What is the Avant-Garde Award?
The NIDA Avant-Garde Award Program for HIV and Substance Use Disorder Research supports individual scientists of exceptional creativity at all career levels who propose high-impact research that will open new areas of HIV research and/or lead to new avenues for prevention and treatment of HIV among people who use drugs. The term “avant-garde” is used to describe highly innovative approaches that have the potential to be transformative.
Avant-Garde Award Program for HIV and Substance Use Disorder Research (DP1)
- The PAR-23-269: NIDA Avant-Garde Award Program for HIV 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).
- Hear from Avant-Garde Investigators
Current and Past Awardees
Gaurav D. Gaiha, M.D., D.Phil, is an Assistant Professor of Medicine at Harvard Medical School; a Principal Investigator at the Ragon Institute of Mass General, MIT, and Harvard; and an Attending Physician in the Division of Gastroenterology at Massachusetts General Hospital (MGH). He received his D.Phil. at Oxford University as a Clarendon Scholar and his M.D. magna cum laude from the Health Sciences and Technology program at Harvard Medical School and MIT. He subsequently completed his clinical training in internal medicine and gastroenterology at MGH and then his postdoctoral research fellowship at the Ragon Institute. His lab’s work is focused on the development of novel T cell–based vaccines for infectious diseases and HIV by eliciting responses that target epitopes derived from structurally constrained viral regions. He has received numerous honors for his work, including a National Institute of Allergy and Infectious Diseases New Innovator Award; a Career Award for Medical Scientists from the Burroughs Wellcome Fund; an award from the Gilead HIV Research Scholars Program; a Krane, MD Award from the MGH Department of Medicine; and the Howard M. Goodman Fellowship.
Project: Harnessing Highly Networked HLA-E-Restricted CTL Epitopes to Achieve a Broadly Effective HIV Cure. The establishment of a persistent HIV reservoir requires that HIV-positive individuals remain on lifelong treatment, which can be a logistical burden for individuals with substance use disorder. Therefore, the creation of a vaccine for HIV would be especially beneficial for them. The development of an effective therapeutic T cell–based vaccine has been hindered by high levels of HIV sequence variability and the polymorphic nature of classical major histocompatibility complex (MHC) class IA alleles. This project aims to overcome these obstacles by leveraging the highly conserved nonclassical MHC class IB allele HLA-E and mutation-resistant HLA-E-restricted CD8+ T cell epitopes identified by a novel structure-based technology to generate a universal T cell–based vaccine for people with HIV.
Schahram Akbarian, M.D., Ph.D., is Professor of Psychiatric Epigenomics at the Icahn School of Medicine at Mount Sinai, New York. He received his degrees from Free University of Berlin, followed by a postdoctoral fellowships at the University of California at Irvine and the Whitehead Institute/MIT and clinical residency at the Massachusetts General Hospital at Harvard. He explores epigenomic and mechanisms in psychiatric and neurological disease. Dr. Akbarian is currently principal investigator in the NIDA sponsored PsychENCODE and Single Cell Opioid Responses in the Context of HIV (SCORCH) consortia and the recipient of numerous awards including the Lieber Prize for Outstanding Achievement in Schizophrenia Research from the Brain & Behavior Research Foundation, the Eva King Killam Award for Outstanding Translational Research of the American College of Neuropsychopharmacology and the Judith Silver Memorial award of the National Alliance for the Mentally Ill.
Project: Single Chromatin Fiber Sequencing and Longitudinal Epigenomic Profiling in HIV+ Brain Cells Exposed to Narcotic and Stimulant: Exploration of genome organization and function in the HIV infected brain is critical for treatment and cure of neurocognitive disorder and for eradicating the viral reservoir. However, at present, the field is limited to snapshots of chromatin structures and function at a single time point – the time of tissue collection. In this NIDA Avant-Garde project, we will embark on ‘retrospective’ epigenomic profiling of single chromatin fibers (including sites of retroviral insertion), and explore the prospect of dynamic changes and even reversibility (or progressive deterioration) of the epigenomic dysregulation in HIV infected cells residing in brain and blood.
Sandra A. Springer, M.D., is Associate Professor of Medicine in the Department of Internal Medicine, Section of Infectious Diseases at the Yale School of Medicine and the Director of the Newington Infectious Disease Clinic at the Veterans Administration Connecticut Healthcare System. Her research program, InSTRIDE, focuses on the intersection of substance use and infectious diseases treatment, in particular integration of medications for opioid use disorder and HIV treatment. She is an infectious disease and addiction medicine physician who has focused her entire clinical and research career on improving the lives of persons who use drugs (PWUD) who have been marginalized from access to treatment through providing integrated addiction and infectious diseases prevention and treatment in community and justice settings. Her goal is to improve interventions that provide low-barrier access to evidence-based addiction and HIV prevention and treatment services to persons who use drugs wherever they may live.
Project: Ending HIV: Bringing Integrated Prevention and Treatment Services to People Who Use Drugs Where They Live: This pioneer award aims to address the gaps in the Ending the HIV Epidemic Plan for PWUD by BRINGING evidenced-based integrated opioid and HIV services to them wherever they live (housed or unhoused) through a mobile hub and spokes model. Mobile hubs that are pharmacies and clinics on wheels will dispense pre-exposure prophylaxis (PrEP), antiretroviral therapy (ART) and medication treatment for opioid use disorder (OUD; MOUD). Community Health Workers from communities affected by overdoses will identify those in need, perform rapid HIV testing and OUD screening, work with telehealth clinicians and in-person pharmacists to provide rapid PrEP, ART and MOUD as part of mobile rapid response teams (the mobile spokes).
Linda Chang, M.D., is a Professor of Diagnostic Radiology & Nuclear Medicine, and Professor of Neurology, at the University of Maryland School of Medicine. She is also an Adjunct Professor in Neurology at Johns Hopkins School of Medicine. Dr. Chang has applied advanced neuroimaging techniques conducted seminal research to evaluate brain injury and monitor treatment effects in HIV patients, including those with substance use disorders. Her work also provided insights regarding possible mechanisms of HIV-associated brain injury. As a Clinician-Scientist and a board-certified Neurologist, she collaborates extensively with investigators across many disciplines, including physics, neuroimmunology, neuropsychology, computational and cognitive neuroscience. Furthermore, her work in substance use disorders contributed to understanding how drugs of abuse can impact neurodevelopment from infancy through adolescence, and neurodegeneration in the aging individuals. Dr. Chang currently serves on the National Advisory Council on Drug Abuse for NIDA and on the Council of Councils at the NIH.
Project: MR-guided focused ultrasound to eradicate CNS viral reservoirs and promote neurogenesis in the HIV-infected brain: HIV-infected individuals need to take life-long antiretroviral medications (ARVs) because these ARVs cannot remove hidden reservoirs of HIV, especially those in the brain. We aim to use MR-guided focused ultrasound (MRgFUS) to safely and transiently open the blood brain-barrier to maximize the delivery of long-acting slow release ARVs, in combination with the AAV-CRISPR-Cas9 technology to eliminate the integrated HIV in the brain. Low-intensity MRgFUS will also be applied to target brain regions involved in addiction for treatments of substance use disorders. These novel projects capitalize on the unique resources and equipment at the University of Maryland, and the outstanding collaborators, to ensure the successful clinical translation of the research towards a cure for HIV.
Alex K. Shalek, Ph.D., is a Core Member of the Institute for Medical Engineering and Science (IMES), an Associate Professor of Chemistry, and an Extramural Member of The Koch Institute for Integrative Cancer Research at MIT. He is also an Institute Member of the Broad Institute, a Member of the Ragon Institute, an Assistant in Immunology at MGH, and an Instructor in Health Sciences and Technology at HMS. Dr. Shalek received his bachelor's degree summa cum laude from Columbia University and his Ph.D. from Harvard University in chemical physics under the guidance of Hongkun Park, and performed postdoctoral training under Hongkun Park and Aviv Regev (Broad/MIT). His lab’s research is directed towards the development and application of new approaches to elucidate cellular and molecular features that inform tissue-level function and dysfunction across the spectrum of human health and disease. Dr. Shalek and his work have received numerous honors including a NIH New Innovator Award, a Beckman Young Investigator Award, a Searle Scholar Award, a Pew-Stewart Scholar Award, and an Alfred P. Sloan Research Fellowship in Chemistry, as well as the 2019-2020 Harold E. Edgerton Faculty Achievement Award at MIT.
Project: Defining the impact of drug use on immune function and fitness against HIV-1: Individuals with substance use disorders (SUDs) – and, in particular, people who inject drugs – are at substantial risk for infection with HIV-1 and other pathogens. To develop effective prophylactics and therapeutics against HIV-1 and other infections for these individuals, we must first understand how SUDs impact the immune system at a cellular and molecular level. The goal of our NIDA Avant-Garde DP1 proposal is to define, at unprecedented resolution, how SUDs influence immune function and response to HIV-1 and other pathogens by developing and applying innovative single-cell and bulk profiling and perturbation tools to inform the design of novel cure and prevention strategies.
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.
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.
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.