Your Avant-Garde award—awarded in 2009—was given for the project entitled “Systems Biology of Immune Reconstitution in HIV/AIDS.” What was your vision for this concept?
My vision was to apply new computational methods to study multidimensional behavioral and biomedical data and use these methods to achieve a systems-level understanding of factors that influence restoration of immune function and other outcomes in people with HIV, and how these factors interact with each other. I felt it was important to derive a more global view of individual health trajectories by examining multiple factors at the same time — demographics, behaviors, substance abuse, mental health, physical health, and laboratory markers of human physiology. Then use this information to develop models that help to explain differences in health trajectories and test if these models are valid across other populations.
How has the award helped you advance this area of science?
The award allowed me to enter the field of big data as it relates to HIV, substance abuse, and co-morbidities — using diverse behavioral, clinical, and biological data, metabolomics, data mining, machine learning, trajectory analysis, and predictive modeling. By integrating data from different platforms, we advanced knowledge of how HIV, substance abuse, and mental health can interact to impact health trajectories through effects on metabolic, inflammatory, stress response, and aging pathways. We also found evidence supporting a biological model of depression involving interactions between stress responses, monoamine metabolism, and mitochondrial pathways — these pathways can be altered in HIV by chronic inflammation, cocaine use, and aging. Our findings suggest that integrated approaches targeting not only the virus, but also inflammation and protective mitochondrial pathways may be beneficial for prevention and treatment of HIV and several co-morbidities including depression.
Have there been any surprises or unusual challenges along the way?
Big data always yield surprises — it is fascinating because you don’t know what you’ll find next, and the pace of gaining new knowledge is quick. As a molecular biologist who recently moved into interdisciplinary science to achieve a more integrated understanding of health trajectories, I was surprised to see such strong effects of education level disparities, depression, and smoking on health trajectories in HIV when compared to the effects of many other factors. When hundreds of variables are examined at the same time and ranked for impact, formal education beyond high school — even one or two additional years — is a strong predictor of better mental and physical health trajectories, while persistent depression and smoking are associated with substantial risk for worse health trajectories. The impact of these factors on health trajectories increases with aging in HIV, especially after age 45 or 50, and these risk factors often co-exist with each other, substance use disorders, and reduced adherence to anti-retroviral medications.
What advice would you give to others seeking similar awards for bold and innovative science?
Have a broad vision about important problems with public health impact. Imagine how new research tools can be used to address these problems in ways that can drive the field forward, and how they can increase translational knowledge. Think about innovative ways to achieve these goals by integrating knowledge from different fields and leveraging the power of computer science.
Where will your vision of HIV/AIDS research take you next?
I plan to study health effects of recreational and medical marijuana to gain a better understanding of the potential benefits and adverse effects, and the science of how these effects are mediated in cells. I’m also interested in research on the biology of risk behaviors relevant for drug abuse and HIV transmission. Based on knowledge gained from interdisciplinary research, I have new ideas that may help shed light on the biology of risky behaviors, addictions, and depression by integrating genetics, biomarkers, and behavioral data. Ultimately, I hope my research can help to inform evidence-based implementation. I feel it is time for new thinking about comprehensive implementation strategies that can improve mental and physical health trajectories in diverse populations, from early childhood through adolescence and in middle- and old-age. As an example, revamping education in ways that better support the development of skills needed for everyday life, social health, and jobs, from decision-making and basic financial literacy to resilience behaviors that protect against stress and other types of adversity. As a scientist involved in research across different fields for many years, my understanding of the broader landscape has increased over time and my priorities have shifted to place more emphasis on prevention and implementation strategies that can improve mental and physical health across a lifespan. Hopefully, new knowledge from interdisciplinary analysis of big data can help to inform these strategies.