Pankaj Jay Pasricha
Research Interests
THE ENTERIC NEUROMUSCULAR DISORDERS AND PAIN (END PAIN) LABORATORY AT STANFORD
The defining theme in my research is the translation of fundamental knowledge to clinical solutions in neurogastroenterology. My laboratory focuses on exploring the molecular mechanisms of disorders of the enteric nervous system (the autonomous nervous system that controls gastrointestinal physiology) and visceral sensory nerves. Within this broad area, we are pursuing several themes, outlined as follows. Our techniques encompass behavioral, electrophysiological (single nerve fiber recordings, patch clamp) as well as molecular approaches.
VISCERAL PAIN. Work in this laboratory represents a systematic approach to uncover the neurobiology of visceral pain in chronic pancreatitis, irritable bowel syndrome and functional dyspepsia and has provided a framework for designing novel treatments for pancreatic, gastric and colonic pain including targeting PAR-2, TRPV1, 5-HT4 and trkA receptors, Kv ion channels and neurotransmitters such as BDNF.
GASTROINTESTINAL DYSMOTILITY. We study models of diabetic and idiopathic gastroparesis. We are focusing on two major questions- what is the biological basis of the gender bias seen in gastroparesis (80% of patients are women) and what are the mechanisms responsible for loss of nitric oxide/nNOS dysfunction including the role of advanced glycation end products (RAGE).
NEURAL STEM CELLS. Our laboratory has been exploring the use of neural stem cells into the gut for restoring function ine cure for this condition. We have shown proof of principle that neural stem cells isolated from the brain can indeed restore function when transplanted into the gut of a mouse with genetically determined dysmotility. We are now working on manipulating a specific signaling pathway (GDNF-RET) to produce an optimal long-term outcome after transplantation. In addition we are attempting to identify the nature of the neural stem cell in the post-natal gut.
CLINICAL AND TRANSLATIONAL RESEARCH. Stanford is part of the multicenter Gastroparesis Clinical Research Consortium (http://www.jhucct.com/gpcrc), a multicenter project funded by the NIH, which I chair. The goal of this consortium is to perform clinical, epidemiological, and therapeutic research in gastroparesis and provide an infrastructure that can rapidly and efficiently design and conduct clinical trials for effective medical, surgical, or other interventions to improve treatment of patients with gastroparesis.
BIOMARKER AND THERAPEUTIC TARGET DISCOVERY.
We have identified several novel therapeutic targets for the development of drugs for visceral pain, nausea and motility. These include PAR-2, TRPV1, D3 antagonists amongst others. In addition we are in the process of setting up high throughput assays for motility in order to facilitate the screening of ligand libraries.
NOVEL ENDOSCOPIC DEVICE AND PROCEDURE DEVELOPMENT.I have more than 30 patents (issued or pending) for devices and other inventions, and work has also been published in leading journals in gastrointestinal endoscopy. I have invented several devices in the laboratory that are now in clinical trials and have expanded the ability to provide effective therapy to patients in a relatively non-invasive (i.e. endoscopic) manner. These include endoscopic cryotherapy, a new design for pancreatic and biliary stents, a new device and method for treating gastroesophageal reflux disease and obesity. These early efforts led to the formation of the “Apollo Group” a think tank composed of several leading endoscopists around the country which amongst other advances, introduced the concept of natural orifice transluminal endoscopic surgery or NOTES. Additional innovations have occurred in gastrointestinal electrical stimulation. This technique has the potential for treatment of a variety of human diseases including visceral pain, nausea, gastroparesis and obesity, amongst others.
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