Search Grants — Free, No Account Required

NIDA - National Institute on Drug Abuse

Project Summary Drug use increases HIV risk and worsens health outcomes in people living with HIV (PLWH). While antiretrovirals are effective for both prevention – using pre-exposure prophylaxis (PrEP) – and for treatment – using antiretroviral therapy (ART) – drug use further impairs medication adherence. It is thus essential to develop strategies to enable people who use drugs to achieve abstinence and prevent relapse, which is expected to reduce HIV risk, burden, and infection. Progesterone and its metabolites regulate drug craving and immune function, making them potential therapeutic targets. However, PLWH and people who use drugs often experience menstrual cycle disruptions, and the impact of PrEP or ART on hormone regulation remains unclear. Understanding these interactions could reveal strategies to reduce drug-seeking behavior and to improve HIV treatment outcomes. In our preclinical work using the EcoHIV mouse model of HIV infection, we observe disrupted estrous cyclicity, altered cytokine expression, and increased risk for cocaine relapse-related behavior. We further observe that ART restores estrous cyclicity and partially reverses altered brain cytokine expression in EcoHIV-infected mice. However, it is unknown whether ART restores cycle regularity in cocaine-exposed, EcoHIV-infected mice or whether PrEP interacts with drug exposure to affect hormonal function. The medial preoptic area (mPOA) regulates both estrous cyclicity and cocaine-related behavior, and our findings suggest EcoHIV infection increases mPOA activation in cocaine-exposed females. Progesterone and its active metabolite, allopregnanolone, act on both neurons and astrocytes. Thus, modulation of mPOA astrocytic and neuronal activity may represent a novel target for reducing drug seeking and neuroimmune dysregulation among those at risk of or living with HIV. This proposal will test the overarching hypothesis that chronic drug exposure and EcoHIV infection interact with antiretrovirals to promote estrous cycle irregularity and cocaine reinstatement via dysregulation of the mPOA. Aim 1 will assess how PrEP and ART impact estrous cyclicity, ovarian reserve, mPOA cellular activity, and neuroimmune signaling following chronic cocaine exposure. Aim 2 will use chemogenetic tools to determine the role of mPOA discrete populations of astrocytes and neurons in cocaine reinstatement after PrEP or ART+EcoHIV. Aim 3 will evaluate whether allopregnanolone administration reduces cocaine reinstatement and alters neuroimmune signaling. Together, these Aims are to expected define the mPOA as a mediator of drug seeking and immune state following treatment with antiretrovirals, and further to identify hormonal strategies to suppress relapse in individuals taking PrEP or with virally suppressed HIV infection.

Houston Endowment

Houston Endowment ($2.0B in assets) supports nonprofits in TX through grants focused on education, arts, environment, community development. Awards range from $5,000 to $400,000.

NCI - National Cancer Institute

PROJECT SUMMARY Pancreatic ductal adenocarcinoma (PDAC) will become the second leading cause of US cancer-related deaths by the year 2030. Primary PDACs are encased within a densely fibrotic, nutrient poor (“desmoplastic”) stroma enriched with extracellular matrix, fibroblasts, and immune cells. In contrast, distant metastatic PDACs grow rapidly within a nutrient replete, loosely fibrotic stroma. The project objective is to define those fundamental TME differences and the fibroinflammatory signaling networks that govern them. The hypothesis is that PDACs remodel metastatic TMEs into a loosely fibrotic, immunodeficient stroma by suppressing pathways that yield fibroinflammatory cytokines. This hypothesis will be tested by two specific aims. Aim 1: Define key differences between primary and metastatic TMEs. Primary versus metastatic TMEs will be interrogated in humans and mice by (1) scoring key histopathological TME parameters across hundreds of primary and metastatic PDAC patient tissue samples; (2) quantifying tumor: stroma cell lineage abundances and communication networks using single cell RNA-seq datasets from PDAC patients; (3) flow cytometric sorting of cell lineages that comprise primary and metastatic TMEs in gold standard PDAC mouse models. The goal of Aim 1 is to discover TME determinants of divergent clinical behaviors and biological properties between primary tumors and distant metastases. Aim 2: Evaluate mechanisms that remodel metastatic TMEs. Genetic and pharmacological gain- and loss-of-function approaches will determine if (1) suppressing inflammatory signals depletes primary tumor fibroinflammatory cytokines from metastatic secretomes; (2) (re)- introducing those cytokines back into metastatic secretomes triggers a desmoplastic stromal response that restrains distant metastatic outgrowth; (3) depleting those cytokines from primary tumor secretomes remodels the desmoplastic stroma to facilitate distant metastatic spread. The goal of Aim 2 is to identify and functionally characterize primary tumor fibroinflammatory signals that are reprogrammed to facilitate distant metastasis. These studies will positively impact cancer research by concretely demonstrating how primary and metastatic TMEs diverge from one another and illustrating precise mechanisms that drive such divergences. The findings are expected to conceptually advance our understanding of cancer progression and rationally inform therapeutic strategies against primary and metastatic tumors, even within the same individual patient(s). This research will be conducted as part of an MD-PhD dual degree fellowship training plan at the University of Miami Miller School of Medicine Medical Scientist Training Program (UMMSM MSTP). The UMMSM MSTP training environment includes access to theoretical and technical instruction, physician scientist mentors, and state-of-the-art facilities for these studies. This proposal seeks to prepare for a training goal of becoming a physician scientist in the field of oncology.

NIA - National Institute on Aging

A. Project Summary: Hematopoiesis is the process where a self-renewing, multipotent hematopoietic stem cell (HSC) produces all the differentiated cells in the blood system. Careful regulation of hematopoiesis by HSCs is required to meet the evolving demands of the body throughout life. To maintain lifelong hematopoiesis, HSCs must retain their ability to self-renew, i.e. to divide without differentiating, and their multipotency, which is their ability to differentiate into all blood cells. However, aging HSCs often develop reduced self-renewal capacity and myeloid biased differentiation potential which may lead to immune deficiencies and other blood disorders. Aging HSCs can also acquire mutations, expand, and produce clonally restricted blood cells through a process called clonal hematopoiesis (CH), which has been associated with an increased risk of developing cardiovascular disease and cancer. The clonal HSCs that produce CH (CH-HSCs) are also functionally heterogeneous as individual CH-HSCs have variable impairment in blood cell production. Additionally, emerging evidence has shown that inflammation can further modify HSC and CH-HSC function. Overall, these observations suggest that aging HSCs become increasingly heterogeneous in humans, and the associated impact of this heterogeneity on hematopoiesis is largely unknown. Our understanding of HSC biology has primarily been driven by important observations made in mice. However, it is unclear if aging human adult HSCs mirror the same functional changes as mice. A key limitation in understanding how human adult HSCs maintain homeostatic hematopoiesis is our in-ability to purify and study specific sub-populations within the human HSC pool. This limitation has led to several important questions. For instance, are there myeloid biased HSCs that expand in older humans, and can they be depleted to restore balanced hematopoiesis as observed in mice? How exactly do aging HSCs become clonally restricted and deregulated under the external pressure of inflammation? Do CH- HSCs express unique biomolecular features that distinguish them from healthy HSCs? To address these questions, this proposal will investigate the cellular heterogeneity of aging adult human HSCs with the hypothesis that there are unique features associated with clonal HSC expansion during aging which can be exploited therapeutically. Guided by strong preliminary data and new state-of-the-art single cell methods, the central hypothesis will be tested by pursuing three specific aims. The first aim will investigate human adult HSC heterogeneity through aging. The second aim will investigate how inflammation impairs aging HSC function and whether inhibiting DAPK1 can mitigate these effects. The third aim will study the role of DAPK1 on HSC function and fitness. This contribution will be significant because it will ultimately uncover important information on HSC heterogeneity as it relates to human health and disease and evaluate a novel target for treating hematologic disorders of the elderly. These results can be used to optimize HSC directed translational research, disease monitoring and therapeutic development.

NIAID - National Institute of Allergy and Infectious Diseases

Project Summary Human humoral immunity is mediated by individual B cells endowed with unique antigen receptors. Following antigen engagement, these cells undergo clonal expansion and differentiation into antibody secreting cells (ASC) and memory B cells (Bmem). During immune responses, B cells undergo somatic hypermutation which changes the genes encoding their antigen receptors, a process that when coupled with selection within germinal centers (GC) improves the quality of their B cell antigen receptors (BCR), typically resulting in higher affinity. Following most productive immune responses, expanded clones undergo a contraction phase reducing their numbers. Within the T cell compartment, chronic antigen exposure to antigen maintains increased frequency of clones, resulting in oligoclonality and a reduction of antigen receptor diversity within the global repertoire. Oligoclonal expansions have been observed in the B cell compartment of older adults as well, however the mechanisms responsible for this effect are not known. Serum antibodies reactive with a wide array of carbohydrate determinants are present in all humans, as are B cells reactive with these carbohydrate structures. In contrast to commonly evaluated B cell specificities that encompass antigens encountered intermittently throughout an individual's lifetime, anti-carbohydrate (AC) responses are driven by glycan determinants derived from the commensal microbiota. Accordingly, these antigens are never `cleared' and are continuously available for immune activation. The effect of this chronic antigen exposure on the AC B cell repertoire is not known. As ACAs are the products of B cells that undergo immune activation including GC involvement, somatic mutation, affinity maturation, and differentiation, we hypothesize the AC-repertoire is subjected to recurrent selection promoting the activation and expansion of only a few clones, thereby becoming increasingly oligoclonal in aged adults. The proposal is focused on evaluating the repertoire, Ab binding properties, and the auto-reactive and anti-microbial potential of the AC repertoire directed at the two most frequently targeted carbohydrates in healthy humans across 6 decades of the human life span. We are using state-of-the-art antigen-specific B cell isolation, BCR sequencing, cloning, and expression to evaluate the diversity and binding properties of the human AC repertoire. We are combining these technologies with high-dimensional cytometric antigen arrays, serum Ab fractionation, functional Ab, and transcriptomic assays to determine changes that occur within the ACA-repertoire across the human lifespan. Our efforts to elucidate the effects of chronic antigen exposure of microbial antigens on the human B cell immune system will illuminate mechanisms causing age-associated loss of B cell repertoire diversity and accompanying immunosenescence.

NIAID - National Institute of Allergy and Infectious Diseases

Program Director/Principal Investigator (Bell, Thomas, J): Project Summary The overarching objective of this proposal is to continue the development of the Human Tissue and Organs for Research Resource (HTORR) as the foremost, project-driven human tissue research resource for organs and tissues for Principal Investigators (PIs) studying the full extent of human biology and disease states across all body systems. Using a project-driven biospecimen collection approach, HTORR provides a diverse range of biospecimens for these studies, such as whole organs, anatomical structures, fluids, tissues, and cells. HTORR’s innovative 360° feedback model spearheads the advancement of HTORR’s scientific tissue collection framework via providing continuous feedback across three foundational pillars of the program: 1) Scientific Support, 2) Sample Diversity, and 3) Career Development of Principal Investigators (PIs). Our pillars identify, define, and align all key foundational elements in the model along with providing a malleable framework for HTORR to evolve in tandem with the NIH’s high priority scientific needs as well as the emerging experimental methodologies of the research community. Relevance: The Human Tissue and Organs for Research Resource (HTORR) is a comprehensive research resource that enables investigators from multiple research fields and disciplines to utilize human biospecimen derived experimental model systems to rigorously study human organ, tissue and cellular function. HTORR provides state-of-the-art research services to support emerging experimental methodologies and new discoveries in human biology, physiology and disease. OMB No. 0925-0001/0002 (Rev. 03/2020 Approved Through 02/28/2023) Page Continuation Format Page

NIMH - National Institute of Mental Health

ABSTRACT The dynamics of HIV infection in the brain is poorly understood. Infected cells that transport HIV across the blood brain barrier and into the brain causes inflammation and subsequent damage to resident brain cells. This manifests as a group of symptoms collectively referred to as HIV associated neurocognitive deficits (HAND). Today, in the post ART era, HAND consists of mild to moderate symptoms. This research is significant because it uses an in vivo model to assess the unique interactions among brain cells and peripheral immune cells in vivo in an HIV infected ASRT treated model. Results from these studies will give a better understanding of the events that define neuroHIV in the ART era.

InterIm CDA

ICDA and community are creating public art, interpretive installations, a new community gathering place, neighborhood walking tours, and more to honor beloved and legendary community leader, Bob Santos at Uncle Bob's Place, Interim's newest low income housing project. Uncle Bob's Place is prominently located in the CID and many elements of the public art and installations will be on the outside of the building for all who visit the CID. This effort will enhance the sense of place, culture, history, purpose, and community in the CID and contribute to keeping the neighborhood strong and intact, even in the face of intense displacement and gentrification pressures.

CID Block Party

Background: The purpose of this project is to create an installation that pays tribute to the small businesses and homes that were lost during the construction of the I-5 highway. By highlighting these stories, we aim to raise awareness and educate people about the impact of infrastructure development on local communities and emphasize the ongoing significance of history in shaping our present and future. We aim to create an impactful installation that not only commemorates the lost homes but also fosters a deeper understanding of the historical, social, and cultural implications of infrastructure development. Objectives: Preserve and honor the memory of the homes and communities that were affected by the construction of I-5. Educate the public about the historical context and consequences of infrastructure development. Foster a sense of connection between past, present, and future generations, emphasizing the enduring relevance of history.

Department of Cultural Affairs and Special Events

COMMUNITY ARTS ACCESS PROGRAM

Idaho Commission on the Arts

Provides general operating support to established Idaho arts organizations for ongoing programming, operations, and capacity building, helping sustain the state's cultural infrastructure.

Idaho Commission on the Arts

The Idaho Commission on the Arts Quick Fund program provides rapid-response grants for arts programming, supporting performances, exhibitions, workshops, and cultural events that bring arts experiences to Idaho communities.

Idaho Community Foundation

Idaho Community Foundation ($200M in assets) supports nonprofits in ID through grants focused on education, community development, health, arts. Awards range from $1,000 to $50,000.

NCI - National Cancer Institute

Identification and Characterization of Mutation-Induced Alternative Splicing Events in Cancer Using Multi-Omics Data Project Summary The goal of this project is to discover mutation-induced alternative splicing events (MAS), understand their functional relevance, and identify neoantigens arising from these events to advance cancer immunotherapy. Large-scale sequencing efforts such as The Cancer Genome Atlas (TCGA) have primarily focused on identifying driver mutations in tumors, including single amino acid changes, insertions, deletions, and alterations that truncate or elongate wild-type protein sequences. However, traditional DNA mutation annotations often rely on canonical transcripts and may overlook alternative splicing events, and some mutations, such as synonymous changes, are considered silent despite their potential impact on splicing. Previously, we developed the MiSplice pipeline to detect mutation-induced splice sites and, when applied to TCGA data, identified thousands of somatic mutations that create cryptic splice sites. In this proposal, we aim to systematically investigate mutation-induced alternative splicing and its functional relevance in cancer, while also identifying the resulting neoantigens by leveraging data from the Clinical Proteomic Tumor Analysis Consortium 3 (CPTAC-3), which includes comprehensive exome sequencing, RNA-Seq, and mass spectrometry data for 774 tumors across seven cancer types, as well as 126 prospective breast cancer samples from CPTAC-2. We hypothesize that mutation-induced alternative splicing plays a significant role in cancer etiology and that the associated neoantigens can serve as novel immunogenic peptide candidates for cancer immunotherapy. We propose to test these hypotheses through two specific aims. Aim 1: Identify mutation-induced alternative splicing events and assess their functional relevance in cancer using multi-omics data (Years 1 & 2). We will use MiSplice to detect mutation-induced alternative splicing events from CPTAC data and evaluate their impact by analyzing changes in protein and phosphorylation expression, as well as pathway activation. Aim 2: Identify neoantigens arising from mutation-induced alternative splicing events with mass spectrometry support (Years 1 & 2). We will construct a tailored protein database that integrates both reference proteins and mutant proteins generated from MAS events. Using state-in-art tools such as PepQuery, we will search for corresponding peptides in the mass spectrometry data, enabling identification of mutant proteins. Neoantigen peptides derived from these expressed mutant proteins will then be prioritized as candidates for cancer immunotherapy.

NIAID - National Institute of Allergy and Infectious Diseases

Abstract: During HIV infection, a reservoir of infected cells is formed that persists during antiretroviral therapy (ART). Although ART is effective at controlling viral replication, people with HIV (PWH) on ART still exhibit elevated levels of inflammation and immune dysfunction, suggesting ongoing immune damage from HIV infection. The mechanisms behind continued immune dysfunction in PWH on ART remain unclear, but it is possible that chronic immune stimulation by virally encoded RNAs and proteins contributes to this process. At the same time, activation and clonal expansion of infected CD4 T cells in response to interactions with cells and cytokines of the immune system contributes to the persistence of the HIV reservoir. Our hypothesis is that bidirectional stimulation between the reservoir and the immune system creates a self-perpetuating cycle that maintains both chronic inflammation and the persistence of infected cells in PWH on ART. If this hypothesis is correct, molecular pathways that contribute to reservoir/immune crosstalk could potentially be targeted to limit reservoir persistence and reservoir-induced pathology in PWH. The goal of this proposal is to comprehensively define the relationship between the immune system of PWH and the HIV reservoir through single-cell analysis of the transcriptome and proteome of immune cells across a large (n=125) cohort of ART suppressed PWH with well characterized HIV reservoirs. Additionally, we will quantify the clonality of the HIV reservoir for each individual and define immune signatures that are associated with clonal expansion of infected cells during ART. This combined dataset will allow us, for the first time, to perform a detailed correlational analysis of transcriptomic and proteomic signatures in the immune system with key reservoir characteristics (size, transcriptional activity and clonal expansion) across a large cohort of PWH. To achieve these goals, we will leverage a unique set of PBMC and plasma samples from 125 ART-suppressed PWH through our collaboration with Dr Sulggi Lee (UCSF), as well as cutting edge multiomic methods that are already established in the Browne lab. If this project is successful, it will generate the most detailed dataset to date describing molecular connections between the HIV reservoir and the immune system, and will suggest novel ways to interrupt the dynamics that drive reservoir persistence and pathogenesis in PWH on ART.

NIMH - National Institute of Mental Health

PROJECT SUMMARY/ABSTRACT People with HIV (PWH) who experience challenges with antiretroviral therapy (ART) adherence are at increased risk for suboptimal treatment outcomes, including viral non-suppression and disengagement from care. Despite advancements in ART delivery options, personalized treatment approaches that integrate patient preferences remain underutilized, particularly among PWH facing psychosocial and documented barriers. Clinical decision support (CDS) tools offer a promising avenue to address this gap by tailoring treatment recommendations based on patient-specific needs and barriers. However, current CDS tools often fail to incorporate rich patient insights available from unstructured electronic health record (EHR) notes or systematically integrate directly reported preferences, limiting their potential to enhance adherence and outcomes. The proposed training and research plan for this K23 will enable José I. Gutierrez, Jr., PhD, FNP- BC, to acquire the expertise necessary to become an NIH-funded independent investigator who designs patient-informed CDS interventions that optimize HIV treatment delivery. Under the mentorship of an experienced multidisciplinary team, Dr. Gutierrez will use a mixed-methods approach to develop foundational components of a CDS prototype that integrates natural language processing (NLP)–derived EHR information with patient-reported preference data. Building on prior work in HIV treatment delivery and preference evaluation, he will pursue the following specific aims: (1) explore HIV treatment delivery preferences, barriers, and facilitators within EHR notes using NLP; (2) identify and quantify patient preferences, barriers, and facilitators using qualitative interviews and MaxDiff; and (3) develop the key features of a CDS prototype that generates tailored suggested actions informed by EHR and patient-preference data, and evaluate its acceptability, feasibility, usability, and intended adoption in a 9-month, cross-sectional, non-clinical user-testing study using standardized vignettes and de-identified/fictionalized cases (no live EHR). This research plan aligns with Dr. Gutierrez's career development goal to gain advanced skills in clinical informatics and NLP, qualitative and mixed-methods research, and patient-informed intervention design. Findings will provide the foundation for a subsequent NIH R01 to rigorously evaluate effectiveness in clinical settings, with the overarching goal of improving ART adherence and treatment outcomes among PWH. 1

NCI - National Cancer Institute

PROJECT SUMMARY Oncogenic mutations in KRAS are nearly universal in pancreatic ductal adenocarcinoma (PDAC) and drive disease initiation, progression, and maintenance. Small molecules that inhibit mutant forms of KRAS (KRASi) and both mutant and wildtype RAS proteins (RASi) have recently emerged with the potential to transform the treatment landscape of PDAC. However, the mechanisms dictating efficacy and resistance to RAS inhibitors remain poorly understood. PDAC development and therapeutic response depends on co-evolution and interaction between tumor cells and the tumor immune microenvironment (TIME). This research proposal focuses on a major goal of our laboratories: to determine how remodeling of tumor-immune interactions contributes to efficacy and durability of RAS inhibition. We have developed immunocompetent mouse models that recapitulate seminal features of PDAC heterogeneity and found that while the KRASG12D inhibitor MRTX1133 and the pan-RASGTP inhibitor RMC-6236 both effectively inhibit the MAPK pathway and illicit potent tumor responses in pre-clinical studies, they result in distinct patterns of response and adaptation in tumor cells and the tumor microenvironment. We hypothesize that these differences result from poorly understood and understudied immune cell intrinsic roles of the RAS family that alter interactions between tumor and immune cells in response to RAS inhibition. Using a multidisciplinary and collaborative approach, this proposal integrates cutting-edge genetic models with innovative molecular and immunological methodology to delineate targetable immunological changes which define distinct patterns of response to KRASi and RASi in PDAC. We propose 2 aims that meet the research objectives of notice of special interest NOT-CA-24-016 (Exploratory Cancer Immunology Projects and Technologies (ExCITe)/PA-25-304, by addressing “fundamental aspects of tumor immunology and/or innovative ways to enhance anti-cancer immunity.” Aim 1 will leverage state of the art single cell technology and high dimensional spectral flow cytometry in mouse models of PDAC to comprehensively establish how TIME remodeling contributes to PDAC response and resistance following RASi/KRASi. Aim 2 will investigate immune-intrinsic roles for wild type RAS activity in the PDAC TIME through novel genetic approaches to determine how non tumor cells contribute to efficacy and resistance of RASi. Taken together, this proposal integrates expertise in PDAC pathobiology, tumor immunology, and applies novel genetic tools to unveil new mechanisms that underlie the efficacy and durability of RAS inhibition.

NHLBI - National Heart Lung and Blood Institute

PROJECT SUMMARY. Cancer cachexia (CC) is a syndrome of progressive body weight loss, muscle wasting, and functional decline that occurs in 30% of all cancer patients, and 70-90% of patients with gastrointestinal, lung, and liver malignancies. CC causes severe weakness and fatigue and increases morbidity and mortality. Twenty percent of cancer patients die of CC, and yet, there are limited therapeutic options. Cardiac atrophy and deficits in contraction and relaxation of the heart occur in CC patients, which contribute to worsened clinical outcomes. Very little is known mechanistically about the cardiac pathology in CC. The long-term objective is to identify molecular mechanisms underlying atrophy and mechanical dysfunction in CC-associated heart muscle disease (cardiomyopathy), with the goal of discovering therapeutic targets to optimize clinical care for CC patients. This project will identify metabolic drivers of CC cardiomyopathy through chemical and genetic targeting of mitochondrial function, which will be accomplished through two specific aims: (1) Pre-clinical cancer cachexia mouse models will be used to identify the role of mitochondrial dysfunction on metabolism and mechanical function in hearts and cardiac muscle cells (myocytes) from mice with CC. Mice with and without tumors will be treated with a mitochondrial stabilizer (SS-31) or vehicle. SS-31 binds to cardiolipin in the inner mitochondrial membrane and stabilizes cristae structure and integrity of energy production machinery. At the study endpoint, mitochondrial function, substrate utilization and energy production, oxidative stress, and cardiac function will be assessed using state of the art methodologies including 3D holotomograpy, cryo-electron microscopy, mitochondrial metabolic flux analysis, isolated cardiac myocyte contractility and calcium cycling measurements, and in vivo cardiac function using echocardiography, electrocardiography, and exercise stress testing. The hypothesis is that improving mitochondrial health will restore cardiac function. (2) An in vitro model of simulated CC-associated cardiomyopathy consisting of primary cell cultures of neonatal rat ventricular myocytes (NRVM) co-cultured with C26 tumor cells will be used to assess small interfering RNA knockdown (KD) of the enzyme prolyl hydroxylase 2 (PHD2). PHD2 KD will be performed in NRVM prior to C26 co-culture to induce acute hypoxia response signaling with the goal of protecting myocytes against mitochondrial destabilization and dysfunction associated with CC. We will use similar methodologies in aim 2 to measure mitochondrial function, cellular substrate utilization and energy production, oxidative stress, and calcium cycling. Together, these aims interrogate molecular mechanisms related to mitochondrial membrane stability and hypoxia signaling in CC- associated cardiomyopathy and identify cause-effect relationships between these mechanisms and contractility and calcium cycling function in CC hearts. These studies will provide new insights about the causes of CC- associated cardiomyopathy, which will enable development of improved treatment options for patients with CC, optimizing quality and length of life for individuals with this devastating cancer-related syndrome.

NIMH - National Institute of Mental Health

Project Summary / Abstract Water insecurity (WI) is a major challenge in sub-Sharan Africa (SSA), where the number of people living with HIV (PLWH) is disproportionately higher, and where populations are most likely to bear the impact of climate- sensitive exposures. The effects of WI on health are well-documented in SSA: emotional distress is associated with lack of safe water, including fear of contamination, worry over safety, and anxiety, increased migration and thus HIV risk, as well as disruptions to health, care engagement, livelihoods, and relationships. Further, the prevalence of WI among PLWH is high, and household WI and food insecurity (FI) lead to poor mental and physical health. WI is also an important determinant of FI, suggesting multiple causal pathways to poor health outcomes. While SSA least contributes to global warming, especially as compared to more industrialized nations, it is expected to be amongst the hardest by climate-sensitive exposures. Water is required for food production and preparation, and WI may directly and indirectly influence health outcomes by impacting FI and health. Among PLWH, WI can lead to dehydration and undermine PLWH’s ability to manage unpleasant side effects associated with ART, including diarrhea, nausea, and vomiting. In Ghana, one of the most vulnerable countries to climate- sensitive exposures in SSA, flooding affects around 45,000 Ghanaians annually while nearly half of Ghana’s coastline is vulnerable to erosion and flooding as a result of sea-level rise and atypical rainfall. Further, an estimated 70% of all disease burden in Ghana is attributed to WI. To effectively intervene, a deeper understanding of the drivers of and sequelae of WI is critical. Therefore, we propose one of the first longitudinal convergent mixed-methods study to quantify and elucidate the impact of WI on HIV, related to climate-related drivers, infrastructure challenges, water accessibility, to inform interventions to address WI among PLWH. In response to our initial R01 submission, NIMH expressed strong enthusiasm for our program of research and awarded our team a 1-year R56 award to collect preliminary data to further support this application. In Aim 1, we will utilize innovative remote sensing technologies to investigate the role of climate-sensitive patterns (droughts, precipitation anomalies, and floods, capitalizing on state-of-the-art satellite technologies) and seasonality on WI in Ghana. In Aim 2, we will determine the impact of WI on HIV treatment outcomes (ART adherence/viral suppression) and opportunistic infections and comorbidities, and the mechanisms through which WI may influence these outcomes (nutritional, mental health, water, hygiene and sanitation, and empowerment pathways). We have already recruited and enrolled a cohort of 503 PLWH for Aims 1 and 2. In aim 3, using intervention mapping framework, we will develop intervention options to mitigate WI and improve health for PLWH, synthesized from theory and literature. Findings from this R01 will a) provide initial data on the drivers of and sequelae of WI and it impact on HIV treatment outcome; b) guide the integration of HIV and water access programs; and c) help identify and prioritize intervention development to address WI among PLWH.

NIAID - National Institute of Allergy and Infectious Diseases

PROJECT SUMMARY/ABSTRACT Systemic lupus erythematosus (SLE) is characterized by increased expression of interferon (IFN)-induced genes, known as the IFN signature, pointing to IFNs as promising therapeutic targets in SLE. Disappointingly, only a subset of SLE patients who express the IFN signature have shown benefit in clinical trials targeting the type I IFN (IFN-I) pathway, and inhibiting IFN-II has completely failed to treat SLE. To date, there is no explanation for this puzzle. Our studies indicate that dysregulated IFN expression is not a unifying feature among patients with SLE, and that the IFN signature is not always analogous to increased levels of IFNs. Instead, based on IFN levels and the IFN signature, patients with SLE can be classified into at least three disease subsets of mechanistic relevance. One subset is distinguished by increased levels of IFN-I alone and is associated with cutaneous lupus. The second subset is linked to systemic disease and is associated with elevated levels of IFN- I in combination with IFN-II and IFN-III, indicating a synergistic effect of IFN types on disease severity. The third subset includes SLE patients whose IFN signature is not explained by IFNs, but rather by stimuli that mimic IFN signaling. Together, the proposed subsets provide novel insights into mechanisms of disease heterogeneity in SLE, as well as a rational explanation for the variable response in clinical trials targeting the IFN-I pathway, even among patients expressing the IFN signature. In this project, we will use unique cohorts of patients with cutaneous lupus and SLE, as well as state-of-the-art technologies, to examine the mechanisms that define clinical endotypes linked to IFN-I, as well as the identity of IFN-independent factors that mirror the induction of the IFN signature in a significant subset of patients with SLE. Our long-term goal is to apply this knowledge to develop precise mechanism-guided preventive and therapeutic interventions for SLE.

Illinois Arts Council Agency

Illinois Arts Council Agency provides grants to support arts and cultural programming, artist fellowships, arts education, and community-based arts projects across IL.

Illinois Arts Council Agency

Supports Illinois arts organizations, artists, and arts education programs through operational support, project grants, and touring grants.

NIGMS - National Institute of General Medical Sciences

Project Summery/Abstract Amid a public health crisis driven by antibiotic-resistant pathogenic bacteria, bacteriophages (phages), which naturally infect and kill bacteria, represent a promising alternative as antimicrobials. However, a significant challenge is posed by diverse bacterial immune mechanisms that resist phage infections. Overcoming this obstacle requires phages equipped with robust anti-immune capabilities. In this context, ΦKZ-like jumbophages (genomes > 200kb) have an exceptional ability to counter various bacterial nucleolytic immune systems throughout infection, with numerous family members targeting key Gram-negative pathogens. The jumbophage ΦKZ is a broad host range killer of the multi-antibiotic-resistant pathogen Pseudomonas aeruginosa and serves as the leading model phage for this family. Immune evasion is largely achieved through the assembly of a bacterial membrane lipid derived compartment termed the “Early Phage Infection Vesicle” (EPIV), which I co-discovered during my postdoctoral work, and a phage-encoded proteinaceous compartment called the “phage nucleus,” which shields the replicating phage genome. The long term goal of this study is to understand three unexplored aspects of jumbophage biology related to the biogenesis and functioning of the EPIV. The EPIV houses early transcription, but the phage has to solve a fundamental challenge not previously solved in bacteria–mRNA export from a lipid-bound compartment and successful docking with ribosomes, which are unusually uncoupled from transcription in this case. I hypothesize that a novel mRNA export channel, analogous to the eukaryotic nuclear pore complex, is assembled by injected ΦKZ proteins to export mRNA to ribosomes. I will uncover this complex using cryo-ET, mass spectrometry and genetics. I will additionally examine the role of EPIV assembly in enabling ‘pseudolysogeny’ in jumbophage infections. This process of phage quiescence was observed in jumbophages long ago but lacks a mechanistic understanding. I hypothesize that the EPIV has the potential to be a stable pseudolysogenic entity inside an infected bacterium that I will test herein with my multidisciplinary approach. Finally, I will attempt to elucidate the mechanism of EPIV biogenesis – it remains entirely unknown how this massive membrane-bound organelle is rapidly assembled within bacteria and how its formation is conserved across diverse jumbophage infections. To answer these questions, I will combine genetic dissection and c-ET to reveal the key participants and early assembly events of this unique phage-driven prokaryotic organelle formation. Overall, my studies stand to uncover fundamentally fascinating bacterial-phage cell biology in addition to innovative and potentially transferable mechanisms to enhance phage success in combating pathogenic bacteria. This research will be conducted at UCSF, which hosts state-of-the-art facilities and a highly intellectual and collaborative research community. It will also provide me with the training in genetics and structural biology that I need to fulfill my postdoctoral training goals and pioneer an independent research program in bacterial-phage interactions.

Africatown-Central District Preservation & Development Association

The Imagine Africatown Fall and Winter Activation project will create a temporary art based neighborhood destination at Midtown located at 2301 East Union Street. The project will celebrate the African American/African Diaspora legacy and culture in the Central District with art, pop up events, and other programming. This project will be completed by March 28, 2019.