OBJECTIVES/SPECIFIC AIMS: To diversify the biomedical research workforce by training postdoctoral scholars and junior faculty from 6 Minority Serving Institutions (MSIs) on practical research skills such as Critical and Creative Thinking, Formulating the Problem, Asking the Right Question, Grant Writing, and Team Science METHODS/STUDY POPULATION: In collaboration with our partners, we identified 11 topics where trainees lack research funding. Next, we identified instructors for these topics. We converted the topics to online module with modules ranging from 2 to 8 weeks. In working with an online education expert, we developed innovative online training using Moodle as the content management system. Scholars complete readings, videos, self-assessments and participate in discussion board each week. In addition, we have weekly synchronous sessions for each module. All scholars are required to take the grant writing module and 8 other modules. After each module, trainees complete a brief survey to evaluate the module. The leaders at the MSI participated in an intensive face-to-face training session on how to be a career coach so that they could be career coaches for the LEADS Scholars at their home institutions. RESULTS/ANTICIPATED RESULTS: In the first year, we selected 13 LEADS Scholars. All but 3 scholars elected to take every module. The 3 scholars did not enroll in the Peer Reviewing module. Results of the brief survey at the end of each module indicate that the scholars value each of the modules and rate them very highly. When 1 scholar wanted to leave the program, we decided to have a conference call with all of the LEADS Scholars to determine what was working and what was not working with the program. All scholars recognized the value of LEADS. Some scholars felt that the weekly synchronous session was too demanding as they have competing demands on their time. We consulted with the leadership at the MSI and decided to modify the requirements of the program such that every synchronous call was not required for successful completion of the module and to earn a badge. Scholars need to have at least 9 badges to earn a certificate. In addition to the training, we decided that scholars would also benefit from mock reviews of their grants. This will help them submit successful grants. We learned that the best way to serve the needs of the scholars is to work iteratively with the scholars and leadership to develop a successful program that most effectively meets their needs of the scholars and helps them launch a successful career. DISCUSSION/SIGNIFICANCE OF IMPACT: Postdoctoral scholars and junior faculty from MSI need practical research training to help launch their research career. We suspect that this is true of many institutions and plan to develop these modules so that they can be widely disseminated to other institutions.

OBJECTIVES/SPECIFIC AIMS: The purpose of this study is to determine if the prevalence of interdisciplinary collaborations has increased over the past 10 years at 1 CTSA-funded institution. METHODS/STUDY POPULATION: We used Scopus to identify all articles published by authors affiliated with any of the Johns Hopkins Institutions for the years 2005, 2010, and 2015. We limited the search by the Scopus Field Codes “Subject Area” to biomedical science only, “Document Type” to articles only, and “Source Type” to journals only. We further eliminated all articles with 1 author or more than 10 authors. This resulted in 2800 articles for 2005, 3987 for 2010, and 4569 for 2015. After exporting the articles, we randomly selected 25 from each of the 3 time periods. Using the World Public Library Outline of Academic Disciplines as a guide, every author was assigned 1 of the following disciplines: Social Science (eg, Psychology), Basic Science (eg, Biology, Chemistry), Agriculture, Computer Science, Engineering, Medicine, Public Health, Nursing, or an Interdisciplinary field (eg, Genetic Medicine) based on their department and school affiliation. Articles with authors who belonged to 1 discipline only were considered single-discipline articles, and articles with authors in a least 2 different disciplines were considered “interdisciplinary.” RESULTS/ANTICIPATED RESULTS: Based on the results of an initial pilot study, in 2005, 24% of articles were interdisciplinary, in 2010, 20% of articles were interdisciplinary, and in 2015, 60% of articles were interdisciplinary. The large gap between the first 2 time periods (2005 and 2010) and the most recent (2015), suggests a possible pattern of increasing growth of interdisciplinary collaborations over time. Expanding this analysis to a much larger sample size will provide additional important evidence. DISCUSSION/SIGNIFICANCE OF IMPACT: Increasing emphasis is being placed on evaluating the effectiveness of the CTSA consortium in achieving its goals and on developing methods to gauge its success. Systematic methods that are easy to replicate across hubs are needed to better understand and track the evolution of scientific collaborations over time. This study outlines a process for determining whether one of the major desirable outcomes of the CTSA, notably the growth of interdisciplinary collaborations, can be determined through the analysis of authorship patterns. Further research is needed to confirm the generalizability of these results across other CTSA hubs.

OBJECTIVES/SPECIFIC AIMS: The prevention, management, and treatment of HIV, STDs, and HCV requires continuous training that reflects contemporary best-practice and innovative care models. In order to improve the NYS AIDS Institute’s comprehensive web-enabled training program, which enhances the capacity of a diverse healthcare workforce, a needs assessment (NA) of our community of practice (CoP) is needed to better understand their training needs, circumstances, and instructional modalities preferences. The goal of the assessment was to better understand our CoP’s preferences of online trainings, and as a result to develop a “responsive design” system that will enhance user’s learning experience thus improving patient care. METHODS/STUDY POPULATION: We developed and deployed an NA survey using REDCap. The instrument consisted in 27 questions related to providers’ preferences on receiving continuing educational training and their use of technologies, including mobile platforms, online modules, webinars, and telehealth. As part of the recruitment strategy, several resources were deployed over a 1-month recruitment period including sequential email blasts, website promotion, and assessment links included in newsletters and social media. Weekly reminders were also used to promote the participation from our CoP. RESULTS/ANTICIPATED RESULTS: A total of 310 respondents participated in the NA, with 85.8% from NYS. 177 were clinicians (20.5% MD, 2.9% PA, 17.3% NP, and 16.3% RN) and 133 nonclinical providers (case/care managers, social workers, public health professionals, coordinators/administrators, and other). The participants worked in hospitals, community health centers, substance use centers, private practices, and state/local health departments. More than 90% of respondents indicated that they preferred both live/in-person and online training, and participants most strongly indicated that they stayed up-to-date on current developments through CDC, the AIDS Institute, and conferences. More than 60% of respondents considered that receiving CE credit for the training was very important and 28% indicated they would use training materials in Spanish if offered. In terms of technology, over 80% of the respondents preferred computers, but more 50% also used mobile devices (computer at home 61.8%, computer at work 85%, tablet 29.9%, iPhone 20.9%, Android 16.6%, other device 2.3%). DISCUSSION/SIGNIFICANCE OF IMPACT: Accessing an online CoP provided a useful opportunity to assess training needs and preferences of clinical and nonclinical providers. Most providers indicated that they were primarily likely to use a work computer to complete online training or secondarily a home computer. With a significant portion of respondents indicating use of tablets, smartphones, and other devices, online training opportunities should be developed with responsive design to assure flexibility and access. In addition to online training, participants indicated that they also strongly valued live, in-person training. Offering training with CDC and the NYS AIDS Institute branding, in Spanish, together with offering continuing education credit, were all seen as desirable training elements. Accessing this online CoP helped streamline and target training priorities and logistics.

OBJECTIVES/SPECIFIC AIMS: The 2 primary objectives were to (i) insure that Scholars can effectively communicate the translational impact of their research to a lay audience and (ii) assess the benefits and efficacy of having community, as well as faculty members, judge the translational impact of KL2 Scholar’s poster presentations. An explicit secondary goal was to further the engagement of community members in CTSI-sponsored translational research. METHODS/STUDY POPULATION: CTSI’s Education, Community Engagement, Discovery and Translation, and Translational Workforce Development Cores created the translational impact questions and evaluation sheets. The Community Engagement and Office of Discovery and Translation recruited community judges from their respective networks and they were assigned to relevant studies. Scholars were provided with the judges scoring template in advance. After the Research Poster Session, the KL2 Scholars evaluated the quality of their presentations and the impact of having feedback from Community Judges. The Community Judges evaluated their perceived “added value” to the research presentations and their interactions with the Scholars. Both Scholars and judges completed evaluations of the poster presentation and judging process, performed on a 5-point Likert scale. RESULTS/ANTICIPATED RESULTS: KL2 Scholars felt that the community impact judges provided valuable feedback on their research (3.8/5) and were satisfied overall with the poster session (3.4/5). In evaluating their own presentations, Scholars tended to rate themselves higher (4.2–4.6/5) on the clarity of their translational impact presentations than the community judges rated the Scholars (4.1–4.2/5). Scholars also rated themselves somewhat higher in the quality of their dealing with any ethical issues and their dissemination plan (4.0/5) than the community judges (3.8/5). Judges were very positive and felt they brought value to the experience (4.2–4.4/5). DISCUSSION/SIGNIFICANCE OF IMPACT: Community judges added qualitative value to the Scholar presentations based on the Scholar and community judge evaluations and based on comparison based on prior year poster sessions. Documenting the degree of impact of the combination of this proscribed poster format and community-judging process awaits future assessment of Scholar presentations before and after the next annual poster presentation.

OBJECTIVES/SPECIFIC AIMS: The goal of this innovative course is to provide community members with sufficient information to either join or decline participation in clinical research. We anticipate that they will gain knowledge in why research is conducted, the ways participants are recruited, the history of research, regulations that guide research today, participant protections, understand the consent process, their risks and benefits of participating in clinical research. METHODS/STUDY POPULATION: We will recruit interested community members via flyers placed at the training location and at other local community centers and agencies that receive heavy foot traffic. The course is listed in the Communiversity catalogue which is distributed in hardcopy (over 30,000) and email each semester. The course will be taught by a longstanding community member and research coordinator at the University of Cincinnati. Each session will be highly interactive including videos, role-play, and discussion of the presented research topics. Evaluation will occur both pre and post-session, along with pre and post-course. RESULTS/ANTICIPATED RESULTS: We anticipate 20–30 participants at each of the 4 sessions. We anticipate that we will learn current perceptions of clinical research and barriers to their participation to enable improved research recruitment. In addition, we will gain new insights into clinical research needs of the community. DISCUSSION/SIGNIFICANCE OF IMPACT: Through these interactive sessions, we will learn why community members participate in research and their barriers to participating. Understanding the perception of research by the target community is critical when developing clinical research recruitment strategies. We will also be developing a more educated community towards clinical research. We will also gain great insight into new clinical research directions as indicated by community members.

OBJECTIVES/SPECIFIC AIMS: The NIH states, “The training of the biomedical workforce has always been an integral part of the NIH mission… It takes just one good mentor to influence the career of a new investigator; it takes a robust culture of mentorship across the research community to strengthen, sustain and diversify the entire biomedical research enterprise.” The University of Minnesota’s CTSI-Education core strives to build and maintain a strong culture of mentoring by providing CTSI KL2 scholars an opportunity to mentor an undergraduate student participating in the Pathways to Research Program (PReP). Using this mentoring model, participants gain valuable benefits and CTSI’s culture of mentoring is strengthened. METHODS/STUDY POPULATION: Participating KL2 scholars are matched with a promising PReP scholar for a 12-week mentored research project. The PReP program selects top candidates through a highly competitive application process. Students work in their mentor’s lab full-time, funded by CTSI-Ed. They engage in additional activities together including a mentor/mentee, an interview activity and 2 social events. Junior faculty scholars are asked to participate as judges at CTSI’s Poster Session and are invited to present at PReP seminars. The program culminates with the announcement of the Junior Mentor of the Year, in which scholars nominate their mentors for the award. Junior faculty mentors receive support through a training course, Optimizing the Practice of Mentoring, mentor orientation and a roundtable discussion with the program director and other mentors. The program’s infrastructure is designed to foster mentee/mentor relationships through faculty and staff support. Junior faculty receive one-on-one coaching when faced with difficult mentoring situations and are recognized for their mentoring successes. RESULTS/ANTICIPATED RESULTS: Junior faculty mentors highly rate the program on the following points; the experience was a good use of time, I am satisfied with my experience, I would recommend this program to faculty colleagues and students. Undergraduates and Professional students rated their mentoring relationship as 1 of 3 best outcomes of the program. In exit surveys, their highly rated program successes include having a network that helps move their career forward, and confidence to persist through training to become a successful researcher. DISCUSSION/SIGNIFICANCE OF IMPACT: Creating a culture of mentoring is important to the strengthen, sustain and diversify the biomedical research workforce. This mentoring model contributes to the mission while vertically integrating CTSI-Ed’s KL2 and PReP programs. On an individual level, junior faculty improve communication and management skills, develop leadership qualities, increase their network, provide a sense of fulfilment and personal growth, and reinforce their own skills and knowledge of subject. They are also provided a top undergraduate student worker fully funded by the program.

OBJECTIVES/SPECIFIC AIMS: Innovation in healthcare is increasingly dependent on technology and teamwork, requiring effective collaboration among diverse disciplines. However, large knowledge barriers exist between these diverse disciplines which hinders effective communication and the innovation processes. We organized an intensive team-based competition event, Sinai MedMaker Challenge, that engaged individuals with a wide range of backgrounds in medicine, biomedical research, computers science, and engineering to collaborate in solving medical problems with technology-based solutions. The learning objectives were to: enable participants to identify healthcare problems which lend themselves to technology-based solutions; delineate key behaviors critical to multidisciplinary team success; identify optimal strategies for communicating in teams; engage and inspire participants to apply knowledge of technology to meaningfully impact clinical care and well-being. METHODS/STUDY POPULATION: The Sinai MedMaker Challenge was a 48-hour team-based competition, modeled after previously held health “hackathons.” Adapting from guidelines provided by MIT Hacking Medicine, the event gathered participants from diverse backgrounds (clinicians, medical students, graduate students in biomedical science and humanities, software developers, engineers, and others), for the purpose of utilizing technology to address pressing problems in the diagnosis, management and/or treatment of pain and/or fatigue. The event flow can be outlined as follows: Phase 1—pre-event brainstorming via Slack and Sparkboard online platforms; Phase 2—problem review with clinical experts; Phase 3—solution pitches, formation of teams, development of prototype solutions; Phase 4—presentations and prizes awarded. The event was sponsored by ISMMS Institutes and Technology Companies. Mentors roamed throughout the event to support the teams in the technical, clinical, and business development aspects of their solutions. RESULTS/ANTICIPATED RESULTS: In total, 78 participants forming 14 teams, worked on the development of software and hardware prototypes (apps/websites, devices, wearables) to address a variety of pain and fatigue problems, culminating in final pitch presentations to a panel of judges comprised of academic experts; innovators and entrepreneurs in the technology start up space. Award recipients were: (1) PT partners, a wearable device for monitoring physical therapy post knee replacement; (2) SickleMeNot, an interactive, multimodal website/app for children designed to assess, monitor and manage pain; and (3) Biolumen, a functional biofeedback system, to treat chronic back pain. Evaluations revealed a high-degree of satisfaction with the event. Several teams continue to develop their prototypes. DISCUSSION/SIGNIFICANCE OF IMPACT: The Sinai MedMaker Challenge (1) was a compelling and productive forum to bring together students, trainees, faculty and other stakeholders to explore tech-based solutions for management, monitoring, and treatment of pain and fatigue; and (2) can be repeated annually, fostering a “Community of Practice,” and expanded to offer pre and post event opportunities to encourage iterative learning and ongoing creative output.

OBJECTIVES/SPECIFIC AIMS: Develop a plain language informed consent template that met IRB and regulatory requirements. Evaluate the effectiveness of the template at improving the readability of informed consents. Field test the informed consent with low health literacy. METHODS/STUDY POPULATION: We conducted a retrospective analysis of over 200 UAMS IRB approved, investigator initiated informed consents from 2013 to 2015 to determine the readability before intervention. The mean grade level readabilities were derived from the results of 3 readability formulas (Flesch-Kincaid, SMOG, and Fry) using open-source readability tools. A plain language informed consent template that meets IRB and regulatory requirements was developed, adhering to health literacy best practices for written communication. The template was made available to investigators as an optional resource, and IRB committees were trained on use of the template. In addition, a focus group will be conducted to qualitatively assess understandability of the template with study participants identified as having inadequate health literacy. Data analysis will include readability assessment of IRB approved informed consents post intervention with and without use of the plain language template, as well as qualitative feedback from focus group participants. RESULTS/ANTICIPATED RESULTS: The retrospective analysis revealed a mean readability of 10th grade for IRB approved informed consents from 2013 to 2015 (n=217). The readability of the developed plain language template was 5th grade. Preliminary post-intervention results show adoption of the template by investigators (n=16) resulted in informed consents with a mean readability of 7th grade (range 6–9th grade), compared to a mean of 10th grade (range 7–11th grade) for the comparator (“no adoption” group, n=24). Data collection will continue through May 2017. The focus group is forthcoming and results will be included in the poster. DISCUSSION/SIGNIFICANCE OF IMPACT: Low health literacy is common in individuals with healthcare disparities and can limit their participation in clinical research. Few studies have examined interventions to address this barrier to research. Preliminary results of this study support the utilization of a plain language informed consent template in investigator-initiated research. Moreover, this study demonstrates the importance of stakeholder engagement among CTSA leadership, health literacy experts, the institutional review board, investigators, and research subjects in the development and testing of this intervention to make informed consents “understandable to the subject” while containing all required elements.

OBJECTIVES/SPECIFIC AIMS: Exposure to theatrical performances holds promise for addressing bioethical issues, but there has been little empirical examination of the impact of dramatic presentation on audiences’ attitudes. This study assessed the short-term impact of the play, Informed Consent, on perceptions of trust, willingness to donate biospecimens, attitudes toward harm and privacy among the general public and in faculty, medical and undergraduate students within an academic medical center in the intermountain west. METHODS/STUDY POPULATION: Surveys were administered before and after a staged reading of the play by professional actors. Pre and post survey responses were linked for each participant. Survey items included the short form Trust in Medical Researchers, and single item questions about group identity, of genetic testing in children, and willingness to donate biospecimens. In total, 3 additional questions about harm, consent, and ethical investigator behavior as represented in the play were asked in the post survey. In addition, respondents were given the option to answer open-ended questions through email. RESULTS/ANTICIPATED RESULTS: Out of the 481 who attended the play, 421 completed both the pre and post surveys, and 166 participants completed open-ended questions online ~1 week after the play. Across all participants, there were significant declines for Trust in Medical Researchers and for the survey item “is it ethical for genetic testing in children for adult onset conditions,” (p<0.001 for both) following the play. There was a significant increase in agreement to improve group identity protections (p<0.001) and no differences on willingness to donate biospecimens to research (p=0.777). When differences were analyzed by race of the participant, non-White participants (n=68) compared with White participants (n=344) were less willing to donate biospecimens in general (p<0.001). Further, non-White participants’ willingness to donate biospecimens decreased (p=0.049) after viewing the play while the white participants’ willingness to donate was unchanged. Qualitative data provided extensive contextual data supporting these perspectives. DISCUSSION/SIGNIFICANCE OF IMPACT: This is one of the first studies to empirically examine the impact of a theatrical performance on both attitudes and behavioral intentions toward research and clinical research participation. Some attitudes changed following the play performance, but there were no significant differences on intention to donate biospecimens for research overall. Future research can further address the value and impact of theatrical performances and other creative arts as tools to engage the public and investigators in dialogue about the ethical issues and complexities in clinical research and further evaluation of the impact of performances on attitudes about research and ethics. Creative arts may be used to motivate investigators and study participants to confront fundamental questions about research participation and trust.

OBJECTIVES/SPECIFIC AIMS: The purpose of this descriptive study is to explore knowledge, attitudes, and behaviors related to genetics and genetic research in a sample of persons of African descent. METHODS/STUDY POPULATION: Data were generated using a cross-sectional survey design. A nonprobability sample of 272 persons of African descent, ages 18 and older, were recruited from the Washington, DC metropolitan area through public advertisement and word-of-mouth. Participants had diverse backgrounds with most born in the United States (93%), female (71%), some college or above education (57%), household income under $40,000 (54%), and some with a reported disability (38%). Before survey recruitment and administration, this study was reviewed and approved by the Howard University Institutional Review Board. RESULTS/ANTICIPATED RESULTS: The majority (79.8%) of the participants considered themselves as having a “fair” to “good” knowledge of genetics. The sample had a 2.24 (SD=77) mean score on the 5-item genetics knowledge questionnaire with total possible mean scores ranging from 0 (no correct responses) to 5 (all correct responses). Most (53.3%) participants believe it is important for persons of African descent to participate in genetic research. However, almost one-half (46.7%) felt that information from genetic research can be used to discriminate against minorities. In terms of behaviors, 83.4% of the participants never had genetic testing conducted. However, an overwhelming majority reported that they would be willing to participate in a genetic research project specifically for detection of risk factors such as cancer (87%), diabetes (89.3%), Alzheimer disease (88.6%), and alcohol use disorder (75%). DISCUSSION/SIGNIFICANCE OF IMPACT: This investigation suggests that persons of African descent generally view participation in genetic research as important and are willing to have their genetic profile analyzed to detect susceptibility to certain diseases. However, ethical issues, such as misuse of genetic research to discriminate against minorities, remain a prominent concern. Further studies are needed to illuminate KABEs and to help identify the role these factors may play in this population’s willingness to participate in testing and research. Such information could provide invaluable insight to the development and implementation of more ethical and culturally competence strategies for recruiting minority participants into genetic research.

OBJECTIVES/SPECIFIC AIMS: The objectives of this study were (1) to examine research participant levels of satisfaction, experiences, and perceptions; and (2) to determine best practices for researchers for engaging research volunteers in clinical trials, and thereby reducing barriers to participation. METHODS/STUDY POPULATION: A self-administered IRB approved survey on satisfaction and perceptions of research participants in clinical and translational studies was developed. The study questions were validated by 5 key informants from each of the 3 research centers who were asked to provide constructive feedback on the clarity and relevance of the questions. The final survey was a 25-item questionnaire that used a Likert scale and focused on 5 domains to reflect satisfaction with “Staff delivery of care,” “Environment,” “Center Operations,” “Study specific questions,” and “overall experiences.” Questions to reflect participant perceptions were open ended. A convenience sample of all participants currently enrolled in research studies at CTSA institutions (GU, HU, and MHRI) was obtained. In total, 131 participants completed the survey. Of these, 15 were “surrogate” partners. RESULTS/ANTICIPATED RESULTS: Eighty-two (60%) of the participants were African Americans, 40 (29%) were Whites; 94 (67%) were first time study participants. Over 90% of those surveyed strongly agreed that they were “treated well,” that their “privacy was respected,” and that they “felt comfortable asking questions of the staff.” Eighty-four percent indicated they would participate in future studies while over 91% indicated they would recommend a family member or a friend. Only 46% of participants coming for their first research visit strongly agreed that the “compensation received was satisfactory.” However, 74% of participants returning for follow-up or who had been enrolled in a previous study felt the compensation was appropriate. Seventy-four percent of those enrolled for the first time indicated “knowing the duration of this study” as compared with only 38% of repeat visitors. When asked what they liked most about participating in a research study their primary responses were “contribution to science” and “knowledge about their diseases.” Conversely, when asked what they liked least about the study they responded that the blood draws were uncomfortable and there were often barriers to transportation and parking. DISCUSSION/SIGNIFICANCE OF IMPACT: The results of this survey demonstrated that the majority of research participants rate their experience as highly favorable even among those who had never participated in clinical research previously. In some existing literature, it has been reported that financial compensation was a major motivation to participation in studies involving healthy volunteers. In this current study, however, financial compensation did not appear to be the primary motivation for participation. The participants’ at all 3 sites stated that the main reason for their participation was the increased knowledge about their disease and the contribution to science. Negative experiences cited were primarily discomfort with blood draw, transportation, and parking logistics. Most importantly, a majority of the participants stated they would participate in future studies and would recommend a family member or a friend for a clinical study. In our sample, there was no difference in the favorable ratings as determined by race/ethnicity. In conclusion, the findings of this study inform the community with regard to how the research participants rate their experiences, and thus motivate others to participate in clinical research. Reasons for participants to withdraw from trials may be associated to their dissatisfaction with a trial or with the study staff. Thus, the degree of satisfaction with the research staff and the trial itself is crucial to reducing drop-out rates and increasing compliance with study procedures. Hence participant satisfaction is key to increasing participation in clinical trials, particularly among African Americans and other racial and ethnic minorities.

OBJECTIVES/SPECIFIC AIMS: Discuss ethical and policy issues that will impact clinical research. Raise awareness of the need to understand internal policies at home institutions Encourage further examination of ways to facilitate clinical research participation. METHODS/STUDY POPULATION: Ethical and policy analysis. RESULTS/ANTICIPATED RESULTS: Ideally, clinical research participants should not be required to pay to participate in research. However, if we go with an equity model, as opposed to an equality model, policies should be changed to allow equal access to research participation. This is a matter of justice and also will enhance the quality of the science. DISCUSSION/SIGNIFICANCE OF IMPACT: Unless steps are taken to make participation in clinical research less burdensome financially for participants, research may slow or results may be biased, because only those who can pay will be able to participate.

OBJECTIVES/SPECIFIC AIMS: The Institute for Transnational Sciences (ITS) has developed novel methods to ethically engage stakeholders across the transnational research spectrum, up to and including public health practice and policy. METHODS/STUDY POPULATION: In 2014, the ITS co-founded The Research, Education, And Community Health (REACH), the mission of which was to facilitate communication, collaborative research, and service activities between faculty and scientists and area community leaders. The intent was to identify and meet the needs of our communities without gaps and/or redundancies, thus better leveraging time, funding, and efforts. RESULTS/ANTICIPATED RESULTS: REACH now boasts 23 Centers, Departments, and Institutes, as well as 39 community organizations, including public and mental health agencies, clinicians, policy makers, family service centers, cultural and faith-based organizations, business, and local schools/colleges. We offer 3 methods for consideration as best practices: (1) a comprehensive community health needs assessment, (2) an “Offer and Ask” community/campus partnership mechanism, and (3) Community Science Workshops, based on the European Union’s Science Shops. DISCUSSION/SIGNIFICANCE OF IMPACT: Results of REACH’s work have been used to provide guidance for enhanced, data-driven programs and allocation of resources for local and statewide initiatives. The organization has evolved into an independent coalition seeking 501(c)3 status and is planning to expand its scope to 5 counties. REACH thus serves as model for successful replication across applicable CTSA hubs.

OBJECTIVES/SPECIFIC AIMS: To describe how Michigan Institute for Clinical & Health Research (MICHR) has engaged communities in its leadership and governance structure. This presentation will describe these practices, how they are being evaluated, and future plans for institute-wide engagement of communities in translational research. METHODS/STUDY POPULATION: Engaged partners from various communities across Michigan in various ways within MICHR’s Community Engagement Program. RESULTS/ANTICIPATED RESULTS: MICHR has utilized participatory practices in the development of the CAB to strengthen existing relationships and build new ones with potential partners. DISCUSSION/SIGNIFICANCE OF IMPACT: MICHR-wide Community Advisory Board (CAB) will ensure community voices are heard and utilized in leadership and strategic decisions for CTSA activities.

OBJECTIVES/SPECIFIC AIMS: The specific objective of this proposal is to identify and validate targetable tumor-associated antigens (TAAs) in ovarian and pancreatic cancer. It is our central hypothesis that the accurate identification and selection of appropriate TAAs will provide a foundation on which to develop of novel and effective cancer immunotherapies. We have formulated this hypothesis on the basis of preliminary results in which we have used high-throughput tandem mass spectrometry (MS) to successfully identify TAAs from melanoma patient tumors. We have subsequently generated TAA-specific T-cells that showed specific recognition and killing of tumor cells, and will form the basis of an upcoming clinical trial for our melanoma patients. We now have extended this antigen identification pipeline into ovarian cancer to accomplish our objective of developing effective T-cell-based immunotherapies for ovarian cancer and pancreatic patients. METHODS/STUDY POPULATION: We have collected patient tumor specimens, and we performed HLA immunoprecipitation, peptide elution, and completed high-throughput tandem MS on these eluted samples to identify TAAs. In addition, we have validated the safety of potential targets through the use of the publicly available RNA sequence data sources GTEX and TCGA. RESULTS/ANTICIPATED RESULTS: To date, we have successfully completed over 60 peptide elutions from ovarian and pancreatic patients samples. In total, we have found several potential novel tumor-associated targets. VGLL1, is one of these identified antigens, and in conjunction with our collaborators, we have successfully generated T-cells against it. Additionally, we have found that VGLL1 is a potential novel TAA for 3 other cancer types, including bladder, gastric, and triple negative breast cancers. We are now focusing our efforts on testing these T-cells against additional ovarian cancer cell lines and these cancer types to determine their specificity. We plan to continue the generation and testing other identified potential TAAs as well. We plan to use these T-cells directly in clinical trials in the future. DISCUSSION/SIGNIFICANCE OF IMPACT: The rationale for this proposal is that through the identification and validation of TAAs, we can open the door to a new world of therapies that can potentially increase the survival rate in a disease with a historically grim prognosis.

OBJECTIVES/SPECIFIC AIMS: The off-target and organ-specific toxicities observed in cancer immunotherapy present an obstacle to T-cell-based therapeutics. A recent clinical trial underscored the need for improved methods to define TCR specificity after melanoma patients treated with TCR engineered T-cells suffered from fatal cardiovascular toxicity arising from the unpredicted recognition of a muscle-specific peptide. METHODS/STUDY POPULATION: To address this drawback to T-cell-based immunotherapies, we developed a novel protein engineering approach to define the peptide specificity of a given TCR. Here, directed evolution in a yeast display system produced a large scale peptide library, where recognition by the melanoma reactive DMF5 TCR acted as the guiding selective pressure. After this technique identified a panel of putative cross reactive peptides, sequence analysis and computational modeling followed by kinetic binding experiments and structural analysis determined the DMF5 TCR recognizes 2 distinct classes of peptides through chemically distinct mechanisms. RESULTS/ANTICIPATED RESULTS: This information led to the rational, structure-based design of additional cross reactive peptides and introduced a unique approach to screen the human proteome and identify the TCR targets which triggered undesired autoimmunity when this molecule was used in clinical trials. DISCUSSION/SIGNIFICANCE OF IMPACT: The distinct chemical nature of the 2 peptide classes suggest TCRs are more cross reactive than previously thought, presenting an obstacle to cell-based immunotherapy. Defining the peptide specificity of TCRs is of high interest to the immunology community, and will lead to improved approaches to designing engineered TCRs for cell therapy.

OBJECTIVES/SPECIFIC AIMS: To compare functional differences in WJ-MSCs-derived from term Versus preterm infants. METHODS/STUDY POPULATION: WJ-MSCs were enzymatically digested from umbilical cord tissue from Term (gestational age ≥37 wk, n=4) and Preterm (gestational age ≤32 wk, n=5) neonates. Cells were characterized by (1) surface antigen markers using flow cytometry, (2) ability to differentiate into adipogenic, chondrogenic, and osteogenic lineages following in vitro stimulation, (3) colony forming unit efficiency, (4) proliferation rates, and (5) cell motility assay. RESULTS/ANTICIPATED RESULTS: WJ-MSCs were successfully isolated from both Preterm and Term groups. Cells adhered to plastic and displayed characteristic spindle-shaped morphology when cultured under standard conditions. WJ-MSCs from both groups expressed surface antigen markers CD73, CD90, and CD146 (≥90%) and did not express hematopoietic markers HLA-DR, CD79, or CD117 (<5%). Preterm and Term cells were capable of differentiating into osteogenic, chondrogenic, and adipogenic lineages. There were no significant differences between the groups when evaluated by colony forming efficiency, proliferation rates, or cell motility. DISCUSSION/SIGNIFICANCE OF IMPACT: These preliminary findings suggest that WJ-MSCs derived from full-term or preterm neonates have similar functional characteristics. Future studies will focus on the regenerative potential of WJ-MSCs from preterm and term infants following changes in the microenvironment (eg, oxygen tension, inflammatory stimulation).

OBJECTIVES/SPECIFIC AIMS: We hypothesize that both NGF and TNF-α contribute to oral cancer pain by upregulating pro-nociceptive inflammatory cytokines. METHODS/STUDY POPULATION: In total, 48 oral cancer patients were evaluated and their pain scores were measured using a validated oral cancer pain questionnaire. Presence of perineural invasion (PNI) was identified from patients’ pathology reports. We utilized The NIH Cancer Genome Atlas (TCGA) Head and Neck Cancer cohort to investigate the association between pain and genes related to NGF, TNF-α, and their receptors (TRKA, P75, TNF-α receptor 1, and TNF-α receptor 2) in oral cancer samples by employing PNI as a surrogate for pain. Demographic characteristics, clinical characteristics, and genes were analyzed using logistic regression models. A xenograft cancer pain model was created by inoculating human oral cancer cells (HSC-3) into the mouse hind paw. Mice (n=6 per group) were treated with anti-NGF alone, anti-TNF-α alone, a combination of anti-NGF and anti-TNF-α, or PBS (vehicle control). Nociceptive behaviors were measured using an electronic paw withdrawal assay. Paw volume was measured using a plethysmometer. Cytokines in the paw tissues were measured using a multiplex assay kit with 28 cytokines. RESULTS/ANTICIPATED RESULTS: Oral cancer patients with PNI report significantly more pain compared with patients without PNI in our patient cohort (p<0.05). From analysis of TCGA data, we found that PNI is significantly associated with lymphovascular invasion, pathological nodal invasion, and pathological tumor staging (all p<0.05). In adjusted models, we observed that the NGF receptor p75NTR (NGFR) and the TNF-α receptor 1 (TNFRSF1A) were associated with PNI (both p<0.05) and significantly correlated to each other (r=0.25, p<0.001). High levels of TNF-α were present in HSC-3 cell lines and the mouse xenograft cancers. In mice with cancer pain, combined treatment with anti-NGF and anti-TNF-α together provided more effective pain control compared with either anti-NGF or anti-TNF-α treatment alone (p<0.05). We found significantly increased levels of MIP3a, IL-1b, IL-2, IL-4, IL-28b, IL-23, IL17a, IL-31, and IL-33 in cancer mice compared with normal mice (all p<0.05). The combination therapy significantly reduced cytokines MIP3a, IL-1b, IL-4, IL-28b, IL-31, and IL-33 (all p<0.05). DISCUSSION/SIGNIFICANCE OF IMPACT: We show that targeting both NGF and TNF-α provides more effective pain relief in an oral cancer model. These results suggest that therapeutic strategies aimed at both pathways could yield improved pain management for oral cancer patients.

OBJECTIVES/SPECIFIC AIMS: To assess the efficacy of exogenous administration of MSCs in animal models of HIE. METHODS/STUDY POPULATION: Adhering to the Systematic Review Protocol for Animal Intervention Studies, a systematic search of English articles was performed using MEDLINE, Web of Science, CINAHL, and Google Scholar. Search term items included mesenchymal stem/stromal cell, hypoxic ischemic encephalopathy, asphyxia, cerebral ischemia, and neonatology. We selected randomized and nonrandomized studies that examined in vivo neonatal models of induced HIE. We excluded studies that combined MSCs with an adjunct therapy. Data were collected on study specifics, MSC characteristics, and outcome measurements. The primary outcome was efficacy of MSC treatment, assessed by functional neurologic measures (cognitive, motor, sensory). Risk of bias was assessed using the SYRCLE’s risk of bias tool and we used the ARRIVE guidelines to describe the quality of study reporting. RESULTS/ANTICIPATED RESULTS: A total of 17 preclinical publications focusing on MSC therapy for HIE met our inclusion criteria. Fifteen of the studies (88%) induced HIE in rodents by ligating the common carotid artery followed by a period of hypoxic exposure. Nine (53%) studies derived their MSCs from rodent bone marrow, whereas the other investigators provided xenografts from human bone marrow or umbilical cord-derived MSCs. Range of MSC dose was between 0.25 and 3.5× 106 cells with 71% of the experiments transplanting the MSCs intranasally or intracerebral. Three studies (18%) administered multiple doses. The cylinder rearing test was the most common (73%) sensorimotor functional outcome performed in the first month following the establishment of HIE. All studies demonstrated a reduction in asymmetrical paw preference after receiving MSC therapy. Lesional size was assessed, using neuroimaging or histologic evaluations, and the majority of studies showed a decreased insult following MSC therapy. DISCUSSION/SIGNIFICANCE OF IMPACT: MSC treatment demonstrates improved functional and structural outcomes that are encouraging for future translational studies.

OBJECTIVES/SPECIFIC AIMS: To characterize the CD4+ T-cell response during CTLA-4 blockade immunotherapy with ipilimumab in patients with metastatic melanoma by correlating cytokine profiles with phenotypic changes in the intratumoral lymphocyte compartment of tumor biopsies obtained before and after treatment. METHODS/STUDY POPULATION: Peripheral blood mononuclear cell samples were obtained from patients with metastatic melanoma undergoing monotherapy with ipilimumab via the Interdisciplinary Melanoma Cooperative Group at New York University Langone Medical Center. We isolated CD4+ T-cells and used a cytometric bead array assay following in vitro activation with anti-CD3, anti-CD28 antibodies to characterize cytokine expression profiles by quantifying IFN gamma, IL-2, IL-4, IL-6, IL-10, IL-17, and TNF-α at 5 time points during therapy. In total, 53 peripheral blood samples were included from 12 patients. To correlate cytokine profiles with CD4+ T-cell phenotypes in the intratumoral lymphocyte compartment, multiplex immunofluorescence was performed using CD4, CD8, CCR7, CD45RO, and FOXP3 antibodies on tumors before and after treatment with ipilimumab. RESULTS/ANTICIPATED RESULTS: Patients with evidence of clinical benefit (CB), as defined by having achieved partial response or stable disease, were compared with nonresponders (NR). All patients had an increase in IFN-γ, IL-2, and IL-10 secretion by CD4+ T-cells during ipilimumab therapy. NR had a statistically higher increase in all 3 cytokines. Mean IL-10 secretion was 22.3-fold higher compared with patients with CB (p value 0.0458; 95% CI=0.6676–43.89). Mean IFN-γ secretion was 12.4-fold higher from baseline levels in NR compared with CB (p value 0.046; 95% CI=0.3589–24.35). Mean IL-2 secretion was 6.9-fold higher in NR compared with CB (p value 0.032; 95% CI=0.9688–12.75). There were no statistically significant differences seen in the secretion of IL-4, IL-6, IL-17, or TNF-α. Multiplex immunofluorescence for immune profiling of 20 pre and post treatment tumor biopsies is ongoing. We expect to see distinct intratumoral lymphocyte compartment changes which correlate with clinical response and the above described differential cytokine profiles. Specifically, we anticipate CB patients will have increased intratumoral effector T-cells and decreased regulatory T-cells when compared with their NR counterparts. DISCUSSION/SIGNIFICANCE OF IMPACT: Cytokine expression profiles of peripheral blood CD4+ T-cells have not been previously correlated with patient response in patients undergoing treatment with ipilimumab. We describe distinct secretion profiles for IFN-γ, IL-2, and IL-10 for CB Versus NR patients. NR had a statistically higher increase in IL-10, an inhibitory cytokine which typically indicates upregulation of regulatory T-cells and consequent immune escape. Increased secretion of IL-2 and IFN-γ suggests skewing towards a Th1 type, anti-tumor effector T-cell response; these cytokines increased with ipilimumab treatment in both patient groups. However, the mean increase was several fold higher in NR. Recent evidence suggests loss of the interferon gamma pathway in tumor cells confers resistance to anti-CTLA4 therapy. Chronic IFN-γ secretion is associated with an exhausted T-cell phenotype and impaired tumor rejection. Therefore, higher increases in IFN-γ secretion by CD4+ T-cells in NR suggest impaired IFN-γ dependent tumor rejection in these patients. Our findings suggest IFN-γ, IL-2, and IL-10 cytokine expression profiles can be useful as biomarkers for response to ipilimumab treatment.