Jennifer A. Manuzak, PhD

My research program investigates the biological mechanisms used to defend specialized barrier tissues, including mucosal surfaces and the maternal-fetal interface, and how these defenses are disrupted by infectious agents and substance use. The ultimate goal of my laboratory is to develop novel therapeutic strategies to fine-tune immunity to prevent and treat infectious diseases and chronic inflammation, with a particular focus on pregnant women and people who use substances, whose distinct biology shapes both disease risk and treatment response.
 
My laboratory pursues two main lines of investigation:
 
1)    Identifying the immune mechanisms underlying HIV and malaria, alone and during co-infection, and translating these insights into novel therapeutic strategies.
 
HIV and malaria remain two of the most globally devastating infectious diseases, with more than 38 million people living with HIV and over 600,000 malaria-related deaths each year. Notably, endemic HIV and malaria overlap geographically, constituting a high risk for co-infection, which accelerates pathogenesis and worsens clinical outcomes for both infections. The immune mechanisms underlying this acceleration have implications beyond HIV and malaria, with relevance to other emerging infectious disease threats and complex co-infections more broadly. My laboratory aims to define these mechanisms and to translate these insights into safer, more effective therapeutic strategies for people living with or at risk for either infection.
 
Current investigations test whether concurrent malaria infection diminishes the efficacy and immunogenicity of novel HIV preventatives; examines how malaria exacerbates mucosal immune dysfunction and microbial dysbiosis during antiretroviral therapy (ART)-treated HIV/SIV infection; and characterizes how HIV/SIV infection amplifies the risk for poor maternal and fetal outcomes due to malaria in pregnancy. We are interested in extending this work to other emerging and neglected infectious diseases and examining their effects on mucosal immunity, the microbiome, and maternal-placental-fetal outcomes.
 
2)    Defining the immune mechanisms by which substance use shapes HIV risk and pathogenesis, and identifying novel prevention and treatment strategies.
 
Substance use, particularly cannabis and methamphetamines, is prevalent among people with HIV (PWH), and among individuals at risk for HIV acquisition. The immune mechanisms by these substances modulate HIV susceptibility, intersect with HIV prevention behaviors, and influence clinical outcomes in PWH remain incompletely understood, with particularly notable gaps for pregnant women and across the lifespan. Addressing these gaps will advance HIV prevention efforts and reveal novel therapeutic targets to improve outcomes among people with or at risk for HIV.
 
Current investigations examine how cannabis use affects update, adherence, and efficacy of pre-exposure prophylaxis (PrEP), as well as immune function, in people with or at risk for HIV; how combined cannabis exposure, ART, and HIV/SIV infection influences maternal, placental, and fetal outcomes; and how rectal and systemic immune biomarkers in people who use methamphetamines associate with HIV seroconversion risk. We are interested in extending this work to additional substances and examining their impact on immunity, pregnancy outcomes, and HIV treatment and prevention strategies.
 

Research Programs

• Impact of malaria co-infection on preventative treatments for HIV/SIV 
• Mechanisms of mucosal dysfunction during HIV/SIV and malaria infection
• Role of immune dysfunction at the maternal-fetal interface during HIV/SIV and malaria infection
• Associations of cannabis use with HIV prevention behaviors and transmission risk 
• Impact of methamphetamine use on biobehavioral determinants of HIV seroconversion 
• Impact of prenatal cannabis use on maternal-fetal interface dysfunction in HIV/SIV infection