Grants for Healthcare Organizations

NICHD - Eunice Kennedy Shriver National Institute of Child Health and Human Development

Project Summary: The University of Rochester’s Golisano IDDRC fosters innovative and collaborative research efforts among multidisciplinary investigators. The center's primary goals include advancing basic and translational science to understand the causes and consequences of intellectual and developmental disabilities (IDDs), sustaining essential research infrastructure, building interactive research teams, attracting and training new investigators, fostering communication and collaboration, and promoting community outreach and education. The Golisano IDDRC operates through four scientific cores: Human Phenotyping and Recruitment (HPR), Translational Neuroimaging & Neurophysiology (TNN), Cell and Molecular Imaging (CMI), and Animal Behavior and Neurophysiology (ABN). The center also focuses on specific research clusters, including rare neurodevelopmental diseases, parental stress and early life exposure, neuroinflammatory mechanisms, autism spectrum disorder, and multisensory integration. The center's efforts are supported by an annual fund for IDD pilot projects and a commitment to evaluating progress and maximizing impact. Our objective is to leverage institutional resources and areas of expertise to optimize the efficiency, innovation, and quality of research to improve the lives of patients and families with IDD.

NIDA - National Institute on Drug Abuse

SUMMARY Despite the success of antiretroviral therapeutics (ARTs), they cannot eradicate HIV from reservoirs within the body, particularly those in the central nervous system (CNS). Moreover, opioids upregulate efflux transporters further promoting subtherapeutic concentrations of ART in the CNS. We have used biocompatible ionic liquids (ILs), molten salts comprised of asymmetric cations and anions, that can ‘tune’ the affinity of nanoparticles to different cell types. Using this strategy, we have developed an IL with a balanced affinity for erythrocytes and microglia which promotes nanoparticle ‘hitchhiking’ on erythrocytes to deliver them to the brain, and cells- selective targeting of microglia once delivered to the central compartment. Preliminary data in rats demonstrate ~48% of injected nanoparticles accumulating in the brain within 6 hours, a vast improvement over current nanoparticle delivery strategies. Preliminary analyses indicated that over 90% of CNS nanoparticles were associated with microglia. We have further demonstrated the capacity to load ART (abacavir) into nanoparticles which retained antiviremic efficacy when administered to HIV-infected human peripheral blood mononuclear cells (PBMCs). We hypothesize that we can further improve the tunable profile of our IL formulation to optimize cargo delivery to the brain and target additional cell types (including astrocytes). We anticipate that this cargo delivery strategy will be safe and efficacious in spite of CNS cell adhesion/transporter changes promoted by opioid exposure/dependence. To this end, we will (Aim 1) generate at least 5 novel ILs, in addition to our current lead, with varied cell-type affinity. We will confirm the preference that ILs confer to simian and human blood components as potential cargo carriers. (Aim 2) We will assess the safety (subacute, acute, subchronic, reproductive, mutagenic) and biodistribution of up to 5 novel ILs in rats that are opioid-naïve or opioid-dependent. ILs will be loaded with a premade scramble Cas9 vector with an eGFP reporter to confirm the capacity to deliver CRISPR-Cas9 constructs for potential HIV cure strategies. Safe ILs with a CNS-favorable biodistribution will be loaded with cART (abacavir, dolutegravir, and lamivudine) and assessed for efficacy in SIV-infected or HIV- infected simian or human PBMCs, respectively, or human microglia. All cells will be opioid-naïve or opioid- exposed. ILs with selectivity for microglia and astrocytes will be prioritized. (Aim 3) IL leads (based on CNS distribution and microglial/astrocytic selectivity) will be assessed for in vivo safety, biodistribution, and acute efficacy in a rhesus macaque model of SIV. In macaques, IL-assisted nanoparticles will be loaded with nanogold, in addition to cART, to confirm the time-course of biodistribution via X-ray. SIV infection will be monitored via CSF and blood draws. Complete blood count, chemistry, and cytokine profiling will be conducted on plasma and/or CSF. ART distribution will be confirmed via LC/MS. Gross histopathology will be conducted on organs and CNS tissues will be additionally assessed for microgliosis, astrogliosis, and sublethal neuronal damage. IL- assisted nanoparticles may realize the goal of achieving safe, cell-specific, CNS drug/cargo delivery.

NIMHD - National Institute on Minority Health and Health Disparities

ABSTRACT The goal of this SBIR by Health Tequity LLC is to develop and assess usability of ACTIVATE artificial intelligence accessibility engine (AIA) for multi-language mobile apps and voice navigation for chronic illness. ACTIVATE AIA makes digital care coordination accessible to improve self-management and outcomes. Problem: Chronic illnesses such as diabetes mellitus and hypertension affect millions of people worldwide and adversely impacts medically low-resourced populations. Digital care coordination programs and remote patient monitoring (RPM) can improve chronic illness care. Yet, challenges remain for low-resourced populations including device access, digital health literacy, clinic staff and providers with digital experience, and programs adapted to culture and setting. Accessibility of digital health for those who speak languages other than English, have vision and manual dexterity challenges, or have low literacy is an unmet need. Almost 68 million people in the US only speak a language other than English. Language translation and voice navigation would make digital care coordination accessible. Solution: The product of this SBIR will be a new ACTIVATE AIA prototype in three languages, English, Spanish, and Tagalog (using a hypertension use case). Patients use myACTIVATE mobile app in their preferred language to connect to a commercially-available blood pressure cuff and automatically transmit data to the community health center, navigate the app by voice, and view and have data read out to them in language. There are few available multi-language, patient-focused care coordination applications that are connected to healthcare providers and even fewer that support voice navigation for accessibility. ACTIVATE AIA fills this gap through these Specific Aims: Aim 1. Develop an artificial intelligence accessibility engine (AIA) for multi-language voice navigation. AI translation models for English, Spanish, and Tagalog will be fine-tuned and the AIA prototype for voice navigation assessed with feasibility performance metrics delivered by month 3. Aim 2. Produce a multi-language myACTIVATE app with voice navigation. Developed JSON function calls and ACTIVATE platform integrations to produce functional English, Spanish, and Tagalog apps with AIA voice navigation by month 4. Aim 3. Conduct Human-Centered Usability Study of myACTIVATE with AIA. Usability assessed among varied patients, providers, and staff (n=24) in California and Hawaii CHCs with System Usability Scale and in-depth, semi-structured interviews by month 6. ACTIVATE AIA will bring accessibility to low-resourced communities to improve chronic illness care and self-management. Investment in AIA commercialization will help scale the initial breakthrough health outcomes of ACTIVATE to many communities that are impacted by health disparities potentially impacting millions of people with chronic illness, improving self-management, and reducing cost to the health system.

NIGMS - National Institute of General Medical Sciences

Abstract Accurate determination of protein–ligand interactions fundamentally shapes drug discovery, directly influencing lead optimization and therapeutic development. Despite advances in X-ray crystallography and cryogenic electron microscopy (Cryo-EM), traditional refinement methods still struggle significantly with intrinsic disorder, flexibility, and conformational heterogeneity. Approximately 69% of Protein Data Bank (PDB) structures contain missing or unresolved residues, especially at resolutions worse than 2.75 Å. This pervasive issue severely limits structural accuracy, particularly for complex, therapeutically critical modalities like macrocycles, PROTACs, cyclic peptides, covalent inhibitors, and metal-containing ligands. Moreover, the accuracy of AI-driven structure prediction models (e.g., AlphaFold, OpenFold) strongly depends upon high-quality experimental data, highlighting the urgent need for improved, ensemble-based structural refinement. Conventional refinement protocols predominantly rely on single-conformer assumptions and simplified stereochemical restraints, frequently missing critical alternative binding modes and ligand-induced structural changes. Simulated annealing (SA) methods help avoid local minima but typically converge on single optimized structures, inadequately capturing true biological flexibility. Conversely, ensemble refinement (ER) explicitly models structural heterogeneity through simultaneous multi-conformer refinement, capturing relevant functional states. However, existing ER implementations generally employ simplistic force fields and basic molecular dynamics (MD), limiting their accuracy, efficiency, and pharmaceutical utility. To overcome these limitations, we propose a novel, unified X-ray/Cryo-EM pipeline integrating our robust, linear-scaling quantum mechanics/molecular mechanics (QM/MM) engine (DivCon), advanced density-driven conformational sampling (including omitted loop and sidechain completion and protonation state determination), automated protomer/tautomer enumeration, and real-space Z-score density difference (ZDD) scoring (XModeScore). Crucially, this new platform will incorporate an integrated GPU-accelerated molecular dynamics engine supporting enhanced MD sampling (e.g., replica exchange, metadynamics, accelerated MD), occupancy/B-factor refinement, and rigorous clustering to efficiently capture biologically relevant conformational dynamics. Commercially, our approach directly addresses longstanding pharmaceutical pain points related to structural ambiguity and disorder, providing chemically realistic, actionable structural ensembles suitable for improved drug design. By automating ligand and protein preparation, rigorously modeling challenging drug modalities, and capturing genuine conformational flexibility, our pipeline surpasses current platforms in structural fidelity, predictive accuracy, and practical applicability to modern therapeutic discovery.

NIDDK - National Institute of Diabetes and Digestive and Kidney Diseases

Abstract Myelodysplastic syndromes (MDS) are a group of diverse malignant hematological disorders that originate from hematopoietic stem cells (HSCs). Increased levels of reactive oxygen species (ROS) and DNA damage are commonly detected in hematopoietic cells from MDS patients. An elevated level of ROS, generated from either endogenous or exogenous sources including oncogene activation, leads to loss of quiescence and self-renewal of HSCs. ROS-induced DNA damage speeds up the aging process of stem cells and contributes to the mutagenesis associated with cancer development. m6A RNA methylation plays a significant role in multiple biological processes by introducing another layer of post-transcriptional regulation of gene expression within cells. The goal of this project is to elucidate the significant role of ALKBH5-mediated epigenetic regulation in the maintenance of genomic stability in hematopoietic stem/progenitor cell (HSPCs) during oxidative stress, and how deregulation of ALKBH5 contributes to promotion of leukemic transformation of HSPCs in the initiation and development of MDS. We found that ROS significantly increased global m6A RNA methylation in human cell lines, and that the elevation of m6A mRNA methylation is required for rapidly repairing ROS-induced DNA lesions and preventing cell death. Interestingly, we found that ALKBH5, the m6A RNA demethylase, is responsible for ROS-induced elevation of m6A mRNA methylation. ROS induced post- translational modification of ALKBH5, and inhibited the demethylase activity of ALKBH5. We showed that forced expression of ALKBH5 inhibited ROS-induced m6A mRNA methylation and significantly delayed repair of ROS-induced DNA damage. Thus, we hypothesize that aberrant expression of ALKBH5 disrupts HSPC functions by negatively influencing genome integrity and survival of HSPCs, thereby contributing to leukemic transformation of HSPCs during the initiation and development of MDS. In this proposal, we will determine 1) the role and underlying mechanism of ALKBH5 in the maintenance of genomic stability in HSPCs in response to oxidative stress; 2) the effects of ALKBH5/Alkbh5 overexpression on the maintenance of mouse and human primary HSPCs during ROS stress in vivo; and 3) whether ALKBH5/Alkbh5 is required for the maintenance of pre-leukemic stem cells (pre-LSCs) in MDS. Our study will provide new insights into novel mechanisms of MDS development and epitranscriptional regulation of gene expression in HSPCs in response to oxidative stress. Additionally, our study will provide the first set of evidence to support a significant role of ALKBH5- mediated m6A mRNA demethylation in the maintenance of normal HSPCs and pre-leukemic stem cell (pre- LSCs).

NCATS - National Center for Advancing Translational Sciences

In CTSA 3.0, we will continue our relentless pursuit to transform clinical and translational research in southeastern Wisconsin and the science of clinical and translational (CT) research. We remain focused on and committed to expansion of an engaged, knowledgeable, and high performing CT workforce, refinement of proficient and innovative infrastructure to support CT research and science and removing all impediments to the performance of research. Our long-standing mission to foster a borderless, collaborative, and synergistic research and research training environment for our multi-institutional translational workforce, our community stakeholders and health system members to advance the clinical/translational science research and improve the health of our community, our nation, and beyond continues to drive our direction. We remain committed to working within the CTSA consortium to learn from our colleagues across the nation and to contribute to the growing body of knowledge in the CT field. The tri-lateral mutually learning ecosystem formed by our workforce, the community, and the health system shapes the framework for strategically moving forward and has led to the concept developed in this application of integrated clinical and research ensembles (ICREs) in which patients, clinical investigators, translational researchers, health system representatives, community members, basic scientists, clinicians and others are brought together. We will further expand our outreach into the communities we serve and will incorporate CT research across the life span. In the end, our goal is to use our hard-earned experience and extended capabilities to address the health needs of our patients and our community while persevering to advance our infrastructure and workforce development programs to meet the standards of the developing field of translational science and research.

OD - NIH Office of the Director

PROGRAM SUMMARY The objective of our LAUNCH program is to continue our global health research training program called the Global Health Emerging Scholars (GHES) designed to create a new community of researchers, educators, and professionals who are prepared to address new and emerging global health challenges. We will build on the last nine years of this training program to create a cadre of new researchers who will dedicate their careers to address the health problems that arise out of the human conditions prevalent in informal settlements (slums) in urban and rural areas. Rather than focusing on individual diseases, we aim to train scholars in a comprehensive, integrated, and multidisciplinary approach to addressing health challenges in informal settlements. This approach has been developed over many years through collaboration among faculty from the four U.S. partner institutions—Yale University, Stanford University, the University of Arizona, University of California, Berkeley, and Harvard University—led by global health research leaders with over a decade of collaboration. Together, core faculty mentors from these institutions conduct research at 25 institutions in 20 countries in Africa, Central and South America, the Caribbean, Asia, the Pacific, and Eastern Europe. The GHES program will address a wide range of health research topics including HIV/AIDS, emerging and high-consequence infectious diseases, non- communicable diseases (NCD), environmental health, mental health, interpersonal violence, substance use, and injuries, all within the framework of informal settlements health. Training will target US postdoctoral fellows and pre-doctoral students and low- and middle-income country (LMIC) postdoctoral fellows. We will recruit 9-10 trainees/year with 60% of them as US postdoctoral fellows. Trainees will spend 8-12-months at an LMIC site under the supervision of the Consortium and their collaborating LMIC mentors. Didactic workshops on global health research methods will be conducted both in-person and online. LMIC trainees will spend 2-3 months at US institutions to undergo training in methods not provided at their institutions. All trainees will be provided with research and career mentorship throughout their training and tracked for career development after completing their GHES-supported research work. This program exposes trainees to a key global health theme—diseases in at-risk populations in informal settlements, both urban and rural, and offers them the opportunity to become experts in this emerging discipline. Ultimately, the program will cultivate a new generation of global health researchers and leaders equipped to tackle the growing health challenges in impoverished communities across LMICs.

NCI - National Cancer Institute

This proposal requests partial support for the 2025 Cancer Cachexia Conference (CCC). The conference will be organized by the Cancer Cachexia Society (CCS), and hosted in Turin, Italy from September 25-27, 2025. Cachexia is present in a significant number of patients at their time of cancer diagnosis and ultimately affects approximately 75% of patients with advanced disease of any tumor type. Cachexia decreases physical function, functional independence, and quality of life - causing considerable patient and family distress. Cachexia also predisposes patients to illness, increases treatment toxicity, reduces treatment efficacy, and decreases survival, with cachexia estimated to be causative in 30% of cancer deaths. Though emerging evidence suggests this number may be much higher. The overall goals of the conference are to foster awareness, understanding, and research of cancer cachexia among scientists at all career stages, clinicians, patients, and caregivers, for the purpose of advancing identification, current management, and future treatment, for this major unmet medical need. The CCC serves as the major conference to help grow this awareness and research around cancer cachexia and remains the only conference devoted solely to this topic. Indeed, other cachexia-related conferences cover a broad array of topics including aging, sepsis, covid, chronic kidney disease, obesity therapy, cardiovascular disease, burn injury, critical illness myopathy, as well as cancer. Importantly, although there has been previous iteration of the CCC, each conference is unique in focusing on new topics within the rapidly evolving cancer cachexia field. In this regard, the 2025 CCC will include several new sessions and speakers and cover topics within the scope of the Division of Cancer Biology’s scientific branches, including a double session on how the tumor microenvironment, tumor metastasis, and immunology impact cachexia, an expanded session on integrated and systems biology (inter-tissue crosstalk) and cachexia, as well as new sessions on central regulation systems of feeding and metabolism in cachexia, and emerging topics including pediatric cancer cachexia. The 2025 CCC will also include a dedicated session on current management strategies for cachectic cancer patients that will be recorded and made publicly available. These novel sessions and topics will be covered whilst simultaneously providing speaking opportunities, training and mentorship for graduate students, postdoctoral associates, physicians in training and early-stage investigators. The impact of this 2025 Cancer Cachexia Conference will be to promote new progress and growth in the clinical investigation of anti- cachexia therapies and to strengthen education and research in cancer cachexia.

NCI - National Cancer Institute

PROJECT ABSTRACT Significant advances in global health have been achieved in recent decades. Yet, serious variances in health outcomes persist, especially among children, adolescents and their adult caregivers. Sub-Saharan Africa (SSA) is one of the regions disproportionately burdened by multiple health threats, including endemic CDs; emerging and re-emerging infectious diseases; increasing incidence of NCDs, and a set of exacerbating factors that have contributed to poor public health and increased overall disease burden affecting children, adolescents and their adult caregivers. Similar trends are documented in several other LMICs, including countries in Asia and Eastern Europe. In light of widespread health challenges and gaps in the translation and uptake of scientific evidence in real-world settings in LMICs, dissemination and implementation science can advance timely and context- specific public health solutions. Moreover, significant methodological advances in data science can create new opportunities to more accurately identify sensitive populations, better understand patterns and mechanisms of health burdens, and allow for more in-depth analysis of implementation gaps and imbalances in healthcare systems and across populations in LMICs. The proposed research training program, entitled “ACHIEVE: Addressing the Research Capacity Gap in Global Child, Adolescent & Family Health Utilizing Implementation and Data Sciences”, focuses on increasing dissemination and implementation science and data science capacity to address global health issues affecting children, adolescents and their adult caregivers. The program addresses the following specific aims: Aim 1: To provide a research training program to five cohorts (~50 trainees) of health care professionals and post-doctoral trainees from the U.S., and post-professional degree graduates from SSA that equips trainees with dissemination and implementation and data science research skills and knowledge through experiential learning, mentoring, “hands-on” immersion in global health implementation and data science research and methodologies, individualized consultation, goal setting and monitoring and web- based support across time; Aim 2: Bring together an interprofessional network of committed mentors from the global north and the global south to promote bi-directional learning and collaboration and ensure quality training for promising new investigators committed to applying dissemination and implementation science and data science research methods to address health gaps impacting children, adolescents, and their families in low-resource settings; Aim 3: To examine the short-term and longitudinal outcomes of the ACHIEVE training program; and Aim 4. Delineate key factors that underlie successful mentorship and training of new investigators– with potential implications for new investigators who are focused on dissemination and implementation science and data science research that seek to address health gaps impacting children, adolescents, and their adult caregivers.

NINDS - National Institute of Neurological Disorders and Stroke

Project Summary This supplement will enable the continued progress of the parent project to develop an AAV gene therapy product for the treatment of mucopolysaccharidosis type IIIB, a disease for which there is no current treatment. Specifically, this supplement performs the process and analytical development to optimize production methods and release criteria for tcm8AAV-coNAGLU as a drug substance prior to cGMP manufacture of the drug product. We will transition production to a suspension platform in order to scale up production volume consistent with the needs of a commercial product. This portion of the aims of the parent project were originally to be performed by the NIH BPN biologics contract development and manufacturing organization (CDMO) during the first and second year of the project, however, changes at NIH have prevented contracting with a CDMO to begin this process. We have the capacity to perform non-GMP virus manufacturing runs to optimize production methods and release criteria; develop master and working cell banks; develop reagent lists and protocols for production; and establish process and analytical methods development supporting characterization of tcm8AAV-coNAGLU (+/-CpG dep) drug substance. We did not have this capacity when the parent grant was submitted and did not budget for this or propose to do these functions at our institution but to have them done by NIH through the CDMO in accordance with the aims of the grant. In order to reach the milestones of the parent project, the process and analytical methods for scale up of tcm8AAVco-NAGLU production must be completed by year 3 in order to allow GMP grade manufacture during year 3 of sufficient quantity of drug substance for GLP toxicology starting in year 3. In cooperation and agreement with the lead development team participants from NIH and the NIH consultants, a statement of work for the planned CDMO contract was assembled. The University of Florida Powell Gene Therapy Center has created a Process and Analytical Development Group and hired scientists with industry experience in commercial AAV vector production to allow us to perform the project specific Process and Analytical Development at UF and at considerably less cost than is anticipated from CDMO bids. Specific aim 1: Perform non-GMP virus manufacturing runs to optimize production methods and release criteria; develop master and working cell banks; Develop reagent lists and protocols for production. Specific Aim 2: Establish process and analytical methods development supporting characterization of tcmAAV8-coNAGLU/CpGdepcoNAGLU drug substance (DS) and drug product (DP).

NIGMS - National Institute of General Medical Sciences

No change from the original submission.

NIMHD - National Institute on Minority Health and Health Disparities

PopCom Health seeks to design and develop an interactive, customizable digital health promotion comic tool for Black/African American (AA) and Latino preadolescents to reduce childhood obesity (OB) risk. Childhood OB continues to be a serious public health issue in the US, with economic, physical, and psychosocial consequences. Over the last three decades, the rate of childhood OB has tripled, with more than one-third of 6 to 19-year old children now considered having overweight or OB, with high rates in low-income groups. This epidemic has profound consequences leading to adverse health outcomes, such as type 2 diabetes, cancer, and increased risk of adult morbidity and mortality. OB can detrimentally impact children’s social and emotional well-being and has been associated with poor academic performance. To help improve the health of future generations, effective and engaging interventions are needed to capture children’s attention in a multi-media environment. We have created a family-centered, interactive, web-based health promotion comic tool focused on reducing childhood OB risk in low-income Black/AA and Latino pre-adolescents under an R21 study funded by the Agency for Healthcare Research and Quality (AHRQ). Results of a 6-week intervention pilot feasibility study were encouraging: the tool was feasible to deliver and acceptable to the child and parent populations, and children receiving the comic tool demonstrated more significant improvements (p<0.05) in vegetable, water, and sugar intake compared to the control group, from pre- to post-intervention. While these results are promising, we found that engagement with the tool diminished over time and improvements in psychosocial variables related to dietary behaviors (i.e., attitudes, behavioral intention, self-efficacy, outcome expectations) diminished at the 3-month follow-up. Building on our previous work, PopCom Health seeks to design an enhanced interactive, culturally relevant and customizable health promotion comic tool for Black/AA and Latino children ages 8 to 12, in which children’s choices affect the storyline and health content. We predict this format will lead to increased engagement with the tool and thus, empower children and improve their attitudes and beliefs related to dietary and physical activity (PA) behaviors. Recognizing caregivers’ role on children’s habits, parents will also receive newsletters reinforcing healthy dietary and PA behaviors at home, which had been developed during the R21 study. The tool will be evaluated remotely through the following Phase I Specific Aims: 1) Design, develop and evaluate the usability of a customizable, 6-week interactive comic structure; 2) Using a three-group pilot randomized controlled trial: a) assess engagement and acceptability of the new comic structure, and b) explore the association between engagement and self-efficacy related to dietary and PA behaviors. Validation of tool engagement will lay the groundwork for Phase II studies to evaluate longer- term effects and the ability of our tool to reduce childhood OB risk and improve dietary and PA behaviors in our target populations.