Research program (2008-present)
Scientific Reviewer: Florida State Bankhead and Coley Cancer Research Program (2010)
Scientific Reviewer: James and Esther King Biomedical Research Program (2010)
Scientific Reviewer: Yorkshire Cancer Research, UK (2011)
Scientific Reviewer: Peer Reviewed Cancer Research program (2011)

1. Protein phosphatase 2A (PP2A) signaling in human prostate cancer: In our recent studies, we identified many differentially-expressed genes and perturbed molecular pathways in androgen-independent (AI) prostate cancer [Cancer Lett. 259(1):28-38, 2008]. Protein phosphatase 2A (PP2A) is one of the important targets, whose catalytic subunit (PP2Ac) was found to be downregulated in LNCaP-C81 (androgen-independent) prostate cancer cells as compared to LNCaP-C33 (androgen-dependent) prostate cancer cells [Cancer Lett. 259(1):28-38, 2008]. Immunohistochemical analysis of clinical specimens also corroborated this finding, suggesting a role of PP2A in prostate cancer. PP2A encompasses a family of serine/threonine phosphatases, minimally containing a well conserved catalytic subunit (PP2Ac). Studies are currently underway to examine the role of dysregulated PP2A signaling in prostate cancer progression by performing in vitro and in vivo functional assays.

2. MicroRNAs in Pancreatic Cancer: Pancreatic cancer is a highly lethal malignancy. Hence, a better understanding of the molecular mechanisms involved in the disease progression and development of novel approaches and tools for pancreatic cancer diagnosis, prognosis and therapy are urgently needed. A new class of gene regulatory RNAs, termed as microRNAs (miRNAs) has gained significant interest for their ability to influence various biological process, including development, differentiation, and malignant transformation. A large number of miRNAs has been identified in humans; however, the target mRNAs have been assigned to only a few of them. We are currently investigating the role of a set of candidate MUC4-targeted miRNAs in pancreatic cancer progression and gene regulation.

3. Mucins as targets for cancer diagnosis and therapy: Mucins are high molecular weight glycoproteins that are widely expressed by the epithelial cells of the gastrointestinal, respiratory and urinogenital tracts. They have gained prominence in recent years due to their multiple implications in cancer development and represent as attractive targets for the diagnosis and therapy [Lancet Oncol. 9(11): 1076-85, 2008; Cancer Res 67, 433-6, 2007]. We have demonstrated the pathological significance of a transmembrane mucin, MUC4, in pancreatic cancer pathogenesis [Cancer Res. 64(2): 622-30, 2004]. Importantly, our recent work has revealed that MUC4 is a novel interacting partner of the receptor tyrosine kinase, HER2, and is implicated in its stabilization and potentiation of downstream signaling [Cancer Res. 68(7): 2065-70, 2008]. We are currently focusing on exploiting the clinical usefulness of mucins in early and differential diagnosis of cancers, their prognostic importance and efficacy of targeting mucins for cancer therapy.

Recent Publications:
1. Srivastava S., Bhardwaj A., Singh S., Arora S., Wang B., Grizzle W.E., and Singh A.P. (2011) MicroRNA-150 directly targets MUC4 and suppresses growth and malignant behavior of pancreatic cancer cells. Carcinogenesis 32(12):1832-9 press)

2. Singh S., Wu S., Varney M., Singh A.P., Singh R.K. (2011) CXCR1 and CXCR2 silencing modulates CXCL8-dependent endothelial cell proliferation, migration and capillary-like structure formation. Microvasc Res. 82(3):318-25

3. Arora S., Bhardwaj A., Srivastava S.K., Singh S., McClellan S., Wang B., Singh A.P. (2011) Honokiol arrests cell cycle, induces apoptosis and potentiates the cytotoxic effects of gemcitabine in human pancreatic cancer cells. PLoS One 6(6): e21573. (featured in news media and blog posts)

4. Bhardwaj A., Singh S., Srivastava S.K., Honkanen R.E., Reed E., and Singh A.P. (2011) Modulation of protein phosphatase 2A (PP2A) activity alters androgen-independent growth of prostate cancer cells: therapeutic implications. Mol Cancer Ther. 10(5): 720-731 (featured in “highlights of the issue”, p709)

5. Bhardwaj A., Singh S., and Singh, A.P. (2010) MicroRNA-based cancer therapeutics: big hope from small RNAs. Mol. Cell. Pharmacol. 2(5): 213-219.

6. Singh S., Srivastava S.K., Bhardwaj A., Owen L.B., and Singh A.P. (2010) CXCL12-CXCR4 signaling axis confers gemcitabine resistance to pancreatic cancer cells: a novel target for therapy. Brit. J. Cancer 103(11): 1671-1679.

7. Singh S., Singh A.P., Sharma B., Owen L.B., Singh R.K. (2010) CXCL8 and its cognate receptors in melanoma progression and metastasis. Future Oncol. 6(1):111-6.

Significant Publications:
1. Singh, A.P., Moniaux, N., Chauhan, S.C., Meza, J.L., and Batra, S.K. (2004) Inhibition of MUC4 mucin expression suppresses pancreatic tumor cell growth and metastasis. Cancer Res. 64(2):622-30.

2. Singh, A.P., Chauhan, S.C., Andrianifahanana, M., Moniaux, N., Meza, J.L., Copin, M.C., Hollingsworth, M.A., Aubert, J.P., and Batra, S.K. (2007) Cystic fibrosis transmembrane conductance regulator (CFTR) regulates the expression of MUC4 mucin in pancreatic adenocarcinoma cells by transcriptional and post-translational mechanisms. Oncogene 26(1):30-41.

3. Singh, A.P., Chaturvedi, P., Batra, S.K., (2007) Emerging roles of MUC4 in cancer: a novel target for diagnosis and therapy. Cancer Res 67, 433-6.

4. Singh, A.P., Bafna, S., Chaudhary, K., Venkatraman, G., Smith, L., Johansson, S.L., Eudy, J, Batra, S.K. (2008) Genome-wide expression profiling reveals transcriptomic variation and perturbed gene networks in androgen-dependent and androgen-independent prostate cancer cells. Cancer Lett. 259(1):28-38

5. Singh, A.P., Senapati, S., Moorthy, P.P., Jain, M., Lele, S., Davis, J., Remenga, S., and Batra, S.K. (2008) The clinical potential of mucins in the diagnosis and therapy of ovarian cancer. Lancet Oncol. 9(11): 1076-85.

-U. S. Patent 710565782 Compositions and methods for inhibiting pancreatic cancer metastasis (2006).
-U. S. Patent PP14090 Generation of a new `Peppermint` mutant genotype. (2003)

-Studies in Singh’s laboratory are funded by research grants from Department of Defense (DoD), National Institutes of Health (NIH) and Institutional start-up funds.

-PC07399302/01/2009 - 05/31/2013
Department of Defense
Protein phosphatase 2A signaling in prostate cancer
Goals: To investigate the role of protein phosphatase 2A signaling in androgen-independent progression of human prostate cancer.
Role: Principal Investigator

-1R03CA137513-01A107/20/2009 - 06/30/2012
National Institutes of Health
MicroRNAs in Pancreatic Cancer
Goals: To investigate the expression and functional significance of the candidate MUC4-targeted miRNAs in pancreatic cancer
Role: Principal Investigator

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