Bonnie Blazer-Yost, Ph.D.
Professor of Biology
Adjunct Professor Cellular and Integrative Physiology
Co-director Center for Developmental and Regenerative Biology School of Science
Indiana University-Purdue University Indianapolis
723 W. Michigan Street
Indianapolis, IN 46204
Phone: (317) 278-1145
Fax: (317) 274-2846
Bonnie Blazer-Yost is a Professor in the Department of Biology at IUPUI with joint appointments in the Department of Integrative and Cellular Physiology and the Department of Anatomy and Cell Biology in the Indiana University School of Medicine. The main focus of her laboratory is the physiology and pathophysiology of barrier epithelial cells. Her group studies how various hormones and other effectors regulate transepithelial ion transport in renal, airway and brain cells. The major projects in the laboratory are directed toward understanding and treating diseases such as polycystic kidney disease, hypertension, metabolic syndrome and hydrocephalus.
One of the current projects is a study of potential drugs to treat autosomal dominant polycystic kidney disease (ADPKD). This is a genetic disease that affects over 1 in 1,000 people. The cystic kidneys grow slowly throughout the patient’s life, causing pressure and pain and eventually in middle to old age result in renal failure in over half the patients. At the time of renal failure, the kidneys can be the size of footballs causing pain and distention of the abdomen. There are no drugs to treat ADPKD and the only thing that can be done for the patients is to aspirate the largest of the cysts to relieve that pain and dialyze or transplant the patients when their kidneys fail. Due to a serendipitous observation that insulin sensitizing agents of the PPARγ class of compounds have the unexpected effect of inhibiting the synthesis of the CFTR Cl- channel in cultured renal cells, the investigators have examined the potential for these agents to inhibit cyst growth in animal models of PKD. The positive results in pre-clinical models suggest that FDA-approved PPAR agonists such as pioglitazone and rosiglitazone may be effective agents for long-term therapy in PKD patients. This research is the culmination of a bench to bedside series of experiments that may result in a new treatment for ADPKD. The clinical trial using pioglitazone to treat ADPKD are funded and initiated in 2016. Other, more preliminary studies to explore new and innovative therapies for the treatment of late-stage PKD are ongoing.
The other major project in the Blazer-Yost laboratory is the study of a pressure- and osmotic-sensitive cation channel known as TRPV4. An unexpected observation has led to the discovery that TRPV4 antagonists relieve hydrocephalus, or “water on the brain” in a rat model of pediatric hydrocephalus. Hydrocephalus is a devastating disease which affects nearly 1 in 1000 births, and has medical costs over $1 billion per year. The accumulating cerebrospinal fluid results in increased hydrostatic pressure causing pain and neuronal destruction and can ultimately cause permanent damage or death. Currently, there are no drugs to treat this disease, with the only viable treatment being surgical intervention. The standard of care is the placement of cerebral shunts to drain the excess fluid, however this approach often results in a less than optimal outcome. Shunt failures due to blockage, infection, and other causes are as high as 50% even in major medical centers which specialize in these procedures. Two chemically distinct forms of TRPV4 antagonists have been shown to be effective in decreasing the hydrocephalus in the rat model. The laboratory members are currently studying the mechanism of action of these compounds using tissue culture and preclinical animal models.
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