Mentoring the next generation of substance use, HIV, and epigenetic researchers in sexual and gender minority health

摘要 Annesa Flentje博士是社区卫生系统和精神病学系副教授， 加州大学旧金山分校的行为科学。她指导早期职业研究人员在 性少数群体和性别少数群体(SGM、非异性恋者和变性人或非双性恋者) 健康，重点关注物质使用、少数人应激和物质使用的表观基因组标记。SGM人 与顺性、异性恋的同龄人相比，他们有更多的物质使用。更高的利率 物质使用归因于少数人的压力暴露(因歧视和耻辱而产生的独特压力负担 在SGM人群中)，并且在存在少数人压力的情况下物质使用增加。此外，独特的分子 在携带艾滋病毒的性少数族裔男性中观察到了药物使用和少数民族压力的特征， 这表明表观基因组的改变可以作为物质使用的生物标志。不幸的是， 迄今为止的研究是有限的，因为这些模型还没有明确地比较艾滋病毒携带者(PLWH) 和生活在没有艾滋病毒的人(PLWoH)。此外，SGM患者有独特的荷尔蒙暴露， 在调查物质使用和物质使用的潜在表观遗传生物标记物的研究中未被考虑 而这些荷尔蒙暴露也可能与表观基因组的变化有关。该项目将扩大Dr。 Flentje的研究计划将荷尔蒙暴露和艾滋病毒状况结合起来，以便能够识别表观基因组 内源性和外源性激素暴露下物质使用的标志物比较 致PLWoH。为了支持她的研究扩展，Flentje博士将接受关于艾滋病毒、激素的额外培训 暴露、显性分析和表观遗传生物信息学分析。这台K24将支持Flentje博士 指导SGM Health中以患者为导向的研究人员，他们将利用现有的调查和表观遗传学数据 队列研究：Pride研究、MACS/WIHS联合队列研究和我们所有人研究计划 1)了解SGM人群中物质使用的关键少数民族压力预测因素，并比较 PLWH和PLWH之间这些预测因子的强度；2)识别内源性和外源性激素 SGM人群中物质使用的预测因素，并确定这些因素的相对强度差异 PLWH和PLWH之间的预测因子；以及3)得出少数应激、物质使用和激素表型 在SGM人群中，识别这些表型的表观遗传标记，并识别这些表型的差异 PLWH和PLWH之间的表观遗传标记。这个K24将支持早期职业研究人员的指导 在SGM健康中，重点关注物质使用、艾滋病毒、激素生物学、表观基因组学和少数族裔压力。它还将 扩展Flentje博士的指导技能，以整合结构以支持受训者在金融领域导航 挑战、还贷申请、家庭建设和情感上的困难。作为物质使用研究 在SGM人群中是一个新兴的研究领域，这是一种促进创新的全国性指导方法 以患者为中心的研究至关重要。

ABSTRACT Dr. Annesa Flentje is Associate Professor in Community Health Systems and Department of Psychiatry and Behavioral Sciences at the University of California, San Francisco. She mentors early career researchers in sexual and gender minority (SGM, non-heterosexual and transgender or gender non-binary people, respectively) health, focusing on substance use, minority stress, and epigenomic markers of substance use. SGM people have greater substance use when compared to their cisgender, heterosexual counterparts. The greater rates of substance use are attributed to minority stress exposure (unique stress burden due to discrimination and stigma among SGM people), and substance use increases in the presence of minority stress. Further, unique molecular profiles of both substance use and minority stress have been observed in sexual minority men living with HIV, suggesting that alterations in the epigenome may serve as biological markers for substance use. Unfortunately, research to date is limited because these models have not explicitly compared people living with HIV (PLWH) and people living without HIV (PLWoH). Further, SGM people have unique hormonal exposures that have been unaccounted for in research investigating substance use and potential epigenetic biomarkers for substance use and these hormonal exposures may also be related to alterations in the epigenome. This project will expand Dr. Flentje’s research program to integrate hormonal exposures and HIV status, to be able to identify epigenomic markers of substance use in the presence of endogenous and exogenous hormone exposures comparing PLWH to PLWoH. To support expansion of her research, Dr. Flentje will receive additional training in HIV, hormone exposures, dominance analysis, and epigenetic bioinformatics analysis. This K24 will support Dr. Flentje in mentoring patient-oriented researchers in SGM health who will leverage survey and epigenetic data from existing cohort studies: The PRIDE Study, the MACS/WIHS Combined Cohort Study, and the All of Us Research Program to 1) understand key minority stress predictors of substance use among SGM people and compare the relative strength of these predictors between PLWH and PLWoH; 2) identify endogenous and exogenous hormonal predictors of substance use among SGM people and determine differences in the relative strength of these predictors among PLWH and PLWoH; and 3) derive minority stress, substance use, and hormonal phenotypes among SGM people, identify epigenetic markers of these phenotypes, and identify differences in these epigenetic markers between PLWH and PLWoH. This K24 will support mentorship of early career researchers in SGM health focusing on substance use, HIV, hormonal biology, epigenomics, and minority stress. It will also expand Dr. Flentje’s mentorship skills to integrate structures to support mentees in navigating financial challenges, loan repayment applications, family building, and emotional hardships. As substance use research among SGM people is an emerging area of study, a national approach to mentorship to promote innovation in patient-centered research is critical.