Infectious Disease

Research Activities

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.

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, pregnant women, and immunocompromised hosts. She studies new viral vaccines and novel methods of antiviral therapy for respiratory viruses including influenza, adenovirus, parainfluenza viruses, and respiratory syncytial virus (RSV). Dr. Englund has a longstanding interest in maternal immunization and is a coinvestigator of maternal immunization studies with influenza virus vaccines in Nepal sponsored by the Bill and Melinda Gates Foundation, in collaboration with colleagues at Johns Hopkins and Cincinnati Children’s Hospital, and RSV vaccines in Seattle As a Clinical Associate at Fred Hutchinson Cancer Research Center, she is actively involved in transplant-related protocols with Drs. Michael Boeckh and Alpana Waghmare in studies of the prevention, treatment and outcome of respiratory viral diseases in transplant recipients of all ages./p>

Dr. Englund’s research group at Seattle Children’s Hospital is part of the New Vaccine Surveillance Network of the Centers for Disease Control (2010 ongoing through 2021), participating in respiratory and gastrointestinal viral surveillance in collaboration with Dr. Eileen Klein, Pediatric Emergency Department. This group assesses vaccine effectiveness of rotavirus and influenza virus vaccines in population-based studies of healthy and sick children and is involved in epidemiological studies of other viruses including respiratory syncytial virus, rhinovirus, EVD-68, and norovirus. 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 and characterize viral respiratory diseases in collaboration with investigators including Jane Kuypers, PhD, Dept. of Lab Medicine, University of Washington (UW), Tim Rose, PhD, Dept. of Pediatric Infectious Diseases and Paul Yager, PhD, Dept. of Bioengineering, UW.

Dr. Englund is a frequent speaker at national and international meetings, and 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 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 current member of the Board of Directors and Influenza Working Group of the Infectious Disease Society of America. She received the Pediatric Infectious Disease Society’s Distinguished Physician Award in 2015.

Lisa M. Frenkel, MD
Professor, Pediatrics and Laboratory Medicine, Adjunct Professor, Global Health and Medicine

The Frenkel laboratory’s focuses on four primary areas of research: First, we are working to understand the mechanisms that despite effective antiretroviral therapy that allow HIV infection to persist, and second, elucidate whether HIV proviruses actively modulate CD4 physiology to directly lead to higher rates of cancers (specifically, human papilloma associated cervical cancers). Third, we conduct "translational studies" in adults and children to understand the establishment and dynamics of HIV-drug-resistant reservoirs. Fourth, in collaboration with bioengineers we are working to develop a rapid, affordable point mutation assay for detection of HIV-drug-resistance that should prove useful in both low- and high-resource communities.

A full listing of my journal publications can be found here.

Matthew "Boots" Kronman, MD, MSCE
Associate 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 a vice-chair of the DHHS Panel on Antiretroviral Therapy and Medical Management of HIV-Infected Children: Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection. 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 bacterial disease pathogenesis and pregnancy associated infections that lead to adverse birth outcomes. The human pathogens that she and her lab study include bacterial organisms that infect humans such as Group B Streptococcus (GBS) and more recently, how viruses such as the ZIKA virus causes fetal injury during pregnancy.

While bacteria such as GBS are commensal organisms, these bacteria can become disease-causing pathogens. GBS are commonly found in the recto-vaginal tract of healthy women but infections can lead to preterm births, stillbirths or severe disease in human newborns. GBS can also infect adults that include the elderly, immunocompromised and diabetic individuals. Studies from the Rajagopal’s laboratory determined the hemolytic toxin found in GBS was not a protein, as previously believed, but a different cell structure known as a lipid (https://www.ncbi.nlm.nih.gov/pubmed/23712433). The finding may prevent the development of a vaccine for GBS, because the molecular structure of lipids prevents the toxin from being inactivated by antibodies — the traditional way that vaccines neutralize toxins made of protein molecules. More recently, the group has shown that the GBS hemolytic toxin destroys neutrophils and evades neutrophil extracellular traps in the placenta leading to fetal injury and preterm labor (https://www.ncbi.nlm.nih.gov/pubmed/27819066). Additional studies to understand how GBS causes disease during pregnancy and in neonates are in progress.

Studies from the Rajagopal laboratory also showed that ZIKA virus infections cause fetal injury using pregnant animal model systems (https://www.ncbi.nlm.nih.gov/pubmed/27618651). Further studies to develop therapuetic models to prevent viral infections during pregnancy are in progress.

A complete list of the Rajagopal lab publications can be found here.

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 immunity against Mycobacterium tuberculosis (Mtb) infection to inform the rational design of an effective vaccine. Working in the mouse model of tuberculosis (TB), his laboratory has recently discovered several barriers that restrict T cell-mediated immunity to Mtb in the lung. These include the inhibition of effector T cell priming by regulatory T cells, the failure of terminally differentiated IFN-?-producing T cells to migrate to the site of infection in the lung, and the functional exhaustion T cells that reside within the lung. Having discovered these barriers, our work now focuses on closing the gaps that limit the translation of this knowledge into an effective TB vaccine. We are working to improve the mouse TB model to better reflect human TB and to exploit this model to gain mechanistic insights and identify correlates of protective immunity. Key findings will be then be tested in the context of human TB.

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
Associate 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 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. Specifically, his lab 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’s research has contributed to defining the natural history of primary infection with human herpesvirus 6B (HHV-6B), a virus that infects most people by age 3 years. Her work has also helped define the epidemiology and disease associations of HHV-6B reactivation following transplantation. Dr. Zerr currently leads a trial through Children’s Oncology Group to determine whether bathing with chlorhexidine gluconate reduces central line-associated bloodstream infections in children with cancer. Secondary aims include determining whether use of CHG 1) reduces acquisition of multi-drug resistant organisms and 2) results in increases in CHG MICs and/or resistance to commonly-used antibiotics in cutaneous bacteria. She collaborates with Drs. 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 a 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 acquired across mucosal surfaces such as the gut and the genital tract, Dr. Jaspan has projects 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. She also has two ongoing studies assessing the effects of hormonal contraceptives on mucosal immunity and microbiota. 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.

Ruth Kanthula, MD, MPH
Acting Instructor of Pediatric Infectious Diseases, University of Washington, Seattle Children’s Hospital.

Dr. Kanthula’s research is on HIV drug resistance related to prophylaxis for (1) prevention of mother to child transmission (pMTCT) and (2) pre-exposure prophylaxis (PrEP), in resource limited settings. Working under the mentorship of Lisa Frenkel, her current research focus is on the implementation of the oligonucleotide ligation assay (OLA), an affordable point mutation HIV drug resistance assay, in conjunction with point-of-care viral load testing to improve virologic and clinical outcomes among HIV-infected children receiving care in two East African clinics.

For more information on this specialty, please visit the Infectious Disease webpage.