Heather Allore, PhDSenior Research Scientist (Geriatrics); Co-Director of Biostatistics Core, Claude D. Pepper Older Americans Independence Center at Yale
Dr. Allore is a nationally recognized biostatistical expert who is an active collaborator with several of the ID T32 Training Program faculty, including Drs. Fikrig, Shaw, and Quagliarello. She is ideally positioned to serve as a co-mentor for trainees for biostatistical and design issues in project development and to assist the ID T32 Training Program in identifying resources within the Pepper Center for data management and analysis support. She has extensive experience in biostatistics, research design, and analysis needs of interdisciplinary studies of aging populations.
Frederick Altice, MDProfessor, Director Clinical & Community Research (Infectious Diseases and Epidemiology & Public Health)
Dr. Altice is the Director of Community and Clinical Research at the Yale University AIDS Program, and he has considerable experience mentoring pre- and post-doctoral students and junior faculty members in infectious diseases. His work has included the construction of large cohorts of injection drug users with and at risk for HIV, development and testing of adherence to HIV therapeutics using directly administered antiretroviral therapy and health care strategies integrating opioid substitution therapy with treatments for infectious diseases. Dr. Altice has successfully trained Dr. Sandra Springer on our T32 award as an Infectious Diseases fellow in our program. Dr. Springer has published several original manuscripts related to her work with Dr. Altice, she has successfully been funded with an NIH K23 award, and she was recently appointed as an Assistant Professor of Medicine, within the Infectious Diseases Section at Yale. He also successfully trained Dr. R. Douglas Bruce, with support outside our T32 training grant. Dr. Bruce has also been highly successful with several original publications, has successfully funded NIH K08 application, and he was also recently appointed as an Assistant Professor of Medicine within the Infectious Diseases Section at Yale.
Choukri Ben Mamoun, PhDAssociate Professor (Infectious Diseases & Microbial Pathogenesis)
Dr. Ben Mamoun’s laboratory studies the mechanisms that control pathogenesis and transmission of the human malaria parasite Plasmodium falciparum with an aim towards the development of new antimalarial therapies. A specific research focus in the laboratory is on the identification and characterization of the transporters and metabolic machineries of the parasite required for the uptake and subsequent utilization of essential host nutrients. Dr. Ben Mamoun’s laboratory employs genetic, biochemical and pharmacological approaches to assess the importance of these molecules in parasite development, multiplication and sexual differentiation. Dr. Ben Mamoun’s laboratory is also working on the validation of conditionally lethal Plasmodium strains, lacking the primary purine transporters, as attenuated malaria vaccines. Other efforts in the Ben Mamoun laboratory include the characterization of host receptors involved in cerebral malaria, the identification of transmission-blocking drugs, and the novel antimalarial therapies.]
Linda Bockenstedt, MDHarold W Jockers Professor (Rheumatology)
Dr. Bockenstedt’s laboratory studies the pathogenesis of Lyme disease, a tick-borne infection with the spirochete Borrelia burgdorferi. She has used the murine model of Lyme borreliosis to investigate the host immune response to the spirochete and define mechanisms by which the spirochete persists in the host. Using molecular genomic, proteomic and imaging approaches, Dr. Bockenstedt’s group is studying host-spirochete interactions that modulate cellular and humoral immune responses to spirochetal antigens; host genetic factors that determine disease severity; and the mechanisms of spirochete persistence despite host protective immunity. Her results have led us to examine the interface between innate and adaptive immunity as the key to effective pathogen control, T and B cell effector functions in disease pathogenesis and in its regression, and persistence of spirochetes by variation in gene expression and by alterations in growth rate.
Richard Bucala, MD, PhDProfessor (Rheumatology, Pathology & Epidemiology & Public Health)
Dr. Bucala’s laboratory studies the pro-inflammatory cytokine MIF and its role in infectious disease pathogenesis. Dr. Bucala has recently cloned several pathogen (parasite)- and vector (mosquito, tick)- encoded orthologues of mammalian MIF that subvert the host immunologic response to infection. Available projects in this area include structural and functional investigations of the interaction of these orthologues with the mammalian host MIF receptor. Genotyping and disease association studies are underway in his group for conditions such as sepsis, bacterial meningitis, and different parasitic and viral infections. Dr. Bucala’s group is characterizing the phenotypic properties of host cells bearing different human MIF alleles to various infectious stimuli. Dr. Bucala is currently serving as the Primary Mentor for one of our trainees, Rita Das, MD.
Michael Cappello, MDProfessor and Director World Fellows (Pediatrics Infectious Diseases, Microbial Pathogenesis & Epidemiology and Public Health)
The focus of research in Dr. Cappello’s has been the pathogenesis of parasitic helminth infections. The majority of this work involves fundamental laboratory investigations of hookworm infection. Dr. Cappello has studied how adult hookworms evade host defenses in order to feed successfully while attached to the host intestine. Using an animal model of infection with the human hookworm Ancylostoma ceylanicum, he has also demonstrated for the first time that immunization with single recombinant antigens confers partial protection against anemia and/or growth delay. This discovery has established the proof of concept for development of a human vaccine. In addition to the work on hookworm pathogenesis, Dr. Cappello has also established important field based immunoepidemiologic studies aimed at characterizing host immune responses to hookworm infection. These studies, which are being conducted in collaboration with colleagues in Ecuador, Peru, Ghana and the Philippines, will establish baseline data prior to the initiation of human vaccine trials, which is a long-term goal of his research program. Dr. Cappello has recently served as the Primary Mentor for one of our trainees, Nisha Manickam, DO.
Joseph Craft, MDPaul B. Beeson Professor, Chief of Rheumatology, Director Investigative Medicine Program (Rheumatology & Immunobiology)
Dr. Craft’s laboratory seeks to define the mechanisms of the activation of reactive T cells in infectious and autoimmune diseases and their capacity to propagate and to regulate B cell help for antibody production. Dr. Craft has demonstrated that gamma-delta T cells are critical for the clearance of flaviviral infections, such as West Nile encephalitis in mice. He has also shown that T cells from mice with systemic inflammatory syndromes are also hyper-responsive to activation through their antigen receptors, compared to T cells from non-immune animals, with this difference apparently an intrinsic (genetic) one. Dr. Craft has been involved in translational research at the intersection of immunology and infectious diseases, and his work will be appealing to many of our fellows.
Peter Cresswell, PhDProfessor, Investigator Howard Hughes Medical Institute (Immunobiology, Dermatology and Cell Biology)
The major interest of Dr. Cresswell’s laboratory is in the mechanisms regulating antigen processing. This is fundamental for understanding how we combat diverse infectious agents. The assembly of a class I-beta2 microglobulin dimer involves two chaperones, calnexin and calreticulin, and the thiol oxido-reductase, ERp57. Calreticulin- and ERp57-associated class I molecules physically associate with TAP molecules, with an MHC encoded glycoprotein, tapasin, serving as a bridge. This complex is generally called the peptide loading complex. How it facilitates peptide loading by MHC class I molecules is under investigation. A second interest is the mechanisms of action of interferon-induced proteins. He has identified a novel protein, viperin, which inhibits human cytomegalovirus replication. Dr. Cresswell has extended our studies to influenza and herpes simplex viruses, and viperin affects their replication also. Dr. Cresswell has expressed great interest in translating his basic research towards clinical medicine, and this training grant will serve as the main vehicle for this new effort by Dr. Cresswell.
Erol Fikrig, MDWaldemar Von Zedtwitz Professor, Howard Hughes Medical Institute, Chief of Infectious Diseases, (Infectious Diseases, Microbial Pathogenesis and Epidemiology & Public Health)
Dr. Fikrig’s laboratory investigates the pathogenesis of, and develops new strategies to prevent, Lyme disease, human anaplasmosis and West Nile encephalitis. Efforts on Lyme disease include exploring immunity to Borrelia burgdorferi, selective B. burgdorferi gene expression in vivo, and the immunobiology of Lyme arthritis. Human anaplasmosis is caused by a newly described obligate intracellular pathogen, transmitted by Ixodes scapularis ticks, that persists within neutrophils. Dr. Fikrig’s group is investigating the molecular strategies that Anaplasma phagocytophilum uses to survive in polymorphonuclear leukocytes. West Nile virus can cause fatal encephalitis, and this lab seeks to understand the pathogenesis of this emerging mosquito-borne disease. Finally, his group is also developing molecular approaches to prevent ticks and mosquitoes from feeding on a mammalian host, thereby interfering with pathogen transmission. Dr. Fikrig’s work spanned the range from basic laboratory research to leading phase I and phase III human clinical trials. Dr. Fikrig was the primary mentor of one of our previous trainees, Dr. Brian Beaulieu and is on the training committee of one of our trainees, Dr. Rita Das.
Durland Fish, PhDProfessor (Epidemiology and Public Health & School of Forestry & Environmental Studies)
Dr. Fish’s research interests are in the areas of ecology and prevention of vector-borne infectious diseases. Recent emphasis has been on tick-borne pathogens causing Lyme disease and human ehrlichiosis (anaplasmosis) in the northeastern U.S. Current projects include natural and artificial regulation of vector populations, vector competence for viral and bacterial pathogens, co-infection and transmissions of multiple pathogens, geographic and spatial analysis of epidemiological data, and the use of satellite imagery to predict vector-borne disease risk. Dr. Fish has also worked closely with Drs. Fikrig, Bockenstedt and Flavell, all members of this training program, to examine the molecular interactions between ticks and pathogens, such as B. burgdorferi and Anaplasma that results in successful transmission of the pathogens from the arthropod vector to the mammalian host.
Richard Flavell, PhD, FRSSterling Professor and Chairman of Immunobiology, Investigator Howard Hughes Medical Institute (Immunobiology)
Dr. Flavell is one of the world's pre-eminent immunologists and his laboratory studies the molecular and cellular basis of the immune response. This group has been instrumental in elucidating the mechanisms whereby the immune response is regulated, so that autoimmunity is prevented and overaggressive responses to pathogens controlled. Finally, Dr. Flavell’s laboratory has discovered the role of several receptor families in the innate immune response, including Toll-like receptors and intracellular Nod-like receptor families. This has led to the elucidation of function of Nod2 in inflammatory bowel diseases and infections and Nalp proteins in the production of IL-1 and other responses related to infections. Dr. Flavell has collaborated with most of the faculty members in this training program in his illustrious career. Dr. Flavell was the Primary Mentor for one of our recent, and highly successful trainees, Fayyaz Sutterwala, MD, PhD.
Gerald Friedland, MDProfessor (Infectious Diseases & Epidemiology and Public Health)
Dr. Friedland’s research interests include the study of the provision of HIV care to vulnerable populations and clinical trials of antiretroviral therapies. He is currently the Principal Investigator of New England ProACT, a regional AIDS clinical trials network specializing in antiretroviral therapy trials and associated with NIH supported HIV clinical trials networks. Dr. Friedland is also actively involved in HIV/AIDS international research aimed at providing access to antiretroviral therapy in resource-limited settings. The major focus of this work is the integration of HIV and TB care and treatment in co-infected patients with the aim of improving diagnosis, treatment and outcome of both diseases. This led to the discovery of extensively resistant tuberculosis (XDR TB) as a major cause of death among HIV/TB co-infected patients in South Africa. He now focuses on the diagnosis, treatment and prevention of XDR TB in HIV infected patients. Dr. Friedland is currently serving as the Primary Mentor for a recent trainee, Sheela Shenoi, MD.
Jorge Galan, DVM, PhDProfessor (Microbial Pathogenesis & Cell Biology)
Dr. Galan’s laboratory studies the pathogenesis of two intestinal pathogens, Salmonella enterica and Campylobacter jejuni. He is interested in characterizing the bacterial determinants involved in these interactions as well as the cell biology and immunobiology of this process. His laboratory also has an interest in vaccine development that stems from Dr. Galan’s discovery of a specialized organelle in Salmonella enterica (the “type III secretion system”) that mediates the transfer of bacterial proteins into host cells. Dr. Galan has harnessed this system for the delivery of heterologous proteins to the Class I and Class II antigen presenting pathways by avirulent strains of Salmonella. Currently his group focusing efforts on the development of an HIV vaccine as well as the application of this system for the construction of biodefense vaccines. Human phase I clinical studies are currently ongoing. Dr. Galan served as the Primary Mentor for one of our previous trainees, Eric Hughes, MD, PhD.
Thomas Gill, MDProfessor (Geriatrics, Epidemiology & Public Health, Investigative Medicine Program), Professor of Medicine, Co-Director of Program on Aging and Pepper Center at Yale, and Principal Investigator on the NIA T32 Geriatrics Training Grant at Yale
Dr. Gill is a renowned investigator on defining the epidemiology of disability development in community dwelling older adults, and will be an ideal collaborator to assess the impact of pneumonia, influenza, and vaccine responsiveness with disability development in frail nursing home residents.
Manisha Juthani-Mehta, MDAssociate Professor, Fellowship Program Director (Infectious Diseases)
Dr. Juthani-Mehta performs patient-oriented research in the field of infections in older adults, with a focus on urinary tract infection in nursing home residents. This includes observational cohort studies investigating clinical criteria that can differentiate the syndromes of asymptomatic bacteriuria and urinary tract infection in older nursing home residents. Other areas of investigation include exploration of differences in host immunity that may cause susceptibility to either asymptomatic bacteriuria or UTI, other urinary biomarkers that might identify those residents that require antibiotic treatment, bacterial characteristics such as biofilm production in residents with recurrent UTI episodes, and vaginal estrogen or cranberry therapy for prevention of recurrent UTI episodes.
Barbara Kazmierczak, MD, PhDPrinciple Investigator (Infectious Diseases NIH Training Grant)
Associate Professor (Infectious Diseases, Microbial Pathogenesis)
Dr. Kazmierczak’s group studies signal transduction networks in Pseudomonas aeruginosa, a gram-negative human pathogen that causes a broad spectrum of human disease. Dr. Kazmierczak is particularly interested in novel types of regulatory networks that integrate information about the bacterial environment with the expression of factors involved in motility, biofilm formation, and Type III secretion of bacterial effectors. Her lab also studies the generation of innate immune responses at mucosal surfaces and how the bacterial virulence factors that we study in the lab influence the outcome of human infections with Pseudomonas aeruginosa. Dr. Kazmierczak served as the Primary Mentor for two trainees, Sailaja Puttagunta, M.D., and Kenneth Muldrew, M.D. She also served on the Training Committee of one of our trainees, Nisha Manickam, DO.
Albert Ko, MDAssociate Professor (Epidemiology & Public Health and Infectious Diseases)
Dr. Ko joined the Yale faculty in July 2010 as Professor and Director of the Division of Microbial Diseases in the Yale School of Epidemiology and Public Health. He has a secondary appointment in the Section of Infectious Diseases in the Department of Medicine. Dr. Ko is a world expert in the pathogenesis of infectious diseases, with an emphasis on leptospirosis. He oversees several international studies, and directly works with patient cohorts in Brazil. He is active in the training of physicians and scientists that are interested in applying molecular and immunologic techniques to underserved populations at risk for infectious diseases throughout the world.
Mike Kozal, MDProfessor and Chief of Infectious Diseases, VA, (Infectious Diseases)
Dr. Kozal’s group focuses on the development of new molecular viral diagnostic assays to improve patient care and to determine the best way to incorporate genotypic resistance assays into chronic viral disease management. Currently, Dr. Kozal’s laboratory has been developing DNA microarrays and Ultra Deep sequencing technology to investigate the impact of low abundant drug resistant HIV and HCV variants on treatment outcomes. In addition, Dr. Kozal is associate director and a central participant in the AIDS clinical trials program and is the Principal Investigator on 9 HIV investigational drug trials. His work provides a bridge between investigative work with patients and laboratory research. Dr. Kozal served as the Primary Mentor for three of our recent trainees: Max Lataillade, DO, Gustine Liu-Young, MD, and Thuy Le, MD.
Priti Kumar, PhDAssistant Professor (Infectious Diseases & Microbial Pathogenesis)
Dr. Kumar’s laboratory is developing RNA interference (RNAi) based interventions for human viral infections. Towards this goal, Dr. Kumar has recently developed a novel technique for the specific delivery of siRNAs into human T cells and tested in vivo efficacy using “humanized mice” (immunodeficient mice transplanted with human hematopoietic stem cells and consequently a human immune system). Antiviral siRNAs delivered by this approach could control HIV in these mice demonstrating the feasibility of RNAi therapy for HIV infection. Dr. Kumar has also developed a novel method for the specific delivery of siRNAs into neuronal cells and used this to treat flaviviral encephalitis in mouse models. The long term goals are to translate this research into viable HIV-AIDS and anti-flaviviral therapy.
Diane McMahon-Pratt, PhDProfessor (Epidemiology and Public Health)
Dr. McMahon-Pratt’s group studies the parasitic protozoan, Leishmania, which causes a spectrum of diseases known as leishmaniasis. Using biochemical and molecular genetic approaches, the laboratory is involved in the study of molecules that are developmentally regulated by the parasite during its life cycle. In addition, the lab is interested in understanding the immune effector mechanisms in the mammalian host that are involved in the control of infection and/or pathogenesis, with the aim to developing a vaccine against leishmaniasis. In these studies, the laboratory collaborates with clinicians and scientists in Brazil and Colombia.
Ruslan Medzhitov, PhDProfessor and Investigator Howard Hughes Medical Institute (Immunobiology)
Dr. Medzhitov’s is focused on the analysis of an evolutionarily conserved family of receptors, called Toll-like receptors, TLRs, that evolved to recognize microbial pathogens and alert the host to the presence of infection. Understanding of the role of TLRs in the human immune system allows developing novel approaches to vaccine development, modulation of a variety of pathological conditions caused by infection and inflammation, as well as autoimmune disorders. Dr. Medzhitov’s group explores ways of manipulating the innate immune system to design better vaccines and to interfere with immunopathological conditions caused by the excessive activation of this system of host defense. Dr. Medzhitov is recognized as the world authority in this area of research. Dr. Medzhitov has served on the training committee of several of our recent trainees, David van Duin, MD, Fayyaz Sutterwala, MD, PhD, and Tomohito Yagi, MD, PhD.
Vincent Quagliarello, MDProfessor, Clinical Chief, (Infectious Diseases)
Dr. Quagliarello’s group’s patient-oriented studies are focused on infections in older adults, particularly pneumonia and urinary tract infection. Dr. Quagliarello is also interested in how selected elderly populations succumb to infectious diseases, and how this is influenced by host innate immune responses that change as we get older. He collaborates with Drs. Fikrig, Flavell, Bockenstedt, Tinetti, Allore, Juthani-Mehta and Shaw in this area, and has a unique access to patient populations that helps facilitate the laboratory studies. Dr. Quagliarello served as the Primary Mentor for 4 previous trainees, who were successful K-award recipients including: Harry Conte, M.D. who was a successful K08 award recipient; Rodrigo Hasbun, M.D., a successful K23 recipient; Manisha Juthani Mehta,M.D., a successful K23 award recipient and current Assistant Professor of Medicine in the Infectious Diseases Section at Yale; and Gulshan Sharma, M.D. a successful K23 recipient from the Section of Pulmonary and Critical Care who is currently Associate Professor, University Texas, Galveston. He also served on the training committees for several of our recent trainees (Martinello, Sutterwala, van Duin, Puttagunta, Liu-Young, Yagi, Shenoi, Joshi). He is PI on an active large R01 proposal for a randomized clinical trial to reduce pneumonia in nursing home residents that can serve as an ideal template to train several new fellows. He has also been recently awarded a K07 Academic Leadership Award from NIA to create a program of interdisciplinary research of infectious disease in aging populations at Yale.
Craig Roy, PhDProfessor (Microbial Pathogenesis)
The focus of Dr. Roy’s research is to understand the molecular and cellular events that enable microbial pathogens to evade host defense mechanisms. In particular, his group is interested in how bacteria that replicate inside mammalian cells modulate vesicular transport following uptake. He has been using the bacteria Legionella pneumophila and Coxiella burnetii as model pathogens to study this process. L. pneumophila is a facultative intracellular pathogen capable of growing within an endoplasmic reticulum-derived organelle in macrophages and protozoan host cells. C. burnetii is an obligate intracellular pathogen that replicates in an acidic phagolysosomal compartment. Despite residing in completely different subcellular organelles, a highly conserved type IV secretion system is utilized by both L. pneumophila and C. burnetii to modulate host cellular functions. For both organisms, substrate proteins translocated into host cells by this system are believed to be the primary determinants of intracellular fate. Additionally, he is investigating how host innate and adaptive immune responses eventually lead to protection and clearance of these pathogens. Dr. Roy has become most interested in translating his effort to clinical medicine, and will serve as an important new member of this training grant.
Eugene Shapiro, MDProfessor (Pediatrics Infectious Diseases, Epidemiology & Public Health, and Investigative Medicine Program)
Dr. Shapiro is director of education for Yale's clinical and translational science award and is deputy director of Yale's Ph.D. program in Investigative Medicine. His research focuses on the effectiveness of vaccines, of the clinical epidemiology of Lyme disease, and of methodologic issues in assuring the validity of observational studies. He has been a mentor for numerous fellows in infectious diseases as well as primary mentor on K awards for several faculty members. Dr. Shapiro is ideally suited to serve as a co-mentor of trainees to correlate laboratory studies with observations in patients, and to guide didactic coursework selection in the Investigative Medicine program.
Albert Shaw, MD, PhDAssociate Professor (Infectious Diseases)
Research in the Shaw laboratory is directed toward understanding mechanisms underlying age-associated alterations in the immune system, and how this relates to the clinical outcome of infection and immunization. Ongoing studies seek to understand age-related changes in the innate immune system in humans, and to correlate such changes with vaccine responsiveness. Other projects include studies on the function of presenilin in cells of the immune system, and the role of mammalian topoisomerases in the control of genomic stability and age-related immunosenescence. He was the Primary Mentor for two of our recent trainees, David van Duin, MD and Tomohito Yagi, MD, PhD. He also serves on the Training Committees for one of our trainees, Rita Das, MD.
Richard Sutton, MD, PhDAssociate Professor (Infectious Diseases and Microbial Pathogenesis)
The Sutton laboratory is focused on the study of human immunodeficiency virus type I (HIV) replication and the development of small animal models of HIV. For example, mice are not susceptible to HIV due to a profound block in HIV assembly and release from cells. His group is exploring the nature of this block and are conducting genetic and high throughput screens to identify human genes that may be able to overcome this deficiency. Dr. Sutton’s lab also utilize replication-defective HIV as a vector to transducer non-dividing cells for gene therapeutic purposes and they are developing novel methods of vector production which no longer rely on transient transfection using plasmids. These vectors are used to investigate other viruses (for example, cellular binding and entry requirements of filo and alphaviruses) and to explore fundamental questions in molecular biology, such as the fidelity of RNA polymerase II and genome-wide identification of active and cell type-specific DNA transcriptional elements.
Mary Tinetti, MDGladys Crofoot Professor of Medicine, and Director of Program on Aging and Pepper Center, (Geriatrics, Investigative Medicine Program & Epidemiology and Public Health)
Dr. Tinetti is a renowned investigator on multi-factorial risk reduction interventions in older adults. As a colleague who has collaborated with Drs. Quagliarello, Juthani-Mehta, Gill and Allore over the past 6 years, she will be invaluable as co-mentor to trainees, particularly regarding pneumonia and urinary tract infection (UTI) in nursing home residents. Specific projects will be focused on developing intervention strategies to prevent infections (e.g., UTI, pneumonia) in nursing home residents.
Christian Tschudi, PhDProfessor (Epidemiology and Public Health)
Dr. Tschudi’s laboratory focuses on the biology of trypanosomes the causative agents of devastating diseases in Africa and South America. Most projects in the laboratory utilize bioinformatics and modern genetic techniques to identify and dissect parasite-specific functions. The long-term goal is to identify candidate molecules that can be targets for chemotherapy. Dr. Tschudi is also interested in understanding gene silencing by RNA interference in African trypanosomes with the objective to uncover its biological function. As RNAi has increased in importance over the past 5 years, Dr. Tschudi’s work has become of greater interest to trainees working on new approaches to these neglected diseases, and his scientific expertise will be of great importance to all our trainees. He will serve as a primary mentor to physicians that request basic research training and as a co-mentor for more translational projects, thereby insuring that these individuals are well-versed in research.