New amfAR Research Awards Bolster Search for HIV Cure
$2.1 million awarded in grants and fellowships to support a range of cutting-edge studies
For Immediate Release
Cub Barrett, Program Communications Manager
NEW YORK, November 16, 2011—Continuing its leadership in the search for a cure for HIV/AIDS, amfAR, The Foundation for AIDS Research, on Wednesday announced a new round of research grants and fellowships totaling $2.1 million.
The bulk of the awards—nearly $1.6 million—will support cure-focused research. Thirteen grants, each between $120,000 and $125,000, were awarded to researchers in locations ranging from Australia to Sweden and, in the U.S., from San Francisco to Baltimore. They represent state-of-the-art efforts by scientists to understand how, where, and why HIV persists in infected people—even while they are on antiretroviral medication (ARVs).
The researchers will employ techniques ranging from using the latest technological advances to applying an old drug to a new problem. For example, while Richard Fox, Ph.D., of the University of Washington will use a newly developed laser dissection technique to examine single infected cells to help determine exactly where and how HIV hides in the body, Hiroyu Hatano, M.D., of the University of California, San Francisco, will assess whether a drug used to treat blood pressure can reduce the growth of fibrous tissue in lymph nodes, thus freeing up immune cells to generate appropriate responses against the virus.
Additionally, as the search for a cure continues to gather momentum, so too does amfAR’s footprint on it. Nicolas Chomont, Ph.D., a researcher at the Vaccine and Gene Therapy Institute Florida in Port St. Lucie, FL, made a seminal finding in the cure research field several years ago with the support of an amfAR fellowship, and recently gained his first grant as an independent researcher from amfAR. He is now mentoring a new fellowship recipient, Remi Fromentin, PharmD., Ph.D., who will develop techniques to test potential HIV cures in a test tube model.
“At amfAR, we’re increasingly excited about the work that emerges from the cure-focused studies we fund, which is why we’re now spending 60 percent of our research grants dollars on cure research,” said amfAR CEO Kevin Robert Frost. “As we keep uncovering new information about the virus, we’re increasingly confident that we will be able to find a cure for HIV/AIDS in our lifetime.”
Other funded projects will target viral infections that are weeks versus millions of years old. For example, Deborah Persaud, M.D., of Johns Hopkins University School of Medicine, will examine how HIV reservoirs become established in people who develop little immune response to HIV infection—children born with the virus and treated soon after birth—to better understand how the virus persists without the confounds of an immune response. In another study, Douglas Nixon, M.D., of the University of California, San Francisco, will examine possible pathways for a cure by targeting ancient retroviruses existing in stretches of DNA that are millions of years old and present in the human genome.
“There’s still so much we don’t know about HIV, but I’m increasingly impressed with how much we can learn about the virus through vigorous, informed, and creative research projects in such a short amount of time,” said amfAR’s vice president and director of research, Dr. Rowena Johnston. “I’m excited about each of these projects not only because they’re seeking answers through so many different means, but because each one will better our cumulative understanding of how to cure HIV.”
In addition, amfAR announced its fifth round of grants awarded through its Mathilde Krim Fellowships in Basic Biomedical Research program, designed to identify, fund, and promote promising young researchers in the HIV/AIDS research field. The four fellowship recipients will each receive $125,000 for their research projects.
“These young scientists represent the future of HIV/AIDS research and are helping to accelerate the pace of research through their creative, innovative projects and fresh way of approaching the virus,” Johnston said. “It’s our hope that they’ll continue their work in the field long after their Krim Fellowship awards, and that they’ll contribute to our knowledge of how the virus works—and how it can be defeated.”
See below for a full list of cure grant and fellowship recipients, as well as a full list of Krim Fellowship recipients, including descriptions of their projects.
amfAR, The Foundation for AIDS Research, is one of the world’s leading nonprofit organizations dedicated to the support of AIDS research, HIV prevention, treatment education, and the advocacy of sound AIDS-related public policy. Since 1985, amfAR has invested nearly $325 million in its programs and has awarded grants to more than 2,000 research teams worldwide.
Paul Cameron, Ph.D.
Monash University, Melbourne, Australia
The role of dendritic cells in HIV-1 latency: A small fraction of HIV-infected CD4+ T cells harbor HIV without actively producing virus, resulting in lifelong infection that is not eradicated by antiretroviral therapy. Dr. Cameron plans to study the role played by dendritic cells both in allowing resting cells to become infected, as well as in suppressing the active production of virus from cells that are already infected. Other negative regulators of virus production will also be studied, in the hope that identifying the mechanisms whereby infected cells harbor latent virus will result in information that could be applied to a cure for HIV infection.
Koh Fujinaga, Ph.D.
Department of Medicine, University of California, San Francisco, San Francisco, CA
Reactivation of HIV transcription via PKC agonists and HDACs: A small proportion of HIV-infected cells becomes quiescent so that the HIV contained in the DNA does not produce virus and the cells harboring the virus survive indefinitely, forming a reservoir that cannot be eliminated. Dr. Fujinaga plans to tease out the complex chain of events that occurs at the level of the cell DNA that allows the virus to sit quiescent. A better understanding of these processes may facilitate the development of therapies to eliminate the reservoir.
Hiroyu Hatano, M.D.
University of California, San Francisco, San Francisco, CA
Administration of an ACE-inhibitor to decrease the latent reservoir: One effect of HIV infection is an increase of fibrous tissue in lymph nodes, which in turn prevents interactions between immune cells and results in an ineffective immune response against the virus. Dr. Hatano plans to test whether one class of drugs used to treat high blood pressure, also previously shown to reduce the formation of fibrous tissue, might lead to more effective immune responses in HIV-infected patients. She hypothesizes this intervention may lead to accelerated clearance of the latent reservoir of virus.
Douglas Nixon, M.D.
University of California, San Francisco, San Francisco, CA
Eliminating the latent reservoir through self-specific antibodies: HIV integrates itself into the DNA of human cells it infects. In evolutionary history, several different types of viruses have also integrated into the genome and become pat of the germ line, and their traces can still be found in our DNA. These ancient human endogenous retroviruses, or HERVs, can become reactivated when HIV infects cells, and the immune system can make antibodies against them. Dr. Nixon hopes that these immune responses can be harnessed to make a vaccine that could be used to specifically target HIV-infected cells for destruction.
Deborah Persaud, M.D.
Johns Hopkins University School of Medicine, Baltimore, MD
Biomarkers of virologic control in early-treated HIV-seronegative children: In most people, HIV infection leads to a chronic state of immune activation that has been hypothesized to contribute to the ability of the virus to persist despite antiretroviral therapy. Newborn infants may acquire HIV from their mother and can be diagnosed with infection before their immune systems mature, leading to a unique situation in which infection is controlled by antiretroviral therapy with very little immune response. Dr. Persaud plans to investigate the size and diversity of the reservoir to uncover some additional mechanisms whereby HIV infection can persist.
Quentin Sattentau, Ph.D.
University of Oxford, Oxford, United Kingdom
Characterization and inhibition of the macrophage reservoir of HIV-1: The role of macrophages, a type of immune cell, in harboring persistent virus is unclear. Dr. Sattentau hypothesizes that macrophages, whose normal immune function involves engulfing dying infected cells, acquire HIV by engulfing infected CD4+ T cells, and can then pass the virus to other susceptible cells, thereby maintaining infection. He will determine whether this mechanism of viral persistence can be targeted by antibodies or different types of antiretroviral therapy.
John Tilton, M.D.
Case Western Reserve University, Cleveland, OH
CD4+ T cell subsets: targets for HIV infection and latency: CD4+ T cells are the major reservoir of HIV and can be divided into several subsets, each of whose contribution to viral persistence is incompletely understood. Dr. Tilton will characterize each type of CD4 cell in terms of whether infection results in abortive, productive or latent infection. This will result in a more complete understanding of how latent viral reservoirs are established and maintained.
John Young, Ph.D.
The Salk Institute for Biological Studies, La Jolla, CA
Sulfonation-dependent reactivation in primary T cell models of HIV latency: One strategy under investigation for curing HIV infection involves reactivating latent HIV so that it can be targeted by antiretroviral therapy. Drugs aimed at doing this have so far been either too toxic or not sufficiently powerful. Dr. Young has identified another pathway through which HIV might be reactivated. He plans to test this hypothesis and to determine whether it might yield safer and more effective drugs to flush the virus out of reservoirs.
Franck Dupuy, Ph.D.; Mentor: Rafick-Pierre Sekaly, Ph.D.
Vaccine & Gene therapy institute, Port St Lucie, FL
Impact of TLR ligands mediated IL-10 production on HIV persistence: HIV infection induces abnormal immune activity and may contribute to the ability of infected cells to survive and produce low levels of virus. Dr. Dupuy plans to investigate the role of a chain of events linked to the damage induced by HIV in the intestinal tract. He will determine whether the immune hormone IL-10, raised in response to intestinal damage, might simultaneously impair the ability of the immune system to destroy the virus, while also enhancing the survival of infected cells. Understanding this chain of events may inform efforts to rid the body of infected cells.
Richard Fox, Ph.D.; Mentor: James Mullins, Ph.D.
University of Washington, Seattle, WA
An atlas of HIV-1 reservoirs, compartments and drug resistant sanctuaries: Curing HIV will require a thorough understanding of the locations in the body in which the infection persists, both anatomical as well as cellular. Dr. Fox will use a comprehensive bank of autopsy tissues to determine the regions of the body and the types of cells in which HIV persists despite antiretroviral therapy. The knowledge gained will allow scientists to direct therapies focused on eradicating the virus from reservoirs and anatomical sanctuaries.
Rémi Fromentin, PharmD., Ph.D.; Mentor: Nicolas Chomont, Ph.D.
Vaccine and Gene Therapy Institute Florida, Port St Lucie, FL
Ex vivo modeling of viral reactivation in virally suppressed subjects: One method hypothesized to cure HIV involves flushing virus out from latently infected cells so that it can be targeted by antiretroviral therapy. Because latently infected cells are so rare in patients, studying how they respond to different therapies has been very difficult. Dr. Fromentin has designed a test tube method to isolate these rare cells from patients and will use this model both to analyze the size of this reservoir of virus, as well as to test new agents that might have curative potential.
Uri Mbonye, Ph.D.; Mentor: Jonathan Karn, Ph.D.
Case Western Reserve University, Cleveland, OH
Purging HIV proviral transcription by targeting activation of P-TEFb: When HIV integrates into human DNA, the neighboring DNA, as well as interactions of proteins with it, sometimes undergoes changes that result in latent infection, in which the virus is not made and therefore not targeted by antiretroviral therapy. Dr. Mbonye plans to study the chain of events that lead to this lockdown of the virus, and more importantly how it can be reversed. His research has the potential to uncover new ways in which virus could be flushed out of latency, an important component of a cure for HIV.
Katherine Thompson, Ph.D.; Mentor: Catriona McLean, M.D.
Alfred Hospital, Melbourne, Australia
Brain HIV reservoirs - their role in cognitive impairment in the ART era: One hypothesized mechanism whereby HIV persists despite antiretroviral therapy involves its ability to infect brain cells, where therapy does not easily penetrate. Dr. Thompson will analyze single cells in the brain to determine which cell types are infected, which result in latent infection, and whether latent infection of brain cells is associated with cognitive impairment observed in some HIV patients. These studies may point to a need to design therapies specifically targeted to infected brain cells.
Mathilde Krim Fellowships in Basic Biomedical Research
Mattias Forsell, Ph.D.; Mentor: Mikael Karlsson, Ph.D.
Karolinska Institutet, Stockholm, Sweden
Regulation of epitope specific antibodies against HIV-1 Env: Despite a concerted effort to design an AIDS vaccine, several characteristics of the virus, such as its ability to present “decoys” to guide the immune system away from making the most effective immune responses, have made the task impossible so far. Dr. Forsell plans to elucidate the mechanisms whereby the immune cells that make antibodies generate responses to different regions of the virus, and how these cells might ultimately be guided towards making antibodies against the most vulnerable regions of the virus. Such information could guide the design of a vaccine against HIV infection.
Katarzyna Hrecka, Ph.D.; Mentor: Jacek Skowronski, M.D., Ph.D.
Case Western Reserve University, School of Medicine, Cleveland, OH
SAMHD1-mediated restriction of HIV-1 infection of myeloid cells: A cell protein called SAMHD1 was discovered earlier to this year to be at least partly responsible for the difficulty in productively infecting two types of immune cells, macrophages and dendritic cells. Dr. Hrecka plans to learn more about how the protein regulates the ability of these cells to be infected, or to produce new viruses after infection. She hopes this information will lead to new ways both to increase the resistance of such cells to HIV infection, as well as to prevent the formation of long lasting reservoirs of virus in these cells that might constitute one barrier to curing HIV infection.
Sebla Kutluay, Ph.D.; Mentor: Paul Bieniasz, Ph.D.
The Aaron Diamond AIDS Research Center, New York, NY
Identification of novel RNA-protein interactions in HIV-1 particle genesis: The life cycle of HIV requires – and can also be disrupted by - interactions between genetic material (RNA) originating either from the virus or the human cell, with proteins made by the virus and human host cell. Dr. Kutluay will study three such proteins, the viral Gag protein that plays an important role in virus assembly, and two cell proteins that impede the ability of HIV to infect cells, APOBEC3G and APOBEC3F. In particular, she will identify the specific stretches of RNA to which the three proteins bind. Her project will increase our understanding of the interactions between proteins and RNA and may provide insights into weaknesses in HIV that could be exploited for the development of new drugs.
Ruth Serra-Moreno, Ph.D.; Mentor: David Evans, Ph.D.
New England Primate Research Center, Southborough, MA
Lentiviral resistance to Tetherin/BST-2: Viruses, such as HIV, must overcome built-in defenses in the host cells they infect. One such defense is tetherin, which tethers newly made viruses to the surface of the infected cell, thus preventing them from infecting other cells. The monkey virus SIV uses the viral protein Nef to counteract tetherin, but in humans HIV has evolved the ability to overcome tetherin using a different viral protein called Vpu, or in some cases the viral protein Env. Dr. Serra-Moreno will probe the processes whereby HIV counteracts the tetherin cellular defense, which might ultimately inform efforts to design new methods to combat the virus.