NIH Funding

David J. Cole, MD

Title: Altering  Post Vaccination T-Cell Contraction
Award# 3 RO1 CA1083672-06 AR#1767
11/01/99-4/3/09
The specific aims of this project are: (1) Define the impact of specific danger signals on the programmed contraction of antigen-specific CD8* T cells; (2) Characterize the role of tissue microenvironment and altered T cell trafficking on post-vaccination programmed T cell contraction; and (3) Define the impact of post-vaccination systemic cytokine administration on programmed T cell contraction.

Title: Targeting the CaSm Oncogene as a Novel Therapy for Pancreatic Cancer
Award# 1RO1 CA12315901 A1
9/18/07-7/31/2012
The specific aims of this project are: (1) Determine whether pacilitaxel tumor priming improves delivery and efficacy for pancreatic gene therapy; and define the efficacy of tumor priming microparticles to deliver gene vectors; (2) Define the impact of tumor priming on the reduction  of CaSm over-expression, and the mechanisms by which it mediates a bystander effect; and define the impact of host immune responses on the CaSm down regulation mediated bystander effect; (3) Define the mechanism by which CaSm overexpression leads to PC oncogenesis; Determine whether specific mRNAs are decapped in a CaSm-dependent fashion; The role of the Xrn1 exonuclease in CaSm-mediated changes in mRNA stability, and determine whether CaSm is associated with specific mRNAs.

Michael I. Nishimura, PhD

Title: TCR Affinity & Therapeutic Efficacy of T Cells
Award# 1RO1 CA104947-01 A2
7/1/07-5/31/12
The goals of this project is to determine if CD4 and CD8 T-cells transduced to express the CD8 independent TIL 1383I can protect mice from tumor growth and mediate regression of established tumors in a preclinical animal tumor model.  In addition, determine how persistence, localization, frequency, tumor antigen loss, and function of TCR gene modified T-cells impact on tumor regression in vivo and determine if tumor antigen vaccines and cytokines impact these parameters.

Kenneth Chavin, MD, PhD

Title:  Protection of Steatotic Liver
Award# 5RO1DK069369-02
9/5/06-7/31/2011
The goal of this project is to define the role(s) of UCP2 in hepatocyte necrosis and apoptosis, and mitochondrial dysfunction in mice with steatotic livers subjected to I/R.  Elucidate the role of the endotoxin receptor, TLR4, in the increased sensitivity of steatotic livers to I/R.  Using isolated hepatocytes, to determine the mechanism(s) by which UCP2 increases the sensitivity of steatotic hepatocytes to necrotic cell death and mitochondrial dysfunction following hypoxia/reoxygenation (H/R) injury.

Prabhakar Baliga, MD

Title:  A Program to Increase Living Donations in African Americans
Award# 2RO1DK062596-06
09/15/07-07/31/2012
The goals of this project is to test the hypothesis that live kidney donation in African Americans will increase with (1) the utilization of educators who are professionally trained to work with African Americans, (2) early identification  and education of African American donors in potentially “high yield” settings, and (3) improved navigation of the African American donors by these educators.

John S. Ikonomidis, MD, PhD

Title: Intracellular Signaling in Thoracic Aortic Aneurysms
Award# 1R21HL089170-01A1
08/01/08-07/31/2010
The primary objectives of this project proposal are designed to identify and validate target proteins that are chronically altered in abundance in rapidly developing ascending aortic aneurysms (ATAAs).  Intracellular signaling events taking place in the endogenous cells present within the aortic vascular wall result in dynamic changes in the production and secretion of extracellular matrix protein components, including the modifying enzymes that drive the remodeling processes. The experimental design is constructed around two specific aims that will generate proof of principle that activation of key intracellular signaling pathways are a  fundamental prerequisite for the induction of aberrant vascular remodeling and the consequent development of ATAA.

Franics G. Spinale, MD, PhD

Title:  Collagenase Inhibition in Heart Failure
Award# 2RO1HL059165-09A2
01/01/98-05/31/2011
The central hypothesis of this project is that matrix metalloproteinase (MMP) induction/activation following MI is type, region and time dependent; and this process can be visualized, quantified and targeted in-vivo.  This project will accomplish the following aims: (1) demonstrate that the induction of MMP types post-MI is region and time dependent through the use of upstream signaling events.  (2) Map the in-vivo spatial and temporal induction in MMP activation in mice post-MI and demonstrate that net proteolytic activity imaged in-vivo is sensitive to genetic/pharmacological modulation. (3) Demonstrate that a unique MMP type, MT1-MMP plays a critical role in post-MI remodeling, that MT1-MMP activity can be quantified within the myocardial interstitium post-MI remodeling, that MT1-MMP activation within the remodeling myocardium and thereby hold diagnostic/prognostic and therapeutic potential for patients that are at increased risk for adverse remodeling and heart failure post-MI.

Title: Endothelin Receptors and Progression to Heart Failure
Award# 5 RO1HL057952-08
01/01/98-11/30/08
Relevance to public health: one of the most common causes of death and disability in this country is from a heart attack; damage to the heart muscle.  Following a heart attack, it is now clear that enzymes are made that continue to chew away at the heart muscle and eventually cause the heart to change shape and fail.  This study will identify how to control a critical enzyme which causes the heart to fail following a heart attack and thereby develop new tests and treatments for patients after a heart attack.