Johns Hopkins University

NIH Research Projects · FY 2025 · 2025-09

American Indian (AI) women experience significant challenges in maternal morbidity and mortality, particularly in rural areas where 40% of AI women reside. This research aims to address these differences by employing AI research methodologies to explore the impact of the AI doula role. By integrating AI-specific protective factors, evidence-based practices, and doula best practices, the project seeks to evaluate the impact of doula support on comprehensive maternal health outcomes, including receipt of guideline-concordant perinatal care, perinatal mood and anxiety disorder (PMAD) symptoms, breastfeeding initiation, and characteristics of labor/delivery, among other areas. Building on a 40+ year partnership between the Johns Hopkins Center for Indigenous Health (JH CIH) and the Navajo Nation, this study will be conducted in collaboration with two rural Navajo communities: Tuba City and Fort Defiance, Arizona. These sites are key hubs for perinatal care and labor/delivery within the largest federally recognized AI nation in the United States. The research is deeply rooted in community-engaged practices, with continuous collaboration with Community Research Councils (CRCs) and community approvals integrated into all stages of the project. Community engagement is central to this study. All research activities will be guided by a CRC of 8–10 Navajo community members, including health providers, counselors, Navajo knowledge keepers, and doulas. Facilitation and ongoing communication with the CRC will be jointly led by the Principal Investigator (Dr. Richards), local JH CIH site coordinators, and study doulas. The study has received strong support from various community organizations and stakeholders, including the Diné Doula Collective, Navajo Breastfeeding Coalition, and local healthcare institutions. Utilizing a Hybrid Type I effectiveness-implementation design, the study focuses on maternal health outcomes, particularly increasing guideline-concordant postpartum engagement, a priority identified by the community. The measurement of costs will provide valuable insights for potential implementing partner organizations and future Medicaid reimbursement. To ensure broad dissemination of our findings, the study will be registered on ClinicalTrials.gov within 21 days of the trial’s start date, with regular updates and adverse event reporting. Results will be submitted to ClinicalTrials.gov within 12 months of study completion. Informed consent documents will include statements about the posting of clinical trial information. We will share our findings with community partners through co-developed lay summaries and presentations, and disseminate results via local newsletters, tribal radio programs, and newspapers. For researchers and policymakers, results will be presented at national conferences, through webinars, and published in peer- reviewed journals.

NIH Research Projects · FY 2025 · 2025-09

Summary – We will establish and validate stable system for CRISPR interference (CRISPRi) and CRISPR activation (CRISPRa) in zebrafish, employing attP safe harbor PhiC31 integration sites. The application of CRISPRi and CRISPRa technologies in zebrafish has the potential to expand its capacity for the study of gene function significantly. It will afford the modulation of promoters and regulatory sequences alike, facilitating efficient loss of function and gain of function evaluation of biological and pathological relevance. We recently developed codon-optimized CRISPRi/a constructs for zebrafish, establishing their function in proof-of-principle experiments, using RNA injection of system components to modulate key genes in established phenotypes. We synthesized a zebrafish codon-optimized cas9 gene, harboring mutations D10A and D839A to render the protein catalytically inactive (dCas9). We then cloned codon-optimized Krüppel associated box (KRAB) and methylated CP2 (MeCP2) inactivating domains or VP64 activator domain downstream from dCas9 for CRISPRi and CRISPRa, respectively. To validate the biological function of our initial CRISPRi construct, we targeted the promoter sequences of key genes in melanocyte differentiation (sox10, mitfa, and mitfb); and melanin production (tyrosinase; tyr). Microinjection of CRISPRi mRNA with single guide RNAs (sgRNAs) targeting their promoters resulted in hypopigmented larvae (epidermal melanocytes and retinal pigmented epithelium. In addition, we evaluated CRISPRi/a modulation of mrap2a, which controls energy homeostasis and somatic growth via inhibition of the melanocortin 4 receptor gene (mc4r). Targeting the mrap2a promoter proximal region with CRISPRa or CRISPRi increases and decreases larval body length, respectively. However, RNA-based injections inherently display time-limited effects whose impact is unreliable beyond the development. Thus, here we propose to establish transgenic lines, stably expressing CRISPRi and CRISPRa from constructs integrated into attP safe harbor integration sites in chromosome 14 facilitated by the PhiC31 integrase (Aim 1). We will screen the efficacy of these new lines via Tol2-mediated delivery of sgRNA expression constructs directed at known genes whose modulation yield readily scored phenotypes, as above. Similarly, we will establish and validate constructs for efficient delivery of sgRNA expression to an alternate attP PhiC31 site in chromosome 24 (Aim2). The lines expressing CRISPRi/CRISPRa will be crossed with the empty alternate PhiC31 site, allowing the use of the second site for targeted integration of sgRNA expression constructs. The establishment of lines established in Aims 1 and 2 will be confirmed by the inclusion of discrete reporter cassettes expressing Cerulean [blue, Aim 1] and Venus [yellow, Aim 2] in the pineal and the lens of the eye, respectively. The efficiency of lines generated in aim 2 will be evaluated using guides designed to the promoters of genes employed in Aim 1 validation. Robust CRISPRi and CRISPRa systems in zebrafish will facilitate efficient assay of candidate gene function and disease relevance through bidirectional modulation of gene expression.

NIH Research Projects · FY 2025 · 2025-09

The Hepatitis B HIV Cure Consortium (BICC) aims to establish a multinational cohort of people with HIV and chronic hepatitis B (PWHHB) in which to apply novel technologies to advance a hepatitis B virus (HBV) functional cure. An HBV cure is needed for the >300 million people with chronic hepatitis B (CHB) and the 10% of people with HIV who also have CHB leaving them at increased risk for liver death and limiting novel HIV treatment options. Functional cure requires sustained loss of hepatitis B surface antigen (HBsAg) off treatment, but HBV control represents a continuum; thus, we investigate factors associated with both HBsAg loss and decline. The science is based on samples from 675 participants (450 PWHHB and 225 people with hepatitis B alone) followed semi-annually from Uganda, Brazil, India, Senegal, and the United States that includes most of the major HBV genotypes. We plan to recruit 40% females. Liver biopsies and large-volume blood draws will be obtained from 90 individuals at study entry and 30 will have repeat procedures performed at year 4. The Virology Core will use state-of-the-art virological assays to characterize blood markers of HBV replication and transcription that will be used by all three projects (Clinical, Immunology, and Translational). The first aim is to build the cohort and a clinical and specimen HBV repository through the Shared Resources Core. This repository will provide all projects with human specimens (blood, liver tissue, peripheral blood mononuclear cells). The second aim is to build research capacity at each of the collaborating sites and to train early-stage investigators providing a pipeline of HBV cure investigators. The third aim characterizes mechanisms of intrahepatic persistence during treatment using novel techniques to study HBV transcription from the HBV replication template, covalently closed circular DNA (cccDNA), and from HBV integrated into the host genome (iDNA) (Translational Project). This project synergizes with the Multiomics Core to study factors associated with cccDNA transcriptional silencing and synergizes with the Immunology Project to find HBV-specific clonotypes in blood that are enriched in the liver. The fourth aim characterizes virological and immunologic dynamics associated with HBsAg loss or decline including virological markers tested in the Virology Core, T-cell and B-cell phenotypes characterized by multiparameter flow, neutralizing antibody responses, and B cell and T cell clonotypes (determined by Immunology and Multiomics Core) with HBsAg loss or decline during HBV treatment. These data are then integrated data to develop a multiscale mechanistic model of HBV control that can provide crucial information needed to develop a functional cure and informs how HIV affects functional cure. All the data generated will be stored in a HIPAA-compliant database and analyzed in the Statistical and Data Management Center. The Administrative Core manages all aspects the different Cores and Projects such as regulatory, financial, specimen allocation, training, travel, so that scientific efforts are maintained towards the goal of HBV Cure.

NIH Research Projects · FY 2025 · 2025-09

PROJECT SUMMARY: BiLDing-ACTION aims to leverage two highly rigorous World Health Organization (WHO) randomized trials to establish a novel longitudinal cohort of prematurely born children in Bangladesh. The project will assess whether antenatal corticosteroids (ACS), versus placebo, improves lung growth and development among premature children born before 34 weeks (Aim 1) and between 34-36 weeks and 6 days (Aim 2) and whether ACS reduces the incidence of lower respiratory infections among prematurely born children in Bangladesh (Aim 3). In Bangladesh and other low- and middle-income countries (LMICs) preterm birth complications are the leading cause of mortality among children. Infants born prematurely are at risk of lung growth and functional deficits and chronic respiratory disease. The magnitude and pattern of lung function impairment and respiratory illness incidence among premature infants and preschool children in LMICs, and whether antenatal corticosteroids (ACS) have an impact on them, are unknown. In this project (Bangladesh infant Lung Development-ACS for Improving Outcomes in Preterm Newborns) we aim to utilize innovative infant and preschool-aged lung function testing and a novel FDA- approved digital stethoscope with automated lung sound analytics to evaluate ACS efficacy, compared to placebo, on lung development among premature children enrolled in the WHO ACTION Trials-I and III. Both studies are double-blinded, placebo-controlled trials of women and babies in Bangladesh. In Aim 1, we will determine whether ACS, versus placebo, improves lung growth and development between 6-8 years-of-age among children born <34 weeks' gestation in Bangladesh. In Aim 2 we will assess if ACS, compared to placebo, improves lung growth and development among late preterm infants in Bangladesh over the first three years of life. We hypothesize lung injury associated with prematurity is mitigated by ACS, and therefore lung function at six years of age (Aim 1a) and at 6 months of age (Aim 2a) and changing longitudinally between 6-8 years of age (Aim 1b) and 6 months to 3 years of age (Aim 2b), will be more favorable among ACS than placebo. Lastly, in Aim 3 we will evaluate whether ACS, compared to placebo, reduces the incidence of lower respiratory infections among school-aged children born <34 weeks gestation (Aim 3a) and severe lower respiratory infections among late preterm infants over the first three years of life (Aim 3b) in Bangladesh. We hypothesize that ACS, compared to placebo, will promote healthier lung development amongst prematurely born infants and children to reduce the incidence of lower respiratory infections. BiLDing-ACTION provides a unique opportunity to advance the healthcare of children born prematurely in low-resource settings, leveraging two prominent, singular WHO trials to strengthen the evidence-base for the early life lung health benefits of ACS for women at risk of premature delivery in LMICs.

NIH Research Projects · FY 2025 · 2025-09

Project Summary Multiple sclerosis (MS) is the most common neurodegenerative disease in young adults. Despite the identification of several molecules that could potentially promote remyelination, the lack of biomarkers of this process is a major roadblock in the translation of these findings to the clinic. Extracellular vesicles (EVs) are a promising platform for biomarker identification and newer methods enable their isolation and characterization from tissues of interest. Our long-term goals are to identify novel biomarkers of demyelination and remyelination to promote identification of novel therapeutic strategies for repair and remyelination in MS. The objectives of this R21 application are to identify biomarkers of demyelination and remyelination by studying altered proteins and lipids in tissue-derived and plasma-derived EVs in a mouse model of demyelination. The rationale for this project, supported by preliminary data, is that tissue derived EVs can be isolated and characterized from mouse or human tissue and profiled using proteomics analyses to identify meaningful biomarkers of the underlying disease process. The proposed research study will pursue two specific aims: 1) to identify proteins in tissue- and plasma- derived EVs specific for demyelination and remyelination in a mouse model of MS and 2) to identify lipids in tissue- and plasma-derived EVs specific for demyelination and remyelination in a mouse model of MS. For both aims we will utilize the cuprizone induced toxic demyelination model and obtain corpus callosum tissue and blood from mice at various time-points in the demyelination and remyelination phases, followed by isolation of EVs. In aim 1 the EVs will undergo proteomics analyses while in aim 2 the EVs will undergo lipidomics analyses. Statistical analyses will then help identify proteins and lipids in EVs that are specific to demyelination and remyelination stages and could serve as potential biomarkers for these processes. This project is innovative in that it proposes to test a novel hypothesis that tissue-derived and plasma-derived EV proteomics could be used to identify novel markers or demyelination and remyelination and also utilizes cutting-edge tools to accomplish the proposed aims. The proposed research is significant because it could identify novel biomarkers for use in trials of therapeutic agents that could promote myelin repair in this chronic disabling neurological disorder.

NIH Research Projects · FY 2025 · 2025-09

The overarching goal of these proposed aims is to better characterize the effects of social, behavioral, and economic (SBE) stigmas on the health of people living with HIV (PLHIV) in the US, improve the measurement of SBE stigmas, and develop strategies to bolster the use of stigma data in the HIV response. Social, behavioral, and economic stigmas are understood to be fundamental drivers of HIV-related and other health differences for populations of people living with HIV. However, there has been limited measurement of the effects of SBE stigmas among people living with HIV, restricting our ability to quantify trends, determinants, health effects, and ultimately to consistently measure the effects of SBE stigma mitigation interventions. Since 2020, the PLHIV Stigma Index 2.0 has collected stigma data from more than 40,000 PLHIV across 32 countries through parallel measurement of HIV-related stigma and stigmas related to different attributes other than living with HIV (demographic characteristics, health behaviors). However, there has been no use of non-attributional stigma items to date which have shown to be important domestically in measuring stigma across converging demographic characteristics. We will leverage the PLHIV Stigma Index platform to collect attributional and non-attributional SBE stigma data, as well as qualitative data, in geographically and demographically varying sites, as prioritized by community leadership. We propose to improve stigma measurement in the PLHIV Stigma Index platform by adding validated SBE stigma tools and assessing their validity and measurement invariance across sites using quantitative and qualitative data collection. We will describe health outcomes of both layered attributional and non-attributional SBE stigma in these distinct sites. Furthermore, community leadership has consistently highlighted that existing stigma data are underutilized to inform national HIV response plans. In response, we will use the consolidated framework for implementation research (CFIR) 2.0 to characterize determinants of limited uptake of stigma data in practice and design optimal implementation strategies to bolster stigma data use in HIV response strategies. The proposed aims are to (1) Characterize structural determinants of stigma and the relationship of stigma with HIV-related and other health outcomes among people living with HIV within and between sites; (2) Optimize measurement of social, behavioral, and economic stigmas experienced by people living with HIV; and (3): Evaluate determinants of stigma data use and characterize strategies to optimize uptake of stigma data in HIV response strategies. These aims are uniquely feasible via a balanced community-academic partnership with the International Community of Women Living with HIV (ICW) North America and community-level networks to support the PLHIV Stigma Index.

NIH Research Projects · FY 2025 · 2025-09

PROJECT SUMMARY Tar DNA/RNA-binding protein 43kDa (TDP-43) is an RNA binding protein mainly localized in the nucleus, serving an essential role in RNA regulation. Our lab has shown that one of TDP- 43’s function is to repress splicing of non-conserved cryptic exons to ensure formation of a normal transcriptome. When TDP-43 is depleted from the nucleus, these cryptic exons get spliced into messenger RNAs. The inclusion of cryptic exons often introduces frameshifts or premature stop codons in mRNAs, disrupting their translation. To complement the loss of splicing repression by TDP-43, our lab has made a construct, termed CTR, that replaces the prion-like C-terminal domain of TDP-43 with a well-characterized splicing repressor domain derived from ribonucleoprotein, PTB-binding 1 (RAVER1). CTR has been shown to repress majority of cryptic exons in mouse embryonic stem cells lacking TDP-43. Cryptic exons of TDP- 43 in mice are distinct from those of primates even though TDP-43’s protein sequence is highly conserved among different organisms. These cryptic exons are diverse and cell type-specific in nature. Our preliminary analyses show that human astrocytes have a unique set of cryptic exons after TDP-43 loss that are not expressed in TDP-43 deficient neurons. Moreover, in preliminary data, we have demonstrated that CTR can rescue the disease phenotypes observed in TDP-43 deficient human ipsc-derived cortical i3 neurons (i3N). CTR can attenuate cell death, aid survival, and decrease cryptic HDGFL2 protein in TDP-43 deficient i3 neurons. The overarching goal of this proposal is that human cryptic exons are species and cell type specific and CTR can repress cryptic exon incorporation and rescue synaptic physiology and cell death in TDP- 43 deficient human cortical neurons. I will test this hypothesis by knocking down TDP-43 using lentivirus containing shRNA against TDP-43 in human cortical neurons, administering CTR by lentivirus transduction, using RNA sequencing, performing immunohistochemical analysis, and conducting mini electrode assay recording and whole-cell patch clamp. In Aim 1, I will determine whether there are cell-specific cryptic exons in human neurons, astrocytes, and oligodendrocyte progenitor cells. In Aim 2, I will determine whether CTR can prevent cryptic exon incorporation and restore normal synaptic function and rescue cell death in TDP-43 deficient human iPSC-derived neurons.

NIH Research Projects · FY 2025 · 2025-09

Stimulation of vestibular peripheral pathways with ‘direct current’, also called Galvanic Vestibular Stimulation (GVS) has been increasingly used in research and as a non-invasive method in the clinic. The goal of the present proposal is to improve GVS effectiveness through local application of drugs in the vestibular sensory organs. We propose a multifaceted approach to investigate these effects at the cellular and behavioral levels. We will use an in vitro preparation of the vestibular sensory epithelium to study the effect of local galvanic stimulation on nerve terminals before and after application of specific antagonists of potassium channels to modify the response properties of afferents. In parallel, we will investigate whether local application of the above drugs can increase the effect of GVS in generating eye movements, particularly at higher frequencies of sinusoidal stimulation, suggesting that it can generate a better vestibulo-ocular reflex at these frequencies if used clinically. The results of these studies will have significant implications for developing more precise and efficient therapeutic approaches by GVS.

NIH Research Projects · FY 2025 · 2025-09

Project Abstract This project aims to assess the capacity of cannabidiol (CBD) to manage alcohol withdrawal and cravings during detoxification of patients with Alcohol Use Disorder (AUD). AUD is associated with physical and psychiatric consequences as well as exorbitant healthcare costs. Attempts to treat AUD are limited by alcohol withdrawal, which can itself lead to seizures and death if it is not adequately treated. Benzodiazepines have long been the gold standard in the treatment of alcohol withdrawal, but this class of medications has drawbacks including abuse liability that limits its utility in an outpatient setting, adverse effects such as delirium and respiratory depression at high doses, and a susceptibility to shortages. Thus, there is a need to identify novel adjunct treatments for the management of alcohol withdrawal that could reduce benzodiazepine use and further attenuate withdrawal. CBD, one of the main cannabinoids in the Cannabis sativa plant, possesses several attributes that could make it a suitable treatment for alcohol withdrawal: it has a relatively benign side effect profile, lacks abuse liability, and has evidence to manage symptoms seen in alcohol withdrawal, including anxiety, insomnia, and seizures. CBD’s potential to help manage alcohol withdrawal symptoms and craving behaviors has been shown in preclinical studies but there is no data on CBD’s role as a treatment for alcohol withdrawal in human participants. This study will fill this knowledge gap by recruiting individuals with moderate-to-severe AUD to participate in a four-day inpatient study where they will be randomized to receive either placebo solution or CBD solution at a daily dose of 10 mg/kg or 20 mg/kg while undergoing supervised medical detoxification. Withdrawal will be assessed by nursing via the Clinical Institute Withdrawal Assessment, revised (CIWA- Ar) and by participant self-report via Alcohol Withdrawal Symptom Checklist (AWSC). CIWA scores will guide administration of benzodiazepines for the treatment of withdrawal symptoms. We will measure sleep quality through both self-report via the Consensus Sleep Diary (CSD) and objective data collected through wrist actigraphy. Alcohol cravings will also be measured via participant self-report with the Alcohol Urge Questionnaire (AUQ). Additionally, we will measure changes in liver function to verify the hepatic safety of CBD at these doses. Analysis will involve comparison between groups of the scores on the assessments of withdrawal, craving and sleep, wrist actigraphy data, total number of lorazepam doses administered over the course of study, and changes in liver function and vital signs. We hypothesize that CBD will be well-tolerated and attenuate alcohol withdrawal symptoms and cravings in a dose-dependent manner compared to placebo. Results from this study could position CBD as a novel agent for the management of withdrawal, sleep and cravings in early abstinence.

NIH Research Projects · FY 2025 · 2025-09

ABSTRACT Understanding the fundamental mechanisms of granuloma breakdown and necrosis in pulmonary TB lesions is a key unmet need. Lung granulomatous lesions from human active TB lung lesions show prominent markers of cellular senescence in myeloid cells, but this aspect of granuloma breakdown has not been well-studied. In the B6.Sst1S mouse model (where granuloma failure also leads to necrosis) we have identified multiple senescence markers analogous to those seen in human TB. Senescent cells are non-replicating, long-lived cells which release signaling molecules (called the senescence-associated secretory phenotype, SASP) that are locally deleterious and promote tissue dysfunction. Our central premise is that non-controlling granulomas (both in predisposed humans and in the B6.Sst1S model) adopt a stress-induced senescence (SIS) phenotype during Mtb infection driven by (i) lipid peroxidation, (ii) Myc activation, and (iii) unresolving proteotoxic stress. These SIS Ms are (i) immunosuppressive (MDSC-like), (ii) long-lived and resistant to early death, and (iii) emit deleterious signals (eg SASP molecules) that inhibit T cell activation and promote recruitment of PMNs and immature Ms. Our data show that SIS-Ms display a Myc-driven phenotype with oxidative stress, dysregulated proteostasis, and hyperactivity of the IFN-I pathway. This fuels a self-sustained, escalating cycle that leads to necrosis occurs via a combination of ferroptotic-like death of SIS Ms and PMN-mediated damage. Underscoring the fact that senescent cells play a causal role in TB progression, we recently found that a 3-drug cocktail of senolytic drugs (dasatinib D, quercetin Q, and fisetin F)--designed to kill the deleterious senescent cells-- significantly reduces lung CFU counts and prolongs survival in Mtb-infected B6.Sst1S mice. Thus, studies of senescence in TB may offer a significant clinical payoff in the form of novel host-directed therapies (HDT) for TB. [NEW] In this application we will establish a detailed temporo-spatial understanding of SIS-Ms and surrounding cells using spatial transcriptomic in 2 species that progress to necrotic TB: B6.Sst1S mice and WT rabbits (Aim 1). We will exploit the new finding of successful HDT activity by a cocktail of 3 senolytic drugs by optimizing the 3 drugs and their interactions with Std-Tx (Aim 2). We will also explore the senescence-driven pathologic pathways in the setting of TB-SIV co-infection using non-human primates (Aim 3).

NIH Research Projects · FY 2025 · 2025-09

PROJECT SUMMARY The latest generations of base editing and prime editing tools can efficiently install genetic variants and correct those associated with disease. However, it is still not practical to treat most patients with rare or unique disease-causing genetic variants because the cost and effort required to optimize an editing strategy and bring it to the clinic is prohibitive. Existing editing therapeutics approved or in clinical trials are all applicable to treat either a common disease-associated allele or a large set of potential disease-associated alleles. For example, the recently approved Casgevy genome editing treatment can be used to cure patients with nearly any beta-thalassemia or sickle cell disease genotype, including rare and common variants. For most types of rare genetic disease, no known genome edit could treat multiple disease-associated alleles. This proposal describes methods to establish generalizable editing strategies that would each be broadly applicable to treat hundreds of rare disease-causing genetic variants, helping to bring the benefits of genome editing to the patients who need them. Two classes of generalizable therapeutics are proposed here. One will address rare loss- of-function alleles such as haploinsufficiencies, recessive hypomorphic alleles, and diseases where expression of a paralogous gene could provide the lacking function. The other class of therapeutics will address rare gain-of-function alleles by allele-specific knockout. These conceptual strategies will be studied in the context of Marfan’s Syndrome, vascular Ehlers Danlos Syndrome, adrenoleukodystrophy, and Charcot-Marie-Tooth Disease. Success would motivate adapting the same development platforms to a plethora of other forms of rare genetic disease. In addition, this proposal aims to establish safer and more effective delivery of genome editors by adeno-associated viral (AAV) vectors, which would be best suited to access the target tissues to correct the above disorders. While AAV delivery of genome editors has proven to be effective in a range of mouse models of genetic disease, it has not been deployed in the clinic due to concerns of continued off-target editing and immunogenicity of the editor. This proposal will overcome the limitations that prevent adapting base editor and prime editor tools to drug- inducible vectors. By establishing potent and drug inducible genome editing AAVs, it will be possible to avoid sustained off-target editing and immunogenicity once the therapeutic editing is achieved.

NIH Research Projects · FY 2025 · 2025-09

PROJECT SUMMARY/ABSTRACT This proposal presents a five-year research career development program focused on the study of the vaginal microbiome and its contributions to bacterial vaginosis (a highly recurrent and common gynecologic condition), with the goal of expanding knowledge on mechanisms for treatment failure and better informing future therapies. The candidate is currently an Assistant Professor of Gynecology and Obstetrics at Johns Hopkins University School of Medicine. The outlined proposal builds on the candidate’s previous clinical experience in recurrent vaginitis and integrates new domains of expertise in clinical investigation, the vaginal microbiome, ‘omics analysis, and bioinformatics. The proposed analyses and didactic work will position the candidate with a unique set of cross disciplinary skills that will enable her to transition to independence as a physician scientist. Bacterial vaginosis (BV), an alteration of the vaginal microbiome associated with vaginal discharge and odor, affects one-third of reproductive age women. BV has been correlated with adverse outcomes including preterm birth and increased risk of STI/HIV acquisition. It is unfortunately highly recurrent, with 25% of individuals experiencing recurrence within 6 weeks of initial treatment and 60% within 1 year. Mechanisms for these poor outcomes are not well understood, though recent data suggests that resistance to metronidazole (the most commonly prescribed antibiotic for treatment) and Lactobacillus iners may play a role. The proposed research aims to evaluate if these mechanisms are responsible for poor treatment outcomes and whether clindamycin, the less commonly prescribed antibiotic for BV, may be more effective than metronidazole for certain individuals. Clindamycin is hypothesized to be superior to metronidazole in those with metronidazole resistance, and for those with Lactobacillus iners present prior to treatment, as it targets lactobacilli while metronidazole does not. Theoretically, eliminating Lactobacillus iners, which is associated with frequent BV recurrences, may allow for a more favorable Lactobacillus spp. to populate (L. crispatus, L. jensenii, L. gasseri: all associated with fewer BV occurrences). The proposed aims will 1) determine the impact of clindamycin treatment on the vaginal microbiota, focusing on Lactobacillus spp. post-treatment, 2) use metagenomics to identify markers of metronidazole resistance and presence of L. iners pre- and immediately post- treatment, relating these factors to clinical outcomes over 6 weeks, and 3) recruit a cohort of individuals with recurrent BV who are treated with clindamycin, following closely with frequent vaginal sampling for 6 weeks post-treatment, characterizing microbiome changes following treatment (specifically timing of Lactobacillus repopulation). The scientific objective is to help inform future BV therapeutic approaches by identifying if clindamycin is a preferred treatment either: 1) for a subset of individuals with BV (those with metronidazole resistance or L. iners present prior to treatment) or 2) as pre-treatment prior to novel therapies such as live biotherapeutics (e.g., vaginal probiotics) which aim to introduce favorable Lactobacillus spp. to the vaginal microbiome.

NIH Research Projects · FY 2025 · 2025-09

Project Summary Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy, offering durable responses in previously untreatable malignancies. However, their use is associated with immune-related adverse events, including pulmonary toxicities such as severe acute respiratory failure (ARF). In fact, ARF is a leading cause of ICU admissions among ICI-treated patients. Despite the increasing prevalence of these events in ICI-treated patients, little is known about the specific clinical and biomarker risk factors for ARF or the impact of specific ARF etiologies on survival outcomes. Existing studies primarily focus on checkpoint inhibitor pneumonitis (CIP), an adverse event associated with ICI therapy. However, these studies often overlook the broader spectrum of ARF etiologies in ICI-treated patients. Consequently, there is a critical need to identify high-risk profiles and evaluate how ARF etiologies, both CIP and non-CIP, influence survival outcomes following ICI therapy. This proposal aims to address these gaps through two specific aims. Aim 1 will identify clinical and biomarker risk factors, including smoking history, pulmonary disease, cancer type/stage, treatment-related characteristics, and blood biomarkers (neutrophil-to-lymphocyte ratios [NLR], absolute lymphocyte counts [ALC], and monocyte counts), associated with ARF in a retrospective cohort of 5,800 ICI-treated patients using real-world clinical data from the Johns Hopkins Precision Medicine Analytics Platform (PMAP). Aim 2 will assess survival outcomes and recovery metrics stratified by ARF etiology, particularly CIP versus non-CIP ARF, to quantify their prognostic impact. This aim involves adjudicating 360 cases of ARF using a rigorous multidisciplinary approach, integrating structured data and clinical review to classify ARF etiologies comprehensively. By addressing key gaps in understanding ARF in ICI-treated patients, this proposal aims to improve early identification of high-risk patients, optimize management of respiratory complications, and provide actionable data to refine monitoring strategies. This research also provides exceptional training in risk factor analysis, advanced survival analysis, and interdisciplinary collaboration, establishing the groundwork for an independently funded research career dedicated to improving outcomes for patients with pulmonary toxicities associated with novel cancer therapies.

NIH Research Projects · FY 2025 · 2025-09

ABSTRACT The proposed research aims to adapt and assess a multi-level intervention package to improve antiretroviral 3 therapy (ART) adherence and viral suppression among women living with HIV (WLHIV) across the lifespan in 4 Blantyre, Malawi. This proposed intervention aims to achieve and maintain viral suppression through improved 5 ART by addressing challenges related to experiences across interpersonal, community, organizational, and 6 structural levels. WLHIV in Malawi experience challenges including violence, social isolation, limited access to 7 quality healthcare, and economic instability. These experiences are often driven by stigma related to HIV and 8 perceived risk behaviors that create obstacles for women and ultimately, epidemic control for HIV. In response, 9 interventions that can reduce both the occurrence and impact of stigma are needed to effectively improve 10 access to quality care, its uptake, and HIV outcomes among women. In response, we have developed a 11 practical, multi-level intervention package that targets facilitators and drivers of stigma at the organizational, 12 community, and interpersonal levels to achieve optimal HIV outcomes. The package aims to innovatively 13 combine evidence-based program components to reduce 1) the occurrence of enacted stigma in interpersonal, 14 community, and healthcare settings, and 2) interrupt key mechanisms through which stigma affects health by 15 improving economic stability, social support, and mental health. This study builds on a strong collaboration of 16 more than 30 years between the Johns Hopkins University, the Malawi Ministry of Health and the Kamuzu 17 University of Health Sciences in Blantyre, Malawi. To accomplish this goal, our specific aims are: 1: Adapt a 18 multilevel intervention package for WLHIV in Blantyre, Malawi using the ADAPT-ITT model; 2: Implement a 19 pilot trial of the adapted multi-level intervention package among WLHIV in Blantyre, Malawi; and 3: Evaluate 20 the implementation process of the adapted multi-level intervention using the Consolidated Framework for 21 Implementation Research (CFIR). Reducing the occurrence and impact of stigma has the potential to support 22 long-term viral suppression, improved health outcomes, and higher quality of life among WLHIV across the 23 lifespan in Malawi. This experienced, multi-disciplinary investigative team brings together clinical, 24 epidemiological, and research expertise across HIV, mental health, stigma measurement and intervention 25 development, as well as decades of experience in clinical trials, research-practice partnerships, and 26 community engagement in Malawi. Our study design elements reflect these rich experiences and leverage 27 both implementation science and conventional observational/interventional approaches.

NIH Research Projects · FY 2025 · 2025-09

PROJECT SUMMARY Antiretroviral treatment (ART) is now universal. In women living with HIV (WLHIV), ART reduces perinatal HIV transmission and improves maternal health. In sub-Saharan Africa, women are surviving healthier and longer in a setting where most of the global HIV infections have occurred. However, other aspects of the lifespan for these women need monitoring and further planning. Specifically, areas related to reproductive health, fertility expectations, aging, and pre-menopause/menopause have not been adequately examined in the African setting. Although ART is effective and safe, its long-term assessment should continue to examine potential interactions with reproductive hormones (RHs) that physiologically impact reproduction and other aspects of health. These reproductive health data are scarce in Africa among aging populations. It should be realized that ART is not limited to treatment of those living with HIV; it will soon encompass wider coverage through pre-exposure prophylaxis and long-acting regimens for women living without HIV. Therefore, a longitudinal assessment of the RHs that influence conception and their potential association with infecundity, premature menopause, and menstrual irregularity is an important, unique priority to address the evolving needs of WLHIV as they age. We propose a longitudinal study of the female anti- mullerian hormone (AMH), a marker of ovarian reserve and produced by the granulosa cells of the ovary, utilizing recently collected samples from WLHIV on lifelong ART in a cohort study called “PROMOTE” (a multi-country, observational study conducted at eight African sites during 2016-2021). In the proposed study, we will use laboratory samples and data from the Blantyre site in Malawi. We have robust data already collected on sociodemographic, sexual, and reproductive health (including use of hormonal contraceptives), and clinical (including viral load and CD4 cell counts) information from baseline and at follow-up visits every six months for approximately five years. We noted an interesting observation at study completion at the Blantyre site: 112 WLHIV on lifelong ART (41% of 273 who did not have a hysterectomy or tubal ligation) never became pregnant during follow-up, and 161 (59%) became pregnant at least once. This raises a question whether HIV/ART (or other related factors) is associated with infecundability. To investigate this observation further, we will measure AMH levels at baseline and at each follow-up visit. We will compare AMH values at baseline from the PROMOTE cohort to measurements obtained from a separate control group of non-pregnant, age-matched, women without HIV recruited from the same clinics in Blantyre, Malawi. The control group will include two groups of women using/not using HCs to allow evaluation of the impact of HCs use on AMH. These data will allow us to determine the association of lifelong ART with AMH and its impact on fecundity. This exploratory study could have high reward to the scientific community involved in reproductive health management.

NIH Research Projects · FY 2025 · 2025-09

PROJECT SUMMARY/ABSTRACT Mary Rooney, PhD, MPH is a junior faculty member at the Johns Hopkins Bloomberg School of Public Health Department of Epidemiology at the level of Assistant Research Professor. She seeks a K01 Mentored Research Scientist Development Award to become an independent research scientist in the area of diabetes prediction and -omics. This research proposal details a 5-year plan to refine current prediabetes definitions to better predict who will develop diabetes and its complications using clinical factors, novel proteomic biomarkers, and polygenic risk scores. The specific aims of this research are to: 1) harmonize datasets and pool participant-level data from 13 epidemiologic cohorts; 2) refine prediabetes definitions by integrating information on clinical factors, novel proteomic biomarkers, and genetic susceptibility; and 3) quantify the associations of clinical, proteomic, and genetic risk stratification groups with risk of diabetes complications. Short-term career goals include advanced training in multiple -omics research, leading a meta-analysis within a consortium and the development and validation of diabetes risk prediction equations. The proposed mentored research and career development activities fill training gaps needed to facilitate Dr. Rooney’s transition into a successful independent researcher. A more precise approach to diabetes risk stratification can inform clinical and public health strategies for the screening and primary prevention of diabetes and its complications.

NIH Research Projects · FY 2025 · 2025-09

ABSTRACT/SUMMARY Pregnancy-related outcomes, and disparities in these outcomes, remain poor and have worsened in recent years. At the same time, the lack of safe and affordable housing has become a national crisis. Despite the strong potential for housing insecurity to impact the perinatal period, there is a paucity of evidence connecting these two areas. The Care, Housing Assistance, Medicaid, and Perinatal (CHAMP) Health Outcomes Study is a highly innovative investigation of the association between housing security and perinatal and infant outcomes. It focuses on the role of federal housing assistance which, through a variety of programs, including Housing Choice Vouchers, public housing, and multifamily housing, limit household spending on rent and utilities. By increasing housing affordability and stability, improving housing quality, changing neighborhood context, and connecting residents with health and social services, federal housing assistance has the potential to improve the quality of care that pregnant individuals receive and, more broadly, shed light on the intersection of pregnancy and housing. The study makes use of a novel dataset linking national Medicaid claims for the years 2016-2023 with U.S. Department of Housing and Urban Development data on the receipt of federal housing assistance. Because individuals who receive housing assistance may be fundamentally different from those who do not, the study makes use of an innovative ‘pseudo’ waitlist control design that leverages the limited supply of housing assistance relative to demand and the random timing of the receipt of housing assistance. The first aim examines the overall relationship between receipt of federal housing assistance and pregnant and postpartum individuals (including pre- and post-natal care and morbidity) and newborns (including low birth weight, preterm birth, and neonatal intensive care admission). The second aim investigates whether these relationships vary across a range of factors including race and ethnicity, neighborhood socioeconomic context, and type of housing assistance. The final aim uses qualitative methods to elicit narratives and perspectives on how housing assistance can support perinatal and infant health through interviews with policy and program officials, practitioners, and people with lived experience.

NIH Research Projects · FY 2025 · 2025-09

Project Summary Understanding trends and patterns in cause of death is essential for designing and implementing effective public health policy. In large parts of the world, most deaths happen outside of a healthcare setting and there is no medically certified record of the cause, stymying efforts to improve health in such settings and also creating downstream effects for health systems globally. Verbal Autopsies (VAs) consist of interviews with a person familiar with the circumstances surrounding a recent death and involve both a structured interview and a free-text narrative. The narrative is currently underutilized or wholly ignored in most settings. Our proposal leverages innovative Natural Language Processing (NLP) tools to ascertain cause of death from VA narratives. Our first Aim produces the most extensive and most heterogeneous collection of VAs with gold standard (medically certified) causes, which is essential for training machine learning and Artificial Intelligence (AI) models. Aim 2 critically evaluates both classical and cutting-edge NLP models to ascertain the cause of death. Along with evaluating the accuracy in ascertaining cause of death, we perform a detailed error analysis to understand potential sources of bias across demographic or other contextual factors that arise from the combination of currently available NLP algorithms and available data to train these models. Ascertaining cause of death is incredibly challenging, and even the most advanced algorithm will make mistakes. Ignoring this reality leads to inaccurate and biased estimates of patterns and trends in cause of death (e.g., the fraction of deaths due to malaria from urban areas compared to rural areas or whether the burden of cardiovascular disease has changed from one time to another). Aim 3 leverages cutting-edge statistical tools and the datasets assembled in Aim 1 to correct for these biases. We also perform detailed sample size calculations to understand the number of VAs required to detect changes in patterns and trends. 1

NIH Research Projects · FY 2025 · 2025-09

PROJECT SUMMARY/ABSTRACT Idiopathic subglottic stenosis (iSGS) is a debilitating and life-threatening disease where scar tissue narrows the airway, severely limiting an individual’s ability to breathe and communicate. The cause is not completely delineated but appears related to the activation of a pro-inflammatory cascade. Treatment is procedural with the goal of increasing airway diameter to improve breathing. The most commonly employed treatment approach is intermittent endoscopic dilation, typically performed every 12-18 months. Adjunctive methods to prolong the period between operations are highly desirable to the iSGS patient community. One promising potential adjunctive method is serial intralesional steroid injections (SILSI), or serial injection of steroids into the affected airway in the clinic setting. While initial single-institution retrospective series showed potential for prolongation of the inter-operative interval, secondary analysis of a multi-institutional prospective cohort study did not show a clear benefit. Given disparate results and the importance of developing effective adjunctive methods, a prospective randomized trial is critical to evaluate the effectiveness and determine which iSGS patients may benefit most from this adjunctive treatment. CCC MPIs, Drs. Alexander Hillel and Alexander Gelbard, along with DCC MPIs, Drs. Dan Hanley and Gayane Yenokyan, will lead a multicenter, prospective, randomized, double- blinded, placebo-controlled trial titled, ASTRO: Adjuvant STeRoid injection Outcomes in idiopathic subglottic stenosis. This trial was developed in partnership with both patient and clinician stakeholders and is designed to evaluate the safety and efficacy of SILSI in iSGS patients. 226 iSGS participants will be recruited across 10 high- volume academic sites and randomized to SILSI or placebo (intralipid preparation simulating appearance of triamcinolone) in a 1:1 ratio following a standardized endoscopic dilation. Participants will undergo a series of three injections, spaced one month apart and beginning one month after endoscopic dilation. Our primary outcome measure is percent peak expiratory flow, which is a biomarker of disease recurrence in iSGS. The study aims are to: (1) Compare change in peak expiratory flow in iSGS patients with and without adjuvant SILSI from 1 month to 6 months after endoscopic dilation (primary endpoint) and 1 month to 12 months after dilation (secondary endpoint); (2) Compare secondary outcomes in iSGS patients with and without adjuvant SILSI including patient-reported outcome measures of breathing, QoL, voice, and swallow function as well as toxicity profile and safety events, including return to the operating room for a recurrent procedure and death; and (3) Characterize heterogeneity in SILSI treatment response based on demographic, clinical, surgeon, and genomic characteristics as assessed using established single nucleotide polymorphisms (SNPs) proven to dictate steroid responsiveness in patients with asthma. This represents the first interventional trial in iSGS and fills a critical knowledge gap by assessing the efficacy and safety of SILSI for iSGS, providing an evidence-based foundation to change clinical practice.

NIH Research Projects · FY 2025 · 2025-09

PROJECT SUMMARY/ABSTRACT Idiopathic subglottic stenosis (iSGS) is a debilitating and life-threatening disease where scar tissue narrows the airway, severely limiting an individual’s ability to breathe and communicate. The cause is not completely delineated but appears related to the activation of a pro-inflammatory cascade. Treatment is procedural with the goal of increasing airway diameter to improve breathing. The most commonly employed treatment approach is intermittent endoscopic dilation, typically performed every 12-18 months. Adjunctive methods to prolong the period between operations are highly desirable to the iSGS patient community. One promising potential adjunctive method is serial intralesional steroid injections (SILSI), or serial injection of steroids into the affected airway in the clinic setting. While initial single-institution retrospective series showed potential for prolongation of the inter-operative interval, secondary analysis of a multi-institutional prospective cohort study did not show a clear benefit. Given disparate results and the importance of developing effective adjunctive methods, a prospective randomized trial is critical to evaluate the effectiveness and determine which iSGS patients may benefit most from this adjunctive treatment. CCC MPIs, Drs. Alexander Hillel and Alexander Gelbard, along with DCC MPIs, Drs. Dan Hanley and Gayane Yenokyan, will lead a multicenter, prospective, randomized, double- blinded, placebo-controlled trial titled, ASTRO: Adjuvant STeRoid injection Outcomes in idiopathic subglottic stenosis. This trial was developed in partnership with both patient and clinician stakeholders and is designed to evaluate the safety and efficacy of SILSI in iSGS patients. 226 iSGS participants will be recruited across 10 high- volume academic sites and randomized to SILSI or placebo (intralipid preparation simulating appearance of triamcinolone) in a 1:1 ratio following a standardized endoscopic dilation. Participants will undergo a series of three injections, spaced one month apart and beginning one month after endoscopic dilation. Our primary outcome measure is percent peak expiratory flow, which is a biomarker of disease recurrence in iSGS. The study aims are to: (1) Compare change in peak expiratory flow in iSGS patients with and without adjuvant SILSI from 1 month to 6 months after endoscopic dilation (primary endpoint) and 1 month to 12 months after dilation (secondary endpoint); (2) Compare secondary outcomes in iSGS patients with and without adjuvant SILSI including patient-reported outcome measures of breathing, QoL, voice, and swallow function as well as toxicity profile and safety events, including return to the operating room for a recurrent procedure and death; and (3) Characterize heterogeneity in SILSI treatment response based on demographic, clinical, surgeon, and genomic characteristics as assessed using established single nucleotide polymorphisms (SNPs) proven to dictate steroid responsiveness in patients with asthma. This represents the first interventional trial in iSGS and fills a critical knowledge gap by assessing the efficacy and safety of SILSI for iSGS, providing an evidence-based foundation to change clinical practice.

NIH Research Projects · FY 2025 · 2025-09

Project Summary: During development, sensory neurons differentiate into subtypes with distinct morphologies, gene expression, and functions. In the retina, the diversity of photoreceptor subtypes is critical for vision and the ability to interact with the environment. This proposal aims to advance our knowledge of cell fate specification by examining how photoreceptors are patterned during development in flies and mosquitoes. In the fly eye, stereotypical and stochastic patterns are overlaid during development. The stereotypical structure of the eye results from a wave of morphogenesis, driven by Hedgehog (Hh) signaling, which promotes expression of Decapentaplegic (Dpp). Overlaid on the regular morphology of the eye, two R7 photoreceptor subtypes are stochastically patterned, controlled by stochastic ON/OFF expression of the transcription factor, Spineless (Ss). My preliminary studies show that Hh signaling coordinates stereotyped and stochastic patterning in the fly eye, requiring activity of the receptor Patched (Ptc), but not Cubitus Interruptus (Ci), the canonical transcriptional effector. I hypothesize that Hh functions through an unidentified transcriptional factor to promote (1) dpp transcription and stereotypical morphological patterning and (2) ss transcription and stochastic R7 subtype patterning. To test this hypothesis in Aim 1, I will analyze the transcriptional and chromatin dynamics of dpp and ss regulation. I will generate a single-nucleus multiomics dataset to identify putative transcription factors mediating Hh signaling and examine their functions in the eye. This aim will address how signaling mechanisms that drive stereotypical patterning are co-opted to produce stochastic patterns during development. Mosquitoes are a disease vector that pose an increasing risk to human health and welfare. In mosquitoes, vision is critical for host-seeking, mating, and foraging behaviors, yet the mechanisms that establish patterning of the mosquito eye are not known. In contrast to the fly eye, R7 subtypes are found in stereotypical stripe patterns in the dorsal and ventral regions of the mosquito retina. I hypothesize that the gene network giving rise to stereotypical PR subtype specification is vital for mosquito survival behaviors. To test this hypothesis in Aim 2, I will generate a single-nucleus multiomics atlas of retinal development in An. gambiae, identify factors with cell-type-specific expression and roles in fly eye development, and validate their expression using IHC and RNA FISH. I will determine roles for Drosophila R7 patterning genes in An. gambiae. Finally, I will determine the functional roles of R7 subtype specification in behavior using host-seeking assays. In my lab, I will dissect the regulatory networks involved in mosquito retinal development, focusing on patterning and cell fate specification. Using the atlas, I will define the roles of ~30 key regulators previously characterized in flies, and compare their functions across species, including Ae. aegypti. I will also identify and test novel regulators of mosquito eye development. These studies will provide the first mechanistic dissection of eye development in mosquitoes, generate insights into evolution of the underlying mechanisms, and establish my independent research program.

NIH Research Projects · FY 2025 · 2025-09

Smart assistive technology (SAT) for individuals with severe vision loss is becoming affordable, thanks to miniaturization of display hardware (head-mounted or phone screen) and more powerful AI software, driven by demand in the consumer market. Unfortunately, these developments do not take into account visually impaired users’ perspective on: 1) ergonomics, i.e., non-visual access to all device functions; and 2) relevance, i.e., functionality that meets their needs and enhances independence. The most often heard complaint is that the device or app overwhelms the user with information, so pertinent information is too hard to find. In this application, four organizations — the Low Vision divisions at Johns Hopkins (JHU) and the Chicago Lighthouse (CLH), Applied Universal Dynamics Corp (AUD) and the Pritzker Institute at the Illinois Institute of Technology (IIT) — are joining forces to address this problem. We are uniquely positioned to do so, through our combined expertise in smart systems design and integration (AUD), clinical and rehabilitative knowledge of the user population (JHU and CLH), and the opportunity to extend the user base to visual prosthesis users (IIT). With the users’ lived experience in mind, we propose to reduce the information overload by defining a gaze-contingent region of interest (RoI) specific to each user’s gaze and remaining visual field, so the AI- supported system will operate on targets within this RoI. In the R61 phase of the project, we will use a head- mounted display (HMD) with built-in eyetracking as the platform; in the R33 phase, a glasses frame with built-in camera and eyetracking will be used, with a smart phone or belt pack computer running the AI engine. The R61 phase will encompass 3 Aims: 1) Formulate user requirements by surveying SAT users (interviews and discussions), and recruit an expert user panel for ongoing feedback; 2) Design and build an HMD-based prototype (H1) for clinical tests, with a software upgrade (H2) based on initial outcomes and feedback; 3) Conduct user training and collect ongoing feedback and performance data for evaluation and re- design. The R33 phase will create the glasses-based system and enhance processing power and customization, through 3 additional Aims: 4) Integrate the glasses frame camera and eyetracker with a speech- enabled belt pack computer (G1), with an upgrade in Year 4 (G2) suitable for take-home use; 5) Enhance user- specific solutions by adding individualized and task-specific RoI adjustments, and add search and hazard warning functions for users with narrow fields; 6) Conduct user training and collect ongoing feedback and performance data for evaluation and G2 upgrades, followed by a 3-month take-home study with performance tests (pre vs, post). The resulting gaze-contingent AI-supported low vision adaptive technology (GALVAT) will be highly adaptive to users’ individual needs and greatly contribute to their functional visual independence.

NIH Research Projects · FY 2025 · 2025-09

The building and then testing of high-quality health care service delivery models and practices is urgently needed to substantially reduce global maternal and infant health disparities. Low-resource settings have some of the worst perinatal health outcomes globally. A constellation of health system and social factors contribute to maternal and infant morbidities, including low rates of receipt of health care and preventive services. Unaddressed postpartum morbidities (e.g., depression) can directly impact the health and well-being of the infant, for whom the first year of life is a crucial time for their long-term health. As such, there have been calls for a redesign of maternal and infant health services and systems. Group care is a promising strategy for maternal and child health care redesign, but has primarily been tested in the antenatal setting. Few studies examine extending group care into the postpartum period, integrating postpartum and well-child care in low resource settings. However, opportunities exist to address ongoing maternal and infant morbidities while supporting the transition of the dyad from postpartum to primary care during this critical time in the life course. In 2022, we collaboratively adapted an evidence-based group healthcare model and co-designed an integrated group postpartum and well-child care model that extends postnatal care to 12 months while integrating it with well-child care so that the health needs of the dyad are addressed simultaneously. This model brings together 8-10 postpartum women with similarly aged infants to engage in care together. Each visit is 2 hours, with the first 30–45 min devoted to standard clinical health assessments for the dyad and participation in self-assessments, followed by 75–90 min of interactive health promotion activities. Using a cluster randomized control trial with mixed methods, we will assess the impact of this innovative and proactive group healthcare model at 16 clinics. We will use the same 3-Step Implementation Model that allowed our team to successfully implement and sustain group prenatal care at seven clinics. We will test the hypothesis that compared to usual care, infants will have increased vaccination rates and women will have decreased postpartum depression, anemia, and hypertension, and more optimal secondary outcomes for the dyad, such as uptake of family planning, exclusive breastfeeding, childhood development, and nutrition. We will also qualitatively explore the health and health-related social needs that arise in the 12 months after birth for both women and their infants and identify clinic- and patient-level implementation facilitators and barriers. This study will be the first to conduct an adequately powered trial of an integrated group postpartum and well-child care model in an LMIC. This rigorous study will have important public health policy implications for the U.S, where maternal morbidity rates are unacceptably high. Results will provide clinical evidence for improved maternal and infant health care in the first year postpartum.

NIH Research Projects · FY 2025 · 2025-09

PROJECT SUMMARY Cabell County, West Virginia has been experiencing an ongoing HIV outbreak linked to injection drug use since 2018 among people who inject drugs (PWID), driven by both syringe sharing and unprotected sex. Little attention has been paid to other infectious diseases that share transmission pathways in the context of this outbreak. Thus, we propose to examine HIV, Hepatitis C, syphilis, gonorrhea, and chlamydia co-infection patterns, identify correlates of co- infection (Aim 1), and assess associations with health-related quality of life (Aim 2) among an existing cohort of 400 rural PWID in Cabell County. We will further explore the decision-making processes of PWID who engage in risk behaviors with known HIV+ partners to identify psychosocial targets for future interventions to prevent infectious disease transmission (Aim 3). To achieve the study goals, we propose conduct Hepatitis C and STI (syphilis, gonorrhea, and chlamydia) testing at the 9 and 12 month follow up visits of the HEARTS of WV study (R01DA059335) to supplement existing HIV testing procedures. We will then conduct a latent class analysis of co-infection profiles using the infectious disease testing results. We will conduct a latent class regression analysis to assess sociodemographic, behavioral, and social network correlates of co-infection profiles. We will then use structural equation modeling to estimate the total, direct, and indirect effects through infectious disease treatment engagement on health-related quality of life. We will then conduct 30 in-depth qualitative interviews with PWID who report engaging in syringe sharing or unprotected sex with known HIV+ partners around their decision making processes for doing so to identify modifiable influences to inform future intervention. This proposal will address key gaps in the existing literature by approaching co-infection holistically among PWID, as most co-infection research to date has focused on a single disease parings or transmission pathway (e.g., sexual risk). Findings from Aim 3 in depth interviews will be used to inform future intervention development and implementation by our local partners at the Cabell Huntington Health Department to reduce disease spread. Importantly, the study activities will all occur within the context of an active HIV outbreak which are increasingly common occurrence in rural communities due to the ongoing opioid crisis, making this a high priority context to study to inform future response strategies.

NIH Research Projects · FY 2025 · 2025-09

PROJECT SUMMARY The Johns Hopkins Wilmer Eye Institute StARR (Stimulating Access to Research in Residency) Program seeks to extend its goal of training clinician-scientists in the areas of clinical and laboratory vision research. The program has 4 goals: 1) recruitment of qualified resident-researchers (scholars) with an interest in studying ocular disease, 2) optimizing the research experience of accepted scholars, 3) preparing scholars for successful clinician-scientist careers, and 4) ensuring successful clinical and surgical training. Recruitment will be facilitated by Wilmer's strong research presence, including over 50 active scientists serving as program faculty with combined annual funding over $30 million, more than any other ophthalmology department. Wilmer scientists work across all core NEI programmatic areas, and benefit from several research-focused Centers housed within Wilmer or the Johns Hopkins Medical campus. The facilities and resources enabling Wilmer's clinical and lab research program are unsurpassed, including the 200,000 sq ft Smith Building, active T32 and P30 grants, and 66 endowed professorships. Wilmer has produced more full-time academics and Department Chairs than any other eye department in the U.S. Wilmer has a strong program training and mentoring clinician-scientists as part of its K12 program, as well as its Rising Professorship program for junior faculty. Additionally, Wilmer provides, and will extend, its resources to residents pursuing research, including grants and endowed support to reward top research. Our program will ensure scholar success by helping them plan their research and overseeing progress via an Advisory Committee of R01-funded scientists, K awardees, and residency leadership. Unique program features include having scholars prepare career development and research plans, which will be reviewed, revised, and approved prior to starting research. The Committee will also ensure progress through semi-annual reviews (written and joint scholar/mentor meetings), written reports with recommendations, and scheduled check-ins. Resident researchers will be prepared for long-term success via training activities including journal clubs and workshops on manuscript writing, grant writing, and career development. Long-term research scholar success will be aided by Advisory Committee reviews beyond the end of the dedicated research period (including a review of drafted K award aims, which will be required from scholars) and formal evaluation for burnout. Finally, StARR residents will have their clinical progress carefully monitored to ensure that they are meeting all clinical milestones, and that research excellence is matched by excellence in clinical and surgical skills.