Defense Date


Document Type


Degree Name

Master of Science


Physiology and Biophysics

First Advisor

John F. Kuemmerle, M.D.

Second Advisor

Chao Li, M.D., M.S.

Third Advisor

Srinivasa M. Karnam, Ph.D.


Crohn’s disease (CD) affects about 780,000 people in the United States alone, and it is estimated that 6-15 per 100,000 persons will receive a diagnosis of this disease each year. There currently is no cure for Crohn’s disease, and available medical therapies simply serve to alleviate the inflammation. This does not help treat fibrostenosis that Crohn’s disease patients may develop, which can only be treated surgically. Finding alternatives to treat CD requires an understanding of mechanisms at the biochemical level. In this thesis, we attempted to gain a better understanding of certain pathways found to be active in Crohn’s disease-affected ileal smooth muscle cells. We found an upregulation of the ER stress pathway via expression of its surrogate, the GRP78 protein. We also showed evidence that the phosphoinositide 3-kinase (PI3K) pathway, a key proliferative pathway, is linked to ER stress in these cells, and is an upstream driving force of the ER stress response. Further research on the link between the PI3K and ER stress pathways needs to be conducted, and can potentially serve as a target for therapeutics to help reduce proliferation in fibrostenotic Crohn’s disease-affected ileal smooth muscle cells.


© Prashant Yadav

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