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University of Nebraska Medical Center

Amar B. Singh, PhD

Professor

402-559-6340

Amar B. Singh

Current Research

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.

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.

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.

Research Opportunities

Our laboratory welcomes curious and fun-loving students.