Serge Barcy, PhD
Research Assistant Professor of Pediatrics, University of Washington School of Medicine, Seattle Children’s Research Institute
Dr. Barcy’s research focuses on characterizing the effector mechanisms involved in the immune control of chronic viral infection. As an immunologist, he has acquired significant expertise and research experience with the immune defenses against viral chronic infections in humans. Dr. Barcy had a unique opportunity as a junior faculty to be part of a successfully funded program project entitled, “Oral pathogenesis and host interactions of KSHV infection.” The main goal of the subproject he supervises, with Dr. Soren Gantt, is to identify the immune correlates in the oral mucosa involved with control of KSHV infection and define the impact of HIV infection. This subproject is based upon Dr. Barcy’s original observation that gamma/delta T cells are involved in the cellular immune response against infection with KSHV. He also supervises the core facility that provides titered virus stocks, KSHV relevant primary and immortalized cell cultures and primary tissue for all of the projects involved in the program project.
Marta Bull, PhD
Research Assistant Professor of Pediatrics, University of Washington School of Medicine, Seattle Children’s Research Institute.
Dr. Bull’s primary research interest includes HIV persistence at mucosal sites with a particular focus on CD4+ T regulatory and memory cells induced by immune responses to chronic infections.. My interest in the mucosal sites are threefold: (1) To define the immunological milieu at mucosal sites and how this pertains to HIV persistence, (2) to evaluate the immune response to chronic viruses, such as herpes simplex virus (HSV) 1, HSV-2, cytomegalovirus (CMV), and Epstein Barr virus and how these contribute to HIV persistence, and (3) to evaluate the viral dynamics and exchange between the genital tract, blood and other tissues. Areas currently under study include the cellular populations associated with HIV shedding from the female genital tract and immune mechanisms that promote HIV persistence at tissue sites as a barrier to a cure for HIV.
Jane L. Burns, MD
Professor of Pediatrics, University of Washington School of Medicine, Seattle Children's
Dr. Burns’ primary area of research for many years has been cystic fibrosis (CF) microbiology, including antibiotic resistance and bacterial pathogenesis. Her studies have used both in vitro and in vivo models of infection. Novel methods of in vitro susceptibility testing have been established, including testing drug activity against bacteria grown in biofilms and examining drug bioactivity in the presence of CF sputum. She has worked with both primary CF cells and immortalized cell lines in tissue culture to examine bacterial pathogenesis including attachment, invasion and apoptosis. In vivo experiments use a mouse model of chronic bacterial infections with Pseudomonas aeruginosa and Burkholderia cepacia complex. Recent work is examining the phenotypic and genotypic adaptations of both organisms to growth within the CF airway. Dr. Burns frequently collaborates with clinical and basic science CF researchers at Seattle Children’s Hospital and the University of Washington. In addition, she directs the Center for CF Microbiology at Seattle Children’s Hospital, which is a core laboratory for the CF Foundation Therapeutics Development Network.
Lawrence Corey, MD
Professor, Laboratory Medicine and Medicine
Adjunct Professor of Pediatrics
Co-Director, Vaccine & Infectious Disease Institute
President and Director, FHCRC
Dr. Corey’s research areas include studies of the immunobiology of HSV, infection and vaccine development for HSV-2, HIV, infections in the bone marrow transplant patient, and the interactions between HSV-2 and HIV-1. Dr. Corey’s major laboratory program involves understanding host responses that influence HSV reactivation and acquisition, with the ultimate goal of developing an effective HSV vaccine. The clinical program in genital herpes includes studies looking at the natural history of subclinical shedding, the transmission of HSV to sexual partners and infants, and the relationship between the host response and viral reactivation of infection. His laboratory also specializes in the detection of antigen specific T cells in mucosal tissues.
Dr. Corey directs a molecular diagnostic laboratory studying novel viral infections, especially in immunocompromised patients. One area of focus is the relationship between viral infection and mortality and graft rejection in transplant patients. Studies examining the relationship between Kaposi’s sarcoma and the acquisition, transmission, and effect of viral replication of HHV-8 are also underway. These studies are performed in collaboration with Dr. Corey Casper and are largely based at the Uganda Cancer Center in Kampala, Uganda.
Dr. Corey is the PI of the NIAID-supported HIV Vaccine Trials Network (HVTN). This is a multi-center, international program for developing and testing candidate HIV vaccines that includes Phase I through Phase III studies.
Janet Englund, MD
Professor of Pediatrics, University of Washington School of Medicine, Seattle Children’s Hospital.
Dr. Englund’s research interests include the study of the diagnosis, prevention and treatment of viral respiratory diseases in children and immunocompromised hosts. As a Clinical Associate at Fred Hutchinson Cancer Research Center, she is actively involved in transplant-related protocols in the prevention and treatment of viral diseases in the transplant recipient. She also studies the development of antiviral resistance and novel methods of antiviral therapy for multiple respiratory viruses including influenza, adenovirus, parainfluenza viruses, and respiratory syncytial virus (RSV). Dr. Englund is interested in maternal immunization and is a coinvestigator of maternal immunization with influenza virus vaccines in Nepal sponsored by the Bill and Melinda Gates Foundation, in collaboration with Drs. Mark Steinhoff, Cincinnati Children’s Hospital, James Tielsch at George Washington University, Joanne Katz at Johns Hopkins University School of Medicine, and Helen Chu and Jane Kuypers at University of Washington.
Dr. Englund’s research group is a member of the New Vaccine Surveillance Network of the CDC, participating in respiratory and gastrointestinal viral surveillance in collaboration with Dr. Eileen Klein, Pediatric Emergency Department, where we work to assess population-based studies of vaccine effectiveness for rotavirus and influenza vaccines. Dr. Englund and her research team are actively involved in studies of new respiratory vaccines and antivirals including vaccines for the prevention of RSV in infants, children, and pregnant women, and antivirals in healthy and immunocompromised children. Her group is also studying new methods to diagnose respiratory diseases in collaboration with Dr. Paul Yager, Dept. of Bioengineering, UW, and Dr. Tim Rose, Dept. of Pediatric Infectious Diseases.
Dr. Englund is active in national and international organizations, including AAP, the CDC-sponsored Advisory Committee on Immunization Practices (ACIP), the FDA Vaccines and Related Biological Products Advisory Committee (VRPBAC), and is a member of the maternal immunization safety group at World Health Organization. She is past president of PIDS, past member of the WHO Influenza working group, and a member of the Board of Directors of the Infectious Disease Society of America. She received the Pediatric Infectious Disease Society’s 2015 Distinguished Physician Award.
Lisa M. Frenkel, MD
Associate Director of the Center for Childhood Infections & Prematurity Research; Professor of Pediatrics, Laboratory Medicine and Global Health, University of Washington School of Medicine.
My work focuses on 3 topics:
First, we aim to understand the mechanisms that allow HIV to persist despite effective ART. We described that transient low-level viremias, or “blips,” during ART were usually comprised of populations of identical env and pol sequences, which suggests that clones of infected cells produced viruses (Journal Virology, 2005). Our subsequent studies revealed that populations of identical viral sequences from the peripheral blood mononuclear cells and sputum (rich in macrophages) increase over a decade in individuals with ART-suppression of viral replication, suggesting that clonal proliferation of cells with provirus sustains HIV infection during suppressive ART (Journal Virology, 2013). And more recently, by documenting that identical HIV env sequences always have identical integration sites in the human genome, and conversely that diverse HIV env sequences always have different integration sites, we proved that HIV-infected cells develop into long-lived clones that persist during ART (Science, 2014). In the latter study we observed that proviruses integrated in proliferating HIV-infected cells in genes controlling immune functions, the cell cycle or cancers had a statistically significant survival advantage over time; suggesting that interference with expression of these genes allows the infected cells to proliferate and/or survive.
Second, we study reservoirs of HIV-drug-resistant variants that influence the efficacy of antiretroviral treatment (AIDS, 2015, in press). We determined that reservoirs of nevirapine-resistant HIV were different in children, with resistant variants persisting for longer periods of time in many infants due to selection during primary infection or transmission of resistant viruses (http://www.ncbi.nlm.nih.gov/pubmed/?term=PMC3038662) and that transmitted HIV drug resistance is increasing rapidly in Kenya (unpublished).
Third, we adapted a low-cost, relative simple assay to detect point-mutations that confer HIV-drug-resistance. We validated reagents across HIV Subtypes, demonstrated the utility of the assay in predicting virologic failure (JAIDS, 2014). Currently, in collaboration with Dr. Michael Chung, we are conducting a randomized-controlled trial in Kenya to evaluate the implementation of this assay prior to 1st-line-ART and determine if it improves virologic suppression; and we are collaborating bioengineering faculty, Drs. Barry Lutz and James Lai, to simplify the assay for point-of-care use.
Sara Healy, MD, MPH
Staff Clinician, Clinical Trials Unit Head, Laboratory of Malaria Immunology and Vaccinology, NIAID/NIH; Clinical Assistant Professor of Pediatrics, University of Washington School of Medicine, Seattle Children’s.
Dr. Healy’s primary area of research is in malaria clinical trials, specifically conducting Phase I/II malaria vaccine trials at the NIH and in Africa and designing and conducting experimental medicine clinical trials to explore malaria stage-specific immunity and attempt to identify novel antigens for future vaccine development. In addition, Dr. Healy has clinical interest in travel medicine and vaccinations.
Matthew "Boots" Kronman, MD, MSCE
Assistant Professor of Pediatrics, University of Washington School of Medicine, Seattle Children’s; Program Director, Pediatric Infectious Diseases fellowship training program; Associate Medical Director of Infection Prevention, Seattle Children’s Hospital.
Dr. Kronman’s primary research interest is antimicrobial stewardship, using the tools of pharmacoepidemiology to understand current patterns of antimicrobial use, identify the unintended consequences of antimicrobial overuse, and ultimately find ways to improve the overall quality of antimicrobial prescribing for various conditions. His clinical time is split between inpatient Infectious Diseases consultations and the outpatient Infectious Diseases Clinic. . He works closely with Dr. Frenkel, the Research Director and Training Grant Principle Investigator, to coordinate all aspects of research training for our fellows. Within the Division, he collaborates with Drs. Zerr and Weissman on projects related to resistant Enterobacteriaceae infections in children. Outside the Division, he collaborates with researchers at the University of Washington (Drs. Rita Mangione-Smith and Tamara Simon) and at other institutions on projects related to antimicrobial stewardship in both inpatient and outpatient settings.
Ann Melvin, MD
Clinical Director, Associate Professor of Pediatrics, University of Washington School of Medicine, Seattle Children’s
Dr. Melvin is director of the Pediatric HIV program at SCH. Her research interests are in the antiretroviral management of HIV disease in children and prevention and management of complications of HIV treatment. Dr. Melvin is principle investigator of the International Maternal Pediatric Adolescent AIDS Clinical Trials unit at the Seattle Children’s Research Institute, sponsored by the NIH. She is also the Senior Faculty Director for Clinical Resources of the Institute for Translational Health Sciences of the University of Washington. She collaborates with Drs. Frenkel, Crowell, Englund and Corey.
Lakshmi Rajagopal, PhD
Associate Professor of Pediatrics, Adjunct Associate Professor of Microbiology and Global Health, University of Washington School of Medicine, Seattle Children’s Research Institute
Dr. Rajagopal’s research interest is to understand signaling events that occur during bacterial disease pathogenesis. The human pathogens that she and her lab study are Group B Streptococcus (GBS) and Staphylococcus aureus. Although both GBS and S. aureus are commensal organisms, these bacteria can also become disease-causing pathogens. GBS are commonly found in the recto-vaginal tract of healthy women but can cause severe invasive disease in human newborns and adults that include elderly, immunocompromised and diabetic individuals. Their studies on GBS are focused on understanding how these bacteria adapt to the environmental niches encountered during their life cycle. Studies from their research have shown that GBS encodes signaling factors such as a serine/threonine kinase; these proteins were previously thought only to exist in higher forms such as eukaryotic organisms. Their research showed that the kinase regulates the expression of the GBS toxin known as hemolysin/cytolysin and also enables the bacteria to adapt to nutrient starvation. In recent studies, they demonstrated that the kinase affects toxin expression based upon its interaction with a DNA-binding response regulator known as CovR. The interaction between the kinase and CovR represents novel findings in bacterial environmental adaptation. Current research is focused toward identifying the environmental cues/signals that are sensed by these bacteria for regulation of toxin expression and virulence. Like GBS, S. aureus are also Gram-positive bacteria that can cause severe invasive disease in humans. They have recently identified a number of novel genes/signaling factors that regulate toxin expression in S. aureus. Current studies are focused on elucidating how these signaling factors regulate toxin expression and S. aureus virulence. The ultimate goal is to use the information gathered from their research to identify novel compounds that can be used to treat these bacterial infections.
Timothy Rose, PhD
Professor of Pediatrics, Adjunct Professor in the Department of Epidemiology and Institute of Public Health Genetics, School of Public Health and Community Medicine, Departments of Oral Biology, School of Dentistry, Epidemiology, and Microbiology, University of Washington School of Medicine, Seattle Children's Research Institute.
Dr. Rose’s and his lab’s research is focused on herpesviruses implicated in cellular transformation and tumor induction, and in the study of host and viral proteins that mediate these effects. In particular, they are studying the viral etiology of Kaposi's sarcoma (KS) and other AIDS-related malignancies with regards to the interactions between viruses (retroviruses and herpesviruses) and cytokines in virus activation and tumor induction. Their research focuses on the Kaposi's sarcoma-associated herpesvirus (KSHV) and its homologs in non-human primates. They discovered the macaque homolog of KSHV and are studying its association with a Kaposi’s sarcoma-like malignancy in macaques, called retroperitoneal fibromatosis (RF), which like AIDS-KS is associated with a retrovirus infection. RF occurs in conjunction with simian AIDS (SAIDS) caused by infection with simian retrovirus 2 (SRV2) or SIV, the simian homolog of HIV. They have identified a second lineage of KSHV-like rhadinoviruses in macaques and are studying its role in RF and other macaque tumors. Ongoing projects include the cloning and sequence of the genome of the new macaque herpesvirus, the identification and characterization of cellular receptors mediating infection by KSHV, the comparative analysis of KSHV and its simian homologs and their role in tumor induction in association with HIV-induced immunosuppression, the characterization of latency and the activating switch to herpesvirus replication, and the development of diagnostic tests for novel viruses.
Sherilyn Smith, MD
Professor of Pediatrics, Co-director Pediatric Clerkship, University of Washington School of Medicine, Seattle Children’s. Dr. Smith’s interests are in medical education, teaching and curriculum development. She is currently the Co–Director of the Medical Student Education Programs for the Department of Pediatrics. Her primary responsibilities are curriculum development, coordination of medical student teaching & faculty development, career advising/mentoring for University of Washington medical students
Kevin Urdahl, MD, PhD
Associate Professor, Center for Infectious Disease Research Affiliate Associate Professor of Immunology and Global Health, University of Washington; Clinical Associate Professor of Pediatrics, University of Washington/Seattle Children’s Hospital
Dr. Urdahl’s research is focused on understanding T cell mediated immunity during Mycobacterium tuberculosis (Mtb) infection, including understanding the factors that promote vs. restrict immune protection. His laboratory has recently discovered that antigen-specific natural regulatory T cells expand during early tuberculosis and impair immunity by inhibiting the priming of effector T cells in the lung draining lymph node. Currently, they are studying how these cells are induced, how they affect T cell priming, and also how they impact and are impacted by vaccination. The lab is also studying how protective CD4 T cell responses are maintained throughout chronic infection with Mtb. They have acquired a wide array of reagents and methodologies for tracking Mtb-specific T cell responses, including the use of Mtb-specific MHC class I and class II tetramers, advanced tetramer-based enrichment techniques for tracking rare populations of antigen-specific T cells, and adoptive transfer of CD4+ T cells from Mtb-specific, T cell receptor transgenic mice. They believe that enhanced understanding of the basic biology of the immune response to Mtb will be critical for the development of an effective vaccine strategy. In the future, they plan to confirm and advance the discoveries they have elucidated in the mouse model in human populations immunized against and/or infected with Mtb.
Thor Wagner, MD
Assistant Professor of Pediatrics, University of Washington School of Medicine, Seattle Children’s.
Dr. Wagner’s research is focused on pediatric HIV, which accounts for 15% of all HIV deaths. His primary interest is understanding chronic HIV infection during antiretroviral therapy. Specifically, why doesn’t antiretroviral therapy eradicate HIV infection? Is there ongoing viral replication? Is there proliferation of cells with viable proviral HIV? Can we identify the remaining infected cells? Is immune tolerance to HIV a barrier to an HIV cure? Answers to these questions should help design new treatment strategies more likely to cure HIV. Dr. Wagner’s other research interest is improving infectious disease diagnostics in low resource settings. Specifically, he is working to develop a point-of-care diagnostic test for infant HIV. Currently there is no simple test to diagnose infants with HIV, and 50% of HIV-infected children die before they can be diagnosed. To accomplish this, he is utilizing state-of-the-art monoclonal antibody screening technology to optimize the sensitivity of immunoassays to detect HIV antigens.
Scott Weissman, MD
Assistant Professor of Pediatrics, University of Washington School of Medicine, Seattle Children’s Hospital.
Since 2000, we have witnessed the worldwide emergence of Gram-negative 'superbugs' such as E. coli ST131 and Klebsiella pneumoniae ST258 which not only encode multiple virulence factors associated with extraintestinal disease, but also Class A enzymes that hydrolyze third-generation cephalosporins and carbapenem antibiotics (CTX-M-15 and KPC, respectively). Dr. Weissman’s lab has developed and used PCR- and sequence-based molecular typing techniques to characterize clinical isolate collections gathered through active and passive surveillance by NIH-funded multicenter studies at freestanding children’s hospitals, the NICHD Neonatal Research Network, and by local and state Departments of Health in California, Minnesota, Oregon and Washington. Specifcally, his lab has developed molecular techniques to characterize the complex spread of plasmid-borne extended-spectrum beta-lactamase (ESBL) and carbapenemase enzymes among Enterobacteriaceae. These molecular studies have shed light on the regional dynamics of antibiotic resistance, a complex mix of autochthonous (“indigenous”) and imported pathogens that circulate through healthy and vulnerable populations alike, both in community and healthcare settings, and will inform the development of “One Health” surveillance systems that may provide for inference of molecular dynamics from pooled clinical microbiology data.
Danielle Zerr, MD, MPH
Division Chief and Professor of Pediatric Infectious Diseases, University of Washington School of Medicine; Affiliate Investigator, Fred Hutchinson Cancer Research Center; Medical Director of Infection Prevention, Seattle Children’s Hospital.
Dr. Zerr’s research has focused on two main areas: (1) Defining the epidemiology of viral pathogens in healthy children and immunocompromised hosts and (2) describing the epidemiology and defining effective prevention strategies for healthcare-associated infections, Dr. Zerr collaborates with Dr. Weissman in investigating the molecular epidemiology of broad-spectrum beta-lactam resistance in pediatric Enterobacteriaceae infections. Currently, they lead a multi-center surveillance study that will result in integrative analyses of patient characteristics, bacterial phylogenetics, and molecular resistance mechanisms in order to better target prevention strategies. Dr. Zerr also leads a trial through Children’s Oncology Group to determine whether bathing with chlorhexidine gluconate reduced central line-associated bloodstream infections in children with cancer. She collaborates with Drs. Corey, Boeckh, Englund, and Weissman.
Claudia Crowell, MD, MPH
Assistant Professor of Pediatrics, University of Washington School of Medicine, Seattle Children’s Hospital, Infectious Diseases QAPI Program Director.
Dr. Crowell’s primary research interests are management of pediatric HIV, and prevention and treatment of complications of HIV and its treatment. She is co-investigator of the International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) unit at Seattle Children’s Research Institute. Dr. Crowell is also a member of the Pediatric HIV/AIDS Cohort Study. She is currently involved in several international and domestic studies examining the neurodevelopmental outcomes of HIV-infected and HIV-exposed uninfected children and studying potential interventions to improve long-term neurodevelopment in these children. Dr. Crowell also serves as a consultant to the Seattle Children’s Hospital Clinical Effectiveness program, assisting with the development and implementation of clinical pathways of care for patients at Seattle Children’s Hospital. She is co-director of the Clinical Effectiveness Research & Writing Team, which aims to publish quality improvement work related to clinical pathways. Dr. Crowell collaborates with Drs. John-Stewart, Benki-Nugent, Melvin and Vora.
Surabhi (Sara) Vora, MD, MPH
Assistant Professor of Pediatrics, University of Washington School of Medicine, Seattle Children’s Hospital.
Dr. Vora’s primary research area of interest is infections in immunocompromised hosts, especially viral and fungal infections in patients with immune deficiency and those who have undergone hematopoetic stem cell transplantation. She is principal investigator for the International Pediatric Fungal Network. Her clinical interests include viral and fungal infections, HIV, travel medicine and tuberculosis. In addition, she serves as a consultant to the Seattle Children’s Hospital Clinical Effectiveness Program, assisting with the development and implementation of clinical pathways of care for inpatients at Seattle Children’s Hospital. She is Co-Director of the Clinical Effectiveness Program Research and Writing Team which works to disseminate the learnings from Clinical Standard Work to quality improvement literature.
Rafael E. Hernandez, MD, PhD
Acting Instructor Pediatrics, University of Washington School of Medicine, Seattle Children’s
Dr. Rafael Hernandez’s research focuses on understanding the pathogenesis of mycobacteria, including tuberculosis and related bacteria. In particular, he seeks to understand how mycobacteria interact with cells of the immune system to promote their own survival and how this interaction can induce drug tolerance in mycobacteria, making them more resistant to killing by antibiotics. He is particularly interested in the role that bacterial efflux pumps play in virulence and also in antibiotic tolerance. The hope is that by better understanding these mechanisms we will be able to devise more effective and shorter treatments for Tuberculosis. Recent work has also focused on applying new insights from studies on M. tuberculosis to developing better treatments for nontuberculosis mycobacteria (NTM) which can be especially problematic in patients with cystic fibrosis or other underlying medical conditions. Dr. Hernandez works closely with Dr. Sherman at the Center for Infectious Diseases Research.
Heather Jaspan, MD, PhD
Assistant Professor of Pediatrics and Global Health.
The Jaspan lab focusses on prevention of HIV infections in infants and adolescents, including the study of immune correlates of protection and vaccine responses in children. Since HIV in children is primarily acquiired across mucosal surfaces such as the gut and the genital tract, Dr. Jaspan has projects focussing on mucosal immunity and its interaction with the microbiome at these surfaces. Further projects study factors influencing vaccine immunity in infants born to HIV-infected mothers, since these infants would be targets for an HIV vaccine. These include studies on the relationship between the gut microbiome and vaccine responses, and the effect of potential suppressor or regulatory cells. Her clinical site is in Cape Town, South Africa, where there is high HIV prevalence, yet strong research infrastructure and collaborators.
Alpana Waghmare, MD
Assistant Professor of Pediatrics, University of Washington School of Medicine, Seattle Children’s Hospital
Research Associate, Fred Hutchinson Cancer Research Center
Dr. Waghmare’s research is focused on respiratory viral infections in immunocompromised adults and children. She is interested in the factors that influence disease progression, with the intent to identify diagnostic, prevention, and treatment strategies. Currently she is focused on the impact of human rhinovirus, the most common virus detected from respiratory specimens in hematopoietic cell transplant recipients. She is working to identify clinical, viral, and host factors that may serve as biomarkers for disease severity. Viral factors she is evaluating include viral load in blood or respiratory secretions, strain type, and shedding duration. Host factors are being evaluated through host cytokine responses and whole blood gene expression profiles. These determinants of disease will serve as biomarkers for risk stratification and can be used diagnostically to predict poor outcome, thus defining patients who warrant aggressive treatment strategies. Additionally, these studies will provide important insight into biologic pathways during infection and define possible targets for intervention. Dr. Waghmare is also involved in clinical trials for novel antivirals for treatment of respiratory viral infections in immunocompromised hosts. Dr. Waghmare works closely with Drs. Janet Englund and Michael Boeckh.
For more information on this specialty, please visit the Infectious Disease webpage.