Sean Ward

Personal Information
Title Professor
Expertise Gastro-Intestinal (GI)
Institution University of Nevada-Reno
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Grants/SubContracts 1
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Gastrointestinal (GI) motor disorders in patients suffering from diabetes mellitus (DM) have an enormous negative impact on their quality of life. Twenty million patients in the USA have been diagnosed with DM, with Type II DM accounting for 95% cases. WHO has estimated that by 2030 over 30 million USA citizens will be diagnosed with type II DM. Up to sixty percent of DM patients develop GI motor complications, including gastroparesis, constipation and fecal incontinence. DM gastroparesis is defined as delayed gastric emptying in the absence of a mechanical obstruction and is associated with symptoms including gastro-esophageal reflux, gastric bezoars, nausea and vomiting, bloating and abdominal pain. Since gastroparesis makes gastric empting unpredictable, blood glucose levels are difficult to control, potentiating the effects of DM. Previous studies, primarily utilizing animal models have suggested that the GI symptoms result from an enteric neuropathy, however recent studies including recent studies from the NIDDK Gastroparesis Clinical Research Consortium (GpCRC), have suggested defects or changes in networks of specialized interstitial cells, termed interstitial cells of Cajal (ICC), responsible for critical roles in gastric motor function. A secondary population of interstitial cells, previously termed “fibroblast-like” but more recently identified as PDGFRa+ cells, acts as mediators of enteric motor neurotransmission and when disrupted would result in loss of functional communication between enteric motor nerves and smooth muscle cells. Investigations into the impact of PDGFRa+ cell loss in DM gastropathy have not been performed in adequate depth. This project will use modern multifaceted structural, molecular and functional approaches to test whether changes in gastric motor activity in patients with DM correlate with changes in PDGFRa+ cell networks by examining: (i) the structural changes that occur in PDGFRa+ cells and their relationship with enteric motor nerves in the gastric fundus and antrum in patients with type II DM. (ii) Changes in cell-specific (PDGFRa+) expression of key genes that make them a critical component of the gastric neuroeffectorsome and (iii) the functional consequences of the molecular remodeling of PDGFRa+ cells in DM tissues compared to non-DM tissues. Information obtained from this proposal will provide novel and innovative information on the structural, molecular and functional changes that occur in PDGFRa+ cells of the human stomach from a healthy state to the pathophysiological state associated with the gastric motor disturbances in patients with DM gastropathy.

Progress Reports
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11/23/2015View Progress Report Document

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Year: 2019; Items: 1

The Role of Prostaglandins in Disrupted Gastric Motor Activity Associated with Type 2 Diabetes.
Blair PJ, Hwang SJ, Shonnard MC, Peri LE, Bayguinov Y, Sanders KM, Ward SM
Diabetes, 2019

Year: 2018; Items: 1

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