OCAST board approves 30 health projects for more than $4 million

May 19, 2011

Thirty Oklahoma health research projects were chosen by a peer review team from a total of 168 applicants and have been approved for funding by the OCAST governing board.  Total investment through OCAST on behalf of the state of Oklahoma is $4,005,219.

OCAST, the Oklahoma Center for the Advancement of Science and Technology, is Oklahoma’s technology-based economic development agency. The Oklahoma Health Research program is the first OCAST program created by the legislature.

The purpose of the health research program is to: (1) strengthen the competitiveness of Oklahoma health researchers for national research funds, (2) improve health care for Oklahomans and (3) strengthen the state’s health care industry.

Research funded under the program investigates the causes, diagnosis, treatment and prevention of human diseases and disabilities and facilitates the development of innovative health care products and services.

C. Michael Carolina, executive director of OCAST, noted the 168 applications represent the pent-up demand for health research in the state. “Of the 168 applicants, 153 were determined to be worthy of funding by the independent peer review team that evaluated the applications for scientific merit and likelihood for commercialization. The 30 who were funded represented the best science among all applicants. That means 123 qualified health research projects were left on the table. It is OCAST's hope they will reapply and win future competitions.”

Approved applications follow:

Oklahoma Medical Research Foundation

• Principal Investigator: Courtney Griffin
  Project Title: Epigenetic Regulation of uPA During Vascular Development
  Award: $135,000 for three years
  The PI has generated a novel mutation in the chromatin-remodeling enzyme Chd4 that results in vascular rupture and massive hemorrhage during embryonic development, both of which are known to cause numerous pathologies in humans, including cardiovascular collapse and aortic aneurysms. These studies will establish whether CHD4 might serve as a novel therapeutic target for cardiovascular diseases stemming from compromised vascular integrity.
• Principal Investigator: Christopher Sansam
  Project Title: The Role of TICRR in the Human DNA Damage Response Award: $135,000 for three years
  This study aims to reveal how cells replicate DNA and respond to DNA damage so the research team may develop effective chemotherapy sensitizers. As part of their efforts to understand the mechanisms of the DNA damage response and DNA replication, the team has identified an uncharacterized protein called TICRR which is required for both DNA replication and the DNA damage response.
• Principal Investigator: William Rodgers
  Project Title: Cytoskeletal Regulation of Raft Structure and Function
  Award: $135,000 for three years
  This research will provide novel insight into how raft microdomains are established and maintained. The findings will show new mechanisms by which the cytoskeleton impacts cellular signaling. This knowledge will assist in designing new strategies to treat diseases that arise from Lck upregulation, which includes certain malignancies and autoimmune diseases.

Oklahoma State University

• Principal Investigator: Robert Alderson
  Project Title: Competing Core Processes in ADHD
  Award: $135,000 for three years
  The proposed study will be the first to experimentally examine opposing predictions stemming from the functional working memory and behavioral inhibition models of ADHD and consequently improve identification of potential core deficits of the disorder.
• Principal Investigator: Junpeng Deng
  Project Title: Structure Function Studies on ROC Dimeric GTPase
  Award: $135,000 for three years
  Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common cause of Parkinson’s disease (PD). There is a critical need to better understand the enzymatic and regulatory mechanisms of LRRK2 to elucidate its roles in PD development. The focus of this proposal is on providing further structural insights into the multi-domain organization in LRRK2, and the enzymatic mechanism of the ROC GTPase domain.
• Principal Investigator: Wendy Picking
  Project Title: TTSS Proteins as Protective Antigens Against Salmonella
  Award: $135,000 for three years
  While vaccination has perhaps been the most broadly powerful disease prevention approach in modern medicine, the continued transmission of infectious diseases in the US and in developing nations underscores the urgent need for more effective vaccines. This research proposes the use of bacterial proteins as a vaccine against infection by Salmonella spp, which cause gastroenteritis ranging from self-limiting to severe and deadly.
• Principal Investigator: Yingmei Liu
  Project Title: An Ultra-Precise Bio-magnetic Scanning Microscope
  Award: $134,400 for three years
  The proposed magnetic scanning microscope can detect tiny magnetic variations and thus reveal the presence of cardiac dysfunctions, make inferences about neural activity inside brains and detect threats to human health. The proposed magnetic microscope could provide a reproducible and unbiased determination of a new drug’s performance between baseline investigations and follow-up investigations.
• Principal Investigator: Daqing Piao
  Project Title: Photonic-needle Assessment of Hepatic Steatosis
  Award: $135,000 for three years
  This research aims to develop and evaluate a technology for rapidly assessing the intensity of liver steatosis (fatty change) and reliably discriminating the macro-steatosis (single large lipid droplet in a hepatocyte) from the micro-steatosis (numerous small lipid droplets in a hepatocyte). Such technologies are urgently needed for liver transplantation to help hepatic surgeons determine if an available organ is within a safe steatosis range.

Oklahoma State University - Tulsa

• Principal Investigator: Amanda Morris
  Project Title: Promoting Mental Health in High-Risk Adolescent Girls
  Award: $135,000 for three years
  This project will examine whether adolescent emotions in daily life influence the development of adolescent depression, substance use and risky sexual behavior among high-risk girls living in the Tulsa area. As such, this study will inform social scientists, policy makers, practitioners and interventionists regarding potential causes of and treatment for depression and related risky behavior.

University of Oklahoma

• Principal Investigator: Roger Harrison
  Project Title: Enzyme Pro-drug Therapy to Treat Metastatic Breast Cancer
  Award: $135,000 for three years
  The purpose of this project is to develop an effective enzyme pro-drug therapy for metastatic breast cancer by evaluating three different enzymes – L-methioninase, cytosine deaminase and purine nucleoside phosphorylase. The results of this project could possibly be commercialized by a biotechnology or pharmaceutical company in Oklahoma or elsewhere, leading to licensing royalties.
• Principal Investigator: John Masly
  Project Title: The Genetics of Morphological Differences in Drosophila
  Award: $135,000 for three years
  The study of the genetic basis of species-specific differences in the size and shape of morphological traits in Drosophila is widely applicable to the study of tissue growth and morphology in other species, including humans and their primate relatives. The proposed work is relevant to public health because information learned from this study can be applied to understanding how changes in genes important for regulating cell and tissue growth translate into human diseases.
• Principal Investigator: Chuanbin Mao
  Project Title: Bifunctional Phage Particles for Targeted Cancer Therapy
  Award: $135,000 for three years
  The assembly of tubulins is important for normal cell division. This project will make a non-toxic biomolecular rod-like nanoparticle, called phage, bifunctional through genetic engineering. This bifunctional bio-particle will be able to target cancer cells, inhibit cell division and induce cancer cell death.

University of Oklahoma Health Sciences Center

• Principal Investigator: Augen Pioszak
  Project Title: Modulation of Class B GPCR Hormone-binding by RAMPs
  Award: $135,000 for three years
  The calcitonin receptor-like receptor (CLR) is a cell surface G protein-coupled receptor that mediates the potent vasodilatory actions of the peptide hormones calcitonin gene-related peptide (CGRP) and adrenomedullin (AM).  Therapeutic agents targeting the CLR-RAMP complexes have the potential to treat migraine headache, acute myocardial infarction, pulmonary hypertension, cancer, and several other disorders. In this study the researcher will seek results that describe how hormones bind to their receptors aiding the rational design of potent and selective therapeutic agents targeting the CLR-RAMP complexes.
• Principal Investigator: Ira Blader
  Project Title: Role of PD-L1 in Ocular Toxoplasmosis
  Award: $127,460 for three years
  Toxoplasma gondii, one of the most prevalent pathogens in the world, leaves victims permanently infected. Such infections can cause serious disease in immunosuppressed people, those infected congenitally and in some cases otherwise healthy individuals. The retina is the most common tissue affected. The ultimate goal of this work is to develop better therapeutics to control Toxoplasma-induced eye damage.
• Principal Investigator: Raphael Pinaud
  Project Title: Estrogen-Modulation of Visual Processing and Plasticity
  Award: $135,000 for three years
  Loss of visual function can severely impact quality of life. This research team will investigate the hypothesis that the visual cortex can itself produce estrogen in a rapid and specific manner that can influence visual processing and plasticity on a time-scale compatible with rapid neuromodulators. More broadly, these studies will reveal novel mechanisms that are important for visual function and for later improving clinical interventions to improve vision.
• Principal Investigator: Junping Chen
  Project Title: Omega-3 and Cardiovascular Function in Pre-Diabetes
  Award: $135,000 for three years
  Studies indicate low-degree chronic inflammation is highly involved in cardiovascular dysfunction (CVD) which is responsible for a majority of the morbidity and mortality in diabetes. In this study, the researcher and her lab attempt to investigate the effect of Omega-3 on inhibiting inflammation so as to improve insulin resistance and cardiovascular dysfunction in pre-diabetic women. Oklahoma has a very high population of pre-diabetes and diabetes, particularly among Native American and Hispanic populations. The outcome of current research study is expected to benefit these populations.
• Principal Investigator: Leonidas Tsiokas
  Project Title: Polycystin-Mediated Ca2+ Signaling in the Primary Cilium
  Award: $135,000 for three years
  Autosomal dominant polycystic kidney disease (ADPKD) affects more than half a million Americans and 12.5 million people worldwide. Mutations in two genes, PKD1 and PKD2, are responsible for this debilitating disease. Their protein products, PKD1 and TRPP2, respectively, are plasma membrane-spanning proteins. This project will test the hypothesis that PKD1 and TRPP2 form a receptor-channel complex at the cilium activated by the secreted Wnt glycoproteins.
• Principal Investigator: Ted Bader
  Project Title: Human Testing of Simvastatin for Chronic Hepatitis B
  Award: $129,835 for three years
  Hepatitis B virus (HBV) infects an estimated 400 million people and causes more than a million deaths per year. Dr. Bader and his team have found that simvastatin, a generic FDA-approved cholesterol-lowering drug, has robust anti-HBV activity in a standard human hepatoma cell line. These findings form the basis of potential treatments that have a patient and societal benefit.
• Principal Investigator: Carol Dionne
  Project Title: Work Task Performance Measures in Amputees with TTAT
  Award: $103,524 for three years
  Trans-tibial amputation (TTAT) is the most frequent type of lower limb amputation surgery due to a traumatic event. Oklahomans with TTAT struggle with job re-entry and retention. A translational, contextual examination is required to study mechanical loads and muscle activity within the prosthetic. Benefits include isolating mechanical loads within the prosthetic and developing therapies.
• Principal Investigator: Anna Csiszar
  Project Title: Novel Mechanisms of Vascular Aging
  Award: $135,000 for three years
  This research team proposes to use innovative approaches, combining studies conducted in vivo and ex vivo with experiments using a novel mouse model of endocrine IGF-1 deficiency. Preliminary studies strongly suggest this approach will enable the team to identify novel pathways involved in vascular aging.
• Principal Investigator: William Sonntag
  Project Title: IGF-1 and the Genesis of Late-life Depression
  Award: $135,000 for three years
  Depression in older adults is an under-recognized and under-treated medical condition. The concept has emerged that age-related alterations in trophic factors and circulating hormones influence depression in the elderly. The goal of this project is to investigate the cellular and molecular mechanisms that contribute to depression in elderly individuals and determine the mechanisms through which IGF-1 alleviates the disease.
• Principal Investigator: William McShan
  Project Title: Mobile Element SpyCIM1 Enhances Survival in S. pyogenes
  Award: $135,000 for three years
  The proposed project will examine the role of chromosomal island SpyCIM1 in promoting survival, virulence and spread to new populations of the pathogen Streptococcus pyogenes. The proposed work could lead to fundamental advances in the knowledge of S. pyogenes genetics and virulence as well as lead to improved patient management and treatment strategies.
• Principal Investigator: Shannon Conley
  Project Title: An Experimental Bi-Modal Treatment Strategy for Glaucoma
  Award: $135,000 for three years
  The goal of this program is to develop a current compacted DNA nanoparticle-based gene therapy technology for the treatment of glaucoma-associated retinal degeneration. Neutral charge nanoparticles can penetrate the cell membrane via nucleolin receptors within 15 minutes. Benefits of the procedure will be prepared for further evaluation.
• Principal Investigator: Zoltan Ungvari
  Project Title: Novel Strategy for Neuroprotection in Neonatal Stroke
  Award: $135,000 for three years
  The long-term goal of this project is to develop novel therapeutic approaches for neuroprotection in infants with neonatal stroke targeting intrinsic antioxidant response pathways. The objective of the proposal is to develop a new fusogenic liposome-based delivery system for resveratrol to help prevent permanent brain damage.
• Principal Investigator: Marie Hanigan
  Project Title: Gamma-Glutamyl Transpeptidase and Cardiovascular Disease
  Award: $135,000 for three years
  The enzyme gamma-glutamyl transpeptidase (GGT1) is elevated in the serum of patients with cardiovascular disease. The hypothesis to be tested in this proposal is that GGT activity on the surface of the foam cells within the plaque has a major role in plaque progression. This work has the potential to lead to new mouse models of atherosclerosis, biomarkers for susceptibility to atherosclerotic disease and new targets for therapeutic intervention in the disease process.
• Principal Investigator: Franklin Hays
  Project Title: hENT Drug Transport in Cancer Therapy
  Award: $135,000 for three years
  The PI’s primary near-term focus is characterizing human Equilibrative Nucleoside Transporter (hENT) drug recognition and transport using structural biology and functional assays. These insights are of paramount importance since hENT expression level and activity has been directly linked to chemotherapeutic outcomes in the treatment of human cancer.
• Principal Investigator: James McGinnis
  Project Title: Nanoceria Protect Rods and Cones in Degenerating Retinas
  Award: $135,000 for three years
  The researcher hypothesizes that nanoceria will protect rods and cones in a rat model that recapitulates a form of autosomal dominant retinitis pigmentosa (RP). The data from these studies will form the basis for FDA approval of nanoceria as an investigational new drug and the extension of their therapeutic use in humans for AMD and diabetic retinopathy.
• Principal Investigator: Miao Zhang
  Project Title: Role of AMP-Activated Protein Kinase in Atherosclerosis
  Award: $135,000 for three years
  The project will study the effects of AMP-activated protein kinase (AMPK) α1 on development of atherosclerosis. This study will advance understanding of how AMPK regulates macrophage cholesterol homeostasis and foam cell formation.
• Principal Investigator: Jian Xu
  Project Title: Diabetes, 26S Proteasomes and Caloric Restriction
  Award: $135,000 for three years
  The proposed project seeks to test the hypothesis that 26S proteasome activation is an early event in promoting diabetes-promoted inflammatory response which can be mitigated by caloric restriction. Since proteasome inhibition (with inhibitor administration) is a recent FDA-approved therapeutic treatment for cancer, the present study may bear promise of treating diabetes with this regimen.
• Principal Investigator: Karla Rodgers
  Project Title: Mechanisms to Regulate VDJ Recombination upon DNA Damage
  Award: $135,000 for three years
  The outcome of this study may provide a useful diagnostic tool in assessing the robustness of DNA repair in developing lymphoid cells. In the long term, this study may lead to treatments that reduce risks of leukemia or lymphomas in patients treated with DNA damaging therapies.