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All application materials are due 5:00 PM, Wednesday, February 1, 2017
Grant information and application instructions are available in December by request.
The adult Infectious Disease and Basic Microbiological Mechanisms Training Program is a Harvard-wide training program dedicated to the education of those infectious disease fellows and PhD postdoctoral fellows interested in pursuing careers as physician-scientists or scientists with a focus on investigation into important questions in non-HIV microbiology and infectious diseases.
Since 1976, the program has been supported by an National Institutes of Health-funded post-doctoral training grant (T32). The training of infectious disease physician-scientist fellows consists of an initial year in clinical infectious diseases (funded by the hospitals), followed by two or more years of mentored research.
The training grant provides support directly to selected infectious disease fellows during their years of mentored research and, by providing support to selected PhD trainees in Harvard Medical School infectious disease and microbiology laboratories focused on areas that have significant clinical relevance, supports the rich research-training environment for scientists within these laboratories.
Laurie E. Comstock, PhD: Symbiotic relationships among intestinal bacteriaAssociate Professor of Medicine (Microbiology and Immunobiology), Harvard Medical School
Joseph El-Khoury, MD: Macrophages and microglia in infection, host defense, and neurodegenerationAssociate Professor of Medicine, Harvard Medical School
Sarah Fortune, MD: Interactions of M. tuberculosis with the hostProfessor of Immunology and Infectious Diseases, Department of Immunology and Infectious Diseases, Harvard TH Chan School of Public Health
Wendy S. Garrett, MD, PhD: Interactions of intestinal microbiota and the immune system in inflammatory bowel diseaseProfessor of Immunology and Infectious Diseases (Genetics and Complex Diseases), Harvard TH Chan School of Public Health
Michael S. Gilmore, PhD: Molecular biology of multi-drug resistant bacterial pathogensSir William Osler Professor of Ophthalmology (Microbiology and Immunobiology), Harvard Medical School
Marcia B. Goldberg, MD: Bacterial host-pathogen interactions and rapid diagnostics of infectionProfessor of Medicine (Microbiology and Immunobiology), Harvard Medical School; Professor of Immunology and Infectious Diseases, Harvard TH Chan School of Public Health; Associate Member, The Broad Institute
Jason B. Harris, MD, MPH: Human immune response to cholera and cholera vaccinesAssociate Professor of Pediatrics, Harvard Medical School
Darren E. Higgins, PhD: Molecular determinants of intracellular bacterial pathogenesisProfessor of Microbiology and Immunobiology, Harvard Medical School
David C. Hooper, MD: Molecular mechanisms and epidemiology of antibiotic resistanceProfessor of Medicine, Harvard Medical School
Deborah T. Hung, MD, PhD: Chemical genetics approach to bacterial pathogenesis:Associate Professor of Microbiology and Immunobiology and of Molecular Biology, Harvard Medical School; Co-Director, Infectious Disease and Microbiome Program, Broad Institute
Dennis L. Kasper, MD: Bacterial-host interactions in symbiosis and pathogenesisWilliam Ellery Channing Professor of Medicine and Professor of Microbiology and Immunobiology, Harvard Medical School
Kenneth M. Kaye, MD: Kaposi's sarcoma-associated herpesvirus (human herpesvirus 8) pathogenesis:Associate Professor of Medicine, Harvard Medical School
Elliott Kieff, MD, PhD: Molecular pathogenesis of Epstein Barr herpesvirus infectionAlbee Professor of Medicine and of Microbiology and Immunobiology, Harvard Medical School
Igor Koralnik, MD: Immunopathogenesis of neurotropic virusesProfessor of Neurology, Harvard Medical School
Jean C. Lee, PhD: Biosynthesis and function of S. aureus extracellular bacterial polysaccharidesAssociate Professor of Medicine, Harvard Medical School
Cammie F. Lesser, MD, PhD: Modeling mechanisms of bacterial pathogenesisAssociate Professor of Medicine (Microbiology and Immunobiology), Harvard Medical School
Marc Lipsitch, DPhil: Effects of host immunity on pathogen populationsProfessor of Epidemiology (Immunology and Infectious Diseases), Harvard School of Public Health
Stephen Lory, PhD: Pathogenesis of opportunistic gram-negative bacterial pathogens of humansProfessor of Microbiology and Immunobiology, Harvard Medical School
Megan B. Murray, MD, MPH, ScD: Epidemiology and genomics of tuberculosisProfessor of Global Health and Social Medicine, Harvard Medical SchoolProfessor of Epidemiology, Harvard School of Public Health.
Edward A. Nardell, MD: Control of multidrug resistant tuberculosisProfessor of Medicine, Harvard Medical School
Gerald B. Pier, PhD: Bacterial pathogenesis and vaccine developmentProfessor of Medicine (Microbiology and Molecular Genetics)
Richard Platt, MD, MS: Epidemiology of infectionProfessor and Chair, Population Medicine, Harvard Medical School; Director of Research, Harvard Pilgrim Health Care
Eric. J. Rubin, MD, PhD: Bacterial genetics of tuberculosisIrene Heinz Given Professor of Immunology and Infectious Diseases, Harvard TH Chan School of Public Health; Assistant Professor of Medicine (Microbiology and Immunobiology), Harvard Medical School
Edward T. Ryan, MD: Immune responses and vaccines for enteric bacteriaProfessor of Medicine, Harvard Medical SchoolAssociate Professor of Immunology and Infectious Diseases, Harvard School of Public Health
Jatin M. Vyas, MD, PhD: Dendritic cells in fungal infectionAssociate Professor of Medicine, Harvard Medical School
Matthew K. Waldor, MD, PhD: Biology and virulence of enteric pathogensEdward H. Kass Professor of Medicine (Microbiology and Immunobiology), Harvard Medical School; Investigator, Howard Hughes Medical Institute; Associate Member, Broad Institute
Rochelle Walensky, MD, MPH: Outcomes research, cost-effectiveness analysis, and infection controlProfessor of Medicine, Harvard Medical School
Suzanne Walker, PhD: Chemical biology, enzymology, antibiotics, glycosyltransferases, and inhibitorsProfessor of Microbiology and Immunobiology, Harvard Medical School; Affiliate Faculty Member, Chemistry and Chemical Biology, Harvard University; Associate Member, Broad Institute
Frederick C. S. Wang, MD: Molecular pathogenesis of Epstein-Barr virusProfessor of Medicine, Harvard Medical School
H. Shaw Warren, MD: Pathogenesis and treatment of sepsis and induced secondary inflammationAssociate Professor of Pediatrics, Harvard Medical School
Sean Whelan, PhD: Transcriptional regulation of viral and mammalian genesProfessor of Microbiology and Immunobiology, Harvard Medical School
Dyann F. Wirth, PhD: Molecular biology of parasitesRichard Pearson Strong Professor and Chair, Immunology and Infectious Diseases, Harvard TH Chan School of Public Health; Senior Associate Member, Broad Institute; Director, Harvard Malaria Initiative, Harvard TH Chan School of Public Health
Priscilla Yang, PhD: Chemistry and biology of host-virus interactionsAssociate Professor of Microbiology and Immunobiology, Harvard Medical School
Antimicrobial resistance mechanisms, discovery of new antimicrobial targets or drugsFortune, Gilmore, Hooper, Hung, Lory, Wirth, Walker
Vaccine and immunotherapy developmentCalderwood, Koralnik, Lee, Pier, Ryan
Emerging and re-emerging infectious diseasesCalderwood, Fortune, Gilmore, Goldberg, Higgins, Hooper, Hung, Kasper, Kaye, Lesser, Lipsitch, Mekalanos, Murray, Rubin, Ryan, Waldor, Walker, Whelan, Yang
Nosocomial infectionsHooper, Lory, Pier, Platt, Walensky
Virulence mechanisms of pathogensCalderwood, Fortune, Goldberg, Harris, Higgins, Hung, Lesser, Lory, Mekalanos, Rubin, Waldor
Host-pathogen interactionsFortune, Garrett, Goldberg, Harris, Hung, Kaye, Kieff, Koralnik, Lesser, Mekalanos, Pier, Waldor, Wang, Whelan
Cell biology of pathogenesisGoldberg, Higgins, Kaye, Kieff, Lesser, Waldor
Host susceptibility to infectionCalderwood, Harris, Ryan
Innate immunity in infectionEl Khoury, Vyas, Warren, Weller
Systemic immune responses to pathogensCalderwood, Higgins, Koralnik, Poznansky, Ryan, Vyas
Mucosal immune responses to pathogensCalderwood, Garrett, Ryan
Oncogenic mechanisms of microorganisms Kaye, Kieff, Wang
Transmission and epidemiology of infectionFortune, Lipsitch, Murray, Platt, Walensky, Wirth
Allison Carey, MDUnder the mentorship of Dr. Sarah Fortune, Dr. Carey is investigating the modulating features and genetic determinants of tuberculosis infection. Tuberculosis (TB), the disease caused by the pathogen Mycobacterium tuberculosis (Mtb), is a global health crisis, with over 9 million new cases of active disease and more than a million deaths annually. Mtb was long thought to be a genetically monomorphic pathogen, but recent work has uncovered substantial genetic diversity among circulating clinical strains. Dr. Carey is interested in the consequences of this genetic diversity in the settings of reinfection and vaccination. She is using genome-wide genetic screening and quantitative molecular tools to explore the impact of clinical strain variation in these scenarios.
Sanjat Kanjilal, MD, MPHUnder the mentorship of Dr. Marc Lipsitch and Dr. Yonatan Grad, Dr. Kanjilal is working to define population dynamics and genotypic correlates of invasion and antibiotic resistance of methicillin-resistant Staphylococcus aureus (MRSA). Advances in bacterial genome sequencing methods, costs, and analytical approaches have resulted in data that can be used to infer transmission patterns in hospitals and communities, to monitor transitions from carriage to invasion, and to correlate genotype with clinically relevant phenotypes. MRSA causes >80,000 severe infections per year and 11,285 deaths and is considered by the CDC to be a ‘serious’ threat. Dr. Kanjilal is investigating the population structure, antibiotic resistance, and virulence factors of MRSA using phylogenetic and statistical tools to analyze a data set of over 1400 genomes from well-characterized isolates. His overall goal is to define the S. aureus genes and regulatory networks that underlie clinically important phenotypes and to define patterns of transmission through human populations.
Philip Lederer, MDUnder the mentorship of Dr. Edward Nardell, Dr. Lederer is working to evaluate the impact of “FAST” (Find cases Actively, Separate temporarily, and promptly Treat effectively) on tuberculosis treatment delays and health care worker infections in Peru.
Fabian Rivera-Chavez, PhDUnder the mentorship of Dr. John Mekalanos, Dr. Rivera-Chavez is investigating the role of complement resistance by Vibrio cholera and other intestinal pathogens during colonization of the intestine.
Jonathan Robbins, MD, PhDUnder the mentorship of Dr. Jeffrey Drovin, Dr. Robbins is studying malaria, a parasitic disease responsible for hundreds of thousands of deaths each year. There is increasing resistance to currently available drugs. New therapies will require a better understanding of the fundamental cellular processes of Plasmodium falciparum, the parasite responsible for most clinical malaria. Dr. Robbins is using a combination of forward and reverse genetic approaches to better understand the cell division cycle of P. falciparum.
Adult Infectious Disease and Basic Microbiologic Mechanisms Training Program
Massachusetts General Hospital
American Association of Immunologists Advanced Course in ImmunologySponsor/Location: American Association of Immunologists, Seaport World Trade Center, Boston, MAWhen: Annually, in July-AugustThis intensive course is directed toward advanced trainees and scientists who wish to expand or update their understanding of the field of Immunology. Leading experts present recent advances in the biology of the immune system and address its role in health and disease. Each day consists of a series of lectures on various topics in the field of Immunology. The overall quality of the course was excellent and assumes each participant has a firm understanding of the principles of immunology.
Harvard University CFAR Workshop on Metagenomics and TranscriptomicsSponsor/Location: Harvard University Center for AIDS Research, Joseph B. Martin Conference Center Harvard Medical School Boston, MAWhen: Annually, in SeptemberThe focus of this five-day intensive workshop was to provide an introduction to fundamental computational skills, genomics study design, and data interpretation. Specific topics covered included an introduction to Unix and R, an overview of metagenomics study design and data analysis tools with a focus on QIIME, and transcriptomics study design and data analysis pipelines. Each day consisted of lectures in the morning and laboratory sessions in the afternoon with access to teacher assistants.
High-Throughput Biology: From Sequence to Networks Sponsors/ Location: Cold Spring Harbor Laboratory, Canadian Bioinformatics Workshops, New York Genome CenterWhen: In the SpringThis week-long intensive course covered the bioinformatics concepts and tools required to analyze DNA and RNA-sequence reads using a reference genome. Two days were focused on DNA sequencing data analysis with topics including reference genome alignment, data visualization, De Novo assembly, small variant calling and annotation, and structural variation calling. The next two days were devoted the RNA-seq analysis with topics including alignment and visualization, expression and differential expression analysis, and isoform discovery and alternative expression. While the course included an introduction to the Galaxy environment, it predominantly focused on the use of command-line tools in the Unix and R environment for carrying out analyses. Data visualization tools were also reviewed. Following the DNA and RNA-seq analysis course segments, two and half days were devoted to pathway and network analysis along with gene function prediction and gene regulation network analysis. Each day consisted of didactic lectures followed by hands-on tutorials using example data sets provided by the course. In the evenings, there were optional hands-on tutorials with additional data sets. Overall, this was an excellent course with outstanding instructors. Basic working knowledge of Unix and R is a prerequisite.
MassBioSciences Career Development WorkshopSponsor/Location: Postdoctoral Associations at Boston Children’s Hospital, Harvard School or Public Health, Tufts University, Dana-Farber Cancer Institute and The Broad Institute hosted at The Broad Institute When: In the SpringThis workshop was organized to bring together area scientists, mostly targeted at postdocs and graduate students. This was a two-day training event to learn about transferable skills, leadership and management styles, non-academic alternative career paths and networking skills. They also provided tools and information to further career development after the workshop.
Strategies and techniques for analyzing microbial population structureSponsor/Location: Marine Biological Laboratories, Wood's Hole, MA. Room/board is provided in class fees. When: Annually in August, 10 days from 8:00 am to 9:00 pm, with one day off.The course is focused on concrete skills for analyzing genomic data of biological populations generated by next-generation sequencing technology ("big data"). The theory, technical aspects, and best practices of data generation and analysis are discussed by experts in the field. Most valuable are the daily programming computer labs with excellent TAs to help with questions. Although prior experience in programming is not required, participants with some familiarity with Unix or R will be able to complete more of the class material.
Note that participants are often accepted after the deadline listed on the website.Contact person for the course if anyone has questions: Ana Weil.
Jonathan Abraham, MD, PhD, 2016 Trainee: Dr. Abraham transitioned to a DP5 award from NIH and a Burroughs-Wellcome Career Award for Medical Scientists. His work focuses on profiling the human antibody response in survivors of viral hemorrhagic fevers and on development of antibody therapies for human viral hemorrhagic fevers and the prevention of late neurological complications of these infections.
Kelly Bachta, MD, PhD, 2014-2016 Trainee: Dr. Bachta has recently begun additional mentored postdoctoral training at Northwestern Memorial Hospital. Under the mentorship of Dr. John Mekalanos, Dr. Bachta’s project focused on the mechanisms of multi-drug resistance in Pseudomonas aeruginosa. Pseudomonas aeruginosa is an opportunistic pathogen that commonly affects immunocompromised hosts including those with cystic fibrosis and neutropenia. These patients tend to receive multiple courses of antibiotics and, as a result, P. aeruginosa is serially exposed to selective pressure to develop and maintain mechanisms of antibiotic resistance. One such mechanism involves the coordination of drug-efflux pumps. P. aeruginosa has several known multi-drug efflux pumps which efflux a variety of antibiotics including beta-lactams, fluoroquinolones and aminoglycosides. Dr. Bachta’s project characterized these efflux pumps with the hope of developing novel inhibitors to expand the array of clinically useful anti-pseudomonal therapies.
Roby Bhattacharyya, MD, PhD, 2012-2013 Trainee: Dr. Bhattacharyya transitioned to a Foundation for Medical Discovery individual fellowship from the Mass General Executive Committee on Research. He is currently a junior faculty member in the Mass General Division of Infectious Diseases.
Dr. Bhattacharyya is working with Dr. Deborah Hung to develop rapid, non-culture based diagnostics for a variety of pathogens and from a range of samples. Dr. Hung has shown that RNA expression signatures can be used to identify a variety of common pathogens rapidly and specifically; the RNA probes used target sequences highly conserved within but not shared between pathogenic species. Moreover, targeting RNA expression signatures of stress response pathways that respond early to antibiotic therapy enables discrimination of susceptible strains from resistant ones. Dr. Bhattacharyya plans (1) To optimize assays for molecular signatures in frequently encountered human pathogens that allow discrimination in patient samples, using nanostring technology, and (2) To characterize the transcriptional response of a panel of frequently encountered human pathogens to an array of antimicrobial compounds. The development of rapid diagnostic methods for important human pathogens has the potential to revolutionize early diagnosis and treatment, particularly in resource-poor settings, with enormous impact on the control and prevention of transmission of infectious diseases. This work has led to one middle-author paper in The Journal of Antibiotics. Dr. Bhattacharyya is the recipient of a KL2 Medical Researcher Investigator Training Award from the Harvard Catalyst and a K08.
Daniel Bourque, MD, 2014-2016 Trainee: Under the mentorship of Dr. Jason Harris, Dr. Bourque is investigating the immune response to cholera. Cholera is a major cause of diarrheal disease globally and accounts for 3 to 5 million cases annually. Dr. Bourque investigates the innate immune response to Vibrio cholerae infection to define the mechanisms that promote long-term immunity from natural infection. The aims of his research are to identify mucosal innate immune pathways and early B cell responses, which lead to the development of long lasting B cell memory after natural infection as compared to oral vaccination. Achieving further insight into the mechanisms of the innate immune response to infection with V. cholerae will provide key insights that may lead to an improved cholera vaccine.
Stephen Carpenter, MD, 2011-2013 Trainee: Dr. Carpenter is a junior faculty member at the University of Massachusetts Medical Center. Under the mentorship of Dr. Samuel Behar, Dr. Carpenter has been investigating the role and function of CD8+ T cells in the adaptive immune response to M. tuberculosis. CD8+ T cells are an important component of the adaptive immune response in the control of pulmonary M. tuberculosis infection, as evidence by increased bacterial burden in the lungs of mice that lack CD8+ T cells. Since the host is unable to clear the bacteria, T cells elicited by M. tuberculosis infection are likely not optimally protective. Over the past year, Dr. Carpenter has been characterizing the mouse response to vaccination with an immunodominant M. tuberculosis secreted antigen (TB10.4). He has found that TB10.44-11 epitope-specific CD8+ T cells elicited by a peptide/Toll-like receptor-agonist/aCD40 injection vaccination strategy are protective, and that this protection appears to be mediated by IFNg secretion from an increased proportion of cells, rather than due to cytolytic molecule production. To comprehensively define functional differences among epitope-specific CD8+ T cells from vaccinated mice, vaccinated/M. tuberculosis-infected mice, and mice challenged with M. tuberculosis alone, he is currently sorting cells for gene expression analysis (Immgen platform).
Yonatan Grad, MD, PhD, 2010-2012 Trainee: Dr. Grad is a faculty member in the Department of Immunology and Infectious Diseases at Harvard School of Public Health. Under the mentorship of Dr. Marc Lipsitch, Dr. Grad investigated the population biology of bacterial pathogens of humans. His work has encompassed three projects:
Dr. Grad’s work has resulted in seven first-author peer-reviewed publications in The American Journal of Epidemiology, The Proceedings of the National Academy of Sciences, Epidemiology, The Journal of Virology, Lancet Infectious Diseases, and mBio and a first-author commentary in mBio. He is the recipient of a K08 award, the New England Regional Center of Excellence in Biodefense and Emerging Infectious Diseases (NERCE) Career Development Award, and the American Sexually Transmitted Disease Association Career Development Award. He gave an invited presentation at the World Health Organization in Geneva on oral cholera vaccine use in epidemic settings.
Michael K. Mansour, MD, PhD, 2011-2013 Trainee: Dr. Mansour holds a faculty position in the Mass General Infectious Diseases Division. Under the mentorship of Dr. Jatin Vyas, Dr. Mansour investigated innate immune interactions with fungal carbohydrate antigens. Despite the significant role carbohydrates play in fungal wall integrity and pathogenesis, the critical steps and contributions made by fungal carbohydrates towards sterilizing anti-fungal immunity have not been defined. Dr. Mansour’s research shows that following macrophage recognition and phagocytosis of beta-glucan, a dominant fungal carbohydrate cell wall component, there is rapid acidification of the phagosome and recruitment of lysosomes in a spleen tyrosine kinase (SYK)-dependent process to these phagosome compartments. These results uncover the critical early steps required by the innate immune system to initiate an anti-fungal carbohydrate-specific response. Dr. Mansour’s contributions to these investigations have led to first-author peer-reviewed publications in mBio and The Journal of Biological Chemistry, and middle-author peer-reviewed publications in Infection and Immunity, Journal of Immunology, The Journal of Infectious Diseases, The Journal of Visualized Experiments, and Integrative Biology. He has given oral presentations of his work at the American Association of Immunology annual meeting, the International Society of Human and Animal Mycology, and Grand Rounds at the American University of Beirut. He was Co-Chair of the 2013 Gordon Research Conference on the Immunology of Fungal Infections.
Dr. Mansour received an Abstract Trainee Award from the American Association of Immunology and the Kass Award for excellence in clinical infectious diseases from the Massachusetts Infectious Diseases Society, as well as a K08.
Kelly Miller, PhD, 2014-2016 Trainee: Under the mentorship of Dr. Marcia Goldberg, Dr. Miller continues her work to characterize interactions of Shigella flexneri and host cells at the molecular level to better understand Shigella pathogenesis. S. flexneri is an intracellular bacterial pathogen that is a significant cause of diarrheal disease worldwide. To establish successful infection bacteria must induce uptake into human colonic epithelial cells, evade host innate immune responses, and spread into neighboring cells within the epithelium. Many steps in this process require the activity of bacterial “effector” proteins that are translocated into host cells using a conserved syringe-like secretion apparatus called a type three secretion system. Dr. Miller is investigating how interaction of bacterial type three secretion system and host proteins interfere with the host cell innate immune response during Shigella infection.
Sungwhan F. Oh, PhD, 2011-2013 Trainee: Dr. Oh transitioned to an individual fellowship from the Crohn’s and Colitis Foundation. Under the mentorship of Dr. Kasper, Dr. Oh has been investigating the role of bioactive lipids in microbiota-host interaction and host immune maturation. Colonization of the gut by commensal microbiota is critical in establishing a healthy host immune system. Considering the important role of bioactive lipid mediators in immune responses, these molecules have been suggested as possibly important messengers driving commensalism-based immune maturation. Lipid mediators can be either microbe- or host derived; hence they might contribute at multiple interfaces between the microbiota and the host. Drs. Oh and Kasper hypothesize that these lipid mediators derived from the host and/or microbe result in signaling to the host immune system. Dr. Oh is investigating these novel lipid mediators and assessing their contribution to both normal immune maturation and upon inflammatory challenges. He is middle author on a paper in Cell.
Dr. Oh received a New Investigator Award from the International Society for the Study of Fatty Acids and Lipids, a Travel Award from the Eicosanoid Research Foundation to attend the 12th International Conference on Bioactive Lipids, an Outstanding Poster Award at the International Winter Eicosanoids Conference, and a K08.
Melisa Osborne, PhD, 2012-2013 Trainee: Dr. Osborne is currently a Postdoctoral Research Fellow at the Rowland Institute. She worked with Dr. Simon Dove to investigate the regulation of gene expression in the pathogenic bacterium Francisella tularensis, the causative agent of tularemia. Her goal was to elucidate the mechanisms by which the putative DNA-binding protein PigR and the tRNA methyltransferase TrmE regulate expression of virulence genes in F. tularensis. In the presence of the small molecule alarmone ppGpp, PigR interacts directly with a complex formed between the proteins MglA and SspA, and this complex is associated with RNA polymerase. Dr. Osborne investigated the mechanisms by which the transferase activity and GTPase activity of TrmE contribute to virulence gene expression.
Anne Piantadosi, MD, PhD, 2016 Trainee: Dr. Piantadosi has transitioned to a KL2 MeRIT fellowship. Under the mentorship of Dr. Pardis Sabeti, she is identifying and characterizing the known and unknown viral pathogens in infectious encephalitis using next-generation sequencing.
Zaida Ramirez-Ortiz, PhD, 2011-2012 Trainee: Under the mentorship of Dr. Joseph El Khoury, Dr. Ramirez-Ortiz investigated the mechanisms by which macrophages and central nervous system endothelial cells interact with the fungal pathogen Cryptococcus neoformans. Professional phagocytes, such as macrophages, are essential in the clearance of Cryptococcus neoformans in the periphery. Macrophages have direct antifungal activity against the yeast, and expression of Toll-like receptors and other Pattern Recognition Receptors allows receptor-mediated endocytosis of the fungal cells. In addition, C. neoformans has evolved mechanisms of evading the effects of macrophages. It is capable of residing inside phagosomal compartments in macrophages, which may contribute to systemic dissemination of the fungus. Brain microvascular endothelial cells have been shown to play a role in C. neoformans pathogenesis during infection of the central nervous system. Brain microvascular endothelial cells binding to C. neoformans can lead to transcellular invasion of the central nervous system. However, the molecular mechanisms involved in the transcytosis of C. neoformans across the blood brain barrier remain to be elucidated.
Drs. Ramirez-Ortiz and El Khoury hypothesized that the scavenger receptor Scarf1 collaborates with Toll-like receptor 2 to mediate transcytosis of C. neoformans. Her work showed that HEK293T cells transfected with Scarf1 are capable of producing IL-8 in response to heat killed C. neoformans, suggesting that the receptor recognizes the pathogenic fungi. She investigated the contributions of Toll-like receptor 2 and Scarf1 in the host response to C. neoformans using mice that lack both. Her work has resulted on one first-author peer-reviewed publication in Nature Immunology. Dr. Ramirez-Ortiz received the FEMS Young Scientist Award and a K01.
Jennifer Reedy, MD, PhD, 2012-2014 Trainee: Dr. Reedy is a junior faculty member in the Mass General Division of Infectious Diseases. Under the mentorship of Dr. Jay Vyas, Dr. Reedy investigated how the innate immune system recognizes and responds to fungal pathogens. Her research focused on the dematiaceous mold Exserohilum rostratum and elucidating the mechanisms by which the innate immune system recognizes and responds to this fungi. Specifically, she analyzed the carbohydrate composition of spores and hyphae of E. rostratum and evaluated the cytokine response elicited by macrophages in response to E. rostratum.
Chanu Rhee, MD, MPH, 2014-2015 Trainee: Dr. Rhee is a faculty member in the Department of Population Medicine, Brigham and Women’s Hospital. Under the mentorship of Dr. Richard Platt, Dr. Rhee focused on studying the epidemiology, surveillance, and prevention of healthcare-associated infections, particularly in critically ill patients. His research project, a multicenter observational study being conducted with the CDC Prevention Epicenters, aimed at improving the public health system’s capacity to accurately track the incidence and burden of severe sepsis and septic shock using objective clinical data captured by electronic health records. In 2015, Dr. Rhee had three first author publications in Critical Care Medicine, Infection Control & Hospital Epidemiology, and Clinical Infectious Diseases, as well as an additional middle author paper in Clinical Infectious Diseases. Dr. Rhee is the recipient of the Thomas Pyle Fellowship, and also a U54 Co-Investigator.
William Robins, PhD, 2012-2013 Trainee: Dr. Robins is an Instructor in Microbiology and Immunobiology at Harvard Medical School. He is working with Dr. John Mekalanos to characterize the transcriptional regulation of V. cholerae, the agent of cholera, during its exit from the host into the environment, with a particular focus on a transient metabolically quiescent state of the organisms. The importance of understanding this state is that where cholera is present, a substantial number of environmental V. cholerae organisms exist as clumps of metabolically-inhibited cells that persist for weeks or months. These conditionally viable environmental cells resist growth using standard methods, but revert to an infectious and virulent form when introduced into animals. Dr. Robins’ goals are to understand the RNA patterns occurring in conditionally viable environmental cells as they form and persist in environmental water and then as they are resuscitated by exposure to autoinducers. He plans to use deep sequencing and RNA-seq on samples obtained through a collaboration with Dr. Shah Faruque at the International Centre for Diarrhoeal Disease Research, Bangladesh and Dr. Stephen Calderwood at Mass General, as well as on samples generated from the laboratory environment. These studies will likely provide important new insights into how V. cholerae survives within the environment, persists, and efficiently re-infects new cholera victims. His work has resulted in one first-author peer-reviewed publication in The Proceedings of the National Academy of Sciences and five middle-author peer-reviewed publications in Nature Biotechnology, Cell Host and Microbe, Infection and Immunity, Microbial Ecology and The New England Journal of Medicine.
Brian Russo, PhD, 2014-2016 Trainee: Under the mentorship of Dr. Marcia Goldberg, Dr. Russo continues working to define molecular mechanisms required for the virulence of the bacterium Shigella, the most common cause of diarrhea among children worldwide. To establish disease Shigella infects epithelial cells lining the intestine and spreads to adjacent cells using actin-based motility. Bacterial effector proteins, delivered into the epithelial cells by Shigella, usurp host signaling to induce macropinocytosis of bacterium by the host cell. These bacterial effector proteins are delivered by Shigella using a highly conserved apparatus known as a type 3 secretion system. Type 3 secretion systems resemble a syringe and are activated upon contact with the host cell membrane. The contribution of host factors to the activity of the type 3 secretion system is poorly understood. The Goldberg laboratory performed a genome-scale selection to identify host genes that contribute to S. flexneri pathogenesis. Dr. Russo is investigating the mechanisms by which genes identified in the selection contribute to S. flexneri infection. His work has resulted in one paper in Nature Microbiology, one in mBio, and one in the Journal Biological Chemistry.
Erica Shenoy, MD, PhD, 2010-2012 Trainee: Dr. Shenoy is currently an Assistant Professor of Medicine, Harvard Medical School, and a faculty member in the Mass General Division of Infectious Diseases. Under the mentorship of Dr. David Hooper, Dr. Shenoy’s research focused on understanding the dynamics and assessment of patient colonization with methicillin-resistant S. aureus (MRSA). Individuals can clear MRSA colonization spontaneously; however, there are currently no formal standardized approaches or generally accepted guidelines for addressing screening for clearance of colonization in the growing pool of patients who have MRSA colonization and/or previous infection. Dr. Shenoy’s research has focused on understanding the dynamics of MRSA colonization and on developing the scientific basis for a streamlined approach to discontinuation of MRSA Contact Precautions. The MRSA Screening Study described in her T32 application was concluded in September 2011 (NCT01234831). In that study, she randomized over 600 patients to either local standard of care or active screening with both culture and PCR methods. The findings from the study have been submitted for publication. In addition to the clinical trial, she has conducted two national surveys to assess the impact of Contact Precautions for MRSA on hospital operations and will begin implementing single PCR for discontinuation of Contact Precautions at pilot sites at Massachusetts General Hospital in the next several months. This work has resulted in first-author peer-reviewed publications in Infection Control and Hospital Epidemiology, BMC Infectious Diseases, The Journal of Clinical Microbiology, and Clinical Infectious Diseases, and middle-author publications in Clinical Infectious Diseases and The Journal of Allergy and Clinical Immunology.
Dr. Shenoy is the recipient of a Mass General Clinical Innovation Award and an NIGMS-supported postdoctoral fellowship from the Harvard Center for Communicable Disease Dynamics. She is co-Principal Investigator on an award from the Center for Integration of Medicine and Innovative Technology, a consortium of Boston-area academic institutions, and is Co-Investigator on an award from the Institute for Health Technology Assessment (inHealth). In addition, she received a Trainee Travel Grant for excellence of her submitted abstract to the 2012 national meeting of the Infectious Diseases Society of America as well as a KL2 Medical Researcher Investigator Training award from the Harvard Catalyst, a Claflin Scholars Award, a K23 and a K01.
Ana Weil, MD, 2014-2015 Trainee: Dr. Weil is currently supported on a K08 and is a junior faculty member in the Mass General Division of Infectious Diseases. Under the mentorship of Drs. Edward Ryan and Regina LaRocque, Dr. Weil investigated factors that modulate the spread of cholera among humans, focusing on the relationship between human gut microbiome species and susceptibility to V. cholerae in household contacts of cholera patients. Analyzing the microbial population structure of samples taken from household contacts of cholera patients, she determined specific bacterial groups associated with a higher likelihood of becoming infected with V. cholerae. She is first author on a publication in the American Journal of Tropical Medicine and Hygiene and a middle author on a publication in mBio.
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