Under the supervision of Dr. Daniel Kuritzkes, Director of AIDS research at BWH and Head of the section of Retroviral Therapeutics for Harvard’s Division of AIDS, the division’s clinical research includes domestic and international studies of HIV infection and basic HIV virology. Dr. Kuritzkes is co-chair of the national ACTG and principal investigator for the entire Harvard ACTU. Dr. Manish Sagar works with Dr. Kuritzkes studying viral evolution of HIV infection. Laboratory research is based at the Channing Laboratory at 181 Longwood Avenue, Boston, at Dr. Kuritzkes’s lab at the Partners Research Center on Landsdowne Street, and at Harvard School of Public Health.
Dr. Paul Sax is the lead clinical investigator for the Center for AIDS Research (CFAR) and AIDS Clinical Trial Grant (ACTG) protocols at BWH, and supervises all clinical, pharmacologic, data management and consultative efforts. Dr. Sax’s ongoing research efforts involve clinical trials of new antiretroviral therapies or strategies and the cost-effectiveness of HIV therapy in collaboration with Dr. Kenneth Freedberg and other investigators at the Harvard School of Public Health and Massachusetts General Hospital. Dr. Sax is also the Editor-in-Chief of Journal Watch HIV/AIDS Clinical Care.
Dr. Sigal Yawetz oversees the Post-Exposure Prophylaxis (PEP) program for occupational and non-occupational exposures to HIV, HIV care for patients of the Boston Hemophilia Center, and HIV care for HIV-1–infected pregnant women. She is the co-investigator, with Dr. Sax, for the ACTG protocols. She is involved in several protocols studying barriers to HIV care and adherence to therapy in HIV-1–infected pregnant women, and the application of laboratory tools for the prevention and management of HIV disease. She teaches HST HIV clinic for ICM and mentors HMS students in clinic.
Dr. Manish Sagar collaborates with Dr. Kuritzkes at the Partners AIDS Research Center (PARC) and BWH. His expertise in process by which HIV-1 enters its target cells is a great asset to PARC and the division.
Dr. Lindsey Baden’s research focuses on two primary areas: infectious diseases in the immunocompromised host, and HIV vaccine development. He is conducting both investigator-initiated and sponsor-initiated studies. In particular, he is involved in active studies of therapy for opportunistic infections such as CMV and invasive mycoses in transplant patients, and is developing a new strategy for tracking infectious complications in critically ill patients.
The basic viral oncology research program focuses on the molecular pathogenesis and oncogenesis of herpes virus infection. Dr. Elliott Kieff’s group studies the molecular mechanism by which Epstein-Barr virus (EBV) causes tumor cancer. Studies of the mechanisms by which viruses transform cells have revealed important aspects of control of normal and tumor cell growth. EBV is one of only a few naturally occurring human tumor viruses. The research objective is to understand the molecular mechanisms by which EBV efficiently transforms human B lymphocytes into perpetually proliferating lymphoblasts and maintains itself in a latent state in the transformed cells.
Dr. Frederick Wang’s research focuses on studies of Epstein-Barr virus infection in cell, animal, and human models to better understand pathogenesis of persistent infection, EBV-induced oncogenesis, and treatment of EBV-associated cancers. Herpes viruses closely related to EBV and naturally infecting New World or Old World non-human primates have been identified, cloned, and sequenced, and the evolution of these related viruses provides unique insights into the molecular biology of this oncogenic herpes virus genus. Genetic systems for making mutant viruses are used to analyze viral gene function in cells, to determine how specific viral genes manipulate host cell gene expression, and to test their effects on viral pathogenesis in the context of organismal infection in non-human primates. Virus-specific immune responses important for control of EBV infection and associated malignancies are dissected from animal model systems and EBV-infected humans. Hypotheses for enhanced therapeutic strategies arising from a better understanding of viral pathogenesis and immune control are being formally tested in translational studies of virus-specific immunotherapy in patients with EBV-induced nasopharyngeal cancer.
Dr. Kenneth Kaye’s group investigates the link between Kaposi’s sarcoma–associated herpesvirus (KSHV) or human herpesvirus 8 (HHV-8) and human malignancy. KSHV is linked with Kaposi’s sarcoma, primary effusion lymphomas, and multicentric Castleman’s disease, an aggressive lymphoproliferative disorder. The goal of his team is to gain a better understanding of the molecular mechanisms by which KSHV exerts tumorigenic effects. Dr. Kaye’s group is also initiating work to identify therapeutic agents for smallpox, an emerging bioterrorist threat.
Dr. Matthew Waldor, a Howard Hughes Investigator, was recruited this year to the division and to the Channing Laboratory. His primary research effort is in the area of molecular bacterial pathogenesis. Dr. Waldor's group is exploring the evolution, pathogenicity, and cell biology of clinically important enteric pathogens including Vibrio Cholerae, Vibrio parahaemolyticus, and enterohemorrhagic Escherichia coli (EHEC).
Dr. Dennis Kasper’s group is studying the molecular basis for bacterial pathogenesis, and is applying this knowledge to understand more fully the interactions of bacterial surface virulence factors with host defenses. His research focuses on two areas: Group B Streptococcus (GBS) and Bacteroides fragilis. Studies of GBS have targeted several related areas. Basic investigations are under way in the biosynthesis of the polysaccharide and the genetic regulation of biosynthesis, carbohydrate chemistry, vaccine development, immune mechanisms elicited in response to glycoconjugate vaccines and surface proteins of GBS. Bacteroides fragilis is the obligate anaerobe most frequently isolated from sites of intraabdominal infection. The research goal is to determine the initial molecular and immunologic events that lead to the formation of intraabdominal abscesses in the infected host. These studies involve the elucidation of how bacteria interact with and adhere to host tissue within the peritoneal cavity to establish and propagate the infectious process. It is hoped that this work will better define the pathogenesis of abscess formation in the host as well as T-cell responses to carbohydrate antigens. This information should provide insights that will further the development of a new class of T-cell biologic response modifiers and/or vaccines.
Dr. Raphael Dolin oversees the Harvard Clinical Research Initiative and the Harvard Vaccine Trials Unit (HVTU), a collaboration between affiliated hospitals initiated to expand and enhance clinical research activities in the HMS community.
Dr. Lindsey Baden is principal investigator of the BWH unit of the NIH HIV Vaccine Trials Network, which is studying vaccine development. He supervises multiple trainees at various stages of career development, including medical students, residents, and fellows.
Drs. Paul Farmer, Sonya Shin, Louise Ivers, Joia Mukherjee, Peter Drobac and Serena Koenig hold joint appointments in the Division of Global Health Equity. Dr. Farmer’s work focuses on the anthropology of infectious disease and engages both social theory and pathophysiology. His research seeks to answer the questions of the effect of large-scale social forces on the distribution and outcome of infectious diseases, the effect of epidemic disease on communities, the effect of scientific error on health policy and practice, the relationship between health and healthcare and human rights, and the effectiveness of projects designed to lessen the impact of epidemic disease.
Dr. Shin’s research focuses on analyzing treatment outcome by risk category and also in employing decision and cost-effectiveness analysis to determine which high-risk groups would benefit from early screening for MDRTB infection.
Dr. Mukherjee’s work focuses on developing predictive algorithms to determine the spectrum of signs, symptoms and clinical illnesses in persons presenting for HIV-related care in rural Haiti and to determine the positive predictive values of the illnesses for CD4 count. She is also studying the clinical outcomes of TB treatment in patients receiving highly active antiretroviral therapy (HAART) for HIV as well as TB therapy versus those who are treated for TB alone.
Dr. Drobac is the Director of Inshuti Mu Buzima, Partners In Health’s sister organization in Rwanda. He has lived and worked in rural Rwanda since 2005, working closely with the Rwandan government to provide high quality health care and social services to nearly one million people in three rural districts, and driving health system innovations to scale.
Dr. Koenig’s research analyzes adherence, health outcomes, and costs of different HIV treatment strategies in Haiti, with the goal of improving HIV treatment outcomes in urban settings where treatment is currently not directly observed.
Finally, Dr. Ivers’ work focuses on HIV and related stigma in rural Haiti, and its impact on the scale-up of HIV treatment in resource-poor countries.
Dr. Eric Rubin's laboratory has developed new tools for studying Mycobacterium tuberculosis and related mycobacteria in an effort to identify genes required for growth, survival, and virulence. His work takes advantage of the recent sequencing of the M. tuberculosis genome to systematically analyze genes to determine their importance in disease using transposon mutagenesis and DNA microarrays. He hopes to use these genes to develop new methods of producing attenuated strains of M. tuberculosis both for use as vaccines and as screening strains for new antibiotics.
Dr. Richard Platt’s research focuses on the epidemiology, consequences, and prevention of nosocomial infections, on infectious diseases in the community setting, and on pharmacoepidemiology. Much of his current work involves the use of the defined populations of large health maintenance organizations (HMOs), their extensive and often automated data, and their ability to make system-wide interventions. Recent research has involved the development of consortia of such HMOs for this purpose. Specific recent topics include the development of population-based methods for assessment of healthcare-associated infections, tuberculosis, and sexually transmitted diseases; the use of prescription drugs and their effectiveness and adverse reactions; neonatal group B streptococcal infection; reduction of inappropriate antibiotic prescribing in hospital and ambulatory settings; and assessment of the impact of these changes on health outcomes.
Dr. Deborah Yokoe’s research has focused on developing more reliable and efficient methods for detection of healthcare-associated infections. She has also made substantial contributions to the identification of community-acquired infections of public health importance such as tuberculosis and sexually transmitted diseases. Her recent publications includes a major 13-center initiative she led on behalf of the CDC’s Prevention Epicenters program; this work confirmed and extended a method she had previously developed to improve surveillance for surgical site infections among inpatients. This work was an important component of the successful competing renewal of the Eastern Massachusetts Prevention Epicenter in 2006. The next phase of her work involves leadership of the national Epicenters program’s initiative to evaluate the utility of her surveillance method for the national Surgical Care Improvement Project (SCIP), a program of the Centers for Medicare and Medicaid Services (CMS). Dr. Yokoe is also a co-investigator in an NIH-funded Models of Infectious Disease Study five-year research project aimed at developing models for the early detection and monitoring of infectious disease outbreaks. She will test new methods and models for inpatient purposes, using the Brigham and Women’s Hospital as the test-bed. She is also a co-investigator in a project funded by the Massachusetts Department of Public Health that will evaluate streamlined methods for bloodstream infection and surgical site infection surveillance, with the goal of informing an expert panel about the feasibility of employing these methods in acute care hospitals state-wide.
Dr. Thomas O’Brien and Dr. John Stelling co-direct the World Health Organization (WHO) Collaborating Center for Surveillance of Antimicrobial Resistance, which is charged with developing infrastructure and tools to advance the initiative of global surveillance of antibiotic resistance. The last four years have seen development and world-wide deployment of a new version of their database software, now WHONET 5.5, wider application of our data conversion utility, BacLink 2 to extract data from hospital laboratory reporting systems and transmit it to CDC, new funding from NIH, CDC, USDA, and WHO, and growth of their development team from two to five members. Especially significant was the incorporation of a time-space statistical scanning software, SatScan, into WHONET and the demonstration that it could detect automatically clusters of in-hospital infections consistent with nosocomial outbreaks in a U.S. hospital and outbreaks of Shigella in Argentina.