Research Career Development Award Research Articles

CAREER DEVELOPMENT AWARDS AT NIA/NIH

Abstract NIA offers a variety of individual research career development (K) awards, which enable scientists to enhance their careers in biomedical research. Mentored career development (K) awards are effective tools at retaining investigators in research careers and contributing to their subsequent research success. Specifically, those who receive K awards are significantly more likely to have subsequent research publications and to apply for subsequent NIH research awards. In this presentation, Dr. Carranza will review different K programs offered at NIA, including those targeted at postdocs, early career faculty, and more senior faculty, as well as clinician-science focused awards.

Incomplete HPV vaccination among individuals aged 27-45 years in the United States: A mixed effect analysis of individual and contextual factors.

10546 Background: In the United States, the Human papillomavirus (HPV) vaccine is approved for use up to age 45. Incomplete HPV vaccination rates among those over age 26, however, remain high. The aim of this study was to examine the independent effects of individual- and neighborhood-level factors on incomplete HPV vaccine series in the United States (US) among those aged 27-45 years. Methods: This retrospective cohort study used administrative data from Optum’s Clinformatics DataMart Database to identify individuals aged 27-45 years who received 1 or more doses of HPV vaccine between July 2019 and June 2022. Multilevel multivariable logistic regression models were applied to the data on 7,662 individuals aged 27-45 years who were fully vaccinated against HPV or not, nested within 3839 neighborhoods across the US. Results: More than half of the participants in this study (52.93%) were not completely vaccinated against HPV. About 64% of the eligible participants aged 27-30 years did not complete their HPV vaccine series. After adjusting for all other covariates in the final model, being older than 30 years old decreased the odds of incomplete HPV vaccine series. Participants living in neighborhoods of South region of the US had enhanced odds of incomplete HPV vaccine series compared to those residing in Northeast region (aOR 1.21; 95% CrI 1.03–1.42). There was significant clustering of incomplete HPV vaccine series at the neighborhood level. Conclusions: This study revealed that individual- and neighborhood-level factors significantly influence HPV vaccination incompleteness in the US. Interventions to improve HPV vaccination uptake and completion should take into consideration both individual- and contextual-level characteristics during design, planning and implementation of policies and programs to improve HPV vaccination coverage and completion in the US and other similar countries. Acknowledgement Dr. Adekanmbi is supported by a research career development award (K12HD052023: Building Interdisciplinary Research Careers in Women’s Health Program-BIRCWH; Berenson, PI) from the National Institutes of Health/Office of the Director (OD), National Institute of Allergy and Infectious Diseases (NIAID), and Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD). Dr. Guo is currently supported by an award (K07CA222343) from the National Institutes of Health, National Cancer Institute (NIH/NCI). Dr. Berenson is supported by an award (PP200048) from the Cancer Prevention and Research Institute of Texas (CPRIT). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or CPRIT. Conflict of Interest: All authors report no conflicts of interest.

Polygenic risk scores for the prediction of common cancers in East Asians: A population-based prospective cohort study.

To evaluate the utility of polygenic risk scores (PRSs) in identifying high-risk individuals, different publicly available PRSs for breast (n=85), prostate (n=37), colorectal (n=22), and lung cancers (n=11) were examined in a prospective study of 21,694 Chinese adults. We constructed PRS using weights curated in the online PGS Catalog. PRS performance was evaluated by distribution, discrimination, predictive ability, and calibration. Hazard ratios (HR) and corresponding confidence intervals (CI) of the common cancers after 20 years of follow-up were estimated using Cox proportional hazard models for different levels of PRS. A total of 495 breast, 308 prostate, 332 female-colorectal, 409 male-colorectal, 181 female-lung, and 381 male-lung incident cancers were identified. The area under receiver operating characteristic curve for the best-performing site-specific PRS were 0.61 (PGS000873, breast), 0.70 (PGS00662, prostate), 0.65 (PGS000055, female-colorectal), 0.60 (PGS000734, male-colorectal), 0.56 (PGS000721, female-lung), and 0.58 (PGS000070, male-lung), respectively. Compared to the middle quintile, individuals in the highest cancer-specific PRS quintile were 64% more likely to develop cancers of the breast, prostate, and colorectal. For lung cancer, the lowest cancer-specific PRS quintile was associated with 28-34% decreased risk compared to the middle quintile. In contrast, the HR observed for quintiles 4 (female-lung: 0.95 [0.61-1.47]; male-lung: 1.14 [0.82-1.57]) and 5 (female-lung: 0.95 [0.61-1.47]) were not significantly different from that for the middle quintile. Site-specific PRSs can stratify the risk of developing breast, prostate, and colorectal cancers in this East Asian population. Appropriate correction factors may be required to improve calibration. This work is supported by the National Research Foundation Singapore (NRF-NRFF2017-02), PRECISION Health Research, Singapore (PRECISE) and the Agency for Science, Technology and Research (A*STAR). WP Koh was supported by National Medical Research Council, Singapore (NMRC/CSA/0055/2013). CC Khor was supported by National Research Foundation Singapore (NRF-NRFI2018-01). Rajkumar Dorajoo received a grant from the Agency for Science, Technology and Research Career Development Award (A*STAR CDA - 202D8090), and from Ministry of Health Healthy Longevity Catalyst Award (HLCA20Jan-0022).The Singapore Chinese Health Study was supported by grants from the National Medical Research Council, Singapore (NMRC/CIRG/1456/2016) and the U.S. National Institutes of Health (NIH) (R01 CA144034 and UM1 CA182876).

A blueprint for a new model of sexual and reproductive health care in subspecialty medicine.

A blueprint for a new model of sexual and reproductive health care in subspecialty medicine.

Pediatric Clinical Pharmacology Research Career Development Award (NICHD)

Pediatric Clinical Pharmacology Research Career Development Award (NICHD)

Promoting the Pipeline of Diverse Individuals Within Gastroenterology: Reflections From AGA FORWARD Program Scholars

Promoting the Pipeline of Diverse Individuals Within Gastroenterology: Reflections From AGA FORWARD Program Scholars

Abstract 2297: Profound anti-tumor efficacy of dual CDK7 and PD1 blockade in novel syngeneic prostate cancer models

Abstract Background: Anti-PD1 immune checkpoint blockade (ICB) has largely failed as a monotherapy for metastatic prostate cancer likely due to inadequate tumor neoantigen load and inadequate T cell filtration (TILs). Strategies to increase TILs that can be tested in novel syngeneic mouse models are needed in order to fulfill this critical medical need. CDK7 is a major regulator of the cell cycle that is under investigation as a novel therapeutic target. CDK7 inhibition can trigger robust anti-tumor immunity by causing genomic instability and DNA damage in lung cancer mouse models. Herein, we characterize our novel syngeneic mouse models and report on the anti-tumor activity of CDK7 alone and in combination with anti-PD1 ICB as an immunotherapeutic strategy. Methods: We generated two models of prostate cancer organoids and syngeneic mouse models. APC and PTEN are tumor suppressor genes commonly lost in metastatic prostate cancer and are emerging as a putative mechanism of resistance to immunotherapy. The MPA and MPP models were established by ex-vivo Lenti-Cas9-sgRNA knock-out of APC or PTEN from the prostate organoids grown in 3D cultures established from the prostate of a MYCT/TP53-/- GEMM. Results: Organoids from the MPA and MPP models form orthotopic high grade prostate adenocarcinoma from 2 to 3 weeks post-implantation and spontaneously develop lung metastases 10-12 weeks after orthotopic implantation. In addition, the MPA model developed immediate castration resistance and neuroendocrine transformation following hormone deprivation in vivo. By contrast, the MPP tumors significantly regressed after in vivo androgen deprivation. Baseline immunoprofiling of the MPA and MPP orthotopic tumors showed increased infiltration from monocytic MDSCs and expression of T cell exhaustion markers. Treatment of the MPA and MPP orthotopic models with YKL-5-124, a CDK7 inhibitor, led to substantial in vivo tumor growth inhibition, which was further augmented by the addition of anti-PD-1 ICB. Immunoprofiling of tumors treated with combined YKL-5-124 and PD-1 blockade showed activation of CD4+ and CD8+ T cells, and a decrease in the Treg, B cell and NK cell population. Conclusions: The MPA and MPP orthotopic models recapitulate the biology and immune suppressive microenvironment of advanced prostate cancer and provide useful tools for immunotherapy drug development. Combination of CDK7 inhibition with anti-PD-1 blockade profoundly inhibited in vivo orthotopic tumor growth in both MPA and MPP model, providing a rationale for exploring CDK7 in combination with PD-1 checkpoint immunotherapy as a novel therapeutical strategy for advanced prostate cancer. Funding Acknowledgements: DRW is funded through 2018YI2295 Prostate Cancer Foundation Young Investigator Award and PC160944 Department of Defense Physician Research Career Development Award. Citation Format: David Wise, Luiza Doro Pereira, Jiansheng Wu, Victor R. Adorno Febles, Jonathan Melamed, Fang-Ming Deng, Hua Zhang, Kwok-Kin Wong. Profound anti-tumor efficacy of dual CDK7 and PD1 blockade in novel syngeneic prostate cancer models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2297.

0562 Associations of Insomnia Symptoms and Unhealthy Alcohol Use with Post-Operative Healthcare Utilization in Veterans Undergoing Decompressive Laminectomy for Lumbar Spinal Stenosis

Abstract Introduction Lumbar spinal stenosis (LSS) affects 11-39% of adults and contributes to significant pain and disability. Decompressive laminectomy (DL) is a common surgical intervention for LSS but many with medical and psychosocial comorbidities may not improve. Insomnia and unhealthy alcohol use, for example, are common among people living with chronic pain and may affect key laminectomy outcomes, such as healthcare utilization rates. We examined associations of self-reported rates of post-DL healthcare utilization in Veterans with insomnia symptoms and alcohol use. Methods We analyzed data from a multi-site prospective cohort study of Veterans with LSS undergoing DL. Participants (N=200) self-reported prior 12-month alcohol use behavior (Short Michigan Alcohol Screening Test; SMAST) and prior two-week insomnia symptoms (Insomnia Severity Index; ISI) prior to surgery; 12-months of post DL healthcare office visits, ER visits, hospitalizations, and mental health visits were reported over the telephone monthly. Negative binomial regression models via incident rate ratios (IRR) compared healthcare utilization rates between individuals reporting alcohol-related problems only (SMAST >2), insomnia symptoms only (ISI ≥ 8), and both to those reporting neither. Results Approximately 52% of participants reported insomnia symptoms, 75% unhealthy alcohol use, and 39% both. Rates of office, ER, and hospital visits were descriptively highest in those reporting insomnia only; mental health visits were highest in those with both insomnia and unhealthy alcohol use. Those with insomnia only had more ER (IRR=2.39, p=.04) and mental health visits (IRR=4.32, p=.03) than those with neither insomnia nor unhealthy alcohol use; individuals with both insomnia and unhealthy alcohol use also had more mental health visits (IRR=4.22, p=.01). Adjusting for covariates rendered IRRs attenuated and statistically nonsignificant, but magnitudes remained high. Conclusion Most Veterans with LSS reported insomnia symptoms and/or unhealthy alcohol use. Those with insomnia symptoms reported the highest rates of healthcare utilization, including higher rates of ER and mental health visits. Insomnia symptoms may contribute to post-operative healthcare utilization, lending support for assessment and intervention of sleep-related problems pre-laminectomy. Support (If Any) This material is based on work supported by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, grant # RX000798. Dr. Tighe is supported by Career Development/Capacity Building Award Number IK2 RX003393 from the United States (U.S.) Department of Veterans Affairs Rehabilitation R&D (Rehab RD) Service. Dr. Bachrach is supported by a U.S. Department of Veterans Affairs Health Services Research and Development Service (HSR&D) Career Development Award (CDA 20-057).

IgM anti-ACE2 autoantibodies in severe COVID-19 activate complement and perturb vascular endothelial function.

BackgroundSome clinical features of severe COVID-19 represent blood vessel damage induced by activation of host immune responses initiated by the coronavirus SARS-CoV-2. We hypothesized autoantibodies against angiotensin-converting enzyme 2 (ACE2), the SARS-CoV-2 receptor expressed on vascular endothelium, are generated during COVID-19 and are of mechanistic importance.MethodsIn an opportunity sample of 118 COVID-19 inpatients, autoantibodies recognizing ACE2 were detected by ELISA. Binding properties of anti-ACE2 IgM were analyzed via biolayer interferometry. Effects of anti-ACE2 IgM on complement activation and endothelial function were demonstrated in a tissue-engineered pulmonary microvessel model.ResultsAnti-ACE2 IgM (not IgG) autoantibodies were associated with severe COVID-19 and found in 18/66 (27.2%) patients with severe disease compared with 2/52 (3.8%) of patients with moderate disease (OR 9.38, 95% CI 2.38–42.0; P = 0.0009). Anti-ACE2 IgM autoantibodies were rare (2/50) in non-COVID-19 ventilated patients with acute respiratory distress syndrome. Unexpectedly, ACE2-reactive IgM autoantibodies in COVID-19 did not undergo class-switching to IgG and had apparent KD values of 5.6–21.7 nM, indicating they are T cell independent. Anti-ACE2 IgMs activated complement and initiated complement-binding and functional changes in endothelial cells in microvessels, suggesting they contribute to the angiocentric pathology of COVID-19.ConclusionWe identify anti-ACE2 IgM as a mechanism-based biomarker strongly associated with severe clinical outcomes in SARS-CoV-2 infection, which has therapeutic implications.FUNDINGBill & Melinda Gates Foundation, Gates Philanthropy Partners, Donald B. and Dorothy L. Stabler Foundation, and Jerome L. Greene Foundation; NIH R01 AR073208, R01 AR069569, Institutional Research and Academic Career Development Award (5K12GM123914-03), National Heart, Lung, and Blood Institute R21HL145216, and Division of Intramural Research, National Institute of Allergy and Infectious Diseases; National Science Foundation Graduate Research Fellowship (DGE1746891)

Bibliometric Approach to Evaluating the Impact of a Building Interdisciplinary Research Careers in Women's Health K12 Research Career Development Program.

Background: Mentored research career development programs are excellent training opportunities for junior faculty/early-stage investigators to transition into independent research careers. However, there is limited evidence that provides guidance on best practices for measuring the impact and reach of these programs, both for individual Scholars and the program as a whole. This article evaluates both the individual and overall impact of the Building Interdisciplinary Research Careers in Women's Health (BIRCWH) National Institutes of Health research career development award at the University of Minnesota. Materials and Methods: BIRCWH Scholars (n = 16) and a comparison group (n = 17) were evaluated on traditional metrics (e.g., publications, grant funding) in addition to bibliometrics (e.g., network growth, interdisciplinary collaborations, international reach, policy impact). Results: Traditional metric findings showed that BIRCWH Scholars had significantly more publications from pre- to post-BIRCWH experience than the comparison group and more grant funding. Bibliometric findings showed exponential network growth, interdisciplinary collaborations, international citations, and policy impact from pre- to post-BIRCWH Scholar experience. Conclusion: Findings from this evaluation have potential important implications. At the Scholar level, the results can be used to provide evidence of research impact in materials developed for merit review and promotion as well as in job and research grant applications. At the program level, the results can be used at the institutional level to gain broad administrative support and leverage additional funds for program activities and for evidence of program success for continuation funding from federal agencies.

The PARP inhibitor ABT-888 impairs the suppressive capacity of regulatory T cells through modulation of FoxP3 and CTLA-4.

Abstract Immune checkpoint blockade (ICB) has achieved long-term survival in melanoma but results remain limited in other solid malignancies including ovarian cancer. Combination treatments are a promising strategy to optimize responses to ICB. We have previously shown that the PARP inhibitor (PARPi) ABT-888 synergizes with CTLA-4 ICB to achieve long-term survival in a preclinical model of ovarian cancer. While the role of PARPi on DNA repair is well established, the impact on T cells is unclear. Published data using PARP1-KO mice suggests that PARP impairs regulatory T cell (Treg) function through modulation of FoxP3. Tregs suppress conventional T cell responses using multiple mechanisms including consumption of co-stimulatory molecules via the inhibitory receptor CTLA-4. Here we sought to define the impact of ABT-888 on the suppressive function of Tregs using FoxP3-eGFP transgenic mice. Using flow cytometry, we examined the levels of FoxP3 and CTLA-4 in Tregs stimulated in the presence of increasing doses of ABT-888 (0 – 50μM). Independent of stimulation, the GMFI of FoxP3 and CTLA-4 were significantly reduced by ABT-888 in a dose-dependent manner (P < 0.05). To test suppressive function, we pre-treated Tregs with increasing doses of ABT-888 prior to use in a standard proliferation assay. Similarly, ABT-888 pre-treatment significantly reduced the suppressive capacity of Tregs in a dose-dependent manner (P < 0.05). Taken together, these data identify a potentially novel area of synergy between PARPi and ICB. Furthermore, these data highlight the immunomodulatory effects of PARPi which are independent of their role in DNA repair. Future studies will focus on the impact of ABT-888 on tumor-associated Tregs and optimization of ICB therapy. This research was supported by NCI R37CA229221 (PI: Adams) and UNM Comprehensive Cancer Center Support Grant NCI P30CA11810. D.F. was supported by the Academic Science Education and Research Training program at the University of New Mexico Health Sciences Center (NIGMS Institutional Research and Academic Career Development Award; K12-GM088021).

Prevalence of Alzheimer's disease and related dementias among older US Medicare beneficiaries with and without HIV: a successive cross-sectional study

BackgroundNearly 50% of people with HIV have at least mild cognitive impairment, even when they are taking suppressive antiretroviral therapy (ART). There is growing concern among HIV researchers that people with HIV will have a disproportionate burden of dementia as they age; however, there is no nationwide population-based research data on changes in trend over time in Alzheimer's disease and related dementias (ADRD) prevalence among older people with HIV versus people without HIV. MethodsWe used 100% of beneficiaries with HIV diagnosis and a 5% national sample of Medicare enrollees in 2007–19 from all 50 US states and District of Columbia. All individuals who reached age 65 years in the calendar year and had at least 3 years of fees for service coverage were included in the denominator. All ADRD cases were identified by International Classification of Diseases, ninth revision, clinical modification (ICD-9-CM) and International Classification of Diseases, tenth revision, clinical modification (ICD-10-CM) diagnosis codes. Prevalence of ADRD was calculated in successive cross-sectional cohorts for each calendar year. Joinpoint regression analysis was performed to compute the average annual percentage change (AAPC) in ADRD prevalence by sex and age groups (65–69, 70–74, 75–79, and ≥80 years) for people with and without HIV, respectively. FindingsWe identified 26 887 and 608 141 ADRD-prevalent cases in all years among 87 216 people with HIV and 2 289 831 people without HIV, respectively. In the overall sample, 55·6% of beneficiaries were female, 84·5% were White, and 8·9% were Black. Mean age at entering the cohort was 73·3 (SD 8·1), More people with HIV were male (65·7%; 34·3% female) compared with people without HIV (43·6%; 56·4%). Mean age was 72·6 (6·7) years for male beneficiaries without HIV, 74·0 (7·8) for female beneficiaries without HIV, 70·0 (5·7) for male beneficiaries with HIV, and 72·8 (7·7) for female beneficiaries with HIV. There were more Black beneficiaries among people with HIV than among people without HIV (7·6%, 8·4%, 30·7%, and 37·1%, respectively). The prevalence of ADRD increased over years among older age groups (≥70 years) especially for people with HIV and female beneficiaries. Among people aged 80 years or older, ADRD prevalence increased from 26·2% to 33·3% for male beneficiaries with HIV and 31·4% to 44·1% for female beneficiaries with HIV, and from 21·0% to 23·5% for male beneficiaries without HIV and 27·4% to 29·9% for female beneficiaries without HIV. The AAPCs for the entire study duration by age groups were highest among female beneficiaries with HIV (range 1·2% [95% CI 0·6 to 1·8] to 3·1% [2·3 to 3·9]), whereas AAPCs estimates among female beneficiaries without HIV ranged from 0% (–0·3 to 0·3) to 0·9% (0·3 to 1·4). InterpretationPeople with HIV had a higher prevalence of ADRD, which increased over time in both male and female beneficiaries, compared with people without HIV. However, the magnitude of the increase was more prominent in female beneficiaries and with increasing age, indicating an increase in the dementia burden over 13 years among people with HIV, especially those who are female and aged 80 years or older. The findings underscore the need to develop clinical practice guidelines that facilitate integration of dementia screening and evaluation into routine primary care of ageing people with HIV, thus targeting resources to the most clinically vulnerable population. Future research is needed to understand factors associated with the increase in dementia among people with HIV. FundingXY and ABB are supported by a research career development award (K12HD052023; primary investigator ABB). XY is also supported by Sustained Training in Aging and HIV Research (R25MH108389; primary investigators Dilip V Jeste and Scott L Letendre. TPG is supported by the MD Anderson Foundation Chair at Baylor College of Medicine and Texas Developmental Center for AIDS Research (P30AI161943; primary investigator TPG).

COVID-19 threatens faculty diversity: postdoctoral scholars call for action.

Despite substantial investment and effort by federal agencies and institutions to improve the diversity of the professoriate, progress is excruciatingly slow. One program that aims to enhance faculty diversity is the Institutional Research and Academic Career Development Award (IRACDA) funded by the National Institutes of Health/National Institute of General Medical Sciences. IRACDA supports the training of a diverse cohort of postdoctoral scholars who will seek academic research and teaching careers. The San Diego IRACDA program has trained 109 postdoctoral scholars since its inception in 2003; 59% are women and 63% are underrepresented (UR) Black/African-American, Latinx/Mexican-American, and Indigenous scientists. Sixty-four percent obtained tenure-track faculty positions, including a substantial 32% at research-intensive institutions. However, the COVID-19 pandemic crisis threatens to upend IRACDA efforts to improve faculty diversity, and academia is at risk of losing a generation of diverse, talented scholars. Here, a group of San Diego IRACDA postdoctoral scholars reflects on these issues and discusses recommendations to enhance the retention of UR scientists to avoid a “lost generation” of promising UR faculty scholars.

A 22-year analysis of the Society for Vascular Surgery Foundation Mentored Research Career Development Award in fostering vascular surgeon-scientists

ObjectiveVascular surgeon-scientists shape the future of our specialty through rigorous scientific investigation and innovation in clinical care and by training the next generation of surgeon-scientists. The Society for Vascular Surgery Foundation (SVSF) supports the development of surgeon-scientists through the Mentored Research Career Development Award (SVSF-CDA) program, providing supplemental funds to recipients of National Institutes of Health (NIH) K08/K23 grants. We evaluated the ongoing success of this mission. MethodsThe curriculum vitae of the 41 recipients of the SVSF supplemental funding from 1999 to 2021 were collected and reviewed to evaluate the academic achievements, define the programmatic accomplishments and return on investment, and identify areas for strategic improvement. ResultsFor nearly 22 years, the SVSF has awarded supplemental funds for 31 K08 and 10 K23 grants to SVS members from 32 institutions. Of the 41 awardees, 34 have completed their K-funding and 7 are still being supported. Eleven awardees (27%) were women, including six of the current awardees (75%). However, only slight ethnic/racial diversity was found in the program. The awardees had obtained K-funding ∼4 years after becoming faculty. Eleven awardees (27%) were supported by Howard Hughes, NIH F32, or NIH T32 grants during training. To date, the SVSF has committed $12 million to the SVSF-CDA program. Among the 34 who have completed their K-funding, 21 (62%) successfully obtained NIH R01, Veterans Affairs, or Department of Defense funding. The awardees have secured >$114 million in federal funding, representing a 9.5-fold financial return on investment for the SVSF. In addition to research endeavors, 11 awardees (27%) hold endowed professorships and 19 (46%) have secured tenure at their institution. Many of the awardees hold or have held leadership positions, including 18 division chiefs (44%), 11 program directors (27%), 5 chairs of departments of surgery (12%), and 1 dean (2%). Eleven (27%) have served as president of a regional or national society, and 24 (59%) participate in NIH study sections. Of the 34 who have completed their K-funding, 15 (44%) have continued to maintain active independent research funding. ConclusionsThe SVSF-CDA program is highly effective in the development of vascular surgeon-scientists who contribute to the leadership and growth of academic vascular surgery with a 9.5-fold return on investment. The number of female awardees has increased in recent years but ethnic/racial diversity has remained poor. Although 62% successfully transitioned to federal funding, fewer than one half have remained funded over time. Retention in research and increasing diversity for the awardees are major concerns and important areas of strategic focus for the SVSF.

MP22-16 DEVELOPMENT OF NON-INVASIVE CLINICALLY APPLICABLE IN VIVO TRACKING OF EXTRACELLULAR VESICLES USING MAGNETIC RESONANCE IMAGING (MRI)

You have accessJournal of UrologyImaging/Radiology: Uroradiology II (MP22)1 Sep 2021MP22-16 DEVELOPMENT OF NON-INVASIVE CLINICALLY APPLICABLE IN VIVO TRACKING OF EXTRACELLULAR VESICLES USING MAGNETIC RESONANCE IMAGING (MRI) Johnny Akers, Paola Aguiari, Hasmik Soloyan, Seda Mkhitaryan, Gevorg Karaptyan, Roger De Filippo, Mya Thu, Laura Perin, and Sargis Sedrakyan Johnny AkersJohnny Akers More articles by this author , Paola AguiariPaola Aguiari More articles by this author , Hasmik SoloyanHasmik Soloyan More articles by this author , Seda MkhitaryanSeda Mkhitaryan More articles by this author , Gevorg KaraptyanGevorg Karaptyan More articles by this author , Roger De FilippoRoger De Filippo More articles by this author , Mya ThuMya Thu More articles by this author , Laura PerinLaura Perin More articles by this author , and Sargis SedrakyanSargis Sedrakyan More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002013.16AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Extracellular vesicles (EVs) derived from amniotic fluid stem cells (AFSC) hold great potential for the treatment of chronic kidney diseases (CKD). We have already shown that AFSC-EVs are renoprotective in a mouse model of CKD, Alport syndrome. However, there is an important unmet need for real-time in vivo monitoring of these therapeutic EVs after they are injected into a subject to understand their safety, targeting, and effectiveness. While current optical imaging solutions like bioluminescence and fluorescence are useful for EV tracking studies in animal models, there is limited utility in clinical applications. Here we present a novel in vivo tracking solution for our therapeutic EVs in Alport mice, utilizing clinically applicable MRI technology. METHODS: To generate trackable EVs, AFSC were labeled with a novel magnetic agent (VSCM). EVs secreted by the labeled AFSC were isolated by ultracentrifugation. The viability and morphology of labeled-cells were evaluated, and the in vitro MR properties of EVs were analyzed by magnetometer. Purity, potency and identity of labeled EV was compared to non-labeled EVs. In vivo biodistribution of labeled EVs was evaluated in WT and Alport mice by MRI at 10 min and 3 hr post injection, and retro-orbital and intra-cardiac routes of delivery were compared. RESULTS: The magnetic label did not affect the physiological characteristics of the cells and did not change identity, purity and potency (therapeutic effect in vivo) of EVs. MRI phantom studies confirmed the in vitro/ex vivo detectability of labeled-EVs. Importantly, as expected MRI studies showed that EV homing to the kidney injected intra-cardiacally into Alport mice was more efficient vs the retro-orbital route, and Prussian blue staining of sections confirmed EV homing to the kidney. CONCLUSIONS: We have developed a clinically applicable novel magnetic nanoparticle agent that can be used to label and track the biodistribution of EVs in the kidney and other organs using non-invasive, safe, and effective MRI technology that’s widely available. This technology is highly adaptable and can be deployed in both preclinical and clinical settings. Source of Funding: The GOFARR Fund; Research Career Development Award, TSRI, CHLA © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e397-e398 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Johnny Akers More articles by this author Paola Aguiari More articles by this author Hasmik Soloyan More articles by this author Seda Mkhitaryan More articles by this author Gevorg Karaptyan More articles by this author Roger De Filippo More articles by this author Mya Thu More articles by this author Laura Perin More articles by this author Sargis Sedrakyan More articles by this author Expand All Advertisement Loading ...

Fostering the Vascular Surgeon-Scientist: A 20-Year Analysis of the Society for Vascular Surgery Foundation Mentored Research Career Development Award

Academic vascular surgeons shape the future of our specialty through rigorous scientific investigation and innovations in clinical care as well as training the next generation of surgeon-scientists. The Society for Vascular Surgery Foundation (SVSF) supports the development of surgeon-scientists through the Mentored Research Career Development Award (SVSF-CDA) Program, providing supplemental funds to recipients of National Institutes of Health (NIH) K08/K23 grants. The ongoing success of this mission was evaluated.

George A. Mashour, M.D., Ph.D., Recipient of the 2021 Excellence in Research Award

George A. Mashour, M.D., Ph.D., Recipient of the 2021 Excellence in Research Award

Transition to Independent Research Funding Among National Institutes of Health K Grant Awardees at Departments of Orthopaedic Surgery.

The National Institutes of Health (NIH) supports mentored research career development awards (K awards) to increase the pipeline of independently funded scientists. This study analyzed the portfolio of K grants that were awarded to orthopaedic surgery departments and characterized the factors that were associated with successful transition to independent NIH research funding, including R01 grants. This was a retrospective cohort study of K-award recipients in orthopaedic surgery departments in the United States from 1996 to 2018. A query was performed on the NIH Research Portfolio Online Reporting Tools (RePORT) database for NIH grants that were awarded to departments of orthopaedic surgery, general surgery, otolaryngology, obstetrics and gynecology, ophthalmology, and urology. Rates of transition to independent research funding were compared by specialty for K grants that were awarded from 1996 to 2011. The percentage of faculty with mentored research career development awards and the return on investment (ROI) were calculated. An internet and Scopus (Elsevier) database search determined the investigator characteristics. The factors that were associated with successful transition to independent funding were determined via chi-square and unpaired t tests. Sixty K-award recipients were identified in orthopaedic surgery departments. Most were men (77%) and research scientists (53%). Fifty percent of the K-award recipients transitioned to independent research funding. Research scientists had the highest rate of transition to independent research funding (71%, p = 0.016) relative to clinicians (0%) and orthopaedic surgeons (40%). Higher levels of publication productivity were associated with successful transition to independent research funding. Similar rates of transition to independent research funding existed among surgical specialties (p = 0.107). Orthopaedic surgery had the lowest percentage of faculty with a K award (1.4%) but had the highest ROI (198%) of these awards. Orthopaedic surgery had similar rates of transition to independent research funding when compared with other surgical specialties but had a lower prevalence of K awards among faculty. Orthopaedic surgeon-scientists have lower rates of transition to independent research funding when compared with their research-scientist colleagues. These findings highlight a need for greater support to foster the pipeline of future NIH-funded orthopaedic investigators. As the largest support of biomedical research in the U.S., the NIH is an important stakeholder in orthopaedic innovations and discoveries. This study highlights barriers in the procurement of NIH funding across surgical specialties and affirms the need for greater resources toward supporting NIH funding in orthopaedic surgery.

Gender Disparity in Grants and Awards at the National Institute of Health.

ObjectiveThe National Institute of Health (NIH) supports the academic career of scientists across the United States (U.S.). It promotes and sponsors scientists in conducting wide-ranging clinical and basic science research. Depending on the duration, research type, and budget, there are various types of grants awarded by NIH. Despite considerable advancement in biomedical sciences, female researchers remain underrepresented in obtaining NIH funding. Through this study, we aim to highlight the gender trends in NIH funding and grants. By doing this, we aim to facilitate effective future policymaking to help achieve gender parity in NIH grants and awards.MethodsThe data were obtained from the NIH Research Portfolio Online Reporting Tool (RePORT). The extracted data by gender were tabulated showing percentages of females as Research Grant Investigators, Research Career Development Award Recipients and Kirschstein-National Research Service Award (NRSA) Trainees and Fellows, recipients of Research Grants, Research Project Grants (RPGs), and R01 equivalent grants including types 1 or 2, over two decades (1999-2019). Absolute percentage change was also calculated and included in the tables.ResultsThe percentage of females as NIH Research Grant Investigators has increased at centers, research centers as well as for RPGs and Small Business Innovation Research and Small Business Technology Transfer (SBIR/STTR) programs. For Research Career Development Award Recipients and Kirschstein-NRSA Trainees and Fellows, the proportion of female pre-doctoral institutional trainees, post-doctoral fellows, post-doctoral institutional trainees, mentored research career awardees, and other research career awardees have steadily increased. However, there was a decrease in the percentage of female pre-doctoral fellow awardees. The percentage of females receiving all RPGs, R01-New (type 1) and R01-Renewal (type 2) grants has also decreased. ConclusionDespite an overall increase in the percentage of female researchers successfully receiving NIH grants and awards, they continue to lag compared to their male counterparts. With the increasing number of female doctoral graduates, it is imperative to address this disparity in NIH funding.

Evaluation of the academic achievements of clinician health services research scientists involved in “pre-K” career development award programs

Research career development awards (CDAs) facilitate development of clinician-scientists. This study compared the academic achievements of individuals in a structured institutional "pre-K" CDA program, the Mayo Clinic Kern Scholars program, with individuals who applied for but were not admitted to the Kern program ("Kern applicants"), and awardees of other unstructured internal CDAs. This was a longitudinal cohort study of clinicians engaged in research at Mayo Clinic between 2010 and 2019. The primary outcome was time to the 15th new peer-reviewed publication after the program start, adjusted for baseline number of publications. Secondarily, we described successful awarding of federal funding by the NIH or VA. The median (IQR) number of baseline publications was highest among Kern Scholars compared to Kern Applicants or other CDA awardees [16 (12, 29) vs 5 (1, 11) and 8 (5, 16); P < 0.001]. After adjustment for baseline publications, the time to 15th new publication was significantly shorter for Kern Scholars than for the two comparator groups (P<0.001). Similar findings were observed with total new publications within 5 years (P < 0.001), as well as number of new first-/last-author publications within 5 years (P < 0.001). The overall frequency of K-awards, R-awards (or equivalent), or any funding were similar between groups, with the exception of R03 awards, which were significantly more common among Kern Scholars (P = 0.002). The Kern Scholars program is a successful training model for clinician-scientists that demonstrated comparatively greater acceleration of scholarly productivity than other internal CDA programs.