Funded Pilot Projects 2014

The ITS received 21 responses to the 2014 PILOTS RFA.  The CTSA Executive Committee met on August 28 and approved 9 applications for funding: 7 PILOTS, 1 NOVEL METHODS, and 1 CAPACITY BUILDING in CLINICAL RESEARCH.  The details of the funded projects are as follows:

Mining the Native Seratonin 5-HT2C Receptor Protein Macrocomplex for New Therapeutics in Cocaine Addiction, PI: Kathryn A Cunningham, PhD
Compromised function of the serotonin 5-HT2C receptor (5-HT2CR) system is a key modulator of neuroplasticity involved in mediating core phenotypic facets of addictive disorders and the propensity for relapse. A deep understanding of 5-HT2CR function and causative role in addiction and other neural disorders is critical in the process of design of new molecular therapeutics approaches to such disorders. One barrier to these efforts is the lack of knowledge of the protein macrocomplex associated with the 5-HT2CR and how these protein partners influence the status of the 5-HT2CR system. The present proposal will address this gap in knowledge. This project is the first to systematically investigate the full-length 5-HT2CR and its macromolecular complex under native and activated conditions.

Mediation Effects of HPV Vaccination on Regional Variations in HPV Types, PI: Jacqueline Hirth, PhD
This study will use data from two nationally representative data samples: the 2003-2012 National Health and Nutrition Examination Survey (NHANES) and the 2008-2012 National Immunization Survey-Teen (NIS-Teen) to: 1) examine the prevalence in HPV types in the Southern regions of the US compared to other regions, and 2) determine whether observed regional differences in HPV rates across time are related to differences in regional vaccine uptake and completion.

The Role of Inflammation in Browning of White Adipose Tissue after Burn Injury, PI:  Tracy Toliver-Kinsky, PhD
Leukocyte infiltration, chronic inflammation, and adrenergic stress experienced by burn victims play causative roles in adipose browning, which subsequently contributes to hypermetabolism after burn injury.  This hypothesis will be tested as follows: Aim 1: to identify cellular sources of inflammation in white adipose tissue (WAT) from burn patients.  Specific leukocyte populations will be identified in WAT from burn patients at various times post-injury using flow cytometry and immunohistochemistry; and Aim 2: to examine the contribution of specific leukocyte populations, inflammatory mediators, and catecholamines to browning in our well-established mouse model of severe burn injury. 

Novel Effects of Simvastatin on Uterine Leiomyomas, PI: Mostafa Borahay, MD
It is hypothesized that simvastatin treatment may reduce the size of uterine leiomyomas by inducing apoptosis and inhibiting proliferation of leiomyoma cells. The objective of this study is to mechanistically determine the effects of simvastatin on the growth of uterine leiomyomas both in vitro and in vivo.

The Pathophysiological Basis of Brain Complications of the Metabolic Syndrome, PI:  Fernanda Laezza, MD, PhD
The proposal stems from the on-going “Obesity and its Metabolic Complications MTT”, led by Dr. Nicola Abate and explores the potential mechanistic links between peripherally-driven metabolic complications induced by deficit in lipid handling and CNS disorders.

Targeted Nanomedicine to Improve Antiepileptic Drug Therapy During Pregnancy, PI: Erik Rytting, PhD
The goal of this project is to develop nanoparticles targeting the brain endothelium in order to improve maternal antiepileptic therapy as well as reduce the risks of developmental complications currently associated with fetal exposure to antiepileptic drugs. 

The in vivo Association of Adipose Tissue Lipid Dynamics with the Production of Atheroprotective HDL Particles in Humans, PI: Demidmaa Tuvdendorj, MD, PhD
The primary goal of projected studies is to evaluate the in vivo mechanistic link between adipose tissue cholesterol efflux and the production of atheroprotective Apo-AI-rich HDL particles in humans.

High-throughput Target Identification of tRNA-derived RNA Fragments, PI: Xiaoyong Bao, Ph.D
This project is focused on a novel family of sncRNAs called tRNA-derived RNA Fragments (tRFs). The overall goal in this research project is to identify consensus functional sequences and mechanism of tRF-target RNA interaction for tRF5-GluCTC by using newly developed methods to control tRF expression, together with systematic biochemical experiments guided by genome-wide computational analyses, via collaboration of three research groups with different expertise.

Towards the Development of a Human Challenge Model for Paramyxovirus Infections, PI:
Roberto P. Garofalo, MD
Under the ITS Capacity Building Grant mechanism our primary goal is to develop a human experimental infection model in adult volunteers as proof-of-concept base for therapeutic trials of paramyxovirus infections. This project represents the first step towards such goal as we plan to isolate clinical strains of RSV and hMPV from infants with clinical bronchiolitis along with the collection of appropriate medical and family history.