OBJECTIVES/GOALS: The research objectives of this project are to elucidate the effects of Bruton’s tyrosine kinase inhibitors (BTKi) of varying target specificity on platelet function with regard to platelet aggregation, adhesion, spreading, and intracellular signaling as measured by kinase phosphorylation. METHODS/STUDY POPULATION: Blood from healthy volunteers was obtained and processed to obtain both washed platelets and platelet-rich plasma. The samples were then treated with one of the BTKi drugs or with vehicle (DMSO) at concentrations matching patient blood concentrations derived from clinical trials and pharmacokinetic studies. The incubated samples were then analyzed in an aggregometer using one of several agonists. Aggregation was stopped after five minutes with a perchloric acid-based lysis buffer. The samples were then analyzed by SDS-PAGE and immunoblotting to quantify BTK protein and BTK phosphorylation. Adhesion was assessed by incubating washed platelets treated with BTKi on microtiter wells coated with fibrinogen or collagen and quantifying adherent platelets by their endogenous acid phosphatase activity. RESULTS/ANTICIPATED RESULTS: We found that ibrutinib, zanubrutinib, and pirtobrutinib all completely inhibited collagen-induced platelet aggregation, whereas they did not inhibit aggregation induced by thrombin, ristocetin, arachidonic acid, or the PAR1 activator peptide SFLLRN (T6). Acalabrutinib inhibited collagen-induced platelet aggregation only at high concentrations (1-2 micromolar). At the lower concentration of 200 nanomolar, comparable to the concentration required for the other BTK inhibitors to completely inhibit platelet aggregation, acalabrutinib failed to inhibit aggregation but did inhibit auto-phosphorylation, indicating an impact on signaling. None of the BTKi drugs inhibited adhesion of platelets to collagen-coated surfaces. DISCUSSION/SIGNIFICANCE: Our data show the inhibitory effect of BTKi on collagen-induced platelet aggregation and signaling. However, it remains unclear whether the inhibition is due to an effect on BTK itself or other related kinases. Better insight into the mechanisms of platelet inhibition by BTKi may help guide the development of BTKi with a lower risk of hemorrhage.

OBJECTIVES/SPECIFIC AIMS: Inpatient palliative care consultation (PCC) of terminally ill patients has been shown to improve patient’s understanding of their poor prognosis. In heart failure patients, PC improves transfer to hospice (or home with hospice) and decreases readmission rates. In patients with end-stage liver disease (ESLD), factors affecting having PCC has been studied, but the impact of PCC on ESLD readmissions has not been evaluated in a nationwide analysis in the US. In this study, among patients with ESLD, we evaluate the impact of inpatient PCC on 1) 30- and 90-day readmission rates, 2) hospital charges (cost) and length of stay (LOS) during subsequent 30- and 90- day readmission. METHODS/STUDY POPULATION: All ESLD hospitalizations within the first nine months of the National Readmissions Database (2010-2014) were used in this study, to allow up to 3 months to follow up. Frequencies and yearly trends of all-cause 30- and 90-days readmissions, and of PCC referral were computed. A propensity-based greedy-algorithm was used to match (1:1) patients with PCC to those without PCC (no-PCC), to create a pseudorandomized clinical study. Comparing PCC to no-PCC, generalized estimating equations were used to estimate the adjusted odds (AOR) of 30- and 90-day readmissions, and of cost and LOS during subsequent readmissions (SAS 9.4) RESULTS/ANTICIPATED RESULTS: In the United States, from January 1st to September 30th of years 2010-2014, there were 67,271 (approximating 150,396 patients) individual records of ESLD patients who survived index hospitalization. The average annual rate of PCC was 5.4%, which steadily increased from 3.84% to 6.50% over the years (p-trend <0.0001). The average 30- and 90-day readmissions rate were respectively 34.9% and 52.3%, and both remained relatively unchanged over the years (p-trends: 0.1948 & 0.5277). After matching, index PCC was associated with 68% decreased odds for 30 day readmissions (AOR: 0.32[0.28-0.37], p-value < 0.0001). When subsequently readmitted within 30 days, previous PCC resulted in a 17% shorter stay (5.7- vs. 6.9- days, p-value:0.0014) and 30% decreased cost ($47,612 vs. $68,043, p-value:<0.0001). Similarly, index PCC was associated with 74% decreased odds for 90 day readmissions (AOR: 0.26[0.24-0.29], p-value<0.0001). With subsequently readmission within 90 days, previous PCC resulted in a 17% shorter stay (5.7- vs. 6.9- days, p-value:0.0013) and 30% decreased cost ($47,520 vs. $68,016, p-value:<0.0001). DISCUSSION/SIGNIFICANCE OF IMPACT: Patients with ESLD who received PCC had a significantly lower rate of all-cause 30- and 90- day readmissions, and consumed fewer resources (hospital stay and cost) during subsequent readmissions. Although PCC resulted in a less futile use of health care resources, its adoption is still remarkably low among ESLD patients. Studies are needed to understand the barriers to PCC and to increase its use.

Every research study that includes volunteer participants requires safety assurances in proportion to the risks of the study. Investigator-initiated clinical research can present unique regulatory challenges particularly for studies with a risk profile that warrants more oversight than minimal risk but less than for large, commercial, or high-risk research. The use of an independent safety officer (ISO) offers a middle way of right-sizing oversight to match the risk. ISOs are clinicians or researchers with relevant expertise who are independent of the investigator and the research study. Their relationship to the study is defined by a formal charter which is aligned with the protocol and Data and Safety Monitoring Plan to address the oversight process, responsibilities of the ISO, and clearly describe the variables to be monitored. The ISO responsibilities include reviewing safety data, adverse events, recruitment, demographics, study progress, data quality, protocol changes, and any new scientific information that pertains to the trial. Finally, the ISO reports in their review on any significant findings may propose modifications to the study or a need to stop the trial.

Implementation science offers a compelling value proposition to translational science. As such, many translational science stakeholders are seeking to recruit, teach, and train an implementation science workforce. The type of workforce that will make implementation happen consists of both implementation researchers and practitioners, yet little guidance exists on how to train such a workforce. We—members of the Advancing Dissemination and Implementation Sciences in CTSAs Working Group—present the Teaching For Implementation Framework to address this gap. We describe the differences between implementation researchers and practitioners and demonstrate what and how to teach them individually and in co-learning opportunities. We briefly comment on educational infrastructures and resources that will be helpful in furthering this type of approach.

Twelve evidence-based profiles of roles across the Clinical and Translational Science (CTS) workforce and two patient profiles were developed by CTS Personas collaborators in 2019 as part of the CTSA Program National Center for Data to Health (CD2H). Based on feedback received from the community, CTS Personas team members collaborated to produce five additional Personas to broaden representation of the CTS workforce and enhance the existing portfolio. This paper presents the rationale and methodology used in the latest CTS Personas initiative. This work also includes an implementation scenario incorporating multiple Personas. Using the new National Institutes of Health’s (NIH) Data Management and Sharing Policy as an example, we demonstrate how administrators, researchers, support staff, and all CTS collaborators can use the Personas to respond to this new policy while considering the needs of service providers and users, CTS employees with short- and long-term needs, and interdisciplinary perspectives.

OBJECTIVES/GOALS: Hepatitis B and C virus causes inflammation of the liver and can lead to cirrhosis, liver failure, and hepatocellular carcinoma. The aim of this study is to generate a modeled estimate of changes in hepatitis B and C prevalence, and future sequelae, that accounts for recent mass migration to the European Union stemming from 50 high-emigration countries. METHODS/STUDY POPULATION: Total migrant population from 2013-2017 was obtained from the Eurostat population database. Demographics including country-of-origin, sex, and age distributions were used to determine migrant contributions to HBV and HCV prevalence where available. Undocumented migration estimates were obtained from the Institute of Migration database. Country-of-origin HBV and HCV prevalences were obtained for the select 50 country-of-origin nations from the Polaris Observatory and from systematic reviews. Disease progression was estimated using HBV and HCV outcome data for total populations from treatment guideline publication from the European Association for the Study of the Liver. RESULTS/ANTICIPATED RESULTS: Between 2013 and 2017, a total of 11,030,786 documented migrants born outside the EU arrived to the 30 nations. Germany, United Kingdom, and Spain received the greatest influx of persons and the majority of migration stemmed from countries in West Asia, the Middle East, and Africa. A significant proportion of total migration was driven by conflict-related crisis in Syria, and East and North Africa. The most significant increases in estimated total hepatitis case numbers, national prevalence increases, and future sequelae were seen in Germany and Sweden. DISCUSSION/SIGNIFICANCE OF IMPACT: Mass migration has significantly changed HBV and HCV disease burden in Europe over the past 5 years. Consequently, long-term outcomes of cirrhosis and HCC are also expected to increase. These increases are likely to disproportionally impact individuals of the migrant and refugee communities. HBV and HCV surveillance and management programs must strategically focus on individuals from high-burden age cohorts and nations. Screening and treatment would aid WHO elimination efforts while benefiting both the vulnerable individuals and host nations through reduction of morbidity, mortality, and associated healthcare expenses.

OBJECTIVES/SPECIFIC AIMS: Our primary objectives were to examine the impact of biologic cost sharing on 1) adherence to biologics and 2) persistence on biologics in inflammatory bowel disease (IBD) patients. Our secondary objective was to assess the effect of biologic cost sharing on clinical IBD outcomes, including rates of hospitalization, abdominal surgery, and corticosteroid treatment. METHODS/STUDY POPULATION: This retrospective cohort analysis used a national insurance claims database (Optum Clinformatics DataMart) to assess adult IBD patients enrolled in medium or large private insurance plans from 2007-2016. Patients were followed for one year of continuous enrollment after their index biologic claim. We assessed adherence to biologic medications (medication possession ratio >0.8) dependent on patient cost sharing, as measured by an employer-plan’s average out-of-pocket biologic medication cost. We also examined the effects of patient cost sharing for biologics on need for hospitalization, abdominal surgery, or corticosteroid treatment. We used multivariate logistic regression models adjusting for clinical and demographic characteristics. We estimated the effect of cost sharing on biologic therapy persistence using repeated measures proportional hazard survival models. RESULTS/ANTICIPATED RESULTS: We identified 2,193 adult IBD patients who initiated biologic therapy and met study criteria (Crohn’s disease 66.1% vs. ulcerative colitis 24.9%, mean age 40.8 years, mean Charlson index 0.50). Median [IQR] out-of-pocket cost per 30-day biologic prescription was $62 [$34 - $157]. 66.9% of patients were adherent to biologic therapy. Higher out-of-pocket costs for biologics were associated with increased odds of nonadherence; patients with ulcerative colitis were more price-responsive than patients with Crohn’s disease or indeterminate colitis (Figure 1). However, higher out-of-pocket biologic costs were not associated with increased odds of all-cause or IBD-related hospitalization, IBD-related surgery, or corticosteroid prescriptions for IBD flares. Patients whose out-of-pocket costs were less than $10 per 30-day biologic prescription persisted on biologic therapy for significantly longer than patients who paid >$10 (Figure 2). DISCUSSION/SIGNIFICANCE OF IMPACT: Nonadherence to biologics increases when IBD patients face higher out-of-pocket costs, particularly for ulcerative colitis patients. However, this is not associated with worse clinical outcomes. Patients with cost-sharing<$10 persisted on biologics longer than patients whose cost sharing exceeded $10.

OBJECTIVES/SPECIFIC AIMS: Intrahepatic Cholestasis of Pregnancy (ICP) is the most common liver disease unique to pregnancy. Progression of non-alcoholic fatty liver disease (NAFLD) has been linked to the dysregulation of bile acid homeostasis. However, an association of NAFLD with ICP has not been previously evaluated. We evaluated the association between ICP and NAFLD and associated metabolic risk factors, including obesity, dyslipidemia, hypertension, and diabetes. METHODS/STUDY POPULATION: A single-center, retrospective case-control study was conducted between January and December 2017 in a primarily Latina population in a New York City health system with a high prevalence of ICP, 2.53% of all pregnancies (compared to 0.32% nationally). Pearson’s chi-square or Fisher’s exact test and Wilcoxon rank-sum tests were performed to evaluate association of ICP with categorical variables and continuous variables, respectively. Unadjusted odds ratios (OR) with 95% confidence intervals (95% CI) were calculated in comparison with the control group for clinically significant outcomes. RESULTS/ANTICIPATED RESULTS: 149 pregnancies complicated by ICP were identified from electronic medical records; 200 controls were matched by delivery year. Hispanic women were more likely to be diagnosed with ICP than non-Hispanic women (OR 1.90, 95% CI 1.87-3.03). ICP and control patients were similar for: median age (OR 1.02, 95% CI.99-1.06), nulliparity (OR.79, 95% CI.48-1.30) and prevalence of hepatitis C (OR 1.35, 95% CI.08-21.67). In regards to metabolic risk factors, ICP patients and control patients were similar in prevalence of obesity (body mass index>30kg/m^2; OR 1.01, 95% CI.62-1.61), hemoglobin A1c>5.5% (OR.80, 95% CI.34-1.9), total cholesterol >200 mg/dL (OR 4.15, 95% CI.83-20.84), and prevalence of hypertension (OR.69, 95% CI.31-1.52). Median bile acid levels were 30.6 µmol/L (IQR 11.6, 32.7) in the ICP group. ICP patients had higher median alanine aminotransferase (ALT) (32 vs. 16 U/L, p<.0001), alkaline phosphatase (181 vs 128 U/L, p<.0001) and total bilirubin levels (0.5 vs 0.35, p<.0001) compared to controls. ICP patients were more likely to have ALT levels > 50 U/L (2 times the upper limit of normal; OR 3.22, 95% CI 1.48-7.03). ICP patients were significantly more likely to have a history of biliary disease (OR 3.29, 95% CI 1.39-7.80). ICP patients were more likely to have evidence of steatosis on liver imaging (OR 4.69, 95% CI 1.68-13.12) than non-ICP patients. When evaluating a diagnosis of NAFLD based on ICD-10 code or evidence of steatosis on liver imaging, ICP patients were significantly more likely to have a diagnosis of NAFLD than controls (OR 5.7, 95% CI 2.08-15.65). DISCUSSION/SIGNIFICANCE OF IMPACT: ICP appears to be associated with NAFLD independently of metabolic risk factors such as obesity, dyslipidemia, hypertension, and diabetes, suggesting a direct link between NAFLD and ICP. If findings are confirmed, ICP patients, especially those with elevated ALT, would benefit from screening for NAFLD and linkage to liver specialty care postpartum.

OBJECTIVES/GOALS: Maternal mental health, such as post-traumatic stress disorder (PTSD), is closely linked to child mental health. PTSD in mothers is associated with their children’s emotional responses. We examined associations between maternal PTSD and child brain function during emotion regulation. METHODS/STUDY POPULATION: Eight children ages 10-12 years, whose mothers had trauma histories, performed the Emotional N-Back task during functional MRI scanning. Mothers and children each reported on their trauma exposure and PTSD symptom severity. BOLD response to fearful faces during the Emotional N-Back was extracted from two specific brain regions of interest, amygdala and anterior cingulate cortex. These regions are involved in emotional response and attentional control, which are processes intrinsic to emotion regulation. An independent samples t-test was conducted on children’s BOLD response to fearful faces, with maternal PTSD symptom severity (high, low) as the independent variable. A parallel analysis was conducted with child PTSD symptom severity (high, low) as the independent variable. RESULTS/ANTICIPATED RESULTS: We found a main effect of maternal PTSD within brain regions of relevance to implicit emotion regulation. Compared to children whose mothers reported low PTSD symptom severity (n=4), children whose mothers reported high PTSD symptom severity (n=4) showed greater responsiveness to fearful faces in anterior cingulate cortex (t=2.04, p=.09,d=1.44) and amygdala (t=2.44, p=.05, d=1.72) at trending significance. A parallel analysis with child PTSD symptom severity showed no differences in brain function by this factor (ps=.55-.61). DISCUSSION/SIGNIFICANCE: Our pilot study is the first, to our knowledge, to examine associations between maternal PTSD and brain function during emotion regulation in their children. This study lays a foundation for future work; our goal is to explore dysfunction in emotion regulation neurocircuitry as one mechanism linking maternal PTSD to their children’s mental health.

OBJECTIVES/GOALS: Provider and hospital factors influence quality, but granular data is lacking to assess their impact on renal cancer surgery. The Maryland Health Service Cost Review Commission (HSCRC) is an independent state agency that promotes cost containment, access to care and accountability. Within HSCRC, we aimed to assess the impact of surgeon and hospital volume on 30-day outcomes after renal cancer surgery. METHODS/STUDY POPULATION: Data on renal surgery were abstracted from the Maryland HSCRC from 2000-2018. We excluded patients younger than 18, patients without a diagnosis of renal cancer, and patients concurrently receiving another major surgery. Volume categories were derived from the distribution of mean cases performed per year. We used adjusted multivariable logistic and linear regression models to identify associations of surgeon and hospital volume with the length of stay, days in intensive care, cost, 30-day mortality, readmission, and complications. RESULTS/ANTICIPATED RESULTS: A total of 10,590 surgeries, completed by 669 surgeons at 48 hospitals, met criteria. The 25th percentile for cases per year was 1, the 50th percentile was 1.2, and the 75th percentile was 2.6. After adjusting for patient factors and cumulative surgeon experience, high volume surgeons had the greatest decrease in length of stay (β: −1.65, P<0.001) and mortality risk (OR: 0.27, 95% CI: 0.10-0.71) compared to rare volume surgeons. Low volume surgeons had the greatest cost decrease (β: -$7,300, P<0.001) compared to rare volume surgeons. Medium volume hospitals had statistically lower average costs than rare volume hospitals (β: $−2,862, P = 0.005). There were no other clinically and statistically significant relationships between volume and measured outcomes. DISCUSSION/SIGNIFICANCE OF IMPACT: Almost half of the urologists studied performed an average of one renal cancer case per year. Greater surgeon volume was associated with shorter length of stay and decreased mortality risk. Hospital volume did not have a meaningful relationship to outcomes. Other factors such as tumor, surgeon, and hospital characteristics or case-mix may associate with outcomes and could be confounders.

OBJECTIVES/GOALS: The major obstacle to an effective cure or remission for HIV infection is the integration of HIV into the genome of long-lived resting cells which constitute the so-called viral reservoir. With this study we want to elucidate the changes of the gut-associated HIV reservoir at different stages of viral suppression METHODS/STUDY POPULATION: Recent studies have shown that after long-term (>7 years) clinical suppression of peripheral HIV RNA, the circulating viral reservoir does not seem to decline further and, in fact may expand. The gastrointestinal associated lymphoid tissue (GALT) harbors by far the largest fraction of the latently infected cells, however not much is known about its changes over time.We thus quantified the HIV viral reservoir in the GALT by identifying HIV viral transcripts via 10X single-cell RNA sequencing at two GALT-sites in five PWH and compared the amount of HIV RNA found in the group of PWH with early (< 7years) vs late (> 7years) peripheral virological suppression (plasma HIV RNA <20copies/mL). RESULTS/ANTICIPATED RESULTS: Study participants had been diagnosed with HIV infection for a median (IQR) of 31 (32-34) years and had consistently undetectable peripheral blood HIV RNA for the previous 8 (4-15) years. In PWH with consistent viral suppression < 7yrs, 4 (2-6) HIV transcripts were identified in the ileum and 25 (13 – 38) in the colon. In PWH with consistent viral suppression > 7yrs, 0 (0-4) HIV transcripts were identified in the ileum and 7 (14-11) in the colon. Based on these preliminary results we plan to expand our cohort and confirm these results using Proviral DNA quantification. We anticipate that the viral decay in the GALT will follow a slower dynamic than what has been reported for the peripheral blood achieving a steady state after more than 7 years of peripheral viral suppression. DISCUSSION/SIGNIFICANCE: Despite the remarkable progress the survival and quality of life of PWH, after forty years from its first discovery, HIV infection remains uncurable. Considering its critical role, efforts are needed to better understand the dynamics of the GALT-associated HIV reservoir.

OBJECTIVES/SPECIFIC AIMS: The study aims to determine the baseline knowledge, attitudes and practices of the professionals (i.e., doctors and nurses) that provide the end-of-life care at an acute community hospital. By obtaining information on what is known, what is believed and what is done by doctors and nurses in end-of-life care, we can identify needs, problems, barriers and possible solutions. METHODS/STUDY POPULATION:. Develop a questionnaire in Spanish addressing knowledge, attitudes and practices about end-of-life care in an acute hospital, define the survey objectives, and develop the survey protocol. o To validate the pertinence and usefulness of each questionnaire item, a panel of experts in palliative and end-of-life care will be consulted. o To finalize the questionnaire, it will be pre-tested with a small number of healthcare providers randomly selected from the survey’s intended population. Implement the questionnaire to doctors/nurses providing direct end-of-life care by purposeful sampling at an acute community hospital. o Beforehand, survey interviewers will be recruited and trained. Perform quantitate and qualitative analyses o Answers to closed-end questions and quantitative data will be tallied using Microsoft Excel and analyzed using STATA statistical software. o Relationship between the participant’s characteristics and their knowledge, attitudes and practices will be assessed using chi-square test. o Answers to open-ended questions in the questionnaire will be collected, analyzed based on their content, and placed in more comprehensive categories by NVivo software. RESULTS/ANTICIPATED RESULTS: It is expected to capture variations and/or consistencies in the amount of knowledge, the type of attitudes and the actual practices among and within physicians and nurses on end-of-life care in a community acute hospital. DISCUSSION/SIGNIFICANCE OF IMPACT: The proposed research is expected to contribute key information from the perspectives of physicians and nurses who deliver end-of-life care in an acute community hospital in Puerto Rico. This contribution is significant because it will serve as the platform to develop culturally-appropriate educational/training materials and, subsequently, implement culturally-responsive guidelines for the care of seriously ill Hispanics, with the expectation of improving their quality of life, and perhaps reducing their medical care costs.

OBJECTIVES/GOALS: The new Kidney Allocation System (KAS) was implemented in 2014 and it is not fully understood how its changes to patient incentives may have impacted dialysis facility waitlisting rates. We examine differences in facility performance and how such differences may have been impacted by this policy change. METHODS/STUDY POPULATION: We used Dialysis Facility Report data from 2011 to 2017 to study waitlisting rates at 3,392 dialysis facilities in the US, using waitlisting counts in the numerator, and the total number of ESRD patients in a facility as the denominator. We examined changes in waitlisting rates over by year at the facility, regional, and national level, and report national trends in waitlisting pre- and post-KAS. Facilities were stratified based on waitlisting rate in 2011 and then we examined whether each facility moved into a higher or lower quartile or stayed in the same quartile in 2017. RESULTS/ANTICIPATED RESULTS: Among n = 3,392 dialysis facilities, the average change in dialysis facility waitlisting rates from 2011 to 2017 was −4.74 percentage points (range -54.4% to 42.3%). Average change in dialysis facility waitlisting rates from 2011 to 2014 was −0.57 percentage points while the average change in dialysis facility waitlisting rates from 2014 to 2017 was −4.17 percentage points. Half of facilities in the 2011 lowest quartile remained in the lowest quartile in 2017; 45% of facilities in the top 2011 quartile dropped into a lower quartile. The middle 2 quartiles were fairly evenly split between worsening, improving, and not changing. DISCUSSION/SIGNIFICANCE OF IMPACT: Average waitlisting rates have declined since KAS implementation. Many facilities switched quartiles from 2011-17 suggesting that facility waitlisting rates are unstable over time. The decline in waitlisting rates post-KAS suggests that new allocation rules may be discouraging patients and/or providers from getting ESRD patients waitlisted.

OBJECTIVES/GOALS: The goal of this project is to characterize the efficacy of FOXA2 as a potential biomarker for patients with metastatic castrate-resistant prostate adenocarcinoma (CRPC) before transitioning to neuroendocrine prostate cancer (NEPC). NEPC currently has no therapeutic options and poor mechanistic understand of its origins. METHODS/STUDY POPULATION: In our study, we have utilized a multi-omics approach to characterize the potential efficacy of FOXA2 as a prognostic biomarker in numerous patient-derived castrate-resistant prostate cancer (CRPC) models. We have performed ATAC-, ChIP-, RNA-seq and proteomics to fully characterize where FOXA2 is binding genome-wide, how FOXA2 alters chromatin accessibility dynamics, identify regulatory gene targets of FOXA2, and identify FOXA2 protein-protein interactors. We have supported these findings using publicly available data from independent CRPC and NEPC patient cohorts and prostate cancer cell models. RESULTS/ANTICIPATED RESULTS: Our findings show that FOXA2 overexpression suppressed androgen signaling and promoted progression to a NEPC phenotype under short- and long-term androgen deprivation conditions, respectively. Further, FOXA2 redirected the chromatin accessibility landscape to be consistent with an NEPC gene expression program, including increased chromatin accessibility for key NEPC transcription factors. FOXA2 ChIP-seq showed FOXA2 to be bound at known NEPC driver genes and epigenetic modifiers across multiple stages of prostate cancer progression. Lastly, we discovered that FOXA2 physically interacts with key NEPC TFs and epigenetic regulators, suggesting that these FOXA2 physical interactions are required for NEPC progression. DISCUSSION/SIGNIFICANCE: This project will determine the efficacy of FOXA2 as a biomarker in advanced prostatecancer samples, which will translate as a potentially useful tool for clinicians to use for treatment of advanced prostate cancer patients.

The All of Us Research Program is an historic effort to gather data over 10+ years from one million or more people living in the United States to accelerate research and advance precision medicine. There is a particular focus on populations historically underrepresented in biomedical research who are often served by Federally Qualified Health Centers (FQHCs). However, FQHCs face significant challenges in participating in research. This paper addresses three common barriers faced by FQHCs and describes a management model that was used to support a group of FQHCs participating in the All of Us Research Program. Specifically, the paper addresses the challenges of building FQHC research capacity to operationalize and manage research activities, transforming and sharing Electronic Health Records and other data, and recruiting and retaining research participants. The central coordination management model, which was used to support the FQHCs, is a generalizable framework and can serve as an exemplar of how to engage FQHCs in other longitudinal research efforts. To date, the FQHCs have enrolled more than 10,000 participants in the All of Us Research Program. Their success is an indicator that with the proper support, FQHCs can successfully implement a complex biomedical research program in the context of their health centers.

Commercializing biomedical discoveries is a challenging process for many reasons. However, Academic Medical Centers (AMC) that have teaching, patient care, research, and service engrained in their mission are well poised to host these discoveries. These academic discoveries can lead to improvement in patient health and economic development if supported to cross the “valley of death” through institutional assistance, by providing guidance, gap funding and product development expertise. Colorado has a vibrant local startup ecosystem, state support for commercialization and entrepreneurship as well as critical mass of product development expertise. University of Colorado Anschutz Medical Campus, as a major AMC, is an engine for growth for the region. This article discusses innovation efforts at the University of Colorado Anschutz Medical Campus as a case study, which is built around two major efforts: the CCTSI and CU Innovations. I-Corps at CCTSI and the SPARK|REACH program of CU Innovations have been instrumental in fostering innovation, commercialization, and entrepreneurship on the campus.