OCAST board approves 23 health projects for more than $3 million

Twenty-three Oklahoma health research projects were chosen by a peer review team from a total of 152 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 $3 million. OCAST, the Oklahoma Center for the Advancement of Science and Technology, is Oklahoma’s technology-based economic development agency.

Another 122 applications were approved by the peer review team; however, funding was available only for the first 23.

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.

The following health research projects were approved for funding:

Immunology

• Principal investigator: Susan Kovats
  Oklahoma Medical Research Foundation
  Project Title: Estrogen Receptor – IRF4 Interactions in DC Development
  Award: $135,000 for three years
  Dendritic cells are important for initiation of innate and adaptive immunity. Inflammation and autoimmunity are associated with de novo dendritic cell development from inflammatory monocytes or bone marrow precursors. Researchers have determined that estrogen receptor signaling is an important regulator of this pro-inflammatory developmental pathway and now seek to understand how this regulation occurs at the molecular level.

Cell and Molecular Biology

• Principal Investigator: Yun Zheng Le
  University of Oklahoma Health Sciences Center
  Project Title: Biology of Outer Blood-retina Barrier
  Award: $135,000 for three years
  There are two blood-retina barriers (BRBs) in the eye. The outer BRB is the Major BRB and is responsible for approximately 70 percent of the retinal blood circulation. Abnormal BRBs are the major pathological changes in diabetic retinopathy. However, the role of the outer BRB in these diseases has not been seriously investigated. In this study the researcher will determine the regulatory mechanisms for outer BRB function and its relevance to the cause of diabetic retinopathy. The results of the study can be used to develop new diagnostics and therapeutics for diabetic retinopathy.
  
• Principal Investigator: David Crawford
  University of Oklahoma Health Sciences Center
  Project Title: UBE2Q2 in Prophase Checkpoint Function and Cancer
  Award: $135,000 for three years
  Cancer still takes the lives of about 40 percent of those afflicted, resulting in more than 500,000 deaths per year in the U.S. and more than 7,000 in Oklahoma alone. Researchers have identified an enzyme known as UBE2Q2 that regulates the way cancer cells respond to treatment with some chemotherapy agents suggesting that aberrant expression of the protein could contribute to the development of cancer and that inhibition of UBE2Q2 might be a very effective tool in cancer treatment. In this proposal, researchers examine these two possibilities to lay the groundwork for development of a new anti-cancer drug.
  
• Principal Investigator: Michael Elliott
  University of Oklahoma Health Sciences Center
  Project Title: Role of Caveolin-1 in Experimental Diabetic Retinopathy
  Award: $135,000 for three years
  This proposal is designed to gain a better understanding of the pathological processes that result in a devastating complication of diabetes and diabetic retinopathy and to develop new therapies for this devastating eye disease. The experiments will test a potential mechanism by which caveolin-1 regulates blood-retinal barrier permeability and how caveolin-1 may be dysfunctional in the diabetic retina.
  
• Principal Investigator: Rita Miller
  Oklahoma State University
  Project Title: The Regulation of Bik1p by Phosphorylation
  Award: $135,000 for three years
  This study on Bik1p, an important microtubule protein, is ultimately directed at improving human health in several areas. Bik1p is part of the mechanism that attaches chromosomes to the microtubules of the mitotic spindle during cell division. Inaccurate chromosome attachments lead to chromosome instability and abnormal numbers of chromosomes. This results in poorer outcomes in human cancer. These studies are expected to elucidate how the regulation of Bik1p contributes to human cancer.
  
• Principal investigator: Marta Alarcon-Riquelme
  Oklahoma Medical Research Foundation
  Project Title: Analysis of the Novel SLE Gene BANK1 on B-cell Function
  Award: $135,000 for three years
  This research group working at Uppsala University has identified the novel lupus gene BANK1 (B-cell scaffold with ankyrin repeats gene). BANK1 is expressed in B cells and two functional variants affect expression of two isoforms of the gene. The isoforms could have different functional fates in the cell. Researchers want to prepare tools to study the isoforms. By studying transformed cell lines genotyped for the polymorphisms of BANK1 they will investigate if markers of early B cell activation may be different depending on the BANK1 genotype. The studies presented here will provide completely new knowledge on the effects of the isoforms of BANK1 on B cell function. Results may lead to novel therapies for lupus.

Chemistry and Biochemistry

• Principal investigator: Kenneth Humphries
  Oklahoma Medical Research Foundation
  Project Title: Mitochondria in Cardiac Ischemic Preconditioning
  Award: $135,000 for three years
  This proposal is aimed at defining the mechanisms whereby mitochondria produce free radicals in a regulated, limited manner that may offer therapeutic targets for initiating the beneficial effects of ischemia preconditioning of the heart (IPC).
  
• Principal investigator: Susan Schroeder
  University of Oklahoma
  Project Title: RNA Structures and Energetics Enabling Cancer Therapies
  Award: $134,999 for three years
  A complete understanding of the energetics and specificity of the binding of a small RNA to an mRNA is vital to capitalizing on RNAi’s potential to cure cancer. RNAi has the potential to elucidate the aberrant gene expression that causes cancer, to facilitate early identification and diagnosis of cancer cells, and to successfully treat cancer by correctly regulating gene expression. While effective delivery of RNAi therapeutics to cells is currently challenging, studying the structure and energetics of prohead RNA nanoparticles will inform and facilitate future delivery vector design, leading to improvement of the tools needed to cure cancer.
  
• Principal investigator: George Richter-Addo
  University of Oklahoma
  Project Title: Unexpected Hypoxic NO Production: The Role of Myoglobin
  Award: $135,000 for three years
  Scientists have discovered the muscle protein myoglobin (Mb) can convert the ubiquitous nitrite anion into nitrous oxide (NO) under hypoxic (low oxygen) conditions. It implies the existence of an alternate pathway for NO production that bypasses the more commonly studied dioxygen-dependent biosynthetic pathway. In this proposed project the researchers utilize their strength in the inorganic chemistry of heme-proteins to determine the factors that lead to NO production from nitrite using Mb and its carefully selected distal pocket mutants. The results of this research will aid in the design of new nitrite-based vasodilator drugs for the control of blood pressure in humans.

Biomedical Engineering

• Principal investigator: Yih-Kuen Jan
  University of Oklahoma Health Sciences Center
  Project Title: Biomedical Analysis of Risk for Diabetic Foot Ulcers
  Award: $135,000 for three years
  The objective of this proposed study is to develop methods to identify risk for diabetic foot ulcers by assessing changes of mechanical and microvascular functions and to assess the efficacy of preventive interventions on reducing incidence of foot ulcers. The researchers will also explore the opportunity to commercialize the computational model.
  
• Principal investigator: Lei Ding
  University of Oklahoma
  Project Title: High-resolution Noninvasive Computational Neuroimaging
  Award: $135,000 for three years
  Brain surgery to excise the epileptogenic zones responsible for epileptic seizure is the best treatment option for medicine-resistant epilepsy patients. However, a large gap exists between the number of potential surgical candidates and the number of patients being treated with surgery due to the lengthy, complex and expensive invasive presurgical evaluation to identify epileptogenic zones. This project intends to support development of an innovative high-resolution computational neuroimaging technology which will lead to an easy-operation, low-cost and non-invasive clinical tool aiding presurgical planning, making the surgery option available to more candidates.
  
• Principal Investigator: Damon Chandler
  Oklahoma State University
  Project Title: Visually Optimal Compression of Medical Imagery
  Award: $102,066 for three years
  The image compression technology developed in this project will improve health care for all citizens in the state by reducing storage space requirements, which translates directly into reduced costs. Considering that medical images require long or indefinite retention periods, a reduction in storage space requirements has the potential to reduce expenses to a fraction of its current costs. In addition, speeding up image transmission and retrieval. This will not only reduce turnaround time but will enhance the productivity of the facility in the long run.
  
• Principal Investigator: Vassilios Sikavitsas
  University of Oklahoma
  Project Title: Tendon Tissue Regeneration
  Award: $135,000 for three years
  Due to poor intrinsic healing capabilities, more than 200,000 Achilles tendon injuries immobilize people for prolonged periods of time each year. Surgical treatments are often accompanied by significant limitations. Thus, the goal of this study is to develop mesenchymal stem cell/decellularized human umbilical vein constructs for tendon regeneration and repair. The investigator hopes to encourage seeded cells to proliferate and differentiate to tenocytic phenotype, and to form appropriately oriented extracellular matrix, and to create tendon-like specimens that can acquire appropriate tensile stress so that they may be implanted as tendon replacements.

Instrumentation/Data Sciences/Clinical Evaluation

• Principal Investigator: Eduardo Yukihara
  Oklahoma State University
  Project Title: Novel Nanophosphors for Dose Mapping in Radiotherapy
  Award: $135,000 for three years
  This proposal improves treatment of human disease by addressing a technological gap in obtaining high-precision measurements of dose distributions in radiotherapy, with significant impact on quality control and dose verification in radiotherapy modalities such as Intensity Modulated Radiation Therapy (IMRT), stereotatic radiosurgery and proton therapy. The project goal is to develop novel nanophosphors with a unique combination of luminescence and dosimetric properties currently unavailable in any single phosphor.

Vascular Medicine/Exercise

• Principal Investigator: Andrew Gardner
  University of Oklahoma Health Sciences Center
  Project Title: Exercise for Women with Peripheral Arterial Disease
  Award: $135,000 for three years
  This prospective, randomized controlled clinical trial will determine the efficacy of exercise rehabilitation in older women with intermittent claudication. The results from this trial may have significant impact in the clinical management of older women with peripheral arterial disease (PAD), who comprise nearly half of all patients with PAD, and who have worse prognosis and greater risk of leading a functionally dependent lifestyle than men.

Nutrition/Psychology/Public Health

• Principal Investigator: Jean Ricci Goodman
  University of Oklahoma Health Sciences Center
  Project Title: Identification of Predispositions for Gastroschisis
  Award: $117,053 for three years
  Gastroschisis is a congenital abdominal wall defect, with significant risk for morbidity and mortality. This study will evaluate a suspected multifactorial etiology of gastroschisis, resulting from the interplay of genetic predispositions in the fetus and/or mother, poor maternal nutrition and environmental vasoactive stimulants. This study will serve to eliminate a critical barrier in the understanding of the etiology of gastroschisis so that preventative measurers can be developed and applied.
  
• Principal Investigator: Solo Kuvibidila
  Oklahoma State University
  Project Title: Effects of Mushrooms on Endothelin-1 Secretion and Cancer
  Award: $135,000 for three years
  Cancer and cardiovascular diseases are the leading causes of death in the U.S. Mushrooms have long been used in Asia for cancer prevention and treatment due to their capacity to boost immunity. This proposed project addresses the issue of possible health benefits of white button, portabella and shitake mushrooms on prostate cancer prevention through endothelin-1. Endothelin-1, a protein secreted by normal and cancer cells, promotes tumor growth and cardiovascular diseases.
  
• Principal Investigator: Jamie Rhudy
  University of Tulsa
  Project Title: Premenstrual Dysphoric D/O and Affective Pain Modulation
  Award: $135,000 for three years
  It is estimated the 3-8 percent of women of reproductive age in the U.S., including Oklahoma, suffer from premenstrual dysphoric disorder (PMDD).This proposed research will use validated and well-controlled experimental methods to examine pain sensitivity and the relationship between emotion and pain (subjective and physiological) across the menstrual cycle in women with and without PMDD. Results from this study can be used to increase our understanding of the mechanisms that contribute to PMDD pain and may ultimately provide insights into how PMDD pain can be prevented or treated through affective mechanisms.

Neurobiology

• Principal Investigator: Kathleen Curtis
  Oklahoma State University Center for Health Sciences
  Project Title: Estrogen, Central Pathways and Body Fluid Regulation
  Award: $111,000 for three years
  Given that women’s reproductive hormones influence cardiovascular function and that body fluid volume is a critical component of cardiovascular function, understanding estrogen’s influence on volume regulation may provide insight into the “cardioprotective” effects of the hormone and, in turn, into increased cardiovascular disease in postmenopausal women. This project proposes to examine the ways in which estrogen affects CNS areas involved in body fluid volume regulation. In addition to exploring the ways in which sex differences affect body fluid regulation and cardiovascular function, this research may lead to the development of preventative and therapeutic treatments for pregnancy disorders as well as diseases associated with aging.
  
• Principal Investigator: Bing Zhang
  University of Oklahoma
  Project Title: Molecular and Genetic Analyses of ALS in Fruit Flies
  Award: $135,000 for three years
  This grant is aimed at studying the cellular and molecular mechanisms by which the mutant SOD1 (the cytosolic copper-zinc superoxide dismutase) causes amyotrophic lateral sclerosis (ALS or Lou Gehrig’s disease). ALS is a devastating and fatal neurodegenerative disease. Patients usually die within 3-5 years after diagnosis. At present, we do not have a good understanding of, or treatment for, ALS.
  
• Principal investigator: Kenneth Miller
  Oklahoma Medical Research Foundation
  Project Title: Forward Genetic Analysis of the Synaptic Gs Pathway
  Award: $135,000 for three years
  The Gs pathway seems to control the turning on and off of synapses, which are the points at which neurons communicate with each other. Several common neurological disorders, including schizophrenia, sleep disorders, learning disorders, and depression, result from aberrant synaptic activity and have been linked to a faulty Gs pathway in humans or model organisms. By adding to the researchers’ knowledge of how the Gs pathway controls synaptic activity through this project, the proteins revealed by the researchers’ genetic screen, or proteins with which they interact, may provide new therapeutic targets for treating some of these afflictions.

Infectious Disease

• Principal investigator: Michelle Callegan
  University of Oklahoma Health Sciences Center
  Project Title: Role of Innate Immune Recognition in Eye Infections
  Award: $135,000 for three years
  This project focuses on the underlying innate immune response to one of the most rapidly blinding infections of the eye, bacterial endophthalmitis. The bacterial host factors that trigger rapid inflammation and eventual vision loss in endophthalmitis have not been analyzed. It is the purpose of this proposal to identify the bacterial triggers that initiate intraocular inflammation and the innate immune receptors that interact with these bacterial triggers to initiate inflammation during endophthalmitis.
  
• Principal investigator: Gillian Air
  University of Oklahoma Health Sciences Center
  Project Title: Role of Glycans in Pathogenesis of Paramyxoviruses
  Award: $135,000 for three years
  Human parainfluenza viruses are a major cause of hospitalization in young children due to croup and pneumonia. Currently, there are no licensed vaccines or drugs against these viruses and there is a need to develop effective control measures. Parainfluenza viruses bind to sialic acid receptors on cell surfaces and are released by the viral neuraminidase activity. A single viral protein is used for binding and release of the membrane-anchored hemagglutinin-neuraminidase (HN). This study’s aim is to determine how these opposing activities are coordinated. This knowledge will help in antiviral drug design.