OCAST board approves 32 health projects, one new scientist award for more than $4 million

Thirty-two Oklahoma health research projects were chosen by a peer review team from a total of 148 applicants and have been approved for funding by the OCAST governing board.  The top-ranked research applications represent a three year investment by OCAST in excess of $4 million.  OCAST, the Oklahoma Center for the Advancement of Science and Technology, is Oklahoma’s technology-based economic development agency.

Another 104 applications were approved by the peer review team; however, funding was available only for the first 32.

One New Scientist award that will provide up to $100,000 per year for each of three years went to Roberto Pezza of the Oklahoma Medical Research Foundation. His chromosome research is expected to have an impact on cancer biology.

The purpose of the health research program is to:  (1) strengthen the competitiveness of Oklahoma health researchers for national research funds, (2) recruit and retain outstanding health research scientists for the state, (3) improve health care for Oklahomans and (4) 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.

OCAST’s New Scientist program allows researchers who are new to their institution to compete for special funding that recognizes their willingness to develop research projects in Oklahoma.

The following health research projects were approved for funding:

Biomedical Engineering

• Principal investigator:  Timothy M. Griffin, Oklahoma Medical Research Foundation; Project Title:  Stimulating endogenous cartilage antioxidant capacity; Award:  $135,000 for three years; The proposed research will provide insight into the appropriate use of biomechanical and antioxidant therapies for treating osteoarthritis.
• Principal investigator:  Wei Yin, Oklahoma State University; Project Title:  Aspirin Protects Endothelial Cells from Secondhand Smoke; Award:  $135,000 for three years; Smoking-related deaths significantly impact Oklahomans and there is an indication that aspirin could have an inhibitory role on endothelial damage induced by second hand smoke. This project will investigate the relationship.
• Principal investigator:  Pete Heinzelman, University of Oklahoma; Project Title:  Proteolytic Antibodies for Alzheimer’s Disease Therapy; Award:  $75,000 for two years; Further development of a recombinant human antibody with proteolytic activity toward amyloid beta, the causative agent in Alzheimer’s disease, can yield a highly efficacious low cost Alzheimer’s therapy. The research is expected to help develop a highly promising new class of Alzheimer’s disease biotherapeutics.

Cell/Molecular Biology

• Principal investigator:  Zhizhuang Joe Zhao, University of Oklahoma Health Sciences Center; Project Title:  Mpl Mutations and myeloproliferative neoplasms; Award:  $135,000 for three years; This study helps delineate pathological implications of Mpl/JAK2 signaling pathway to define targets for therapeutic drug development to treat neoplasms and other hematological diseases.
• Principal investigator:  Jennifer Hernandez Gifford, Oklahoma State University; Project Title:  WNT regulation of steroidogenesis in female infertility; Award:  $135,000 for three years; This research will provide new targets and strategies to expand our knowledge about hormonal regulation of folliculogenesis and could improve treatments for female factory fertility and ovarian pathologies.
• Principal investigator:  Yogita Kanan, University of Oklahoma Health Sciences Center; Project Title:  Role of tyrosine sulfation in the function of CFH; Award:  $135,000 for three years; Targeted for development of new health research approaches in Oklahoma, this project could impact methods for treating age-related macular degeneration.
• Principal investigator:  Christopher M. West, University of Oklahoma Health Sciences Center; Project Title:  Skp1 Function in O2-Sensing in Protists; Award:  $135,000 for three years; Research proposed here will help to define which functions of Skp1 are important for O2-signaling in Dictyostelium.
• Principal investigator:  Krysten Farjo, University of Oklahoma Health Sciences Center; Project Title:  Defining the Role of RDH10 in Embryonic Development; Award:  $135,000 for three years; Retinoic acid (RA) is a potent signaling molecule which plays a crucial role in embryonic development. Results of this project are expected to expand understanding of the deregulation of embryonic retinoic acid synthesis and will create a scientific foundation for development of diagnostics and therapeutics to treat and prevent miscarriages and birth defects caused by disrupted RA homeostasis.
• Principal investigator:  Tyler Johannes, University of Tulsa; Project Title:  Artificial Control of Protein Expression in Microalgae; Award:  $135,000 for three years; The goal of this project is to develop a controllable protein expression system in microalgae. A desirable outcome is modifying the chloroplast genome of microalgae, and initiating the development of a potential microalgae-based treatment for Celiac disease.
• Principal investigator:  Roberto Pezza, Oklahoma Medical Research Foundation; Project Title:  The Role of Mnd1 and Hop2 in Homologous Recombination; Award:  $135,000 for three years; Homologous recombination repairs double-strand breaks but can be associated with genome instability. Genome instability is implicated in tumor progression in a variety of tissue types. A long term goal is to understand the role of homologous recombination and its regulation in organismal health.

Chemistry and Biochemistry

• Principal investigator:  Donghua H. Zhou, Oklahoma State University; Project Title:  Structure of lipid storage protein by solid-state NMR; Award:  $135,000 for three years; The study should provide clues for how to influence the balance between fat storage and burning, and to eventually help discover new therapeutic strategies to prevent or treat obesity and related issues.
• Principal investigator:  Jialing Lin, University of Oklahoma Health Sciences Center; Project Title:  Role of a bax binding protein in bax oligomer assembly; Award:  $135,000 for three years; Targeted for development of new health research approaches in Oklahoma, this project could impact methods for treating macular degeneration. The principal investigator will identify a Bax binding protein and characterize its role in assembly of Bax oligomer.
• Principal investigator:  Paul H. Weigel, University of Oklahoma Health Sciences Center; Project Title:  Tissue ECM Turnover, Stress Detection and HARE Signaling; Award:  $135,000 for three years; The HA Receptor for Endocytosis (HARE) is a scavenger receptor that removes glycosaminoglycans, dead cells, and heparin from blood and lymph. Recent findings that HARE is a cytokine-signaling apoptotic cell receptor and a MAP kinase signaling receptor show that its function is more than to just remove tissue matrix and cellular debris. This project will test HARE with a verification expected to stimulate further studies to understand it and how to use the sensing system to diagnose, prevent or treat infections, cancer and arthritis.
• Principal investigator:  Steven D. Hartson, Oklahoma State University; Project Title:  Neoplastic Roles for the Molecular Chaperone Hsp90; Award:  $135,000 for three years; Small molecules that inhibit Hsp90’s chaperone function can be selectively toxic to cancer cells. Results should reveal mechanism of tumoricidal activity, add another set of structure-activity relationships and guide the development of promising compounds.

Infectious Disease

• Principal investigator:  William D. Picking, Oklahoma State University; Project Title:  Targeting shigella secretion to prevent dysentery; Award:  $135,000 for three years; This project will exploit the S. flexneri type III secretion system to prevent disease caused by sigella flexneri.
• Principal investigator:  Wenxin Wu, University of Oklahoma Health Sciences Center; Project Title:  Innate response to swine-origin influenza A/H1N1 virus; Award:  $135,000 for three years; The impact of this project could help scientists better understand the connection between human lung organ culture models and human lung responses to influenza. The investigator will examine the innovative hypothesis that estrogen in pregnant women facilitates S-OIV-stimulated excessive proinflammatory cytokine responses in human lung via modulation.

Neurobiology

• Principal investigator:  Wayne C. Drevets; Laureate Institute for Brain Research; Project Title:  Neuroimaging biomarkers of major depression; Award:  $130,416 for three years; Functional magnetic resonance imaging could have an impact on patients who suffer depression and need antidepressants drugs to improve. The research is expected to confirm such results.
• Principal investigator:  James B. Rand, Oklahoma Medical Research Foundation; Project Title:  Synaptic mutations and oxidative stress; Award:  $135,000 for three years; The proposal study will identify the mechanism that triggers oxidative stress, a condition that can negatively impact synapses.
• Principal investigator:  Anne Kasus-Jacobi, University of Oklahoma Health Sciences Center; Project Title:  Therapeutic use of Carcinine in Progressive Retinopathy; Award:  $135,000 for three years; The goal of this project is to determine the efficacy of chronic carcinine treatment in protecting cells of Leber Congential Amaurosis and Retinitis Pigmentosa. If successful, this study will form the basis for development of carcinine for therapeutic utilization in a broad spectrum of retinopathies.
• Principal investigator:  W. Kyle Simmons, Laureate Institute for Brain Research; Project Title:  Insula Topology in the Healthy and Eating Disordered; Award:  $125,176 for three years; Little is known about the insular cortex’s functional organization or the roles it play in the host of psychiatric illness. The knowledge acquired in this project will move the field forward toward improved biomarker-based diagnoses of these disorders, as well as the possibility of novel, highly-focused interventions.

Nutrition, Psychology, Public Health

• Principal investigator:  Brenda J. Smith, Oklahoma State University; Project Title:  Dysregulation of bone metabolism in type 2 diabetes; Award:  $135,000 for three years; The project will study skeletal health to find ways to provide advance treatment for potential osteoporotic fractures now known to be prevalent in patients suffering from type 2 diabetes.
• Principal investigator:  Hiroyuki Matsumoto, University of Oklahoma Health Sciences Center; Project Title:  Role of Omega-3 in the Suppression of Diabetes Pathology; Award:  $135,000 for three years; This effort will study a fat-1 mouse model to study the beneficial effect of omega-3 toward an obesity-associated disease, diabetes. The results will answer the questions whether omega-3 suppresses the progress of diabetes and can lead to an aggressive dietary supplementation of omega-3 to pre-diabetes and diabetes patients.
• Principal investigator:  Jennifer Peck, University of Oklahoma Health Sciences Center; Project Title:  Environmental Determinants of Gestational Diabetes; Award:  $86,244 for two years; Emerging evidence suggest environmental contaminants may alter glucose homeostatis and contribute to the pathogenesis of diabetes. This study will address the knowledge gap by evaluating environmental determinants of disturbed glucose metabolism during pregnancy. The research could help reduce the impact of gestational diabetes mellitus-related pregnancy.

Physiology/Pharmacology

• Principal investigator:  Craig Stevens, Oklahoma State University – Center for Health Sciences; Project Title:  Novel opioid action at toll-like receptors; Award:  $126,090 for three years; The outcome of the study is expected to lead to increased understanding of the opioid effects on immune cells and could pave the way for new treatments involving immune or glial cells, of the brain.
• Principal investigator:  Brian P. Ceresa, University of Oklahoma Health Sciences Center; Project Title:  Regulating of EGFR-mediated corneal wound healing; Award:  $135,000 for three years; The project is expected to support treatment of corneal wounds in part by biochemically inhibiting the molecular mechanism of receptor degradation.
• Principal investigator:  Randle M. Gallucci, University of Oklahoma Health Sciences Center; Project Title:  The Role of IL-6 in Diabetic Wound Healing; Award:  $135,000 for three years; Disregulation of skin wound healing is a common complication in diabetes. The aims of this proposal are to expand the basic scientific knowledge concerning diabetic wound healing with the potential long-term goal of developing wound healing treatments.
• Principal investigator:  Sarah X. Zhang, University of Oklahoma Health Sciences Center; Project Title:  Targeting Histone Deacetylase in Diabetic Retinopathy; Award:  $135,000 for three years; Diabetic retinopathy is a major cause of blindness for diabetes patients and there are few effective drug treatments available. The goals of this project are to understand how histone acetylation and histone deacetylase are implicated in diabetic retinopathy and to evaluate the therapeutic effects of inhibitors on retinal vascular pathologies associated with retinopathy.

Instrumentation/Data Sciences/Clinical Evaluation

• Principal investigator:  Madona Azar, University of Oklahoma Health Sciences Center; Project Title:  Identification of predispositions for gastroschisis; Award:  $134,997 for three years; With underserved communities and Native Americans in mind, this research is looking to assess the utility of an assay and two novel tests:  a novel marker of glycemic variability and a non-invasive measure of skin fluorescence performed early in pregnancy.

Biophysics

• Principal investigator:  Aihua Xie, Oklahoma State University; Project Title:  VSM Library for Infrared structural biology; Award:  $135,000 for three years; A promising new approach to drugs that bind to catalytic sites is to develop drugs aimed at allosteric inhibition. The goal of the research is to develop a powerful and innovative technique, time-resolved infrared structural biology, to improve our ability in elucidating the catalytic mechanism of enzymes.

Genomics and Gene Expression

• Principal investigator:  Zongchao Han, University of Oklahoma Health Sciences Center; Project Title:  ROD Photoreceptor Gene Targeting:  Viral versus Nonviral; Award:  $135,000 for three years; Disorders of the retina and retinal pigment epithelium represent a specific class of genetic diseases for which there is no proven therapy. The immediate goal is to develop a safe and efficient therapeutic delivery system for clinical applications in the field of ophthalmology.

Cancer Etiology and Prevention

• Principal investigator:  Xingmin Wang, University of Oklahoma Health Sciences Center; Project Title:  GSTA4 and Colorectal Cancer Chemoprevention; Award:  $135,000 for three years; In this project, the principal investigator will study a theory for colorectal cancer that postulates certain colonic commensal bacteria as initiators of carcinogenesis. The project will provide evidence about the cause of colorectal cancer and permit fresh strategies for prevention.

Obesity

• Principal investigator:  Jana Barlic, Oklahoma Medical Research Foundation; Project Title:  The Role of the Chemokine Receptor CXCR4 in Obesity; Award:  $135,000 for three years; Clear understanding of the role of the chemokine system in diet-induced obesity and adipose tissue inflammation is relevant to several human diseases including diabetes and cardiovascular disease. The results of this project will reveal novel and important information on functions of the chemokine system in obesity and may reveal new opportunities for therapeutic interventions in obesity-linked diseases.