Medical School Hotline

As part of its mission, the John A. Burns School of Medicine (JABSOM) is dedicated to research and translating discoveries into practice. Uniquely located in the mid-Pacific, JABSOM is a leader among community-based medical schools, focusing on improving the health of ethnic groups, and conducting research with those groups in a culturally relevant manner. Advanced medical and biomedical research at JABSOM has received international recognition for pioneering work, which includes areas in human fertility, human heredity, comparative genetics, evolution theory, infectious disease, pharmacology, and cross-cultural psychiatry.

To facilitate investigators with research awards, the JABSOM Grants Development Office (GDO) was established in 2003 to aid in grants preparation and submittal process. The office works closely with the Dean's Office, the Fiscal Office, and the Office of Research Services (ORS). The ORS is responsible for policy interpretation and institutional signatory authorization on all outgoing proposals. The GDO is responsible for designing and administering effective procedural systems that help increase the probability of award success. The office reviews proposals, collaborative agreements, and financial and personnel requirements. It also assists with budget preparation and grants writing. After a project is funded, the office ensures that all requirements are met for implementation.

In fiscal year 2017 (July 1st 2016 through June 30th 2017), JABSOM placed third in total award dollars for UH Manoa at 20.9% ($61.53 million). Of the total extramural funding, JABSOM was awarded over $35.45 million in research dollars.¹ The following list of initial research grants and principal investigators were awarded in fiscal year 2017. This list does not include incremental, supplemental, or time and cost extension awards.²

Department of Anatomy, Biochemistry, and Physiology

Stefan Moisyadi — Nanobody Research Fund. Nanobodies are a new candidate class of therapeutics. Therapeutic nanobodies could be manufactured in a patient's cells by injecting non-integrating, long term expression plasmid vectors into muscle tissue. Long term Nbs expression vectors termed Uroboros were constructed and targeted important inhibitory immune checkpoint receptors including: PD-L 1 (the ligand of the PD-1 receptor in T-cells), CTLA-4, CD47, and the T-cell stimulatory molecule Fe OX40L. The goal is to prevent the development of mouse mesothelioma and lung carcinoma tumor xenographs Qy expressing key Nbs from within the tissues of live mice.

Monika Ward — The Role of the Y chromosome Encoded Gene Zfy2 in Spermatogenesis will advance understanding of genetic regulation of male reproduction. Considering that Y chromosome deletions are the most common genetic cause of male infertility in humans, this work has potential to guide future infertility treatments.

William Ward — The Role of ORC Proteins in Polar Body Extrusion. A remarkable event in reproduction is the sequestration of 3/4 of the meiotic DNA during oocyte development into two polar bodies with minimal cytoplasm. This event provides the future embryo with the large cytoplasmic store and the haploid maternal genome needed for its development. Several laboratories have shown that actin and associated proteins are required to complete these two asymmetric polar body extrusions (PBE) [1–4]. The project team has identified a protein associated with DNA replication, the licensing factor ORC4 that forms a lattice-like shell around the chromosomes that will be eliminated in the polar bodies in both meiotic divisions. The project terms this shell the ORC4 Cage. By specifically targeting the formation of the ORC4, it is demonstrated that it is required for PBE. This is the first chromatin associated protein that is asymmetrically associated with only the extruded set of chromosomes.

Department of Cell and Molecular Biology

Pietro Bertino — Preclinical Development of TVAX: An Advanced Multi-Antigen Vaccine for Therapy and Prevention of Malignant Mesothelioma aims to generate more specific, and therefore less harmful, immune responses with the use of advanced anti-cancer vaccines.

Olivier Le Saux — Exploring the physiological roles of ABCC6 in vascular biology. The mechanistic hypothesis is that ABCC6 is an upstream regulator of a pathway that modulates PPi production and adenosinergic signaling affecting ectopic calcification, and atherosclerosis. The restoration of ABCC6 plasma membrane localization and function will ameliorate these functions.

Kathryn J Schunke — A Novel Inhibitor of HIF Action in the Heart. The HIF axis is an ancient response to the rise in atmospheric oxygen and controls many aspects of cellular homeostasis. In this study a potent and previously unsuspected regulatory mechanism for HIF that may directly influence the course of myocardial infarction will be investigated. The identification of a new oxygen-dependent regulator of HIF may provide a target for new therapeutic approaches to ischemic heart disease.

Department of Medicine

William Boisvert — Role of CD98 in smooth muscle cell proliferation. This research will test if CD98 is a key player in vascular remodeling in atherosclerosis via its ability to regulate proliferation of vascular smooth muscle cells.

William Boisvert — Treatment of Atherosclerosis with Interleukin-10. The work proposed in this application will reveal if IL-10 expressed via the macrophages in the artery wall will succeed in quelling the vascular information and ultimately slow down the development of atherosclerosis.

Michelle Diane Seidel — Role of Tcf21 in Cardiac Fibroblasts. This proposal hypothesizes that Tcf21 plays a key role in regulating cellular functions of the cardiac fibroblast.

Cecilia Shikuma — Extended Immunologic Analyses for ‘Hepatic Safety of Raltegravir-based and Efavirenz-based Antiretroviral Regimens in Antiretroviral-Naive HIV-infected Subjects Co-Infected with Hepatitis C’. Utilizing banked peripheral blood mononuclear cells from a study conducted in Vietnam entitled “Hepatic Safety of Raltegravir-based and Efavirenz-based Antiretroviral Regimens in Antiretroviral-Naive HIV-infected Subjects Co-Infected with Hepatitis C”, this study will assess levels of monocyte activation markers, and CD4 and CD8 T cell activation and negative checkpoint receptors. These parameters will be correlated with liver fibrotic and neuropsychological changes on study.

Department of Native Hawaiian Health

Claire Townsend Ing — PILI ‘Ohana Dissemination Project will assist in developing the partnering community-based organizations’ capacity to sustain the delivery of the PLP and/or PIC and to engage in future health disparities research through various strategies including workshops on grant seeking and writing, research methods and evaluation strategies, and advocacy.

Claire Townsend Ing — Examining hypertension and cardiovascular disease risk in Native Hawaiian communities. This project aims to comprehensively examine multilevel risk factors and assess their contribution to HTN and CVD risk in NH.

Dee-Ann Carpenter - Kukalahale — Learning Project will provide: (1) wrap-around coordination of new and existing serves; (2) a more complementary/comprehensive set of existing complementary/comprehensive set of existing and new services and programs to address student gaps in knowledge/skills; (3) school community home visits, Kuder Career Counseling, blue-collar fire-fighter training for entry-level exams; and (4) Native Hawaiian cultural education activities. The University of Hawai‘i will evaluate the project's process, effort, and effectiveness using qualitative and quantitative methods, as well as assist in the development of health literacy/educational programming.

Marjorie K.L.M. Mau — Diabetes Prevention Program Outcomes Study. The objective is to evaluate the long-term effects of active diabetes prevention program interventions on the prevalence of the composite diabetes-related microangiopathic and neuropathic outcomes.

Department of Obstetrics, Gynecology and Women's Health

Michael Carney — Evaluation of Metronomic Chemotherapy Regimens in Ovarian Cancer Models. This pilot project goal is to form a research team composed of an oncologist and two basic researchers interested in identifying and evaluating low-dose, orally administered chemotherapy regimens for the treatment of ovarian cancer. Using xenograft models, proof-of-concept data on the impact of metronomic regimens on ovarian cancer will be gathered that can subsequently be used to submit an R21/R01 grant. The long-term ambition of ultimately proposing clinical trials for ovarian cancer patients. The results of this project should help the development of therapeutic ideas, and generate new models of drug resistant ovarian cancer.

Jennifer Elia — Assessment of One Key Question (OKQ) Perceptions among Providers and Patients in Hawai‘i will explore provider and patient perspectives on OKQ and its future use in primary care settings.

Reni Soon — Expanding Reproductive Healthcare Access for Adolescents in Primary Care Settings at a Community Health Center: A CBPR Project. This proposal is a pilot intervention to improve reproductive health services for adolescents and young adults at the Wai‘anae Coast Comprehensive Health Center.

Department of Pediatrics

Marian Melish — Effect of Doxycycline on Developing Coronary Abnormalities in Kawasaki Disease (KD). The project will test the hypothesis that there is a significant elevation in biomarkers related to vascular damage in children with acute KD and coronary artery abnormalities (CAA) compared with children with uncomplicated KD; and that a 3 week course of doxycycline during the critical period of vascular damage will decrease the levels of these biomarkers and prevent the progression of vascular damage.

Department of Surgery

Junji Machi — Detection of Metastases in Lymph Nodes Using Quantitative Ultrasound. The University of Hawai‘i and Kuakini Medical Center and Riverside Research Institute of New York will investigate the use of novel ultrasonic methods for discriminating cancer-containing and cancer-free lymph nodes of cancer patients. Emphasis will be on improving sentinel-node dissection biopsy procedures particularly for breast-cancer patients. Success in this project will benefit lymphnode evaluations of all types, not only for breast cancer, but also for a range of other cancers, including colorectal, stomach, and lymphatic.

Department of Tropical Medicine, Medical Micro and Pharmcology

Michelle Louise D'antoni Brogan — Targeting of Chemokine Receptors to Probe Neurocognitive Impairment in HIV. Samples from a single arm clinical trial at the Hawai.i Center for AIDS, whereby 24 HIV-infected individuals with HIV-associated neurocognitive disorder on combination antiretroviral therapy received a CVC intensification regimen for 24 weeks, will be studied.

Melissa A Agsalda-Garcia — Optimizing Mitochondrial DNA Measurement to Assess Risk of Relapse in Childhood Lymphoma Including Children in Hawai‘i will measure mtDNA and MRD in blood and bone marrow from children being treated for NHL.

Mukesh Kumar — Defining the function of Schlafen4 in the pathogenesis of flavivirus encephalitis. The objective of this proposal is to define the role of miRNAs in ZIKV replication and pathogenesis.

Axel T Lehrer — Preclinical Development of a Thermostable Trivalent Filovirus Vaccine. The goal is the development of a thermostable (dry) non-replicating, trivalent filovirus vaccine candidate based on recombinant virus subunits that is safe and effective in protecting civilian and military populations against infection by lethal strains of Ebolavirus and Marburgvirus.

Iain S Macpherson — Multiplexed Single-cell Proteomics using Covalent Aptamers, Microfluidics, and High-throughput Sequencing. This research project is to develop methods to better diagnose cancer in Hawai‘i.

Lishomva Chakanga Ndhlovu — Reversal of Adaptive Immune Dysfunction in Shock and Kill HIV Cure Strategies. This study seeks to facilitate the elimination of HIV infected cells through increased antiviral T cell function. The study will achieve this through a novel immune regulatory pathway that when blocked restores T cell function capable of depleting latently HIV infected T cells. This study will be extended to the SIV infected non-human primate model of AIDS to confirm whether this novel strategy specifically targets and destroy latently infected cells.

Napapon Sailasuta — Critical Role of Cytotoxic T Cells in HIV Neuropathogenesis will provide expertise in magnetic resonance spectroscopy (MRS) and magnetic resonance imaging (MRI) for the project.

Bruce Shiramizu — (PQ5) Informing anal neoplasia differences/similarities in HIV-serodiscordant individuals. The project proposes to identify molecular biomarkers and Raman spectra fingerprints in anal neoplasia from HIV-serodiscordant couples to assess a unique role that HIV plays in anal neoplaia pathogenesis.

Bruce Shiramizu — Hawai‘i IDeA Center for Pediatric and Adolescent Clinical Trials (HIPACT). The project will establish the Hawai‘i IDeA Center for Pediatric and Adolescent Clinical Trials (HIPACT) as a partner in the IDeA States Pediatric Clinical Trials Network (ISPCTN). HIPACT will work with ISPCTN to launch and enroll infants, children, and adolescents from Hawai‘i from rural and underserved communities and across IDeA partner institutions in ISPCTN approved trials.

Bruce Shiramizu — JABSOM Raman-Enhanced Screening Protocol Expanding Cancer Testing. To generate preliminary data and show “proof-of-concept”.

Saguna Verma — Under Attack: Modulation of the Blood-testes Barrier by Zika Virus. Understanding how ZIKV gains entry into the immune privileged site of the testes and the role of inflammatory mediators in facilitating this process will fill the fundamental gap of the mechanism of testicular infection of ZIKV and facilitate development of strategies to prevent virus-testes entry.

Angel Yanagihara — Pathogenesis of Life Threatening Box Jellyfish Envenomation and Irukandji Syndrome. Box jellyfish stings pose a public health threat in tropical and subtropical coastal areas. Irukandji syndrome is a complex, potentially life-threatening clinical sequelae of box jellyfish envenomation. The research will clarify the role of the jellyfish pore-forming protein (or porin) in Irukandji syndrome. This improved understanding will guide the development of more effective treatments.

Angel Yanagihara — Venom Inhibitor Test Methodology will research, develop, and document appropriate test methodologies, models, and/or protocols for assessing the effectiveness of venom inhibiting substances.

Department — Dean's Office

Katalin Csiszar — Collaborative Mentoring and Research Support for Project Olona. The proposed collaborative mentoring, research, and research infrastructure support program is designed to advance the educational, scientific, innovational, and social enterprise goals of Project Olona by furthering interest in undergraduate and graduate education, active student research, and career development among underserved and Native Hawaiian students.