Eva Lee, professor in the H. Milton Stewart School of Industrial and Systems Engineering and director of the Center for Operations Research in Medicine and Healthcare, is leading the systems modeling and predictive analysis components of a study investigating the biochemical mechanisms behind cocaine and anti-retroviral drug interactions in mouse models of AIDS.
Researchers agree cocaine injures the heart and predisposes users to HIV/AIDS because of risky behaviors. What’s more, the anti-retroviral medicines used to treat HIV/AIDS also may adversely affect the cardiovascular system. Used together, cocaine and anti-retroviral therapy can amplify the injury from each.
Lee is working with cardiac pathologist William Lewis, who is the principal investigator of the study and a professor of pathology and laboratory medicine in Emory University School of Medicine. The team also includes consultant Michael Kuhar, PhD, Candler Professor of Neuropharmacology and Georgia Research Alliance Eminent Scholar at Emory School of Medicine and Yerkes National Primate Research Center; and former Emory faculty member and consultant David Harrison, MD, currently at Vanderbilt University.
For her part, Lee says that “the model must be capable of incorporating large amounts of heterogeneous data, including genomic, biochemical, physiological and pathological.” Continuing, she states that “identifying the discriminatory features and constructing the predictive systems network will offer fundamental understanding of cocaine, HIV/AIDS and antiretroviral nucleosides interaction at multiple levels.” Lee is encouraged that “this will shed light on promising avenues for improving treatment strategies.”
It is estimated that more than 34 million Americans have used cocaine and more than 1.5 million are habitual users. Meanwhile, more than a million Americans are infected with HIV or have full-blown AIDS.
According to Lewis, for decades, cocaine has been thought to increase the risk for HIV infection. He states that “HIV/AIDS, along with the use of cocaine and NRTIs [nucleoside reverse transcriptase inhibitors] may lead to cardiomyopathy, a prevalent, life-threatening illness.” Though antiretroviral drugs have increased survival rates in those with HIV/AIDS, Lewis says that “unfortunately, these drugs may be cardiotoxic.”
Continuing, he explains that “research from our laboratory and others has shown that genetic products of HIV, along with antiretroviral drugs, increases cells’ oxidative stress, which causes damage to the heart cells, eventually leading to heart failure. Cocaine, HIV/AIDS and antiretroviral nucleosides interact at multiple levels.”
About the study, Lewis says that the researchers want to understand “which switches are being turned on and which switches are being turned off at the level of the gene. This will enable us to formulate a testable hypothesis on what mechanisms lead to cardiomyopathy and heart failure in AIDS and non-AIDS conditions.”
The study is being funded through a new $5.7 million grant from the National Institute on Drug Abuse of the National Institutes of Health.
Industrial and Systems Engineering