Gastroenterology & HepatologyDepartment:
Bio , Pub Med , Curriculum Vitae
Dr. Winston received a B.S. from Louisiana State University in 1983 and a Ph.D. from UT Southwestern Medical School in Dallas in 1990. He completed a two year Molecular Genetics fellowship at Baylor College of Medicine and then worked as a Research Associate at Baylor College of Medicine for four years in the laboratory of Rodney Kellums. Here, Dr. Winston identified genetic regulatory elements directing expression of the murine Adenosine Deaminase gene to the fetal placenta and to the forestomach using transgenic mice as an assay system. Dr. Winston was promoted to Instructor in the GI division, Department of Pediatrics, Baylor College of Medicine. He joined the Division of Gastroenterology and Hepatology, Department of Internal Medicine at UTMB in June 1997 as an Instructor and was promoted to Assistant Professor after three years. Dr. Winston's principle function was to establish a lab capable of studying molecular mechanisms of pain in inflammatory and functional G-I disorders using rodent models.
PhD, Biochemistry, University of Texas Southwestern Medical Center - Dallas, TX, 1990
BS, Biochemistry, Louisiana State University - Baton Rouge, LA, 1983
Molecular Genetics, Baylor College of Medicine - Houston, TX, 1993
Although pain is a cardinal feature of pancreatitis, the underlying biological mechanisms are poorly understood. The vanilloid receptor (TRPV1) is an ion channel that is activated by heat and by various inflammatory mediators and functions as a molecular transducer of noxious stimuli into nerve impulses in primary sensory afferent neurons. This channel is expressed on 80% of pancreatic afferent neurons. Capsaicin activated current is increased 2 to 4 fold in rats with acute necrotizing pancreatitis, but there is no increase in TRPV1 expression. Recent findings indicate that increased production of nerve growth factor in pancreatitis may be linked to increased TRPV1 activity. Further experiments are in progress to define the molecular mechanisms responsible for this increase in TRPV1 function in pancreatitis. Additional studies address the efficacy of various TRPV1 antagonists in the treatment of pain and inflammation in pancreatitis.
Irritable Bowel Syndrome (IBS) is a functional bowel disorder of unknown etiology defined by symptoms including abdominal pain and alterations in bowel habits that occur in the absence of detectable ongoing organic disease. Human studies demonstrate that IBS is associated with a state of chronic visceral hypersensitivity suggesting that processing of visceral sensory information is altered. However, little is known about changes in the processing of visceral information occur. Our long-term objective is to identify key molecular events responsible for the perpetuation of the sensitized state and provide targets for new pharmacological approaches to the treatment of this syndrome. To attain this goal, we have developed a rat model of chronic visceral hyperalgesia produced by irritation of the colon of neonatal rats. We have identified gene expression profiles in the colon, sensory neurons and spinal chord associated with chronic visceral hyperalgesia. There are an ongoing collaborative studies with clinicians to determine whether any of the genes identified in the colon can serve as biological marker (s) of post-infectious IBS. Gene expression profiles in colon show alterations in genes that regulate smooth muscle contractility; studies are in progress to determine whether there is an increase in smooth muscle contractility in this model.