Abstract: he K01 Mentored Research Scientist Development Award will provide Dr. Michael Li with invaluable research experience, mentored training from interdisciplinary faculty, and training activities in a combination of behavioral and basic sciences, which will prepare him well in his career as a biobehavioral researcher in addiction medicine and HIV treatment/prevention. This K01 mechanism will support Dr. Li’s research and training efforts to develop expertise in the following areas: (1) neurally regulated “stress” gene expression markers and links to addiction and HIV disease progression; (2) cultural competence and ethical conduct; (3) technical assay and substantive analytic methods in gene expression research; (4) clinical trial methods; and (5) professional development. Dr. Li has assembled an interdisciplinary mentorship team who will support key aspects of his training and research. Dr. Steven Shoptaw is a highly productive and influential researcher in addiction medicine, and he has an extensive track-record mentoring people who later became successful independent researchers. Co-mentor Dr. Steven Cole has pioneered the field of social genomics, and will direct Dr. Li’s training in transcriptomic methods. Dr. Jesse Clark will guide Dr. Li in clinical trial operations and safety procedures, and Dr. Thomas Belin will provide extensive mentoring in advanced statistical methods and inferential frameworks in clinical trials. Dr. Li proposes to investigate whether a neurally regulated “stress” gene expression pattern can serve as a clinically meaningful, non-abstinence-based endpoint for contingency management for methamphetamine (METH) use disorder (MUD) in MSM living with HIV. Abstinence determined by urine testing has been the only standard clinical outcome for MUD treatment, but provides an incomplete picture of patient recovery. The gene expression pattern called the conserved transcription response to adversity (CTRA) may provide insight into changes in both psychosocial health and pathogenesis over the course of MUD treatment. The CTRA is marked by upregulated expression of pro-inflammatory genes and downregulated expression of Type I interferon genes in response to negative psychosocial experiences such as depression, anxiety, and violence, problems also comorbid with METH use. The CTRA also involves some of same gene regulatory pathways that contribute to METH-related pathogenesis, such as those involving inflammation and innate antiviral responses (relevant to PLWH). My proposed research will use a two-arm clinical trial design (N=55) with 35 HIV-positive MSM with MUD receiving contingency management for METH reduction, and 20 HIV-positive MSM who qualify as a non-substance-using control to accomplish the following aims: 1) to investigate whether CTRA gene expression coincides with METH use and viral load; 2) to investigate whether psychosocial indicators of addiction are associated with CTRA; and 3) to conduct an exploratory pilot investigation to determine the degree to which CTRA mediates the association between METH use and viral load. Together, this K01 research project and training plan will play a fundamental role in my early success as an independent substance use and HIV researcher.

Project Number: 1K01DA051329-01A1

https://reporter.nih.gov/search/P51IV4WiG0m3UfJ8wdV_1w/project-details/10161548

 

Contact PI/ Project Leader

LI, MICHAEL JONATHAN, POSTDOCTORAL SCHOLAR (mjli@mednet.ucla.edu)

 

Organization

UNIVERSITY OF CALIFORNIA LOS ANGELES

 

PUBLIC HEALTH RELEVANCE: Determining whether a patient is both feeling better and improving physiologically when treating people living with HIV (PLWH) for methamphetamine use disorder (MUD) requires identification of a clinically significant measure separate from abstinence. My proposed K01 activities open the exciting opportunity to address this challenge by testing a gene expression pattern identified by the field of social genomics, which may provide insight into both psychosocial health and biological processes that impact chronic disease risk in PLWH receiving MUD treatment. Support from this K01 will facilitate my training in transcriptomics, clinical trial methods, and ethical/culturally competent practices, all of which will help me achieve my long-term career goal—to be a leading researcher of biomarker assessment tools for PLWH receiving addiction treatment.

 

 

Project Start Date: 01-April-2021

Project End Date: 31-March-2026

Budget Start Date: 01-April-2021

Budget End Date:31-March-2022

 

NIH Categorical Spending

Funding IC:  NATIONAL INSTITUTE ON DRUG ABUSE/ FY Total Cost by IC: $189,401