Amar B. Singh
   

Associate Professor, UNMC Department of Biochemistry and Molecular Biology

Amar Singh
402-559-6340(Office)
    Location: BCC 6.12.400
402-559-8811 (Lab)
    Location: BCC 6.12.412
Fax: 402-559-6650
Email

Education/Training:
Ph.D, Banaras Hindu University

Research:
 Molecular Mechanisms of Inflammatory Bowel Disease and Colon cancer; and Renal Pathobiology”

Research Opportunities in my laboratory:

 

Inflammatory Bowel Disease and Colon Cancer: The long-term focus of the research of the Singh Lab is to develop preventive strategies aimed at minimizing the risk of Inflammatory Bowel Disease (IBD) and colorectal cancer, and to develop non-invasive therapeutic options. Of note, IBD is a broad term that describes conditions with chronic or recurring immune responses and inflammation of the gastrointestinal tract. Moreover, IBD patients are at higher risk of developing colon cancer than their normal counterparts. However, precise cause of IBD or why these patients are at increased risk of developing colon  cancer is unknown, and until we understand more, effective prevention or a cure will not be possible.

In our investigation, we have taken a multidisciplinary approach and are investigating the roles and regulation of mucosal epithelial barrier especially the tight junction (the most apical cell-cell adhesion), Cellular stress response (autophagy) and Gut Microbiota in regulating the intestinal epithelial cell health and communication with their microenvironment. Our investigative approach is multidisciplinary and involves cell and molecular biology, electrophysiology, in vitro and in vivo modelling using 3-D organ culture and murine models of IBD and colon cancer, in-silico and nematode (C. elegance) modelling. This research has led to the identification of specific biological mechanisms (both intestinal epithelial cell intrinsic and extrinsic) underlying key steps in deregulated mucosal immune homeostasis and inflammation-associated epithelial injury/repair. We also collaborate extensively with researchers in the areas of mucosal immunology, bioinformatics and imaging to address overarching challenges in this area, and clinicians on “bedside-to-bench” research approach. We are also in the process of developing potential biomarkers for assessing potential risk for disease severity and progression to colorectal cancer.

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Obesity, Microbiota and Intestinal Diseases: A causal link between diet, intestinal inflammation and colon cancer is well recognized and obese individuals are more susceptible to colon cancer. The obese individuals also possess leaky/hyper-permeable gut. Importantly, gut barrier deregulation is central to the undesired antigen-immune interaction and inflammation. A dynamically balanced gut microbiome helps maintain normal gut homeostasis. A symbiotic feedback relationship between the gut microbiome and colonic epithelial homeostasis may help maintain this delicate homeostatic balance. Nutritionally imbalanced diet dysregulates this dynamic balance and modulates the mucosal epithelial and immune homeostasis to increase susceptibility to gastrointestinal diseases and associated cancer. Recent studies have suggested key role of the deregulated gut microbiota in multiple human diseases especially IBD and colon cancer. The composition of microbiota differs between individuals and functional differences or translocation of microbiota can affect health and disease. Our laboratory is investigating potential causal association between intestinal barrier deregulation and gut microbial complexity, in causal association with obesity, IBD and colon cancer. In addition to the 3-D organ culture and mouse model of obesity, we are employing the worm (C. elgans) modeling to ask our investigative questions.

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Renal Injury/Repair and Renal Clear cell carcinoma: Apart from the intestine, we are interested in understanding molecular undertakings of the renal injury/repair and renal clear cell carcinoma. Here, also we are interested in elucidating potential physiological and pathological role of TJ proteins in regulating renal tubular epithelial cell morphogenesis and potential deregulation during diseases and malignancies.

 

Vacancies: Our laboratory welcomes curious and fun-loving students.

Last Five year Publication:

  1. Ahmad R, Kumar B, Pan K, Dhawan P, Singh AB (2017). HDAC-4 regulates claudin-2 expression in EGFR-ERK1/2 dependent manner to regulate colonic epithelial cell differentiation. Oncotarget  (in Press).

  2. Ahmad R, Kumar B, Chen Z, Chen X, Müller D, Lele SM, Washington MK, Batra SK,  Dhawan P, Singh AB (2017). Loss of claudin-3 expression induces IL6/gp130/Stat3 signaling to promote colon cancer malignancy by hyperactivating Wnt/β-catenin signaling. Oncogene. 2017 Aug 7. doi: 10.1038/onc.2017.259. PubMed PMID: 28783170.

  3. Ahmad R, Rah B, Bastola D, Dhawan P, Singh AB (2017). Obesity-induces Organ and Tissue Specific Tight Junction Restructuring and Barrier Deregulation by Claudin  Switching. Sci Rep. 2017 Jul 11;7(1):5125. PubMed PMID: 28698546.

  4. Ahmad R, Sorrell MF, Batra SK, Dhawan P, Singh AB (2017). Gut permeability and mucosal inflammation: bad, good or context dependent. Mucosal Immunol. 2017 Mar;10(2):307-317. PubMed PMID: 28120842.

  5. Singh AB, Uppada SB and Dhawan P (2017). Claudin proteins, outside-in signaling, and carcinogenesis. Pflugers Arch. 2017 Jan;469(1):69-75. doi: 10.1007/s00424-016-1919-1.. PubMed PMID: 27988840.

  6. Singh AB (2016): EGFR-signaling and Autophagy: How They fit in the Cancer Landscape. Editorial. Journal of Adenocarcinoma. 2016; 1.2:9:1-5.

  7. Ahmad R, Dhawan P and Singh AB (2016): Cancer Stem Cell and Gastrointestinal Cancer: Current Status, Targeted Therapy and Future Implications. Biochem Pharmacol (Los Angel). 5:202. doi:10.4172/2167-0501.1000202.

  8. Bhat AA, Ahmad R, Uppada SB, Singh AB, Dhawan P. Claudin-1 promotes TNF-α-induced epithelial-mesenchymal transition and migration in colorectal adenocarcinoma cells. Exp Cell Res. 2016 Nov 15;349(1):119-127. PubMed PMID: 27742576.

  9. Singh AB and Dhawan P (2015). Claudins and cancer: Fall of the soldiers entrusted to protect the gate and keep the barrier intact. Semin Cell Dev Biol. 2015 Jun;42:58-65. PubMed PMID: 26025580.

  10. Bhat AA, Pope JL, Smith JJ, Ahmad R, Chen X, Washington MK, Beauchamp RD, Singh AB and Dhawan P (2015). Claudin-7 expression induces mesenchymal to epithelial transformation (MET) to inhibit colon tumorigenesis. Oncogene. 2015 Aug 27;34(35):4570-80. PubMed PMID: 25500541.

  11. Pope JL, Ahmad R, Bhat AA, Washington MK, Singh AB, Dhawan P (2014). Claudin-1 overexpression in intestinal epithelial cells enhances susceptibility to adenamatous polyposis coli-mediated colon tumorigenesis. Mol Cancer. 2014 Jul 6;13:167. PubMed PMID: 24997475.

  12. Ahmad R, Chaturvedi R, Olivares-Villagómez D, Habib T, Asim M, Shivesh P, Polk DB, Wilson KT, Washington MK, Van Kaer L, Dhawan P, Singh AB (2014). Targeted colonic claudin-2 expression renders resistance to epithelial injury, induces immune suppression, and protects from colitis. Mucosal Immunol. 2014 Nov;7(6):1340-53. PubMed PMID: 24670427.

  13. Sharma A, Bhat AA, Krishnan M, Singh AB, Dhawan P (2013). Trichostatin-A modulates claudin-1 mRNA stability through the modulation of Hu antigen R and tristetraprolin in colon cancer cells. Carcinogenesis. 2013 Nov;34(11):2610-21. PubMed PMID: 23880304.

  14. Pope JL, Bhat AA, Sharma A, Ahmad R, Krishnan M, Washington MK, Beauchamp RD, Singh AB, Dhawan P (2013). Claudin-1 regulates intestinal epithelial homeostasis through the modulation of Notch-signalling. Gut. 2014 Apr;63(4):622-34. PMID: 23766441.

  15. Rosen MJ, Chaturvedi R, Washington MK, Kuhnhein LA, Moore PD, Coggeshall SS,  McDonough EM, Weitkamp JH, Singh AB, Coburn LA, Williams CS, Yan F, Van Kaer L, Peebles RS Jr, Wilson KT (2013). STAT6 deficiency ameliorates severity of oxazolone colitis by decreasing expression of claudin-2 and Th2-inducing cytokines. J Immunol. 2013 Feb 15;190(4):1849-58. PMID: 23303670.

  16. Singh AB, Sharma A, Dhawan P (2012). Claudin-1 expression confers resistance to anoikis in colon cancer cells in a Src-dependent manner. Carcinogenesis. 2012 Dec;33(12):2538-47. PMID: 22941059.

  17. Zhang MZ, Yao B, Yang S, Jiang L, Wang S, Fan X, Yin H, Wong K, Miyazawa T, Chen J, Chang I, Singh A and Harris RC (2012): CSF-1 signaling mediates recovery from acute kidney injury. J Clin. Inves. 2012 Dec 3;122(12):4519-32.

  18. Chaturvedi R and Singh AB (2012): HER-2 as a Therapeutic Target in the Gastric Cancer: Is it Sufficient? Indian Journal of Gastroenterology) Editorial. 2012 Jun;31(3):103-5.