The 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.