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.
Samir M. Fakhry, MD, FACS
Dee W. Ford, MD, MSCR
Title: Critical Care Excellence in Sepsis and Trauma - CREST Award# RC1MD004405-01 09/01/2009-03/31/2012
This research addresses broad challenge area health disparities and specific challenge topic, 09-MD-101: Creating Transformational Approaches to Address Rural Health Disparities. A quasi-experimental clinical trial will test the effectiveness of the Critical Care Excellence in Sepsis and Trauma Program (CREST). The objective is to improve patient outcomes for sepsis and trauma by educating providers and providing access to specialist consultation via telemedicine technology to participating rural hospitals in the South Carolina (SC) Lowcountry and PeeDee regions.
Shikhar Mehrotra, PhD
Title: Oxidative stress and AICD in memory T cell persistence Award # 1R01CA138930-01A2 (NIH/NCI) 06/02/2010 - 04/30/2015 Role: Principal Investigator The major goal of this project is to identify targets that could be used to improve survival of effector CTL and long-term memory development in preclinical animal model for adoptive T cell therapy of melanoma.
Title: Development & Characterization of Tyrosinase Epitope Specific TCR Transgenic Mice Award # 5R21AR056524-02 (NIH/NIAMS) 04/18/2009 – 03/31/2012 Role: Principal Investigator The major goals of this project is to develop and subsequently characterize a Tyrosinase Epitope Specific TCR Transgenic Mice using a CD8 independent high affinity TCR isolated from an MHC class-I restricted CD4+ T cell from tumor infiltrating lymphocytes (TILs) of a patient with metastatic melanoma.
Title: Isolation and Characterization of Prostrate Antigen Specific High Affinity TCR Award # 5R21CA137725-02 (NIH/NCI) 06/01/2009 – 5/31/2010 Role: Principal Investigator The major goals of this project is to isolate T cell clones bearing high affinity T cells receptors (TCR) reactive with prostate specific membrane antigen (PSMA) and prostate stem cell antigen (PSCA) from healthy adult women.
Title: Modulating tolerance in a spontaneous mouse model of autoimmune vitiligo Award # 1R01AR057643-01 (NIH/NIAMS) Role on Project: Co-I The major goal of this application is to understand the mechanism responsible for development of spontaneous vitiligo using our novel TCR transgenic mouse model.
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.