What is the Avant-Garde Award?
The The NIDA Avant-Garde Award Program for HIV/AIDS and Substance Use Disorder Research supports individual scientists of exceptional creativity who propose high-impact research that will open new areas of HIV/AIDS research and/or lead to new avenues for prevention and treatment of HIV/AIDS among drug abusers. The term “avant-garde” is used to describe highly innovative approaches that have the potential to be transformative.
Avant-Garde Award Program for HIV/AIDS and Substance Use Disorder Research (DP1)
- The PAR-20-221: NIDA Avant-Garde Award Program for HIV/AIDS and Substance Use Disorder Research (DP1) is part of the Director’s Pioneer Award mechanism at NIDA that supports investigators with exceptional creativity proposing high impact research projects that will open new areas of HIV/AIDS research relevant to substance use disorders (SUD) and lead to novel avenues for prevention and treatment of HIV/AIDS among people who use drugs (PWUD).
Current and Past Awardees
Michael Emerman, Ph.D., is a Professor in the Divisions of Human Biology and Basic Sciences at the Fred Hutchinson Cancer Research Center in Seattle and Affiliate Professor in the Department of Microbiology at the University of Washington. He trained with two Nobel laureates; a Ph.D. in Cellular and Molecular Biology at the University of Wisconsin-Madison with Dr. Howard Temin and continued postdoctoral training at the Pasteur Institute in Paris with Luc Montagnier. His lab has focused on the molecular and cellular biology of HIV including studies describing the evolutionary battle between viruses and their hosts, called paleovirology, that is used to understand how HIV became a human pathogen. He has published including many studies on host restriction factors and viral accessory genes. He was awarded the Retrovirology Prize in 2017 and the Conference on Retroviruses and Opportunistic Infections (CROI) Bernard Fields Lecture in 2020.
Project: HIV-CRISPR: A novel approach to the comprehensive discovery of HIV latency factors: The most significant obstacle to HIV clearance is that of viral latency since a silent HIV genome is not recognized by the immune system or by antiviral drugs. We propose a novel and powerful approach to understanding HIV latency based on an innovative genetic screening method called HIV-CRISPR that uses the packaging of CRISPR guides into budding HIV to serve as a readout for the effects of host genes on HIV. We combine genetic screens with low doses of latency reversal agents to identify targets that more broadly activate HIV from latency while providing a greater degree of specificity. We also study how drugs of abuse influence HIV latency pathways.
Leor Weinberger, Ph.D., is the Bowes Distinguished Professor, Director of the Gladstone/UCSF Center for Cell Circuitry, and Professor of Pharmaceutical Chemistry and Biochemistry & Biophysics at University of California, San Francisco. His lab pioneered the study of HIV’s latency circuit, showing that Tat fluctuations (transcriptional ‘noise’) drive latency. These studies overturned dogma by showing that HIV encodes a ‘hardwired’ latency circuitry that is evolutionarily optimized. In 2020, he was asked to give a TED talk (TEDMED, 2020) on his theory of antiviral ‘hijacker’ therapies (Therapeutic Interfering Particles, TIPs) that helped convince the US Dept. of Defense to launch the INTERCEPT program—a $40M investment that funded over a dozen academic virology labs worldwide. His work has been recognized by a number of awards including being named a Pew Scholar, a Sloan Research Fellow, a W.M. Keck Research Excellence Awardee, a Blavatnik Fellow, and he is also an NIH Director’s Pioneer and New Innovator Awardee.
Project: A Gene Drive Therapy for HIV: single-administration intervention for high-risk groups: Dr. Weinberger proposes development of a first-in-class horizontal ‘gene drive’ therapy for HIV, which his group theoretically predicted (Weinberger et al. J Virol. 2003; Metzger et al. PLoS Comp. Biol. 2011). These viral hijacker therapies would effectively reach the most at-risk populations, particularly people who inject drugs in resource-limited settings, and be single administration, resistance-proof HIV interventions that could dramatically reduce HIV transmission. This proposal will test safety and efficacy of a prototype gene-drive hijacker therapy to establish feasibility and will test tolerability in a Phase-I clinical trial.
- 2019 Awardee
Dr. Dolores Albarracín, Ph.D., is a Professor of Psychology and Business at the University of Illinois at Urbana-Champaign, where she specializes in the study of attitudes and persuasion, behavior change, the intention-behavior relation, and the effects of behavioral and clinical treatments in the area of HIV/HCV. Originally from Argentina, Dr. Albarracín received her Ph.D. in Social Psychology from the University of Illinois at Urbana Champaign. Before her appointment at the University of Illinois, Dr. Albarracín was also a tenured professor at the University of Florida and the University of Pennsylvania. Dr. Albarracín is an international leader in the psychological processes underlying behavior change and social influence and applications to health promotion and HIV prevention. She has received many prior awards and is a fellow of the Society for Experimental Social Psychology, the Society for Personality and Social Psychology, the American Psychological Association, and the Association for Psychological Science.
Project: Digital, Community-Led, Social Action Initiative to Reduce Opioid Vulnerability And HIV/HCV In Rural Areas of the Midwest And Appalachia: Dr. Albarracín proposes to develop and evaluate a transformative virtual initiative for protecting rural drug-using populations (ages 18-35) from HIV/HCV outbreaks in the midst of the opioid epidemic. Although the origins of the opioid crisis are complex, social determinants of health, misconceptions about opioids, and a culture of isolation and despair are among the most critical causes. The digital platform (a) will incorporate Big Data methods to identify efficacious messages, misconceptions, and debunking messages, and (b) will foster positive social interactions between people who use opioids and other members of their community.
- 2018 Awardees
Catherine A. Blish, M.D., Ph.D., FIDSA, is an Associate Professor of Medicine and Immunology at the Stanford University School of Medicine. She received her M.D. and Ph/D from the University of Washington and completed residency in internal medicine and fellowship training in infectious diseases at the University of Washington and the Fred Hutchinson Cancer Research Center. She joined the Stanford faculty in 2011, where her research is dedicated to learning how to harness the immune system to prevent and cure diseases. Her lab is perhaps best known for redefining our understanding of the diversity of human natural killer (NK) cells, a critical first line of defense against viruses and tumors. Her lab continues to explore human natural killer cells sense and respond to a diverse array of pathogens, including HIV, dengue virus, and influenza.
Project: Targeting Natural Killer Cells to HIV in Intravenous Drug Users: Dr. Blish proposes a novel approach to fight HIV by using natural killer cells to optimally target HIV strains transmitted through injection drug use. Current approaches focus on targeting HIV strains transmitted through sexual contact, which could differ in immune response properties unique to injection drug users. This approach could be valuable in the development of vaccines and therapeutics for HIV prevention and cure strategies.
Nathaniel (Ned) R. Landau, Ph.D., is a professor in the Department of Microbiology at the NYU School of Medicine. He received his Ph.D. at MIT and did post-doctoral studies at UCSF. He has investigated the molecular mechanisms of HIV entry, the role of lentiviral accessory proteins and host restriction factors to HIV. At the Aaron Diamond AIDS Research Center, he discovered a genetic alteration that protects individuals from HIV infection which served as the basis for the development of HIV fusion inhibitors. He later joined the faculty of the Salk Institute. His current research focus is on the development of a therapeutic dendritic cell vaccine for HIV. He is an Elizabeth Glazer Scientist of the Pediatric AIDS Foundation and has been supported by the American Foundation for AIDS Research (afAR).
Project: Therapeutic Dendritic Cell Vaccine for HIV: Dr. Landau proposes to develop a therapeutic vaccine that enhances the immune response against HIV so that patients can discontinue or reduce antiretroviral drug regimens. The long-term misuse of drugs including alcohol, methamphetamine and opioids is associated with suppressed immune responses. For such individuals, stimulation of an immune response via a vaccine could slow disease progression. Moreover, minimizing the need for treatment would be beneficial for those who may be less able to adhere to complex antiretroviral drug regimens.
Sara L. Sawyer, Ph.D., is an Associate Professor in the BioFrontiers Institute and the Department of Molecular, Cellular, and Developmental Biology at the University of Colorado at Boulder. Dr. Sawyer received her Ph.D. from Cornell University in 2003 and then conducted postdoctoral research at the Fred Hutchinson Cancer Research Center until 2007. In 2011, Dr. Sawyer received a PECASE award from President Barack Obama for her research and mentoring activities. Dr. Sawyer has garnered international recognition for her studies of primate genetics and genomics, and how they facilitate viral infections both in the lab and in nature. Her lab continues to work towards an improved understanding of the primate animal models critical for HIV-1 vaccine development.
Project: Hunting the HIV-1 Unicorn: Dr. Sara Sawyer proposes to open an exciting new platform for vaccine development. Currently, most HIV infections are HIV-1. A hindrance to HIV-1 vaccine development has been the lack of an effective animal model system in which to study transmission and develop vaccines. Dr. Sawyer proposes to harness mammalian genetics to identify an improved model, which could open up a whole new avenue of HIV/AIDS research.
- 2017 Awardees
Michael Farzan, Ph.D. is a Professor and Co-chair of the Department of Immunology and Microbiology at the Scripps Research Institute. Dr. Farzan received his Ph.D. from Harvard Medical School, where he came up through the ranks to be promoted to Professor of Microbiology and Immunology in 2012. His work at Harvard and Scripps has focused on the entry processes of HIV-1 and other enveloped viruses, ultimately culminating in development of a novel HIV-1 entry inhibitor that can be combined with established gene therapy systems to provide vaccine-like protection in rhesus macaques. His lab is currently focused on optimizing this approach as a vaccine and therapy for HIV-1 infection, and on improving its safety by developing means to regulate its expression in vivo.
Project: A safety switch for an effective HIV-1 vaccine: Dr. Farzan plans to use preclinical models to explore safe and effective gene therapies for the long-term prevention of HIV infection in high-risk populations, such as injection drug users. He will use an adeno-associated virus to deliver broadly neutralizing antibodies (bNAbs) or eCD4-Ig, proteins that prevent HIV-1 from infecting cells. His group will also explore safety switch mechanisms to control bNAbs and eCD4-Ig, thereby increasing safety during long-term exposure to these molecules.
Eric M. Poeschla, M.D. is Professor of Medicine and Chief of Infectious Diseases at the University of Colorado School of Medicine, where he holds the Tim Gill Chair in HIV Research. He graduated from Yale Medical School and completed his clinical residency in internal medicine at UC San Francisco, followed by a fellowship in infectious diseases and molecular virology at UC San Diego. Before joining the University of Colorado, he was on the faculty of the Department of Molecular Medicine at the Mayo Clinic. His research group investigates the roles that cellular proteins play in viral replication cycles, including HIV-exploited factors and innate immune system factors that mediate frontline antiviral defenses and prevent cross-species virus transmission. They are interested in cellular systems that sense and respond defensively to viral RNA and DNA and also prevent autoimmunity to self nucleic acids.
Project: Novel Approaches to Innate Immunity Against HIV-1 and Other Co-infection Viruses: Dr. Poeschla will use animal and human cells to explore the use of viral RNA-dependent RNA polymerase (RdRP) to enhance broad-spectrum (innate) immunity against various viruses, including HIV-1. Evidence suggests that this stable innate immune system activation does not trigger autoimmunity or inflammatory pathways. This approach may also protect against viruses that infect people with addiction.
Peter S. Kim, Ph.D. is the Virginia & D.K. Ludwig Professor of Biochemistry and a member of the ChEM-H Institute at Stanford University. He is former President of Merck Research Laboratories (2003-2013) and earlier, Professor of Biology at MIT, Member of the Whitehead Institute and Investigator of the Howard Hughes Medical Institute. He is an elected member of the National Academy of Sciences, National Academy of Medicine and National Academy of Engineering. Dr. Kim is known for his seminal discoveries about how proteins cause viral membranes to fuse with cells and has pioneered efforts to develop an HIV vaccine based on stopping membrane fusion with antibodies. His lab continues in efforts to create vaccines against viruses including HIV and in understanding viral membrane fusion and its inhibition.
Project: Making the HIV-1 gp41 pocket amenable to small-molecule drug discovery: Dr. Kim’s group proposes a strategy that alters the HIV-1 gp41 region, thereby increasing structural rigidity in this region. This will enhance testing of new therapeutics that target the gp41 pocket to prevent HIV infection. Because the pocket is structurally similar across different HIV-1 strains, these therapeutics could treat patients, including people with substance use disorders, who are at higher risk of developing resistance to one or more classes of anti-HIV drugs.
- 2016 Awardee
Stuart A. Lipton, M.D., Ph.D. is the Hannah and Eugene Step Distinguished Professor and Chair in the Neurodegenerative Disease Center at Scintillon Institute in San Diego. He is also adjunct professor of Neurology and Neuroscience at the University of California, San Diego, The Scripps Research Institute, and Yale School of Medicine. Dr. Lipton was trained at Cornell University, the University of Pennsylvania, and Harvard University. Lipton completed his PhD thesis research, clinical residency, and a postdoctoral fellowship at Harvard. He is best known for first describing the mechanism of action and contributing to the clinical development of the FDA-approved Alzheimer’s drug, memantine (Namenda®), and for co-discovering the posttranslational redox modification termed S-nitrosylation. Lipton pioneered the study of the pathogenesis of HIV-associated cognitive disorder. In addition, his group also discovered the NR3 (now known at GluN3) family of modulatory NMDA receptor subunits, characterized the molecular pathways for protecting neurons with erythropoietin, and discovered the transcription factor MEF2C. They showed that MEF2C is also regulated by S-nitrosylation and serves as a master swtich for neurogenesis from human neural stem cells. Dysregulated MEF2C is involved in the pathogenesis of Parkinson’s disease, Alzheimer’s disease, Autism-Spectrum Disorder, and Vascular dementia.
Project: Novel Proteomics Approach to HIV-Associated Neurocognitive Disorder & Drug Abuse: Dr. Lipton will study an innovative approach using new Mass Spectrometry (MS) techniques that allow unprecedented analysis of free radical-induced protein modifications, which are involved in the pathogenesis of of brain damage in HIV-associated cognitive disorder (HAND), methamphetamine drug abuse, and other neurodegenerative diseases. The work will identify biomarkers of the disease process as well as potential new therapeutic targets.
- 2015 Awardees
Don C. Des Jarlais, Ph.D. is the director of research for the Edmond de Rothschild Chemical Dependency Institute of Mount Sinai Beth Israel. He is professor of Psychiatry and professor of Preventive Medicine in the Department of Psychiatry at the Icahn School of Medicine at Mount Sinai and a Guest Investigator at Rockefeller University. Dr. Des Jarlais received his PhD from the University of Michigan. Dr. Des Jarlais has extensive experience, with almost three decades of work in epidemiological research on HIV/AIDS and drug use in many different countries. His research has been quite productive, generating peer papers in the Lancet, New England Journal of Medicine, JAMA, Science and Nature. In addition to the Avant Garde project, his current research focuses on ending HIV (and hopefully HCV) epidemics among people who use drugs.
Project: Combined Prevention to Reduce Initiation into Injecting Drug Use: Dr. Des Jarlais will lead a multi-component HIV prevention intervention study in two sites with growing concerns about heroin use — New York City and Tallinn, Estonia in Eastern Europe. Researchers will focus on combining a number of interventions with demonstrated effectiveness in reducing the number of drug users who transition to injection drugs.
Eli Gilboa, Ph.D. is the Joe Enloe Dodson professor in the Department of Microbiology & Immunology, member of the Sylvester Comprehensive Cancer Center, and Director of the Dodson Interdisciplinary Immunotherapy Institute at the Miller School of Medicine, University of Miami. Her received his PhD from the Weizmann Institute in Israel and conducted his postdoctoral research at Massachusetts Institute of Technology in Boston. Dr. Gilboa is known for his pioneering work in gene therapy for genetic disorders, HIV/AIDS, and cancer. The current research in the Gilboa lab is focused on developing a combination of cell-targeted immune stimulatory treatments for HIV/AIDS and cancer using a novel nucleic acid aptamer drug and drug delivery platform.
Project: Reversing HIV T cell Dysfunction by Aptamer Targeting of Therapeutic siRNAs: Dr. Gilboa proposes the development of novel drugs that successfully restore the function of T cells — important in immune response — and would have the potential to be therapeutically transformative for AIDS patients, including substance users in whom drugs further undermine their immune function.
Nichole Klatt, Ph.D. Nichole Klatt, PhD, is an assistant professor in the Department of Pharmaceutics in the School of Pharmacy at the University of Washington (UW), where she joined as a faculty member in 2012. She is also an adjunct professor in the Molecular and Cellular Biology Program at UW and in the Program in Pathobiology, within the Department of Global Health at UW, and a core staff scientist at the Washington National Primate Research Center. Dr. Klatt received her PhD from Emory University in Immunology and Molecular Pathogenesis, and was also a visiting PhD student at the University of Pennsylvania in the Cellular and Molecular Biology program. Dr. Klatt performed her postdoctoral research in the Program in Tissue Immunity and Repair of the Immunopathogenesis section of the Laboratory of Molecular Microbiology, in the National Institute of Allergy and Infectious Diseases at the National Institutes of Health. Dr. Klatt’s laboratory studies mucosal immunity in the context of pathogenesis, prevention, and cure research in HIV infection, with the goal to develop novel therapeutic and curative interventions and prevention strategies for HIV.
Project: Impact of Cannabis on Inflammation and Viral Persistence in Treated HIV/SIV: Dr. Klatt proposes development of HIV cure strategies by using non-psychoactive cannabinoids as potential therapeutic agents. Since cannabinoids, derivatives of cannabis, have been used to treat nausea and pain and have been shown to be anti-inflammatory in animal models, Dr. Klatt theorized that cannabinoids could be effective in reducing inflammation common in HIV patients.
Alan D. Levine, Ph.D. is a professor in the Departments of Medicine, Molecular Biology & Microbiology, Pathology, and Pharmacology at Case Western Reserve University School of Medicine. He is also the Chief Operating Officer of the Case/University Hospitals Center for AIDS Research (CFAR). Dr. Levine received his PhD from Yale University, conducted postdoctoral research at Stanford University with Nobel Laureate Roger Kornberg, and joined the faculty at Case Western in 1995. He is internationally recognized as an expert in cytokine biology, mucosal immunology, and T cell dysfunction in Crohn’s disease. His laboratory investigates cross-regulation among the triad of mucosal T cells, the intestinal epithelium, and the luminal microbiome, with a focus on microbial dysbiosis, intestinal permeability, epithelial tight junction regulation, and T lymphocyte activation and co-stimulation in HIV infection and inflammatory bowel disease.
Project: Repairing the Intestinal Epithelium from the Dual Action of HIV and Drug Use: Dr. Levine will investigate the loss of intestinal barrier protection initiated by HIV infection and the resultant, systemic inflammation due to chronic exposure to gut-derived microbial products. This situation is exacerbated in the drug-abusing HIV infected population in whom drugs exert toxic effects on the gastrointestinal tract which synergize with HIV.
Julie Overbaugh, Ph.D. is a Full Member, Human Biology Division, Fred Hutchinson Cancer Research Center. The focus of research in the Overbaugh lab is on mechanisms of viral pathogenesis. Her lab studies several retroviruses, with a particular focus on those that lead to a prolonged chronic asymptomatic infection followed by eventual development of immunodeficiency disease (FeLV, SIV and HIV). Studies of her group focus on how the properties of the virus itself influence the eventual outcome of infection. These studies include a detailed analysis of the sequence and biological characteristics of viruses that spread from host to host. Her group studies process that contribute to persistence of these viruses once infection is established, and the processes of evolution and adaptation that result from selective pressures in the host, such as changes in cell tropism/receptor specificity and immune escape. Trainees in her lab engage in studies of viral evolution, virus-host cell interactions, and viral immunology.
Project: Towards a More Relevant Model of HIV Infection: SHIV macaque models provide an important benchmark for preclinical HIV-1 research, serving as a gatekeeper for advancing vaccine and other prevention approaches. The ability of such models to predict intervention(s) that will be efficacious in humans depends to a large extent on how faithfully the model recapitulates key features of HIV-1 transmission and pathogenesis in humans, including both sexual and parenteral transmission. To date, SHIVs have largely been selected by trial and error using the most readily available HIV-1 variants, often those that have been adapted to replication in cell culture (lab-adapted HIV-1 variants). As a result, few SHIV models incorporate key features of naturally occurring viruses including those found in injection drug users. Dr. Overbaugh has found several barriers to HIV-1 replication in macaque cells that are specific to transmitted/founder (T/F) viruses circulating in humans. She also has found that IFN-stimulated responses have a pronounced effect on the replication of SHIVs encoding circulating T/F envelope variants in macaque T cells, but not on adapted SHIVs. In addition, the macaque CD4 receptor is generally a poor receptor for T/F variants, but it is a functional receptor for lab-adapted variants, which potentially explains the bias towards developing SHIVs based on lab-adapted HIV-1 variants. While T/F variants can be adapted to use the macaque CD4 receptor, adaptation leads to antigenic changes that alter recognition of several broad NAbs that are currently the centerpiece of HIV-1 vaccine efforts. Dr. Overbaugh proposes to define the mechanisms underlying the envelope-mediated restrictions to HIV-1 replication in macaques, to define the consequences of these changes for the utility of the model, and to identify pathways to developing rationally designed SHIVs with enhanced utility for preclinical studies of HIV-1 vaccine and prevention methods.
Tariq M. Rana, Ph.D. is a Professor of Pediatrics and V/C for Innovation in Therapeutics at the University of California San Diego School of Medicine, where his laboratory studies RNA regulation of development and disease. Dr. Rana's laboratory has discovered fundamental structural and functional features of small RNAs required for gene silencing. In addition, his laboratory has uncovered mechanisms involving small RNAs and RNA-protein complexes in regulating host-pathogen interactions. Dr. Rana received his Ph.D. from the University of California at Davis and he was an American Cancer Society fellow at the University of California at Berkeley. He was a Professor of Biochemistry and Molecular Pharmacology and founding Director of the Program in Chemical Biology at the University of Massachusetts Medical School, Worcester, Massachusetts, prior to joining the Sanford-Burnham Medical Research Institute in 2008. He held Sanford-Burnham Professorship and served as the founding director for the RNA Biology Program from 2008 to 2014.
Project: Modeling HIV/AIDS Associated Neurological Disorders with Human Pluripotent Cells: Dr. Rana will use an innovative approach to better understand the molecular mechanisms of brain disorders caused by HIV and its interaction with the damage from the use of methamphetamine. This project will build miniature models of the brain — developed with stem cells — to investigate brain injuries caused by HIV that are associated with neurocognitive disorders and the interactions with methamphetamine exposures.