Stephen Waggoner, PhD, is an assistant professor in the Center for Autoimmune Genomics and Etiology (CAGE) at Cincinnati Children's Hospital Medical Center. Dr. Waggoner received his PhD from the University of Virginia, conducted postdoctoral research at the University of Massachusetts Medical School, and joined the faculty at Cincinnati Children’s in 2013. He has garnered international recognition for his discovery that natural killer (NK) cells play crucial regulatory roles during persistent virus infection involving suppression of virus-specific T cell responses. His lab continues to explore the relevance of this phenomenon to chronic infection, vaccine efficacy, autoimmune disease, and age-associated immune dysfunction.
Project: A revolutionary vaccine approach to prevent HIV infection in substance abuse: Dr. Waggoner’s group will play an important role in the ongoing science of HIV vaccine development. His project will focus on preventing natural killer cells from destroying activated helper CD4 cells, to strengthen vaccine effectiveness. The CD4 helper cells support the functioning of the immune system against infections, including HIV. A vaccine that enhances the immune system’s long-term ability to resist infection could enhance the antibodies against HIV and delay progression to AIDS in vulnerable populations. This will be particularly valuable among drug users who are much less likely to be treated and to have some of the worst outcomes.
Heinrich Gottlinger, MD, joined the Program in Gene Function and Expression at the University of Massachusetts Medical School in September of 2004. He received his MD from the University of Munich in 1983. From 1984 to 1989 he was a post-doctoral fellow, first at the Institute of Immunology, University of Munich, and later at the Dana-Farber Cancer Institute in Boston. Before joining UMMS, he was a faculty member in the department of pathology at Harvard Medical School. In addition to the 2014 Avant-Garde award, Dr. Gottlinger is also the recipient of a prestigious National Institutes of Health MERIT (Method to Extend Research in Time) Award.
Project: Mechanism of HIV cell-cell transmission of relevance to substance users: Dr. Gottlinger will explore the roles of two specific proteins involved in HIV’s movement from an infected to an uninfected cell. Because this route of infection allows HIV to evade the immune system’s antibodies, a clearer understanding of this process can inform new strategies to prevent HIV and slow HIV disease progression. Such strategies could be especially relevant for injection drug users, who may be exposed to HIV through sharing syringes that contain infected cells.
Melanie Ott, MD, PhD, is a Senior Investigator at the Gladstone Institutes, a research center dedicated to fundamental studies of virology and immunology, cardiovascular disease and neurology. She is also a Professor of Medicine at the University of California, San Francisco. Dr. Ott studies host-virus interactions with a focus on HIV transcription and the molecular mechanisms of HIV-associated chronic immune activation.
Project: A new model of accelerated immune aging in HIV-infected drug users: Dr. Ott will investigate the role of an enzyme (SIRT-1) in slowing accelerated immune aging resulting from either long-term HIV infection or regular drug use. Because SIRT-1 appears to protect against overworked immune activation that can eventually exhaust immune cell functions, new therapies aimed at this enzyme could delay immune aging and its related health risks in HIV-infected drug users.
Warner C. Greene, MD, PhD, is Director, Senior Investigator, and Nick and Sue Hellmann Distinguished Professor of Translational Medicine at the Gladstone Institute of Virology and Immunology (GIVI), a research center dedicated to fundamental studies of modern virology and immunology with a focus on HIV and AIDS. He is also President of the Accordia Global Health Foundation, whose mission is to build alliances to fight infectious disease in Africa. Dr. Greene is also a Professor of Medicine, Microbiology, and Immunology at the University of California, San Francisco (UCSF). The ongoing research in Dr. Greene’s laboratory focuses on the molecular basis for HIV pathogenesis, transmission, and latency.
Project: HIV without AIDS: A radically different approach to help the developing world: Dr. Greene’s research team is taking a unique approach to treat HIV infection -- rather than attempting to suppress the virus, they are investigating a way to modify how an animal model responds to the virus. By inhibiting the caspase I enzyme and preventing the inflammatory and immune responses that lead to the death of specific immune cells (CD4 T-cells) following HIV infection, their approach could prevent further CD4 T-cell loss that eventually results in clinical progression to AIDS. A single inhibitor could be significantly more cost-effective than combination antiviral therapies, providing a much-needed treatment option for vulnerable populations like injection drug users in the developing world, who likely have limited access to antiviral medications.
Richard Sutton, MD, PhD, is Associate Professor of Medicine (Infectious Diseases) and of Microbial Pathogenesis at the Yale School of Medicine. He is a clinician-researcher who devotes about half his time to clinical duties and has the uncommon gift of being able to bridge the gaps between laboratory science and clinical issues. His research has focused on HIV replication and the development of small animal models of HIV; HIV vectors; HIV replication and gene transfer into non-dividing cells. He has used cutting-edge genetic methodologies to probe virus interactions host in HIV.
Project: Host genetic control of HIV: Dr. Sutton’s research team plans to identify those rare genetic mutations that account for why a small percentage of HIV-infected individuals do not suffer any ill effects or need to take antiretroviral medications. Sutton will integrate a variety of techniques to isolate specific protective genes, including viral growth assays, the latest genomic technologies, and genetic analyses of family members (for example, siblings, parents, children, aunts, uncles, and cousins) to better understand inheritance patterns for these protective genes and to identify which variants are responsible for control of HIV.
Timothy J Cardozo, M.D., Ph.D. is Associate Professor; Graduate Student Advisor; Course Director Department of Biochemistry and Molecular Pharmacology, New York University Langone Medical Center. He has broad research interests including molecular design, informatics, drug discovery, and HIV vaccine development. Dr. Cardozo has formed collaborations that span the fields of immunology, virology, bacteriology, biochemistry, cancer research, neuroscience, pharmacology and structural biology. His research has already contributed much to HIV vaccine research. His .work was among the first to identify epitopes hidden in the HIV sequence variable loops that are conserved across many HIV strains. He has brought a three-dimensional approach to integrating virology and immunology.
Project: Combined cocaine and HIV vaccine: Dr. Cardozo’s group plans to test a combined anti-cocaine/HIV vaccine in animal models. The ultimate goal is to produce a clinical-grade vaccine, the prototype of which is sought by the end of the project period. A successful vaccine of this kind would treat cocaine addiction while preventing HIV infection in those receiving the vaccine. Compared to the general population, women and disadvantaged minorities show higher incidence of cocaine use linked to HIV infection. This combined vaccine could be a high-impact intervention for these populations.
David Smith, M.D. is Associate Professor of Medicine, Department of Medicine, Division of Infectious Diseases, University of California, San Diego School of Medicine. He is a translational virologist and infectious disease physician who has contributed to our understanding of HIV transmission, superinfection, and virologic compartmentalization. He has been at the forefront of characterizing HIV transmission networks using molecular epidemiologic techniques.
Project: Molecular epidemiology for HIV prevention for drug users and other risk groups: Dr. Smith’s group will develop a novel system that integrates information regarding patient demographics, geographic location, drug use, and HIV viral strain in order to map patterns of new HIV infections as they occur in real time. A successful system would allow for the quick delivery of tailored prevention resources to affected communities based on their unique characteristics (e.g., injection drug use or methamphetamine use and sexual transmission). The ultimate goal is to stop HIV clusters from developing or expanding, particularly among substance using populations.
Samuel Friedman, Ph.D. is Project Director, Principal Investigator, Senior Research Fellow, National Development Research Institutes, New York, NY. He is one of the world’s leading experts on the epidemiology of infectious disease transmission in injection drug users (IDUs).He has developed and implemented new approaches for understanding the epidemiology of HIV among IDUs such as understanding the importance of social factors and networks in HIV transmission.
Project: Preventing HIV transmission by recently-infected drug users: Dr. Friedman’s research team plans to identify people newly infected with HIV and link them to care, since the first few months of infection represent a period of high infectivity and risk behavior. Novel interventions that include community alerts and education within affected drug using and other social networks and venues, and efforts to prevent stigmatization of the newly-infected, will be developed and tested to prevent further spread within the community.
Jeremy Luban, M.D. is Professor of Molecular Medicine and the David L. Freelander Memorial Professor in HIV/AIDS Research at the University of Massachusetts Medical School, Worcester, MA. He has made seminal contributions to our understanding of host factors that are important for HIV-1 replication or which confer immunity to the virus.
Project: Human genes that influence HIV-1 replication, pathogenesis, and immunity in intravenous drug users: Dr. Luban’s group plans to develop new methods for studying the ways in which human genes can influence whether an exposed person will become infected with HIV or, if infected, how the disease will progress. These studies will guide future strategies aimed at preventing and treating HIV among drug abusers.
David D. Ho, M.D. is Senior Physician, Irene Diamond Professor, The Rockefeller University and Scientific Director and Chief Executive Officer of the Aaron Diamond AIDS Research Center. Dr. Ho has made seminal contributions to HIV/AIDS research and is an outstanding physician-scientist. In 1996, Dr. Ho’s leadership in the HIV/AIDS field was recognized by Time Magazine’s naming him ―"Man of the Year."
Project: Monthly Antiretroviral Therapy Using Multispecific HIV Neutralizing Antibodies
Combination antiretroviral therapy consisting of orally administered, anti-HIV medications taken daily has revolutionized the treatment of HIV/AIDS. However, treatment failures continue to occur in a significant fraction of those treated, often due to incomplete patient adherence to the prescribed regimen. Dr. Ho aims to develop a revolutionary HIV therapy—with particular relevance for drug users who struggle with adherence—bi-specific or tri-specific antibody-like molecules that could be administered monthly. A once-a-month treatment would improve the feasibility of directly observed therapy, an evidence-based adherence intervention. Antibodies are not only well tolerated and have an excellent safety record, but can also be administered infrequently because of their long half-life. This research program has the potential to lead to the next generation of medications to treat HIV; medications that could dramatically increase patient adherence and lead to decreased treatment failures and better clinical outcomes.
Eric M. Verdin, M.D., is a senior investigator and associate director of the Gladstone Institute of Virology and Immunology and professor of medicine at the University of California, San Francisco. Research in his laboratory focuses on the mechanism of HIV transcription.
Project: Novel Model for HIV Latency in Primary Memory T Cells
The long-term persistence of HIV in a latent state in patients treated with HAART prevents the eradication of the disease and forces patients to remain on HAART for their entire life. At this time, our understanding of how latent HIV infection occurs is basic. Dr. Verdin’s project aims to develop a new single-cell technology to examine how HIV latency is established and maintained, and how the virus becomes reactivated, in primary human lymphoid cells. By observing the fate of the virus in single cells, Dr. Verdin hopes to be able to devise novel strategies to eliminate latent HIV infection, or to restrict the latent pool to a size that can be controlled by the immune system.
Benjamin K. Chen, M.D., Ph.D., assistant professor in the Department of Infectious Diseases at Mount Sinai School of Medicine, New York, is an investigator of exceptional vision and promise. He developed a methodology that enables visualization of fluorescently tagged HIV virus particles that may answer long-standing questions about cell–cell mechanisms of viral transmission.
Project: Imaging Virological Synapses During Parenteral HIV Transmission
The understanding of how the HIV virus spreads among injection drug users is limited by a poor understanding of the first events that occur following HIV transmission. This research uses sensitive virus tagging approaches and mouse models with humanized immune systems to study the sequence of interactions between HIV-infected cells and uninfected cells. These studies may lead to the development of vaccines or other preventive approaches to inhibit these initial interactions that occur during intravenous transmission.
Dana H. Gabuzda, M.D., is a professor of neurology (microbiology) at the Dana Farber Cancer Institute and Harvard Medical School, in Boston. She is a leading researcher in the areas of HIV molecular biology and pathogenesis, particularly neuropathogenesis. Her cutting-edge research has significantly increased understanding of HIV replication and pathogenesis.
Project: Systems Biology of Immune Reconstitution in HIV/AIDS
A major challenge in HIV research is to restore immune function in HIV-infected individuals. HIV infection depletes CD4 T cells, leading to immunodeficiency and death. Highly active antiretroviral therapy (HAART) restores CD4 T cell counts to normal levels in a majority of individuals who achieve suppression of HIV to undetectable levels. However, the magnitude of CD4 T cell recovery is variable, and many people on HAART have poor CD4 T cell recovery. The research will lead to a better understanding of the mechanisms that determine CD4 T cell restoration in IV drug abusers and other populations infected with HIV, and may identify new therapeutic strategies to improve restoration of immune function in these populations.
Jonathan Karn, Ph.D., is a professor and chairman of molecular biology and microbiology at Case Western Reserve University, in Cleveland. He is a creative molecular biologist whose research on novel therapeutic technologies could have an impact on the HIV/AIDS epidemic worldwide.
Project: Manipulating Epigenetic Control Mechanisms to Control HIV Transcription
Most individuals treated with antiretroviral drugs have little to no detectable HIV in their blood; however, this does not mean that the virus has been cleared from the body. Unfortunately, the virus can reemerge, leading to renewed active infections when treatment stops or fails. This research will focus on finding natural mechanisms that could block HIV replication and provide long-lasting suppression of HIV.
Rafick-Pierre Sekaly, Ph.D., co-director and scientific director of the Vaccine and Gene Therapy Institute in Port St. Lucie, Fla., is an internationally recognized leader in the field of human immunology and translational medicine, specifically the immune response to HIV infection.
Project: Novel Concepts for the Eradication of HIV
The HIV-1 reservoir is a small pool of persistent long-lived and latently infected resting memory CD4 T cells. Eradication of this HIV reservoir is one of the last steps to be conquered in order to develop a cure for this disease. Dr. Sekaly's research will probe for a mechanism explaining the existence of HIV reservoirs. His studies of pathways that can be targeted to purge HIV from its reservoir could ultimately lead to novel immunological interventions for the treatment of HIV.
Ileana Cristea, Ph.D., assistant professor in the Department of Molecular Biology at Princeton University, Princeton, N.J., is a young investigator of exceptional talent and promise whose research creatively applies technology to address significant biological issues. She developed a methodology that allows tracking of protein localization and elucidation of interacting partners. Dr. Cristea applied this technology first to study the virus–host interactions for Sindbis fever (caused by a mosquito-borne virus) and has extended this technology to the study of other virus–host interactions, including human cytomegalovirus and HIV.
Project: Proteomic tools to uncover the role of chromatin remodeling in HIV-1 infection
The HIV virus contains relatively little genetic information. Therefore, it usurps much of the host’s cellular machinery for its own purposes. This study focuses on HIV’s ability to hijack key proteins involved in the regulation of gene expression. A strength of this proposal is its unique ability to perform a comprehensive screen of interactions between viral and host proteins.
Jerome Groopman, M.D., professor of medicine, Dina and Raphael Recanati Chair at the Harvard Medical School and Chief, Division of Experimental Medicine at the Beth Israel Deaconess Medical Center in Boston. Dr. Groopman's research focuses on basic mechanisms of hematopoiesis, cancer, and HIV/AIDS. He is a renowned translational physician-scientist whose research provided key information on hematological abnormalities in AIDS patients early in the HIV/AIDS epidemic. He studied how HIV elicits immune responses suppressive of marrow stem cell replication and maturation and also conducted the first clinical trials demonstrating that colony-stimulating factors could restore cell number and function.
Project: Inhibition of HIV at the Immune Synapse Utilizing Novel Ligands and Receptors
Cells of the immune system form complexes (the immune synapse) that are very efficient at passing HIV to uninfected cells. This study seeks to develop agents that will block virus propagation from the immune synapse. This project has the potential to develop new therapeutics that block movement of HIV-infected cells throughout the lymphatic system.
Julio Montaner, M.D., professor of medicine at the University of British Columbia and Head, Division of AIDS Canada; Director, British Columbia Centre for Excellence in HIV/AIDS, Providence Health Care; adjunct professor, Department of Psychiatry, University of California, San Diego. Dr. Montaner studies the role of HAART (Highly Active Antiretroviral Treatment) as HIV prevention at a population level. Immediate past president of the International AIDS Society, Dr. Montaner is a highly regarded HIV/AIDS clinician who performed pioneering work on the development of HAART therapy. He is now directing more of his research focus on HIV prevention.
Project: Seek and Treat for Optimal Outcomes and Prevention in HIV & AIDS in IDUs
Preliminary evidence suggests that expanded HAART coverage among injection drug users will decrease new HIV infections within the population, including but not restricted to injection drug users. This project will test the existing evidence. If successful, it could lead to decreased sickness, death, and hospital utilization by injection drug users. The project’s results could have dramatic consequences for the control of the HIV epidemic around the world.