University Of Hawaii At Manoa

NIH Research Projects · FY 2025 · 2022-03

PROJECT SUMMARY Despite great promise, immune checkpoint inhibitors (ICIs) have had only modest impact on breast cancer patients’ survival. Mechanistic studies into the interplay between the immune system and the tumor cells identified the tumor microenvironment (TME) as the critical factor in dictating the impact of ICIs on tumor progression. Clinical advancements in ICI efficacy will require combinations with agents that can induce a broad shift in the microenvironmental milieu, which may prove especially important for highly aggressive tumors. Inflammatory breast cancer (IBC) is a rare and highly lethal breast cancer with few therapeutic options. In phase II clinical trial for triple-negative IBC patients, we found that anti-EGFR antibody panitumumab (PmAb) combined with preoperative chemotherapy led to a high treatment response. We further found that in IBC models, PmAb reduced the expression of immunosuppressive chemokines and led to increased infiltration of cytotoxic T cells; suggesting a broad shift from an immunosuppressive to immunoreactive TME. Building on these preliminary findings, we propose to determine the mechanism by which EGFR promotes the expression of immunosuppressive chemokines and if, in turn, this effect is responsible for the observed immunosuppressive TME in IBC. While EGFR inhibition has been examined as a way to target tumor cell proliferation and survival, to our knowledge, no other group has examined EGFR as a modulator of the TME in IBC. We propose 3 aims: Aim 1: Determine the mechanism by which the EGFR pathway modulates the TME in IBC. We hypothesize that the EGFR pathway induces an immunosuppressive TME in IBC through EGR1-regulated expression of immunosuppressive chemokines. We will test this hypothesis via in vitro assays and our novel humanized IBC immunocompetent mouse model. Aim 2: Evaluate the combination of immunotherapy with EGFR inhibition in IBC. We hypothesize that EGFR-targeted therapy will enhance the efficacy of immunotherapy in IBC by shifting the TME from an immunosuppressive to an immunoreactive phenotype. We will test the efficacy of targeting EGFR and inhibiting immune checkpoints in combination using the novel IBC humanized mouse model and triple-negative breast cancer immunocompetent mouse models with intrinsic and acquired resistance to ICIs. Aim 3: Determine the clinical relevance of EGFR-modulated TME changes in IBC. We hypothesize that reduced expression of EGR1 and its likely transcriptional targets correlates with TME immunoreactive status and predicts IBC patient response to PmAb-based therapies. We will assess the clinical relevance of our pathway using an IBC genomic dataset and multiplexed immunostaining on an IBC tissue microarray and IBC tissues from an ongoing PmAb clinical trial. Upon completion, we expect to identify TME changes that predict patient response to EGFR-targeted therapy and establish a novel EGFR-based combination therapy with ICIs for patients with IBC. Beyond IBC, our research will broaden our understanding of how we can modulate the TME as a potential therapeutic approach.

NIH Research Projects · FY 2026 · 2022-01

PROJECT SUMMARY/ABSTRACT Errors in dietary assessment methods attenuate the association between diet and chronic disease outcomes, such as obesity and cancer, which derails efforts to aggressively pursue policies directed to improving dietary intakes in the population. Harnessing the capabilities of mobile-based and image-based technology tools offer an opportunity to reach a wide audience via cost-effective, convenient, timely, and familiar channels. Properly constructed and validated, these tools would eliminate the labor-intensive coding required for traditional paper and interview methods. Successfully creating tools which tap into several specialty areas of science and behavior requires a multidisciplinary team of scientists. For several, the research group represented in the proposal have been committed to advancing dietary assessment methods. We have made progress with harnessing the availability of the ubiquitous and popular mobile telephone, passive methods, and the Automated Self- Administered 24-Hour Dietary Assessment (ASA24). Our research group represents a partnership between nutrition scientists/epidemiologists, engineers specializing in image analysis, Registered Dietitians, and biostatistions. Having completed multiple studies demonstrating the efficacy of the Technology Assisted Dietary Assessment (TADA) system through the use of the mobile food record (mFR) app, we recognize the value of having multiple validated tools available to better accommodate diverse research questions, variations due to age or levels of cognition. The Nutrition for Precision Health powered by the All of Us Research Program provides a unique opportunity to test multiple methods of dietary assessment using modern and novel methods. To fully take advantage of this opportunity, we will deploy ASA24 web-based tool; the Mobile Food Record (mFR), an image based app; and a passive method, the Automatic Ingestion Monitor v2 (AIM-2). Further, we will combine methods and include the ASA24 as a dietary record and the ASA24 combined with the mFR. Advancing technology tools would facilitate precision dietary assessment and research translation to better comprehend eating behaviors, define diet-disease relationships, and assess the effectiveness of intervention programs.

NIH Research Projects · FY 2026 · 2022-01

Project Summary/Abstract The overall goal of this project is to use approaches from statistics and computer science to solve significant chal- lenges in the analysis of metabarcode and metagenomics data. Metagenomics, the study of combined genomes of organisms present in a single community, is an emerging highly interdisciplinary field that combines genomics, bioinformatics, systems biology, among other areas. Metagenomics has many applications to public health es- pecially in the areas of pathogen detection, human microbiome analysis, and biodiversity monitoring. The larger objective of this proposal is to leverage the use of the open source software, tronko, a fast approximate likelihood phylogenetic placement method that I developed for taxonomic classification, which is the first phylogenetic place- ment method that truly enables the use of large-scale reference databases and next generation sequencing data desired as queries. Tronko will be used to solve fundamental problems in analyses of metabarcode and metage- nomic data in addition to developing an application to analyses of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequences that will greatly enhance the utility of environmental monitoring of SARS-CoV-2. The specific aims of this proposal are to (1) solve an important theoretical problem by applying a rigorous species delineation to assignment, (2) to apply tronko to solve an important practical problem of estimating the compo- sition of SARS-CoV-2 lineages in wastewater surveillance samples, and (3) to develop a rapid custom reference database builder for analyzing metabarcode and metagenomics data. For Aim 1, different phylogenetic groups have different variability in different parts of the tree, therefore, I plan to use Bayesian methods to estimate effec- tive population sizes locally to establish appropriate cut-off thresholds for species assignments in different parts of the phylogeny. Current methods use arbitrary thresholds for delineation of taxonomic groups and this method would provide an elegant solution to a long-standing limitation in species classification. For Aim 2, SARS-CoV-2 monitoring of wastewater is an effective strategy for early detection of outbreaks. I plan to build a pipeline, and subsequently a web portal for researchers, that uses tronko to first detect the virus within a wastewater sample then subsequently uses an expectation-maximization algorithm to estimate the proportions of viral strains. This aim would greatly aid public health researchers in assessing and managing the pandemic since no established methods are currently available for this type of analysis. For Aim 3, current custom reference database builders require weeks if not months of consecutive computational time in addition to access to a large amount of data storage. I propose to build a method which can be completed within a day. The method will perform in silico amplification of primers and subsequently use the amplified fragments in a kmer-based approach for identifying relevant sequences within a nucleotide database with utilization both across a network connection and a local database. Execution of these aims will solve important theoretical, practical, and computational problems in the field of metagenomics.

NIH Research Projects · FY 2025 · 2021-09

PROJECT SUMMARY/ABSTRACT Intermittent energy restriction (IER) has been suggested to have important advantages over daily ER (DER) in producing sustained weight loss and reducing cancer risk. While IER is already being promoted in the general population to improve health and longevity, supportive evidence is urgently needed from rigorously conducted randomized trials. We propose a six-month randomized trial to demonstrate the superiority of IER over DER in reducing ectopic fat and total fat mass, and in improving cancer-related biomarkers and gut microbiome functions. Our previous work strongly suggests that ectopic fat, independently of total adiposity, plays an important role in the etiology of, and in the racial/ethnic disparities in, obesity-related cancers. We reported striking racial/ethnic differences in the strength of the association between body mass index (BMI) and risk of obesity-related cancers in the Multiethnic Cohort (MEC). We observed corresponding disparities in the propensity to accumulate visceral and liver fat among the same five ethnic groups in a recent MRI-based study and demonstrated an independent association of a robust biomarker-based visceral fat score with incident breast cancer in MEC. Additionally, we adapted an IER protocol combined with a Mediterranean dietary pattern (IER+MED) and demonstrated its feasibility, safety and greater efficacy over an active comparator (a heart- healthy DER approach) in reducing total and ectopic adiposity and improving beneficial gut microbiome functions in a 12-week randomized trial among 60 middle-aged adults of various Asian ethnicities with visceral obesity. We now propose the Healthy Diet and Lifestyle Study II, a 24-week randomized trial of IER+MED vs. MED/DER among 260 middle-aged Oahu adults of East-Asian, Pacific Islander or white ethnicity with VAT greater than the population median. The intervention will be delivered through 16 focused and customized consultations with research dietitians and will consist of an IER+MED (IER is 70% energy restriction on two consecutive days and a euenergetic MED diet for the other five days of the week) or the MED with a 20% daily energy restriction (MED/DER). Dietitians will monitor dietary compliance using the mobile food record (mFR) and compliance to a common physical activity recommendation using interviews and actigraphy throughout the intervention. We will compare IER+MED vs. MED/DER for reduction in MRI-measured visceral and liver fat and DXA-measured total adiposity (Aim 1) and for improvement in cancer-related biomarkers (IGF-1, IGFBP3, insulin, HOMA-IR, leptin, adiponectin, S HBG, hsCRP) and fecal metagenomic markers of microbial metabolite production (Aim 2). We will also investigate behavioral predictors of adherence to the prescribed IER, including psychosocial measures of self-efficacy and outcome expectancies, and dietary patterns based on timing and frequency of eating episodes (Aim 3). This study will provide robust effectiveness data for IER on lowering cancer related risk factors and inform future translational and dissemination research to reduce cancer risk in various US populations.

NIH Research Projects · FY 2025 · 2021-09

There is strong evidence that cancer treatment contributes to increased comorbidity, functional decline, and accelerated biologic aging. Resistance training (RT) interventions may help to minimize this functional decline by increasing lean mass. Patients diagnosed with colon cancer are particularly likely to benefit from RT interventions given the high prevalence of involuntary loss of skeletal muscle mass (sarcopenia) at diagnosis, which is associated with chemotherapy- associated toxicities, and poor prognosis. Epigenetic clocks, which predict chronologic or phenotypic age based on specific patterns of DNA methylation (DNAm), are easy to assay, well- validated markers of biologic aging. Those with higher epigenetic age acceleration (AgeAccel; DNAm-estimated age adjusting for chronologic age) are at an elevated risk for morbidity (early onset of functional impairment, frailty and other aging syndromes) and mortality, independent of other predictors of longevity. We hypothesize that colon cancer patients with higher blood AgeAccel will be at greater risk for chemotherapy toxicities, dose reductions, and delays, that AgeAccel will increase during colon cancer chemotherapy, and that a RT intervention can reduce the rate of epigenetic aging. We further hypothesize that AgeAccel measured in blood and tumor tissue will be related to colorectal cancer molecular subtypes and patient prognosis. We plan to investigate these hypotheses in collaboration with the Resistance Training to Reduce Chemotoxicity in Colon Cancer (FORCE) clinical trial. This clinical trial of RT in stage II and III colon cancer patients includes detailed treatment and participant information, tumor specimens, longitudinal collection of blood and multimodal measures of body composition. Our aims will investigate whether several measures of blood AgeAccel at baseline relate to the incidence of moderate/severe chemotoxicities, and relative dose intensity. We will assess the rate of blood epigenetic aging over chemotherapy, and whether this rate is modified by RT. We will evaluate whether AgeAccel estimated in blood and tumor tissue differs by colorectal cancer molecular subtypes and associations with overall survival, recurrence, comorbidity accumulation, and trajectories of muscle mass. Together, these analyses will provide novel insight into the biologic processes of aging that predict tolerance for cancer treatment and patient prognosis to inform appraisal of whether AgeAccel may serve as a useful tool to guide clinical care.

NIH Research Projects · FY 2025 · 2021-09

The Center for Pacific Innovations, Knowledge, and Opportunities (PIKO) will build a statewide clinical and translational research (CTR) infrastructure to improve the health of Indigenous Pacific People (IPP) – defined as Native Hawaiians, Other Pacific Islanders, and Filipinos. IPP comprise 40% of Hawaii’s population and have disproportionately high rates of physical and mental health conditions compared to Whites and Asians. They also make up a majority of Hawaii’s other medically underserved and vulnerable populations. PIKO represents a partnership between the University of Hawaii (lead), Hawaii Pacific University, Chaminade University of Honolulu, and a statewide network of practice-based organizations (PBO) and community-based organizations (CBO). PIKO emphasizes the T3 (efficacy studies) to T5 (adoption and institutionalization) domains of CTR where the social determinants of health are strongly operative. PIKO takes a team-science approach to transform current CTR paradigms and to accelerate CTR advances to improve IPP health. PIKO comprises seven Cores: Administrative; Professional Development; Pilot Projects Program; Biostatistics, Epidemiology, and Research Design; Community Engagement and Outreach; Clinical Research and Regulatory Support; and Tracking and Evaluation. The University of Hawaii committed $2 million over 5 years to PIKO. The Overall Specific Aims are: Specific Aim 1: Build a robust CTR infrastructure by establishing and implementing CTR activities within and across PIKO partnering institutions; by leveraging resources and expertise of other research infrastructure programs; by creating CTR registries of academic mentors, community leaders, junior investigators, and study participants; and by implementing efficient and effective administrative operations and communication strategies. Specific Aim 2: Strengthen and diversify the CTR workforce by identifying IPP and non-IPP investigators for CTR careers; by enhancing the mentoring and professional development of CTR investigators and community leaders; by supporting culturally responsive and scientifically meritorious CTR pilot projects; and by engaging PBO/CBO to actively participate on all aspects of CTR. Specific Aim 3: Disseminate and implement CTR findings by providing strategic investments in PBO/CBO to strengthen trust-based relationships; by strengthening a statewide network of PBO/CBO to serve as dissemination and implementation partners; by convening an annual conference that brings together CTR investigators and PBO/CBO stakeholders to share best practices, discoveries, and dissemination and implementation strategies; and by leveraging data science strategies to disseminate data and findings that are user-friendly, easy to understand, and accessible. By the end of this 5-year project, PIKO will have promoted high-impact transformative CTR to improve the health of IPP and other marginalized communities in Hawaii.

NIH Research Projects · FY 2024 · 2021-09

PROJECT SUMMARY/ABSTRACT Brachytherapy procedure is one of the most popular treatment modalities for prostate cancer where cancerous cells are irradiated and destroyed locally by the radioactive dosage of seeds implanted by the surgeon. The success of brachytherapy heavily relies on safe and precise placement of the seeds in or adjacent to the cancerous cells. The procedure demands a very experienced surgeon who have developed an intuitive feel in needle insertions and is able to guide the needle into a desired location with hand-eye coordination and assistance of an imaging device. However, with conventional rigid needles, only a straight path is achievable towards the target, and thereby seed placements require several insertions with a high tissue damage on the needle’s path. A recent study has shown that guiding the needle in a curvilinear approach will decrease the number of needle insertions required and provide other dosimetric benefits. Lack of actuation and control (after the needle is inserted into the patient’s body) is another factor that make the procedure challenging. A flexible 3D steerable “smart” needle with multi-directional actuation and a reliable guidance control and guidance can aid the surgeon to perform the task with more accuracy, reduced invasiveness, and in a curvilinear approach. Furthermore, teleoperative guidance for the smart needle will endow the robotic instrument with intelligence. On the other hand, in-depth understanding of the needle-tissue interaction mechanism (with intraoperative model parameter updates and shape- and force-sensing) is a key factor in development of an appropriate control and guidance strategies to compensate for system uncertainties. This work will first develop an active “smart” brachytherapy needle that will provide robust actuation, shape- and force-sensing, and 3D motion in tissue. Then a teleoperative interface with robot-driven smart needle will be developed to perform semi- automated brachytherapy. Realistic analytical and computational models of needle-tissue interactions will be developed using realistic tissue characteristics. These models will be used in the control system as dynamic models to make appropriate decisions during an insertion task. The innovative features of our proposed methods rely on our cutting-edge smart needle design, new dynamic models, shape- and force-sensing, and control algorithm specifically developed for this application. The present studies will develop a clinically acceptable size “smart” surgical needle with a robotic control interface and evaluate its impact in brachytherapy procedure. Utilization of active and passive flexible needles for diagnosis and therapeutic procedures is a rapidly advancing filed. This proposed research has a high potential to lead to a revolutionary needle insertion practice in healthcare that is also beneficial to various needle-based procedures such as drug delivery, biopsy, and interventional therapy where an accurate placement is needed with minimal tissue damage.

NIH Research Projects · FY 2025 · 2021-08

Project Summary/Abstract. Women with dense breast have not been shown to benefit by increased cancer detection of volumetric digital breast tomosynthesis (DBT) but may benefit by lower recall rates. DBT screening biopsy rates are similar to 2D digital mammography; higher for first screening exams, lower thereafter with adjustment for age and breast density. In the U.S., 71% of biopsies do not result in a breast cancer diagnosis among women ages 40-79 who undergo breast cancer screening. To address the high rate of unnecessary biopsies, an innovative way to use FDA-approved breast imaging protocols has been developed to acquire multispectral images to measure the lipid/water/protein (L/W/P) composition of suspicious breast lesions. Malignant breast tissue has unique L/W/P composition fractions when compared to normal or benign breast tissue. This proposal aims to increase biopsy yield (BI-RADS-PPV3) through combining L/W/P biological biomarkers with quantitative morphological and textural image analysis. This combination of composition and physical descriptions of suspicious breast lesions is called q3CB. The benefits of adding q3CB to the current DBT screening/diagnostic imaging paradigm, that may already include computer aided detection, is not known. This study is designed to compare the expected biopsy yield with and without q3CB in a clinical reader study and explore how q3CB may be combine with existing technologies. The central hypothesis is that biological L/W/P fractions in breast tissue in combination with analysis of morphological and textural tissue characteristics will yield significantly higher breast cancer specificity than conventional interpretation of DBT alone. The objective is to better identify suspicious breast lesions that need to be biopsied for malignancy in women currently recommended for biopsy. The long-term goal is to reduce unnecessary biopsies and increase biopsy yield. Our rationale for the proposed research is that biological L/W/P descriptions of breast lesions will lead to more specific biopsy decisions and a better understanding of cancer types. Specifically, the project aims are 1) develop q3CB lesion signatures for distinguishing breast cancer lesions from benign lesions, using 600 prospectively-acquired DBT exams of women recommended to undergo biopsy; 2) conduct a clinical reader study to compare radiologists' performance on standard-of-care FFDM or DBT without and with the inclusion of q3CB signatures; 3) Investigate the utility of q3CB lesion signatures in a screening paradigm to improve sensitivity and specificity on CADe-identified suspicious lesions in the tasks of assessing malignancy as well as in associating with their association with cancer subtypes; Exploratory) explore the added sensitivity and specificity of dual-energy DBT in phantom studies that explore lesion size, composition, and breast density. The innovation of this study is the full characterization of lipid/water/protein lesion composition with DBT and how it complements existing computer aided diagnostic programs paired with clinical radiologists providing evidence ready for clinical translation of this unique and emerging technology.

NIH Research Projects · FY 2025 · 2021-08

Project Summary/Abstract. Excess adiposity is associated with metabolic changes that significantly increase the risk of developing 13 types of cancer. It is estimated that up to 20% of cancer cases are caused by obesity and that obesity prevention can play a significant role in the reduction of cancer incidence. Among obese adolescents, the most rapid weight gain has been shown to occur between 2 and 6 years of age. Despite clear connections between these factors and obesity risk, the study of obesity in early childhood is limited by the lack of body composition technologies appropriate for this age range. The long term goal of the Shape Up! Keiki is 1) to provide pediatric phenotype descriptors of health derived from detailed body shape scans from high-speed and high depth resolution 3D cameras, and 2) to provide the tools to visualize and quantify body shape in research and clinical practice. Our approach addresses technology issues that have hindered body composition research in this age range including participants' inability to hold still, follow directions, small body size, and rapid fluid shifts. To develop our body composition models, we will recruit 360 ethnically-diverse children from birth to 5 years stratified by sex and BMI-Z. Our central hypothesis is that optical estimates of body composition suitably represent a 5-compartment (5C) body composition model for studies of adiposity and health in young children and are superior to that of simple anthropometry and demographics. Our specific aims and subaims are as follows: 1) identify the statistical shape descriptors from 3DO scans that best represent 5-compartment body composition in an ethnically-diverse pediatric population, 1(a) identify the relationships that best link 3DO shape descriptors of body subregions (arms, legs, trunk), and matching volumes and body composition measures, 1(b) calibrate automated 3DO anthropometry to clinically relevant girths and lengths, Exploratory) identify accessible combinations of 3DO and TBW that can be calibrated to criterion 5C measures of fat and hydration, 2) identify the factors that define the precision of accessible 3D optical body composition estimates to monitor change in body composition and metabolic health interventions, 3) contrast the association of body shape, 3DO, and 5C criterion body composition to pediatric health indicators including clinically relevant exposures (SES, nursing duration, birth method, nutrition) and development. The rationale for this study is that early life access to accurate body composition data will enable identification of factors that increase obesity, metabolic disease, and cancer risk, and provide a means to target interventions to those that would benefit. The expected outcome is that our findings would be immediately applicable to accessible gaming and imaging sensors found on modern computers.

NIH Research Projects · FY 2025 · 2021-07

PROJECT SUMMARY/ABSTRACT Native Hawaiians and Pacific Islanders (NHPIs) experience a disproportionately higher prevalence of cardiometabolic diseases, primarily Type-2 diabetes mellitus (DM), than other U.S. racial/ethnic populations. Compared to White residents, NHPIs have a ~2.5-fold higher incidence and earlier onset of diagnosed DM with significant differences in DM disparities appearing at age 35. NHPIs also have the lowest levels of educational attainment, lowest mean income, highest rates of poverty, and higher exposures to DM risk factors compared to other major racial/ethnic groups in Hawaii, and also reside in environments that include low neighborhood socioeconomic status (nSES). The coincidence of disparities in DM prevalence and adverse social environments implicate complex interactions that may impact gene pathways relevant to the onset of DM. However, the interactions between the social environment and biological mechanism(s) that underlie DM health disparities of NHPIs are unknown. The detrimental effects of social environments, such as nSES, may include an increased prevalence of chronic low-grade inflammation known to contribute to DM. Epigenetic mechanisms (e.g. DNA methylation) regulate transcription of pro-inflammatory genes of monocytes, a key mediator of inflammation. Our preliminary data in NHPIs with DM that completed a lifestyle intervention revealed significant genome-wide changes to the DNA methylation and gene expression states of pro-inflammatory genes that were associated with their monocyte inflammatory activity and glycemic control. In another study, we observed significant changes to the gut microbiome, dysbiosis of which may also be an underlying attribute of DM, in NHPI youth that correlated with social network influences and health behaviors that modified their risk for DM. Lifestyle- associated changes to the gut microbiome impacts DNA methylation through bioavailability of substrates essential to the epigenetic machinery. Thus, we propose a hypothesis that the social environment conditions the epigenomic landscape and gut microbiome composition that regulate inflammation and metabolic pathways underlying DM. To test this hypothesis, we aim to identify an epigenetic signature of DM risk in monocytes from a new cohort of NHPIs and that of their social networks, and examine associations with neighborhood- and interpersonal-level social factors using a cross-sectional study design (Aim 1). We will then explore the mechanistic basis to which this signature may underlie innate DM-relevant traits by examining associations with inflammation, inflammatory activity, and gut microbiome composition/diversity (Aim 2). Finally, we will determine the degree to which this signature may prospectively be predictive of DM outcome (Aim 3). Addressing these aims will yield novel datasets of NHPIs in a health disparate population for determining the relationship between the “immunoepigenetic-gut microbiome axis” and DM risk within the context of the social environment and provide new insight into the etiology of DM disparities in NHPIs, with generalizable implications for improving early identification of DM to enable preventative strategies in populations suffering from social/health inequities.

NIH Research Projects · FY 2025 · 2021-06

MARC@UHM will strive for “Hoʻoulu nā laeʻula akeakamai”, a Hawaiian phrase meaning “good mentoring leads to well-trained scientists.” According to the Chronicle of Higher Education, the undergraduate (UG) student body and faculty at the University of Hawaii at Manoa (UHM) are the most diverse in the nation, but inequities persist. Only 8.5% of PhD candidates in STEM-related programs at UHM are underrepresented (UR) backgrounds. UHM has a rich pool of UR students who are not entering STEM-related PhD programs and therefore are not contributing their cultural diversity to our nation's scientific workforce. Thus, the mission of MARC@UHM is to provide training in biological research for a diverse group of UHM students, including Hawaiian/Part Hawaiian, other Pacific Islanders (Samoan, Tongan, Micronesian, Guamanian/Chamorro, mixed Pacific Islander), Filipino, Hispanic, African American; underrepresented Asians (e.g., Cambodian, Vietnamese, Laotian); those from disadvantaged backgrounds, including low social-economic and residents of rural outer islands; and students with apparent and non-apparent disabilities. MARC@UHM's objectives are to i) enroll 10 students annually and teach them to identify important research questions, design and conduct rigorous and reproducible experiments, and analyze data and interpret results, ii) provide each trainee with 4 semesters of mentored research and a summer research experience; iii) develop skills trainees need to be competitive in graduate school and in careers as research professionals, and iv) assist each trainee in applying to at least 5 graduate school programs early in the senior year. An estimated >900 UR STEM students in biomedical research are eligible for the MARC@Hawaii Program. The Training Plan starts with recruiting high school seniors entering UHM, especially those from the outer islands, to a Pre-MARC (The Ma Mua MARC) Program as freshman and sophomores. The Ma Mua MARC encourages UR STEM majors to consider research as a career option, invites them to attend MARC-seminars and functions, and creates a community of peers. The 2-year program from juniors and seniors begins with a summer workshop, “Let's get started” where trainees and research mentors are paired. The Plan includes: a 2-credit course each semester designed specifically for MARC trainees, 4 semesters of mentored research, a summer research experience (either at UHM or working with a collaborator of their UHM mentor at an external site), a short workshop, attending a national meeting annually, and presenting their research at professional meetings. Over 25 UHM faculty and 10 faculty at external sites with diverse backgrounds in ethnicity, age, gender, and rank will participate. The primary outcome measure is the number of trainees graduating with BA/BS in 4-years who transition to research-intensive Graduate Programs. Thus, MARC@UHM seeks to increase Hawaii's UR citizens who transition to research careers, as they bring diverse cultural backgrounds, life experiences, ideas, and interests to biomedical research.

NIH Research Projects · FY 2025 · 2021-04

Brown adipocytes exposed to cold dissipate heat via adaptive thermogenesis. Adaptive thermogenesis is a physiological response that contributes to energy homeostasis and restricts obesity development in rodents and humans. Activation of adaptive thermogenesis by cold exposure depends on sympathetic/beta-adrenergic signals and thyroid hormones (TH) and is induced by glutathione (GSH) depletion via elevation of reactive oxygen species. TH levels in BAT are locally regulated by iodothyronine deiodinase 2 (DIO2), while GSH is enzymatically converted into its reduced form by GSH peroxidase 1 (GPX1). Besides their crucial role in the activation of BAT adaptive thermogenesis, both DIO2 and GPX1 are selenoproteins, i.e. a class of proteins containing in their active site selenium (Se) as the amino acid selenocysteine (Sec). Sec is decomposed by the enzyme Sec lyase (Scly) into H2Se. Sec comes from either dietary sources or selenoprotein degradation. Hence Scly-mediated Sec decomposition triggers a Se recycling process required to maintain optimal levels of selenoproteins, particularly when Se is limiting. Se recycling is key for energy balance, as disruption of the Scly gene in mice (Scly KO) leads to weight gain worsened by Se deficiency. In wild-type rodents, Se deficiency upregulates Scly and decreases BAT Se levels, DIO2 and GPX1 activities. It is unknown if Se recycling modulates BAT Se levels, impacting DIO2 and GPX1 synthesis and activities, ultimately contributing to cold- induced adaptive thermogenesis. Our long-term research goal is to determine the molecular mechanisms through which Se metabolism regulates energy homeostasis. The overall objective of this research proposal is to determine the role of Se and Scly-mediated Se recycling in linking selenoprotein degradation and synthesis with adaptive thermogenesis in brown adipocytes. In Aim 1, we will determine if dietary Se intake regulates Se metabolism, especially Scly-mediated Se recycling, impacting responses to cold exposure in BAT. In Aim 2, we will determine if Scly is required for cold-induced adaptive thermogenesis in BAT. In Aim 3, we will determine if Scly participates in selenoprotein degradation in brown adipocytes. By studying both Se intake and metabolism, especially Se recycling, using novel in vitro and in vivo models, this conceptually and technically innovative project will clarify the modulatory effect of dietary Se on brown adipocyte physiology, providing new insights into the mechanistic role of Scly in the control of energy expenditure in mammals.

NIH Research Projects · FY 2024 · 2020-09

PROJECT SUMMARY/ABSTRACT There are over 18 million Latinos under the age of 18 in the US, and they make up one-fourth of the total youth population. There is consistent and rigorous evidence that Latino youth have historically had the worst patterns of health care access and utilization of any group of youth, even after controlling for variables such as insurance and family income. Access to care is even worse for the over 50% of Latino youth who have immigrant parents. These disparities are likely the result of multiple levels of youth and family, community, policy and societal factors. There is a dearth of evidence, however, on both the individual influence and the joint influence of these levels. California is an ideal state in which to study the complexities of access to care for Latino youth because it has the largest Latino and immigrant populations in the country with considerable variability in family citizenship and documentation compositions. State and national health surveys do not commonly measure the many dimensions of family citizenship and documentation statuses and health care eligibility, and these surveys generally have limited measures of health care access and utilization at the youth- and family-levels. The California Health Interview Survey (CHIS) is the largest annual representative statewide health survey in the country and collects data on youth and parent citizenship and documentation statuses, which allows for the unique opportunity to examine the effects of variabilities in family citizenship and documentation statuses on health care access and utilization for youth. We plan to conduct a follow-up study of 1,000 Latino youth and their families in the 2021 and 2022 CHIS waves. Our approach will allow us to combine baseline CHIS data with newly collected data from follow-up interviews and county-level data to examine disparities in youth's access to and utilization of health care. We will also determine how disparities vary by youth, parent and sibling citizenship and documentation compositions and the extent to which youth and family, community, policy and societal factors influence them. Using the NIMHD Research Framework and Warnecke et al.'s model for population health and health disparities, we will address 4 specific aims in the context of families' citizenship and documentation status compositions: 1) estimating the disparities in access to and utilization of health care for Latino youth according to youth- and family-level factors; 2) understanding the processes and facilitators that increase the likelihood that Latino youth access and use services; 3) identifying how parental trust in health systems and institutions influence the determinants of health care access and utilization for Latino youth; and 4) understanding how variations in county-level policy and societal contexts influence health services use for Latino youth. The project will provide critical information on how the effects of multiple levels of influence affect access and utilization of care for Latino youth and will offer evidence to guide policy and practice interventions to improve access to care for Latino youth.

NIH Research Projects · FY 2025 · 2020-08

This application proposes to continue the “Cancer Research Education, Advancement, Training and Empowerment” (CREATE) program at the University of Hawai‘i Cancer Center (UHCC), a successful research experience for undergraduate and first-year graduate students with a focus on cancer health disparities. The program addresses the over-arching goal to enhance the training of a workforce that can meet biomedical, behavioral, and clinical research needs to lower cancer incidence and mortality in the Pacific. Special features of CREATE are the ethnic diversity of our interns reflecting Hawaii’s population, the inclusion of students from the University of Guam, and the opportunity to work on projects related to cancer health disparities. During the last 4 years, the 85 undergraduate (70% female) and 10 graduate trainees (80% female) combined, reported Native Hawaiian/Pacific Islander (24%), Filipino (28%), Asian (38%), Latino (4%), European (2%), African American (1%), and unknown (3%) ancestry. CREATE’s success is demonstrated by the high degree of satisfaction, the high proportion of undergraduate students entering graduate and medical school (66%), and 24 peer-reviewed papers co-authored by CREATE interns during 2021-2024. The program takes advantage of the excellent research opportunities arising from the distinctive population and environment in Hawai‘i and the Pacific with strong multi-disciplinary collaborations within the University of Hawai‘i and with the University of Guam. Besides the 8-week hands-on experience, CREATE includes a curriculum of workshops and multi- disciplinary seminars, career development activities and events, near-peer-mentoring, and a poster session. The program goal will be achieved through the implementation of two aims: 1. Provide hands-on summer research experiences and a multi-disciplinary curriculum to undergraduate students residing in the Islands of Hawai‘i and the Pacific with an expected outcome of increasing interest and research efficacy and the development of a supportive network to pursue a science degree and a career in cancer health disparities. 2. Offer first-year graduate students living in Hawai‘i and the Pacific in cancer-related fields of study the opportunity to gain research experience during the summer after their first academic year. Working in our multiethnic environment or unique cancer biology labs will enhance their skills to address causes, diagnosis, prevention, and treatment of cancer and offer opportunities to conduct their thesis research. Given the limited opportunities to gain research experience in the unique Pacific environment, this innovative 8-week research experience in cancer biology or population sciences supplemented by a structured curriculum will help to address the lack of biomedical researchers who understand cancer health diversity in Hawai‘i and the Pacific. This opportunity will enable students with diverse backgrounds in Hawai‘i and in the Pacific to pursue successful careers along the cancer research continuum.

NIH Research Projects · FY 2025 · 2018-08

Project Summary – OVERALL We seek to strengthen and enhance the Integrative Center for Environmental Microbiomes and Human Health (ICEMHH). Our center was established in response to the 2016 announcement of the National Microbiome Initiative (NMI). The NMI was conceived through the recognition that humans are both connected to and reliant upon the microbial communities that constitute the Earth’s microbiomes, in the environment as well as the human body. The NIH plays a central role in funding this effort, “with a particular emphasis on multi-ecosystem comparison studies, and investigation into the design of new tools to explore and understand microbiomes” [NIH Human Microbiome Project]. The focus of the ICEMHH is the interface between the microbial environment and human health, and our research includes clinical, biochemistry and landscape ecology studies. The University of Hawaiʻi brings three compelling strengths to microbiome research: the uniquely tractable and environmentally complexed landscape of the Hawaiian Islands, an exceptionally qualified biology faculty, including an integrated cohort of junior microbiome-focused faculty, and a dedication to the diversity of people that live on the Islands. As the most diverse biome on Earth, Hawaiʻi offers the unique opportunity to study the effects of steep, orthogonal, ecological gradients on human health, vis a vis their microbial symbionts, from mountain to sea, and in both urban and rural settings. The proposed projects aim to address how environmental variables influence microbial assembly, and how, in turn, this impacts host and human health. Our research leverages the natural ecological complexity and phylogenetic diversity of our archipelago to understand the interplay between environmental microbiomes and human health within natural settings. Using invertebrate model hosts and clinical research, we disentangle the mechanisms underlying these landscape-level patterns. Our projects build upon the knowledge, infrastructure and resources developed in Phase 1 to grow center renown, sustainability and capacity. Our long-term goal is that ICEMHH serve as a world-class model for linking environmental microbiology with human health sciences. In this way, the Center will provide lasting contributions to the State of Hawaiʻi, and beyond.

NIH Research Projects · FY 2026 · 2017-08

PROJECT SUMMARY / ABSTRACT – Overall The COBRE-Diabetes Phase 1 gave the University of Hawaiʻi at Mānoa (UHM) the ability to begin building a Diabetes Research Center (DRC). We were able to mentor 7 Research Project Leaders and 7 Pilot Project Investigators in Phase 1 in diabetes mellitus (DM) and insulin resistance (IR). Our DRC spans departments and across campus borders to promote research aimed at improving the metabolic health of the people of Hawaiʻi and the Pacific region. The Center has been built upon the strengths of Hawaiʻi’s spirit of collaboration, intrinsic ethnic and cultural diversity, and existing strengths in diabetes research. In the US, approximately 11.3% of the population has diabetes and 38.0% are prediabetic. Diabetes is more prevalent among racial/ethnic minority populations particularly in Native Hawaiians and Pacific Islanders: 27.7% and Asian: 19.3% compared to White: 12.2% in 2022. The Center will leverage Hawaiʻi’s ability to link basic science mechanisms underlying diabetes through translational research. In Phase 1, the COBRE-Diabetes was focused on understanding the etiology of DM and transitioned into studying diabetic complications. In Phase 2, our emphasis will be on DM complications since these occur at higher rates in minorities than non-Hispanic whites. Racial and ethnic disparities in Hawaiʻi have been observed in DM complications. Thus, the research projects proposed include: developing minimally invasive sweat sensors for clinical complications, exploring the genomics of diabetes and stroke in Native Hawaiians, and understanding the etiology of diabetic autonomic neuropathy in a rodent animal model. The Research Projects Leaders (RPLs) will be supported by the Administrative and Mentoring and Metabolic and Analytic Cores. Pilot projects are also proposed to fund two projects a year so that when RPLs graduate there will be new RPLs in the pipeline. The school of medicine and UHM will also recruit 4 new tenure-track Assistant Professors whose research complements and focuses on translational DM and IR. Community engagement will include an annual symposium with a science track and a community track with opportunities for researchers, academics, clincians and community members to attend and network with those who are working in the field of diabetes health research and health care disparities AND increased presence on our website and social media platforms. The Phase 2 overall goals are to: 1) Expand the multi-disciplinary research capacity of the DRC through the mentoring of new Research Project Leaders, 2) Strengthen the center through promoting scientific and community interactions, continued development of DRC faculty, and the recruitment of 4 new faculty to the center, and 3) Enhance the research infrastructure of the DRC and the institution through the expansion of the Metabolic and Analytic Core. Our DRC goal is to develop a translational research environment to advance DM research in a collaborative environment. This should lead us to become a strong, self-sustaining Center that will be supported by institutional and peer-reviewed grant funding.

NIH Research Projects · FY 2024 · 2016-09

ABSTRACT The principal objective of this second cycle of Hawaii IDeA Center for Pediatric and Adolescent Clinical Trials2 (HIPACT2) is to capitalize on the success of the first fouryears of HIPACT as a productive and engaged Environmental Influences of Child Health Outcomes IDeA States Pediatric Clinical Trials Network (ECHO ISPCTN) site. The first four years of HIPACT launched ECHO ISPCTN clinical trials, engaged new junior investigators in ECHO ISPCTN endeavors and built pediatric clinical trials capacity at HIPACT's partner institutions. As a relatively small ECHO ISPCTN site with a historical paucity of pediatric involvement in clinical trials, HIPACT successfully inspired and engaged new junior faculty across the spectrum of professional development activities. The initial success of HIPACT spirited the momentum for academic and community efforts to participate fully in the planning of HIPACT2 including newly committed partners. We have established a mechanism to participate in HIPACT2 by engaging pediatric and maternal-fetal medicine faculty through the Hawaii Pediatric Research (HIPR) Scholars Program. Moreover, we will endeavor to feed into the pipeline of ECHO ISPCTN activities with the goal of increasing the number of junior faculty involved in HIPACT2. With the overarching goal to improve the health and wellbeing of the diverse multiethnicpopulations in rural and underserved areas of Hawaii including indigenous Hawaiian communities, and immigrant populations of Pacific Islanders and Asians, HIPACT2will capitalize on established HIPACT partnerships with Hawaii Pacific Health (HPH) Kapiolani Medical Center for Women and Children (KMCWC), and Waianae Coast Comprehensive Health Center (WCCHC). The following Specific Aims are proposed: Aim 1: To actively contribute to and participate in ECHO ISPCTN pediatric clinical trials; Aim 2: To provide access to clinical trials to benefit rural and underserved infants, children, and adolescents, many of who are Native Hawaiians, Pacific Islanders, and Asians; Aim 3: To participate in the “science” of ECHO ISPCTN multicenter clinical trials research; Aim 4: To mentor a cadre of junior faculty via the Hawaii Pediatric Research (HIPR) Scholars Program. Taken together, HIPACT2 will act as an eager partner in ECHO ISPCTN in this second five-year cycle of funding with a strong historical track record of engagement and achievement, institutional support, and newly committed partners. It will enrich opportunities for faculty research training and education, participation in collaborative multicenter clinical trial research, and engage rural and underserved communities to improve health outcomes in Hawaii and across the nation.

NIH Research Projects · FY 2025 · 2014-08

The overall goal of the Hawaiʻi National Cancer Institute Community Oncology Research Program (NCORP) is to provide access and facilitate enrollment of Hawaii’s unique population to NCI sponsored trials. Thus we will work to accrue a representative population of our catchment area. Our NCORP is the primary provider of NCI clinical trials and cancer care delivery research (CCDR) in the State of Hawaiʻi. The Hawaiʻi NCORP supports an integrated network of affiliates and sub-affiliates with an extensive menu of cancer studies, research infrastructure and data management. Our NCORP has successfully extended CCDR studies from the originally designated sites to other hospital affiliate sites with plans to further extend them to physician office sites. We solicit community input from patient advocates in our community to review the suitability of trials as well as to address their healthcare needs. Non-medical oncology community investigators and staff have leadership responsibility in imaging, prevention and CCDR studies. Our NCORP leaders have extensive experience in cancer clinical trials, health care delivery and issues affecting our unique population. They have served on multiple NCI committees. Participation in NCI’s personalized medicine, cancer control, prevention, treatment and CCDR research will further reduce cancer health care gaps and the cancer burden for the people of Hawaiʻi and beyond.

NIH Research Projects · FY 2025 · 2013-12

Individuals raised within the Pacific Rim, including Native Hawaiians (NH), Filipinos, and other Pacific Islanders, i.e., Pacific People (PP), bring unique geographic, ethnic, and cultural perspectives to research. Yet, they remain underrepresented in research-oriented careers. They bring a personal perspective to research in health disparities, as they are burdened by many of the same communicable (malaria, TB, AIDS, dengue) and non-communicable diseases as other minority groups (e.g., diabetes, cardiovascular disease, obesity). Since receiving a MHIRT award in 2013, a Training Program designed for Pacific Peoples was developed at the University of Hawaii (UH) that provided training in all aspects of research, with an emphasis on health disparities in tropical medicine. The proposed MHRT Training Program is built on that foundation, but has shifted the focus from laboratory-based biomedical research to research on social, behavioral, and public health aspects of health disparities impacting NH/PP communities. Dr. V. Nerurkar, Chair of Tropical Medicine, Medical Microbiology and Pharmacology (T3MP), and Dr. J.K. Kaholokula, Chair of Native Hawaiian Health (NHH), will co-direct the revised program, providing complementary expertise in biomedical and behavioral sciences. Faculty in NHH, T3MP, the Cancer Center and Departments of Nutrition, Psychology, Public Health, and Social Welfare at UH join the revised Hawaii-MHRT Training Program. Annually, 5 undergraduate and 5 pre-doctoral trainees will receive MHRT training, since this is the point of highest attrition of NH/PP in the educational pipeline. Training includes: 1) a Spring semester course covering the basics principles of research; 2) working with UH and national and international mentors to develop research projects; 3) attending an 8-day Pre-Travel Workshop on health disparities; 4) conducting research (under-graduates and graduates 10-12 weeks; pre-doctoral 1 to 2 semesters) at one of 4 national or 3 international sites; 5) analyzing results and interpreting data at a Post-Travel Workshop; 6) creating “E Ho‘oulu haumana” (Hawaiian for “emerging students”), a public presentation of research results for families, friends, and faculty; and 7) continue conducting research and receiving mentoring for career development until graduation and beyond. Trainees will have the opportunity to work on culturally-relevant projects important to the communities; for example, conduct research on 1) diabetes prevention in a community of migrants from the Marshall Islands at the University of Arkansas; 2) obesity prevention in American Indian women at the University of Washington; 3) hypertension intervention with NH/PP living is Seattle with Washington State University; 4) prevention of smoking on cancer prevalence at the University of Guam; 5) health problems of transgender women at the Thai Red Cross, Thailand; 6) community-based initiative to respond to Ebola outbreaks at the University of Liberia; and 7) prenatal care of pregnant women in rural villages in Cameroon. Pre-doctoral students will present their results at departmental seminars and local and national meetings. The Hawaii MHRT Training Program goal is to increase the number of NH/PP students who are trained in research incorporating a diversity of ideas, culture, and talents while tailoring their research to be community and culturally sensitive.

NIH Research Projects · FY 2025 · 2012-09

This renewal application seeks support for the infrastructure of the Multiethnic Cohort (MEC) Study, which was established in Hawaii and southern California in 1993-1996 to study risk factors for cancer and other chronic diseases. The study was designed to take advantage of the sociocultural heterogeneity of the two geographic areas, as well as the expertise of the investigators in nutrition, population cancer differences, and genetics. It is the most heterogeneous cancer cohort in existence. It achieves high cost-efficiency by significantly supplementing active follow-up information with computerized linkages to SEER cancer registries, vital statistics, hospital-discharge diagnoses, medical claim data, electronic medical records and geospatial information. At baseline, the cohort included information on 215,000 adults aged 45-75 years. The resource was later expanded to include a prospective biorepository of blood specimens from ~70,000 of the participants and urine specimens on a large subset. Leadership of the MEC entails a highly interactive, team-science approach, and the investigators have amply demonstrated their willingness to share data/samples, and to participate actively in consortia. Research accomplishments include significant contributions to understanding both genetic and environmental risk factors for cancer. Over 291 papers describing our findings have been published during the current grant cycle. In addition, over the last 28 years, 129 NIH grants/supplements have been built around the MEC (77 were active in the current cycle), and more than 136 students and postdoctoral fellows have been trained on the study. This application describes our aims over the next 5 years for maintaining and enhancing the infrastructure of the MEC, as well as plans for methodological research. We project adding 7,253 incident cancer cases in the new 5 years, to the current 48,064 cases; 2,670 of these cases will have pre-diagnostic blood samples, to be added to the current 10,957 cases. We will add 6K FFPE tumor samples to the current ~13K. In addition, this grant renewal will make possible the continuation of a well-integrated program of research aimed at evaluating lifestyle, environmental, and genetic risk factors and area-level attributes for cancer and other common chronic diseases, taking advantage of new approaches, such as dietary quality indices, exposomics, genomics, epigenomics, microbiomics, metabolomics and multilevel exposures, including geospatial analysis. The MEC will allow the testing of innovative research hypotheses aimed at ensuring that population differences in cancer risk and outcomes are investigated and that progress in disease prevention applies to all populations.

NIH Research Projects · FY 2025 · 2012-09

Abstract This application for renewal of the Cardiovascular T32 training program at the University of Hawaii draws on the strengths of our Center for Cardiovascular Research (CCR) and our established graduate program in Cell and Molecular Biology. We also have maintained and enhanced an alliance with the Cardiovascular Division at Stanford University Medical School to enrich the local academic environment and increase the number of seasoned senior investigators available as mentors for our trainees. In recent years our medical school has embarked on a new direction, emphasizing basic investigation that has instilled new energy into our graduate programs. We have moved into a modern campus on the shore of Honolulu and attracted nationally competitive investigators. Our Cardiovascular Center has recruited or developed 6 independent investigators who have a principal focus on cardiovascular investigation. In addition we have a group of UH faculty with established research programs pertinent to cardiovascular science. We now have the critical mass of investigators needed for a successful T32 program. During our first cycle of funding we were the only T32 in the State. During both cycles we have had success in training under-represented minority scientists and in helping our trainees to obtain independent grant funding. During the past cycle we also saw the development of a joint T32 between the Cancer Center and USC as well as a K12 program in Tropical Medicine. We assisted both programs in their applications and they have helped to augment our training efforts and the pool of young investigators at the School. We still have our roots in our minority-serving, clinically-focused school, but are adding an important level of scientific sophistication to serve our special location and multiethnic population. During the third cycle of funding, described in this application, we will continue to place our best graduate students and postdoctoral fellows in laboratories devoted to cardiovascular projects, and provide mentoring that will help them succeed. They will benefit from an established curriculum, CCR core resources, and will also be able to draw upon the Stanford Cardiovascular Division for world-class expertise and research resources. We request support for three graduate students and three postdoctoral fellows per year. We expect, on average, that the graduate students will be supported for no more than three years and the postdocs for no more than two years before they either finish or obtain independent funding. Thus we anticipate supporting approximately 7 individual postdoctoral fellows and 5 graduate students during the 5 years of this program. Our goal is to train our next generation of cardiovascular investigators, with special attention to the priorities of our local population.

NIH Research Projects · FY 2024 · 2009-09

PROJECT SUMMARY: OVERALL The Pacific Island Partnership for Cancer Health Equity (PIPCHE) is a 17-year collaboration between the University of Guam (UOG) and the University of Hawai‘i Cancer Center (UHCC) that continues to advance cancer health equity, increase the cancer research and education capacity, and decrease significant cancer disparities in Pacific Islands Populations. Americans of Pacific Islander ancestry are a highly underserved and vulnerable minority with a disparate cancer burden, including significant underrepresentation among cancer and biomedical researchers and healthcare providers, which further exacerbates the disparities. The overarching goal and long-term objective are to promote cancer health equity and mitigate the impact of cancer on Pacific Island Populations through increasing cancer research leadership and capacity in Hawai‘i, Guam and the United States Affiliated Pacific Islands, which comprise the Pacific Island Populations addressed by this project. As the only National Cancer Institute-funded Partnership serving the underrepresented Pacific Island region, PIPCHE will accomplish its goals through the following specific aims: (1) Continue to develop a diverse portfolio of Pacific Island Population-focused cancer research projects that include clinical, basic, and population health sciences, (2) Collaborate with local and regional Pacific Island community organizations that work with underrepresented Pacific Island Populations to promote cancer health equity and enhance opportunities for research training and workforce development, (3) Sustain, strengthen, and continuously evaluate of all the Partnership’s research, core activities, and research education programs, (4) Enhance and implement evidence-based, relevant, cancer-related public health interventions and cancer, prevention and control strategies with and within underrepresented communities, and (5) Expand the scientific collaboration among PIPCHE members and other faculty within the two institutions, with an emphasis on recruiting Early Stage Investigators of Pacific Island ancestry. PIPCHE will carry out these aims by continued investment in four Cores (Cancer Outreach, Research Education, Planning and Evaluation, and Administration), which provide the infrastructure and governance of the Partnership. The proposed Shared Resources (Biostatistics, Epidemiology, Information Technology, and Cancer Registry) will provide essential technical and scientific support to the PIPCHE student scholars, trainees, and the proposed full research projects and pilot projects that specifically address the cancer disparities of the Pacific Island Populations. Using its arc of cancer equity, PIPCHE has identified 10 major domains (education/health literacy, policy, environment, lifestyle, culture/community, biology, treatment, healthcare access, psycho-social, and socio-economic status) that influence Pacific Islander cancer health disparities/equity. Each of the research projects, cores, and infrastructure affects one or more of the domains, and therefore knowledge about the action of PIPCHE’s work is value added and helpful, as individuals as a team, while working towards Pacific cancer health equity.

NIH Research Projects · FY 2026 · 2007-06

The John A. Burns School of Medicine of the University of Hawaii proposes to continue to develop the Pacific STEP-UP Program to provide research training and mentoring to high school students interested in health sciences in the State of Hawaii, and the six US and US affiliated territories in the Pacific (Region E). For the past 5 years, Pacific STEP-UP has enrolled 104 students in the NIDDK STEP-UP summer program, and exposed other students to laboratory sciences during the school year. We continued to build capacity for laboratory research in the Pacific colleges where there was none before us. We tracked 375 STEP-UP alumni from as early as 2005 to find that a majority pursued college education with a science emphasis, and many also sought post-graduate training and terminal degrees. Pacific STEP-UP remains the only formalized hands-on research training program for high schools in the US Pacific, amid the urgent need to build and foster a pipeline of individuals seeking health research careers in order to combat major health issues in this region of the world. With confidence that Pacific STEP-UP has established roots in the region, we will continue our research training and mentoring program but charting a new course under framework of One Health. The new strategy and approach in research training, mentoring, and in capacity building will further NIDDK STEP-UP’s reach into the Pacific communities by bringing awareness of the interdependency of the well beings of humans, animals, and their environment; and their impact on health-related issues. The goal is to seed and shape scientific views and interests that value One Health research as the means to address pertinent health issues in these communities, and grow a cadre of scientists readied to research for solutions. In doing so, we will fulfill NIDDK’s STEP-UP mission to build a pipeline of future scientists interested in tackling health and disease questions related to NIDDK from multiple angles and multi-disciplinary approach under One Health. Accordingly, we propose three Specific Aims. (1). Recruit best qualified high school students (11th and 12th grade) from the seven US State and Territories in the Pacific into the STEP-UP Summer Research Program, and track the cohort’s academic progress for a minimum of 5 years. (2). Provide individualized research experience (and related education and training) that stresses One Health approach, local community or population, and NIDDK mission relevance. Provide STEP-UP alumni with follow up, and research-focused, mentoring extending for 9 months. (3). Seed and nurture interests in One Health in high school students while strengthening local colleges’ capacity to enable laboratory-, field-, and community-based research with a focus on One Health concepts, all in support of the Pacific STEP-UP program by expanding application pool and research opportunities, and strengthening the research training program.

NIH Research Projects · FY 2026 · 2001-09

OVERALL SUMMARY The Hawaii Institutional Development Award (IDeA) Network of Biomedical Research Excellence (HI-INBRE) is a collaborative outreach partnership between the University of Hawaii at Manoa (UHM), the state’s Primarily Undergraduate Institutions (PUIs) and University of Hawaii Community Colleges (CCs). The long-term goals are to strengthen and expand the biomedical research capacity within the state of Hawaii, to nurture research collaborations within Hawaii and throughout the greater INBRE network, to enhance professional development of faculty and students at Hawaii INBRE partner institutions, and to provide research resources to partner institutions. In our current cycle (INBRE IV), we established new funding mechanisms for promising investigators at different career stages at the PUIs and CCs. These INBRE investigators were provided funds and strong mentoring, thereby establishing research programs within conventional teaching institutions. Another accomplishment of INBRE IV was the enhancement of hands-on research experiences and career enhancement activities for students throughout the Hawaii INBRE network. For the next cycle (INBRE V), we will build on these successes and strengthen the statewide network through targeted efforts to invest in research capacity and the diverse human potential of Hawaii INBRE partners. Hawaii INBRE V will focus on promoting effective data and resource sharing within the statewide network and the INBRE Western region, to build stronger collaborations between Hawaii INBRE and other research programs such as the Hawaii Centers of Biomedical Research Excellence (COBREs), and to enhance science and technological capacity of Hawaii’s workforce. With guidance from our Steering Committee and our seasoned External Advisors, we will accomplish the following specific aims: Specific Aim 1: To strengthen the biomedical research expertise and infrastructure of HI-INBRE participating institutions. Specific Aim 2: To provide support to postdoctoral fellows and faculty at participating institutions via our Developmental Research Project Program. Specific Aim 3: To provide student research experiences (SRE) at PUIs and CCs as a crucial first step in establishing a pipeline for these students to pursue biomedical research and workforce careers. Specific Aim 4: Expand and enhance a state-of-the-art Data Science Core to support Hawaii INBRE researchers and students

NIH Research Projects · FY 2025 · 1997-09

PROJECT SUMMARY/ABSTRACT With continued support from the National Institute on Minority Health and Health Disparities (NIMHD) through the RCMI U54 RFA-MD-22-002, the goal of Ola HAWAII is to improve minority health and reduce health disparities for those communities in Hawaii which suffer disproportionately in health outcomes and healthcare access. In the next five years, the objective of the Center is to lead and advance minority health and health disparities research in Hawaii. Ola means “health” and “to heal” in Hawaiian and HAWAII designates both our island homeland and our aspiration “Health And Wellness Achieved by Impacting Inequalities”. Specific Aim 1: Enhance institutional capacity to facilitate basic biomedical, clinical and behavioral research. a. Manage, coordinate and supervise Ola HAWAII activities and resource allocation. b. Develop and institute a plan for the dissemination of research findings, including health policy development through UHealthy Hawaii. c. Implement a rigorous evaluation process for continuous improvement. Specific Aim 2: Address health disparities and health-related concerns of underserved communities. a. Nurture trust-based collaborations with communities through capacity building and resource sharing to address community-identified, health-related concerns. b. Promote and facilitate community participation in all aspects of health disparities research, including dissemination of research outcomes to community, academic, and policy partners. Specific Aim 3: Mentor and support a diversified health disparities research workforce. a. Customize and expand the Pilot Projects Program to support post-doctoral fellows, junior faculty, and other early-stage investigators. b. Personalize and enrich the Mentoring Bootcamp Program to accelerate lead investigator research success. Specific Aim 4: Enhance the quality and productivity of health disparities and health-related research through world-class research facilities and services. a. Strengthen and sustain core facilities and resources. b. Expand and diversify core user base, capability, and reach. c. Implement a personalized Research Studio Program. Ola HAWAII will continue to be led by the MPI team of Jerris R. Hedges, MD, and Noreen Mokuau, DSW, who will work closely with an exemplary team to achieve the aims. By building on its successes and integrating innovative new approaches, Ola HAWAII will have a profound impact on health disparities research in Hawaii.