Medical Student Research Fellowship for Summer 2008

Mentor: Don Rockey
Department: Medicine
Room number: J5.144
Mail Code: 8887
Phone number: 214-645-6344
E-mail: don.rockey@utsouthwestern.edu

Two Projects

Project I title: The role of zipper-interacting protein kinase in cirrhosis and portal hypertension

Human subjects IRB approved project number (where applicable): N/A

Animal subjects IRB approved project number (where applicable): 1075.05.03

Project Type Patient-based

Brief Description of Project:

Title: The role of zipper-interacting protein kinase in cirrhosis and portal hypertension.

Background: Portal hypertension, like essential hypertension results from an imbalance of vasoconstrictive and vasodilatory factors that regulate smooth muscle cell contraction and thus vascular resistance. In portal hypertension, we have identified smooth muscle-like cells known as hepatic stellate cells as key regulators of sinusoidal constriction and thus intrahepatic vascular resistance. These cells become hypercontractile once the liver is injured and stellate cells become activated. Further, a number of signaling systems in stellate cells regulate their contractility. One such pathway involves zipper-interacting protein kinase (ZIPK), which regulates Ca2 -independent phosphorylation of smooth muscle cells through either phosphorylation and inhibition of myosin phosphatase, the myosin phosphatase inhibitor CPI17, or direct phosphorylation of myosin light chain. ZIPK is regulated by multisite phosphorylation.

Hypothesis: ZIPK plays an essential role in regulation of stellate cell contraction, and moreover, it is likely to be regulated after liver injury and stellate cell activation.

Aim: The aim of this project is to determine the expression and function of ZIPK in normal and activated stellate cells, and to manipulate ZIPK function in models of portal hypertension.

Project II title: Predicting the etiology of gastrointestinal (GI) hemorrhage

Human subjects IRB approved project number (where applicable): N/A

Animal subjects IRB approved project number (where applicable): N/A

Project Type Patient-based

Brief Description of Project:

Title: Predicting the etiology of gastrointestinal (GI) hemorrhage based on history and physical findings. Hypothesis: A careful history and physical examination is able to predict the cause of GI bleeding in many patients who present to the hospital with GI hemorrhage. Aim: Perform a prospective study of medical students, housestaff, fellows, and attendings to determine whether the cause of bleeding can be accurately predicted based on history and physical examination, and if so, what features are important.

Previous Research Activities or Publications with Medical Students:

1. Edwards C, Reynolds C, Feng H, Rockey DC. Effect of the nitric oxide donor, V-PYRRO/NO, on portal pressure and sinusoidal dynamics in normal and cirrhotic mice. (Submitted)
2. Collins B, Choy-Smith C, Holzknecht Z, Sempowski G, Rockey DC. Aging and hepatic fibrogenesis: differential immune system regulation. (Submitted)
3. Yoo D, Rockey DC. Endothelin receptor modulation after hepatic stellate cell activation in liver wound healing. (Submitted)
4. Rockey DC, Shi Z, Weymouth N, Tuvia S, Reynolds C, Chung JJ. Smooth muscle actin mediates hepatic myofibroblast contraction and motility in vivo during wound healing. (Submitted)