OBJECTIVES/SPECIFIC AIMS: Rheumatoid arthritis (RA) is one of the most prevalent systemic autoimmune diseases. It is caused by a combination of genetic and environmental factors. In humans, the intestinal microbe Prevotella copri strongly correlates with RA in previously untreated new-onset rheumatoid arthritis (NORA) patients. Metagenomic assembly of P. copri from NORA patients and healthy controls suggests genetic differences between P. copri from each group. In order to test the hypothesis that genetic differences in P. copri from arthritis patients promote arthritis, I am performing genomic comparison of primary P. copri isolates from NORA patients and healthy controls, and analysis of the immune response to P. copri in mice. Mice colonized with P. copri have increased susceptibility to DSS-induced weight loss and death compared with uncolonized controls. Future experiments will assess the local and systemic immune response in P. copri-colonized, DSS-treated mice. If this work is successful, then it may be possible to exploit genetic variation in P. copri. This could lead to new biomarkers for human disease or even insight into drug metabolism. METHODS/STUDY POPULATION: To validate a strategy to screen for the presence of P. copri in feces, qPCR primers were designed to amplify 8 regions across the 3.5 Mb P. copri reference genome using NCBI PrimerBlast. Primers were validated with DNA from feces for which P. copri abundance was previously determined by 16S rDNA sequencing. P. copri genome-specific primers were used to screen bacterial isolates from NORA patients and healthy controls. The 16S V3-V4 region was sequenced and compared with the P. copri reference 16S sequence to confirm >97% similarity. Genomes of 2 NORA patient isolates were sequenced on Illumina MiSeq, and sequences were compared with the reference genome. A strategy was developed to colonize mice with P. copri: 3-week-old C57BL/6 mice were treated with antibiotics in drinking water for 2 weeks, then switched to water for 2 days before oral gavage with P. copri; 6–7 days after inoculation, P. copri colonization was assessed by plating feces from inoculated mice, and by qPCR of fecal DNA with P. copri-specific primers. A systemic immune response to P. copri was assessed by microbe-specific ELISA for IgG and IgA in the sera of colonized mice. RESULTS/ANTICIPATED RESULTS: P. copri was detected in the stool of 20% of healthy individuals and 50% of NORA patients. P. copri was isolated form 4 healthy individuals and 6 NORA patients. Whole genomes of 96 primary isolates from NORA patients and healthy controls will be sequenced on the Illumina HiSeq platform, and their genomes will be assembled and compared using Spades software. For 2 P. copri isolates for a NORA patient, 89% of 250 bp reads aligned >95% to the P. copri reference genome. Mice can be colonized with P. copri gavaged at >106 CFU. P. copri-specific IgG and IgA were detected in the sera of colonized mice. DISCUSSION/SIGNIFICANCE OF IMPACT: Several primary isolates of P. copri have been collected from healthy controls and NORA patients, which will enable whole genome comparison of these isolates. For the 2 P. copri isolates sequenced, 89% of 250 bp reads aligned >95% to the P. copri reference genome, indicating variability between NORA patient P. copri strains and the P. copri reference genome. The establishment of colonization of mice with P. copri will allow further characterization of the immune response to P. copri at steady state and under pro-inflammatory conditions. Further, the systemic immune response to P. copri indicates that this microbe may have potential to play a role in systemic disease.

OBJECTIVES/GOALS: Gender affirming medical care such as hormone therapy surgery can greatly impact the emotional wellbeing and quality of life of transgender and gender-nonconforming individuals. In the US, insurance coverage for these services vary greatly. This project will focus on how insurance denial of gender affirming care can impact emotional wellbeing. METHODS/STUDY POPULATION: Data was collected via the LITE Connect study, a multi-institutional cross-sectional survey conducted among transgender and gender non-conforming adults in the United States and Puerto Rico from 2020 to 2021. The survey collected 2,125 responses concerning demographic data, insurance status, desire to access gender affirming care, history of insurance denial of gender affirming care, psychological distress (measured via Kessler 6 scale), self-harm, and suicide. The study population consisted of respondents who have sought GAMC in their lifetime, and further separated into individuals who have had insurance denial of gender affirming care versus those without insurance denial. Odds ratios were examined for categorical variables and linear regression was conducted for Kessler 6 score. RESULTS/ANTICIPATED RESULTS: Of the 2125 respondents, 1274 (61%) have sought out GAMC. Of those seeking GAMC, 451 (35.4%) have experienced an insurance denial. Preliminary analysis of the odds ratios of insurance denial versus demographic identifiers found no significantly increased odds ratios with respect to race, gender, or age. Given the impact GAMC has on quality of life, we theorize that difficulty accessing gender affirming care would be associated with greater psychological distress. Linear regression found a statistically significant impact of insurance denial of GAMC on Kessler 6 responses (Beta = 0.9684, R^2 = 0.0069). With adjustments for age, gender identity, race, and insurance status, linear regression found denial of GAMC led to a 1.28 increase in Kessler 6 score (CI [0.59, 1.98], p < 0.05). DISCUSSION/SIGNIFICANCE: This study examined the association between access gender affirming care and emotional wellness as measured by the Kessler 6 scale. We have found a statistically significant correlation between insurance denial of GAMC and psychological distress, indicating an avenue for intervention for a vulnerable population.

OBJECTIVES/SPECIFIC AIMS: Describe (1) the components of the research navigation service and consultation/onboarding program, (2) use and adoption of the services, and (3) the overall satisfaction from the research community. METHODS/STUDY POPULATION: Duke offers 2 programs to support researchers: Research Navigation and Researcher Onboarding. The services aim to connect researchers to resources, offices, funding opportunities, and other collaborators. The general Research Navigation Service is an on-demand “hotline,” where navigators answer questions from researchers across the institution, helping them understand processes, best practices, and how to locate resources or potential collaborators. Navigators can be reached via the myRESEARCHhome portal, email, or by phone. The researcher onboarding program is a free 1:1 consultative service, focused on the researcher’s individual portfolio, stage of career, and immediate plans in the research arena. The goal is to equip researchers “from the start” to be successful. Researchers are identified via the new faculty hire list, or by referral. Both services are provided by the myRESEARCHnavigators team, who are trained in a variety of research areas, from basic to clinical to social sciences, and are familiar with Duke. RESULTS/ANTICIPATED RESULTS: Use of both services has increased substantially over the year. Of the almost 200 faculty members hired into the School of Medicine in 2017, ~75% have taken part in the onboarding program, and 91% have rated the service as 5-stars. The content of the sessions will be described. The Research Navigation service has fielded hundreds of calls since its inception, with topics including Equipment and Facilities (55 requests), Study start up (44 requests), Innovation and Technology (15 requests), and Regulation and Policy (25 requests). Categorization of requests, users of the services, and other information about the programs will be described. DISCUSSION/SIGNIFICANCE OF IMPACT: The navigation and onboarding services are proving to be a successful way to increase efficiency and understanding of processes and resources across the institution. Feedback from the users, coupled with high referral rates to the programs, suggests that the program is helping researchers feel better equipped with regard to their research planning, conduct, and analysis.

Objectives/Goals: The importance of interprofessional communication in healthcare is well documented. However, there has yet to be a theoretical framework for understanding this complex phenomenon. The purpose of this project was to develop a situation-specific theory about the culture of communication in the interprofessional healthcare setting. Methods/Study Population: We conducted individual virtual qualitative interviews with 16 healthcare professionals at different levels and from various disciplines. Participants were practicing clinicians at a tertiary care academic medical center. We transcribed audio-recordings of the interviews verbatim and aligned each transcript for accuracy, confidentiality, and representativeness. Data analysis was conducted using dimensional analysis, including open- and theoretical-coding utilizing an explanatory matrix for theory generation. Results/Anticipated Results: Our findings produced a situation-specific theory on the culture of interprofessional communication in the healthcare setting. Participants described the environments in which they practiced in terms of hierarchical system structures and through a conceptual perspective of resource investment. In other words, they viewed their time and their effort as valuable – and notably, scarce – resources, which they invest in patient care, interprofessional communication, and other tasks. There are two key pathways that characterize the culture of interprofessional communication: collaborative communication and transactional interactions, depending on whether an individual perceives the goals of another person, department, or level of the hierarchical institution as aligned with their own goals. Discussion/Significance of Impact: Positive cultures of interprofessional communication in the healthcare setting depend on perceived goal alignment among individuals, departments, and leadership. Future research can explore how perceptions of goal alignment are developed and empirically test this situation-specific theory in other healthcare system settings.

OBJECTIVES/GOALS: Low birth weight and preterm birth are significant contributors to infant mortality in the United States that disproportionally impact Black pregnant persons and their offspring. Although these outcomes are linked to chronic stress, the contribution of race-related stress remains largely understudied. METHODS/STUDY POPULATION: We investigated the effect of race-related stress on weight and gestational age at birth in a prospective cohort of 115 pregnant Black persons recruited at Grady Memorial Hospital in Atlanta, Georgia. The Index of Race-Related Stress Brief (IRRS-Brief), Perceived Stress Scale (PSS), and Stressful Events Questionnaire (SEQ) were collected at study enrollment during pregnancy. Neonatal birth weights and gestational age were collected via standardized medical record abstraction. We conducted linear regressions to determine whether greater race-related stress was associated with lower weight and gestational age at birth, while controlling for sources of prenatal stress. RESULTS/ANTICIPATED RESULTS: Global racism (total IRRS score) was significantly associated with birth weight when controlling for prenatal perceived stress and stressful life events within the last six months since study enrollment (beta=−16.7, p=.035). Neonatal gestational age was associated with both global racism (beta=-0.03, p=.028) and individual racism (IRRS’Individual’ subscale score) (beta=-0.09, p=.032) when controlling for prenatal perceived stress and stressful life events within the last six months since study enrollment. These results suggest that greater race-related stress contributes to lower weight and gestational age at birth in pregnant Black persons. DISCUSSION/SIGNIFICANCE: Future studies are necessary to determine the mechanisms by which race-related stress contributes to these adverse birth outcomes and to inform the development risk-assessment tools and interventions to mitigate the threat of race-related stress on adverse birth outcomes in high-risk populations.

The purpose of the article is to describe the progress of the Clinical and Translational Science Award (CTSA) Program to address the evaluation-related recommendations made by the 2013 Institute of Medicine’s review of the CTSA Program and guidelines published in CTS Journal the same year (Trochim et al., Clinical and Translational Science 2013; 6(4): 303–309). We utilize data from a 2018 national survey of evaluators administered to all 64 CTSA hubs and a content analysis of the role of evaluation in the CTSA Program Funding Opportunity Announcements to document progress. We present four new opportunities for further strengthening CTSA evaluation efforts: (1) continue to build the collaborative evaluation infrastructure at local and national levels; (2) make better use of existing data; (3) strengthen and augment the common metrics initiative; and (4) pursue internal and external opportunities to evaluate the CTSA program at the national level. This article will be of significant interest to the funders of the CTSA Program and the multiple stakeholders in the larger consortium and will promote dialog from the broad range of CTSA stakeholders about further strengthening the CTSA Program’s evaluation.

The potential for physicians, clinicians, and health professionals to contribute to the advancement of medical therapies through clinical research is significant. Yet, a lack of exposure to, or practical training in, the conduct of clinical research can inhibit health profession trainees from considering research careers, thus perpetuating the already limited influx of new talent. To enhance the sustainability of career pathways into research for all trainees, including those from traditionally underrepresented communities, trainees must experience early exposure to research concepts through robust training and hands-on opportunities. In 2015, the Duke Office of Clinical Research created a Research Immersion elective for Duke’s Master in Biomedical Sciences program, which prepares students for additional health professional training. The course trained students through didactic and practical experiences, with a unique interprofessional mentorship team including both principal investigator and clinical research professional mentors. Following eight cohorts of iterative course optimization, students’ confidence increased in all 24 research competencies assessed. A cross-sectional analysis of post-course outcomes in May 2024 revealed 40.4% of students had continued in research after the program and 60.6% had continued their health professions education. We attributed this success to applied learning and clear expectations and guidelines to support the mentor-student relationship.

Despite having the same underlying genetic etiology, individuals with the same syndromic form of intellectual developmental disability (IDD) show a large degree of interindividual differences in cognition and IQ. Research indicates that up to 80% of the variation in IQ scores among individuals with syndromic IDDs is attributable to nongenetic effects, including social-environmental factors. In this narrative review, we summarize evidence of the influence that factors related to economic stability (focused on due to its prevalence in existing literature) have on IQ in individuals with syndromic IDDs. We also highlight the pathways through which economic stability is hypothesized to impact cognitive development and drive individual differences in IQ among individuals with syndromic IDDs. We also identify broader social-environmental factors (e.g., social determinants of health) that warrant consideration in future research, but that have not yet been explored in syndromic IDDs. We conclude by making recommendations to address the urgent need for further research into other salient factors associated with heterogeneity in IQ. These recommendations ultimately may shape individual- and community-level interventions and may inform systems-level public policy efforts to promote the cognitive development of and improve the lived experiences of individuals with syndromic IDDs.

OBJECTIVES/GOALS: To evaluate access to Pre-Exposure Prophylaxis (PrEP) medications for transgender individuals examining how systemic and sociocultural obstacles play a role. Additionally, analyzing the impact of trans-exclusion in clinical trials investigating PrEP efficacy on the trans-HIV care model. METHODS/STUDY POPULATION: By examining the clinicaltrials.gov database, inclusion and exclusion criteria will be collected for Phase III trials of FTC/TAF (Descovy) and FTC/TDF (Truvada) as PrEP for Human Immunodeficiency Virus (HIV). Secondly, trends of physicians’ prescription of PrEP will be analyzed to track post-approval usage and deduce the acceptance and adherence of PrEP by transgender patients. Thirdly, post-approval marketing strategies of PrEP medications will be documented to see key demographics that biopharmaceutical companies are targeting. Finally, relevant literature about trans healthcare will be analyzed to identify key short fallings to support conclusions and justify recommendations for greater transgender clinical trial enrollment and reformations to current standard practices. RESULTS/ANTICIPATED RESULTS: After a preliminary literature review of published Phase III trials for Descovy and Truvada , there is a marked lack of transgender patient enrollment. Contemporary literature argues that this lag in enrollment has downstream effects on trust and acceptance of PrEP as safe and effective by cohorts in the transgender community. The examination of prescribing information for Descovy and Truvada for PrEP reveals a minimal effort to advise doctors of the increased risk for infection in the transgender demographic. Through continued research, I expect to elaborate on the cross-discipline impacts of trans-exclusion, including increased rates of HIV infection, sociocultural and financial barriers to PrEP, and stigmatizing doctor interactions with transgender patients. DISCUSSION/SIGNIFICANCE: The current trans-HIV treatment paradigm lags behind in its sensitivity and nuance, preventing the most equitable distribution of care. Only with more inclusion of transgender individuals in clinical trials can we hope to promote greater awareness and trust for PrEP as effective for HIV.

OBJECTIVES/GOALS: The Stanford CTSA Program has started to create Clinical Research Units (CRUs) with the goal to establish CRUs in all clinical departments by the end of 2020. CRUs will be responsible for managing the portfolio of projects proposed and conducted by faculty within departments. CRUs will be responsible for reviewing all clinical research studies. METHODS/STUDY POPULATION: CRUs will be an integral part of the Stanford’s research infrastructure, tasked with 5 key functions to ensure clinical research conducted by Stanford investigators: scientific merit, feasibility, funding, compliance, progress. Each CRU will review all clinical research projects proposed by investigators within the department prior to moving forward with IRB review. Studies will be evaluated annually to ensure compliance with the protocol, applicable laws and regulations, and recruitment goals. The Stanford CTSA will provide guidelines, SOPs and personnel to assist CRUs. In fall 2019, a landscape analysis of SoM clinical departments was conducted to identify:

1. 1) similar existing CRU-like systems,

2. 2) unique needs of departments/divisions for developing CRUs and

3. 3) barriers to implementation.

RESULTS/ANTICIPATED RESULTS: Challenges the pilot CRU has faced include communication and concerns regarding additional obstacles to conducting research. However, as study teams moved through the initial CRU formation, the feedback was overwhelmingly positive. Study teams were appreciative of the constructive feedback and the support for setting up studies. Results from the landscape analysis identified CRU-like systems in 5 departments and highlighted concerns regarding resources needed to implement CRUs. Based on feedback from the landscape analysis, a faculty and operational lead was identified in each clinical department to oversee CRU implementation. Facilitated by CTSA personnel, CRU leads have met quarterly since April 2019. Meetings consist of discussing expectations, sharing ideas and identifying potential roadblocks. DISCUSSION/SIGNIFICANCE OF IMPACT: CRUs will constitute a new organizational structure that consists of teams of investigators and staff to promote high quality, efficient clinical research and enhance collaborative opportunities. The CRU leadership will champion new initiatives in CTR and create pathways for investigators to access research infrastructure and resources. CONFLICT OF INTEREST DESCRIPTION: NA.

OBJECTIVES/GOALS: Non-operative management is preferred for pediatric solid organ injury (SOI). Despite this children treated at adult trauma centers (ATC) are more likely to be treated surgically and have worse outcomes than those treated at pediatric trauma centers (PTC). We hypothesize there are disparities by sex and race in management of pediatric SOI at ATC vs PTC. METHODS/STUDY POPULATION: Retrospective review of the National Trauma Data Bank (NTDB) from 2010-2018 was conducted. Inclusion criteria were age£18 and injury to spleen, liver or kidney. Outcomes at American College of Surgeons accredited ATC, PTC, and combined ATC/PTC trauma centers were evaluated. The primary outcome was operative management. Secondary outcomes include length of stay, and in-hospital complications. Multivariate logistical regression adjusting for race, sex, and insurance type will be performed. RESULTS/ANTICIPATED RESULTS: 40,111 children were treated for SOI from 2010-2018. 39.3% were treated at an ATC and 26.4% at a PTC. Of children treated at an ATC, 62% were White, 17% were Black, and 1% were Asian. Children treated at the PTC were 60% White, 20% Black, and 0.9% Asian. Primary insurance type was Medicaid for 33% of patients at an ATC and 39% at PTC. Median length of stay at ATC and PTC was 4 days (2-7) and 3 days (2-6) respectively. 3.85% of patients at ATC underwent splenectomy compared to 0.8% at PTC. It is anticipated that further analysis will demonstrate that ICU admission, transfusion, embolectomy, and other operative interventions will be more prevalent at ATC than MTC. Moreover, we anticipate that multivariate logistical regression will show the odds of receiving operative management at each center differ by race, sex and insurance type. DISCUSSION/SIGNIFICANCE: Initial analysis of the NTDB from 2010-2018 shows that children treated for SOI at ATC receive operative interventions more often than those treated at PTC. Elucidating disparities in SOI care is an important step towards minimizing the impact of these disparities and better allocating resources such that they may be eliminated.

OBJECTIVES/GOALS: As the clinical and translational research enterprise evolves toward addressing health equity and the science of translational science, the CE Brokers are exploring new avenues for impacting the CTSA consortium. METHODS/STUDY POPULATION: Since 2013, managers of Community Engagement (CE) programs across the NCATS CTSA institutes have met monthly to build connections, share knowledge, and advocate for the boundary spanner role. As the clinical and translational research enterprise evolves toward addressing health equity and the science of translational science, the CE Brokers are exploring new avenues for impacting the CTSA consortium. The CE Brokers are composed of 140 individuals from 58 CTSA-associated institutions, and have a long history that has fostered rich, trusting relationships. The growth and strength of this group has primed it to pivot with the new NCATS direction to contribute meaningfully to the science of community engagement and continue the work of improving health equity within the communities we serve. RESULTS/ANTICIPATED RESULTS: In 2022; we surveyed its members about their roles and responsibilities; the ways the network has contributed to their hub’s adoption and development of best practices and innovations; resources and lessons learned; the creation of opportunities for members to collaboratively conduct and disseminate original research; and research on the science of CE. Grounding ourselves in this initial data, we have developed interview questions to take the inquiry further, by gathering qualitative data on the impact of the group: How the Brokers group impacted them personally and professionally; How the Brokers impacted the work of their CTSA; In three words, describe the group; How could the CE Brokers contribute to the science of community engagement? DISCUSSION/SIGNIFICANCE: Together, we will identify themes supported by quotes to inform how the CE Broker group is most effectively moving the CTSAs’ mission forward and how it can be improved. These will be shared at the Translational Science Meeting, 2023.

ABSTRACT IMPACT: Rapid launch of a virtual internship can address clinical and translational science training needs of the New Jersey Alliance for Clinical and Translational Science (NJ ACTS) workforce during a pandemic. OBJECTIVES/GOALS: The global pandemic has necessitated innovate strategies for training clinical and translational scientists. With trainees largely restricted from campus, the Workforce Development Core of the NJ ACTS Hub sought to develop and evaluate a virtual 8-week internship program for professional and graduate students within the NJ ACTS community. METHODS/STUDY POPULATION: Establishment of the internship required a systematic approach to 1) recruiting projects and supervisors, 2) collecting and evaluating 90 applications, 3) screening and selecting finalists, and 4) onboarding interns that spanned 7 weeks. Core Leads and Researchers within NJ ACTS developed 8 projects to be performed remotely by 11 interns. Leads and co-leads from the Team Science, Special Populations, Community Engagement, Informatics, and TL1 Cores and Programs designed projects. During the internship, participants engaged in a series of career development training and one-on-one mentoring through weekly meetings. The internship culminated in a final symposium open to the entire clinical and translational science community. RESULTS/ANTICIPATED RESULTS: Interns spanned different educational programs - pharmacy (36%), medicine (18%), and undergrad (9%)/graduate education (36%). Interns included women (63%), students from underrepresented backgrounds (27%) and students who were first in their family to pursue advanced education (18%). Project topics included competency assessment, COVID-19 clinical trials, marketing materials, community engagement salons, eSource for clinical trials, team science projects, and REDCap utilization. Using a 4-point Likert scale to evaluate competencies, the baseline strengths of interns included team-based science (mean/SD: 3.5 ±0.7). Trainings were designed to address gaps in intern skills including developing written and graphical abstracts (mean/SD: 2.2 ±0.9) and effective LinkedIn pages (mean/SD: 2.4 ±1.0). DISCUSSION/SIGNIFICANCE OF FINDINGS: Taken together, the rapid development and launch of a virtual internship program can increase participation of trainees in CTSA Hub research activities and address gaps in their clinical and translational skill set. Plans are to host virtual internships each semester to enhance workforce training and collaboration across Hub Cores.

OBJECTIVES/SPECIFIC AIMS: To provide students an opportunity to select health care-oriented course work that reflects both their interests and the increasingly diverse spectrum of health professions education and health care careers. To increase the opportunity for students to enter professional schools and health care professions with enhanced engagement and experience. METHODS/STUDY POPULATION: The 4-credit elective (Selective) curriculum is a component of the 38 credit Duke School of Medicine Master of Science in Biomedical Sciences (MBS) program which is completed over 10.5 months. Students work closely with their advisors to choose activities that reflect their interests. Selectives are offered by an array of schools, institutes, and programs within Duke University, including: the School of Medicine, School of Law, Global Health Institute, Bioethics and Science Policy Master Program, Clinical Research Training Program, Center for Documentary Studies, and Medical Informatics. Students may also pursue directed studies in areas such as health policy, or an inter-professional trip to Honduras. In addition to the course-based Selectives, three research practicum options are offered: Community Engagement, Clinical Research (Duke Office of Clinical Research), and a self-selected mentored research experience. Finally, the MBS program offers 2 in-house specific Selectives: Fundamentals of Learning: Theory and Practice, and Planning for Health Professions Education. RESULTS/ANTICIPATED RESULTS: The MBS program accepted its first cohort of students in June 2015. Two cohorts have graduated and the third has begun (n=30, 2016; n=42, 2017; n=43 enrolled, 2018). Our students come from diverse background with a third from populations historically underrepresented in STEM due to race/ethnicity, and another third underrepresented due to other factors such as low socioeconomic status, first generation to college, LGBQT, and those from rural and immigrant communities. Thus far, Selective distribution has been: Clinical research practicum (7, 2016; 14, 2017; 9, 2018); Mentored research practicum (2, 2016; 1, 2017); Community engagement practicum (7, 2016; 4, 2017; 5, 2018); Planning for health professions educations (14, 2016; 32, 2017; 33, 2018), Fundamentals of learning: Theory and Practice (7, 2016; 17, 2017; 18, 2018); documentary film (1, 2016); inter-professional trip to Honduras (2, 2016, 2, 2017). Since the implementation of the curriculum, at least 53 of 70 students who have applied (76%) were admitted to health professions or other graduate schools despite having lower initial MCAT and undergraduate GPAs in aggregate than the average of students who matriculate to allopathic medical school programs: 41 to medical schools, 3 to dental school, 2 each to osteopathic and physician assistant schools and 1 each to physical therapy, business school and law school. Eighteen of the 2016 graduates, and 21 of the 2017 graduates work in research for their gap year following graduation, the majority being employed in our institution’s research programs providing a pipeline of trained research assistants and coordinators. DISCUSSION/SIGNIFICANCE OF IMPACT: Lessons learned by implementing our curriculum include the following: (1) students are eager to explore different areas of health care; (2) collaboration across schools, centers, departments, institutes, and offices increases our ability to identify common areas of interest; (3) implementing a diverse curriculum can be challenging due to the need for significant organization and planning; (4) the diversity of courses can be a source of confusion when there is a lack of standardization in learner expectations; (5) continued collaboration across, schools, centers, institutes programs, health professions and sections requires a significant amount of time and expertise. However, our programs demonstrate significant positive impacts both on students and at the institutional level. Our program shows that a diverse curriculum leads to a high number of students engaged in pursuing and successfully continuing a health profession education. Institutional benefits include a robust pipeline for a diverse research workforce.

OBJECTIVES/SPECIFIC AIMS: The primary goal of this project is to verify murine findings in the human setting. METHODS/STUDY POPULATION: The methods include primary cell isolation and culture, FACS, adoptive transfer, 3D-cell culture, histology, immunofluorescence, xenograft, and tissue recombination. The study population includes patients undergoing radical prostatectomy due to hyperplasia or adjacent bladder or prostate cancer. RESULTS/ANTICIPATED RESULTS: Having verified similar sensitivities to androgen receptor (AR) inhibitors between naive murine and human basal prostate stem cells, we anticipate that autoimmune inflammation in humans affects the response of basal prostate stem cells in a manner similar to the murine setting as well. This includes increased proliferation, differentiation, and response to AR inhibitors. DISCUSSION/SIGNIFICANCE OF IMPACT: The identification of survival mechanisms used by basal prostate stem cells in an androgen deprived environment may give insight to the process by which prostate cancer becomes androgen independent. The effect of inflammation on proliferation, survival, and AR signaling in these cells may also provide information relevant to cancer initiation and progression.

OBJECTIVES/GOALS: The Association for Clinical and Translational Science (ACTS) offers important inter-institutional communities through Special Interest Groups (SIGs). New to the SIG ecosystem is the Justice, Equity, Diversity, and Inclusion (JEDI) SIG. METHODS/STUDY POPULATION: Formed in 2022, the JEDI SIG is a growing community of individuals seeking to develop papers and products relating to improving health equity and workforce diversity within the Translational Science Community. Within this context, diversity is broadly defined to include groups at a negative power differential within US society. RESULTS/ANTICIPATED RESULTS: Comprised of 54 individuals spanning 29 institutions as of our first meeting in October 2022, the JEDI SIG is a welcoming group for ACTS members looking to make a difference. We have developed working groups to develop SIG-directed projects, and we look forward to expanding our activities in the future. DISCUSSION/SIGNIFICANCE: In this poster we will share key information about the new JEDI SIG including monthly meeting times, current activities, and ideas for future work.

OBJECTIVES/SPECIFIC AIMS: Women with pulmonary arterial hypertension (PAH) exhibit superior right ventricular (RV) function and survival compared with men, a phenomenon attributed to poorly understood cardioprotective effects of 17β-estradiol (E2). We hypothesize that E2, through ERα, attenuates PH-induced RV dysfunction by upregulating the pro-contractile and pro-angiogenic peptide apelin. This ERα-mediated increase in apelin is mediated by the myocardial remodeling effector bone morphogenetic protein receptor 2 (BMPR2). METHODS/STUDY POPULATION: ERα, BMPR2, and apelin were measured (western blot) in RVs from patients with PAH-induced RV failure and in RV homogenates from male or female Sprague-Dawley rats with sugen/hypoxia (SuHx) or monocrotaline (MCT)-induced PH. H9c2 rat cardiomyoblasts and cardiac endothelial cells were stressed with TNF-α (10 ng/mL) or staurosporine (50 nM)±E2 (100 nM; 24 h). ERα-, BMPR2-, and apelin-dependence were evaluated by siRNA (5 pM). Downstream apelin target and pro-survival factor ERK1/2 expression was measured (western blot). p<0.05 by ANOVA was considered significant. RESULTS/ANTICIPATED RESULTS: ERα correlated positively with BMPR2 and apelin expression in SuHx-RVs and human RVs. Treatment of SuHx-PH rats with E2 or ERα agonist increased RV BMPR2 and apelin, whereas RV apelin was decreased in E2-treated hypoxic ERα knockout mice (p<0.05), but not in ERβ knockout mice. In H9c2 cells, E2 or ERα agonist attenuated TNF-α- or staurosporine-induced decreases in BMPR2, apelin, and phospho-ERK1/2 (p<0.05 for all endpoints). E2 protection was lost in presence of siRNA directed against ERα, BMPR2, or apelin (p<0.05). ERα was necessary for E2-mediated increases in BMPR2, apelin, and ERK1/2, and BMPR2 was required for the E2-mediated increase in apelin (p<0.05 for siRNA vs. scramble). ERα, BMPR2, and apelin protein was increased in decompensated human RVs but downstream phospho-ERK signaling was disrupted. DISCUSSION/SIGNIFICANCE OF IMPACT: E2, via ERα, increases BMPR2 and apelin in the failing RV and in stressed rat cardiomyoblasts. The E2-mediated increase in apelin is BMPR2-dependent and likely occurs through direct binding of ERα to the BMPR2 promoter. Harnessing this E2-ERα-BMPR2-apelin axis during RV compensation may lead to novel, RV-targeted therapies for PAH patients of either sex.