Your Avant-Garde award—awarded in 2008—was given for the project entitled “Inhibition of HIV at the Immune Synapse Utilizing Novel Ligands and Receptors.” What was your vision for this concept?
My vision was to pursue a central finding in how the virus first enters the body and is passed on to vulnerable cells of the immune system. This occurs at a junction between a specialized white cell and the key orchestrator of the immune response, the helper T-cell. My idea was to first study whether newly discovered naturally occurring proteins in the body could block the handing-off of HIV from the white cell to the T-cell at this unique junction termed the “immune synapse.” Then, I wanted to know how certain drugs of abuse, including cannabinoids and cocaine, might enhance the transmission of the virus so that specific targeted therapies might one day be developed to protect people from contracting the virus.
How has the award helped you advance this area of science?
The award was essential in providing the funds with the creative freedom to pursue this unique avenue of research, a high-risk project since it had never been addressed before, but which promised to yield novel insights about HIV and how drugs of abuse might facilitate its chances of infecting a person and then passing into the bloodstream.
Have there been any surprises or unusual challenges along the way?
There were numerous challenges, mostly technical in constructing model systems in the lab with the different cell types that make up this immune synapse. But we succeeded in positioning the specialized white cells within proximity of not only helper T-cells but also the lining cells of blood vessels and lymphatic channels (“endothelium”). Our hypotheses were also assessed experimentally. We found that cocaine has profound effects on the behavior of these cells and partners with HIV to enhance infection and dissemination of the pathogen. Interestingly, cannabinoids proved to be much less potent in this regard, so we decided to focus on cocaine and then methamphetamine.
What advice would you give to others seeking similar awards for bold and innovative science?
Think creatively, meaning a high-risk, high-return idea in an area that has not been deeply studied. Marshal your background in cellular biology, virology, molecular techniques and any other applicable field to maximize the potential impact of tackling a new hypothesis.
Where will your vision of HIV/AIDS research take you next?
The award catalyzed my thinking about unaddressed aspects of HIV/AIDS research and drugs of abuse. I received an RO1 to study how cocaine may change the workings of the cell (“the cytoskeleton”) in ways that facilitate HIV escaping the defenses of the immune system. This led me to a second avenue of research that melds cutting-edge biology with molecular effects of illicit drugs, specifically methamphetamine, on disabling T-cells. We found that this drug altered what are called “microRNA” which ordinarily serve to oppose HIV from taking root in the cell. Our vision is to contribute new knowledge on how such drugs partner with this pathogen and then to ultimately study ways to sever that partnership.