Infectious Disease

Research Activities

Marta Bull, PhD
Research Assistant Professor of Pediatrics, University of Washington School of Medicine, Seattle Children’s Research Institute.

Persistence of HIV in mucosal sites may provide a significant reservoir for HIV, even in patients undergoing ART therapy, and might act as a barrier to a cure. Dr. Bull has been studying factors that promote persistence and replenishment of the reservoir, including defining the immunological environment within mucosal sites, assessing viral dynamics and shedding, and the likely contribution of other chronic or persistent viruses to the maintenance of reservoirs.  Much of Dr. Bull’s work has focused on HIV in the female genital tract, where she is focused on defining immune T cell populations and understanding the factors that affect viral RNA shedding and reservoir maintenance.

Co-infection with other chronic viruses, particularly herpesviruses including HSV-1, HSV-2, CMV and EBV, is very common in HIV-infected individuals. Dr. Bull is investigating the role of these infections in HIV reservoir persistence to investigate the hypothesis that the immune response to these co-infecting viruses results in CD4+ T cell proliferation and a subsequent increase in reservoir size. She is studying the relationship between subclinical herpes shedding and HIV DNA concentration, cytokine production and HIV envelop diversity to gain a better understanding of the role of these coinfections in promoting HIV persistence.

Dr. Bull’s research evaluates the role of CD4+ T regulatory cells in HIV, and is interested in the role of this population of cells in the context of vaccines. She is interested in studying whether antigen given to people can shift their CD4 T cell profile toward a more immunosuppressive state, which would potentially make a vaccine less effective. Given Dr. Bull’s expertise in mucosal tissues and the immunologic environment in mucosal sites, she would be interested in industry collaborations focused on gaining a better understanding of the impact of and interplay between systemic vaccines and mucosal sites.

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 leads the division’s quality improvement program.  Specific projects include increasing compliance with antibiotic toxicity monitoring for inpatients and improving inpatient-to-outpatient transfer of care for patients receiving outpatient parenteral antibiotic therapy.  Dr. Crowell collaborates with Drs. John-Stewart, Benki-Nugent, Melvin and Vora.

Horacio Duarte, MD
Acting Instructor, Pediatric Infectious Diseases, University of Washington School of Medicine, Seattle Children’s Hospital

Dr. Duarte’s research applies methods from decision analysis, health economics, and infectious disease modeling to optimize the treatment and prevention of HIV in Sub-Saharan Africa.  Currently, he is focused on evaluating the cost-effectiveness of various diagnostic and treatment strategies aimed at addressing the challenges posed by HIV drug resistance in Kenya.

Janet Englund, MD
Professor, Department 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  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.

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 RSV, 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.

A full listing of her publications can be found here

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.

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 Mycobacterium tuberculosis (MTB) and related bacteria. In particular, he seeks to understand how mycobacteria interact with cells of the immune system to promote their own survival and in particular how this interaction  induces drug tolerance in mycobacteria, making them more resistant to killing by antibiotics. One focus of his research is focused on understanding the role bacterial efflux pumps play in these processes. To conduct this research Dr. Hernandez employs a combination of bacterial genetics with mammalian cell culture and zebrafish animals models. 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 MTB 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. Dr. Hernandez also serves as the director of the Cystic Fibrosis (CF) Isolate Core at Seattle Children’s Hospital, which distributes bacterial isolates from CF patients to researchers nationally and internationally to facilitate CF 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 pediatric HIV 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 three ongoing studies assessing the effects of hormonal contraceptives and intravaginal practices 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 where she has many outstanding collaborators.

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.

Jairam Lingappa, MD, PhD
Associate Director, International Clinical Research Center (ICRC); Professor of Global Health and Medicine; Adjunct Professor of Pediatrics.

Dr. Lingappa has been a faculty member at the University of Washington since 2004 and is currently a Professor in the Departments of Global Health and Medicine and Adjunct Professor in the Department of Pediatrics.  He received his B.A. in Physics from Swarthmore College, Ph.D. in Biophysics at Harvard University and M.D. at the University of California. He completed residency training in Pediatrics and a fellowship in Pediatric Infectious Diseases at the University of Washington.  From 1998 to 2003, he served as an officer with the US Public Health Epidemic Intelligence Service and subsequently as a medical epidemiologist at the U.S. Centers for Disease Control and Prevention in Atlanta, Georgia. 

Dr. Lingappa’s research is primarily focused on studies in African heterosexual HIV-1 discordant couples: stable couples with one partner HIV-1 infected and the other HIV-1 uninfected.  Over the last decade, he has focused on conducting translational research studies to understand the sexual transmission and pathogenesis of HIV-1 infection and to identify host biological correlates for outcomes from exposure to HIV-1.  In this context he collaborates with US domestic and international researchers to integrate genomics, proteomics and microbiome laboratory studies with state-of-the-art statistical analyses to identify host factors that could be targeted for public health HIV-1 prevention interventions. Most recently his collaborative studies have succeeded in identifying variants in the host gene, CD101, as carrying significant risk of HIV-1 infection.  He is currently funded with through grants from the US National Institutes of Health, and Centers for Disease Control and Prevention.

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 Faculty lead for the research recruitment service for the Institute for Translational Health Sciences of the University of Washington. She collaborates with Drs. Frenkel, Crowell and Vora.

Nicole M. Poole, MD, MPH
Acting Instructor of Pediatric Infectious Diseases, University of Washington School of Medicine

Dr. Poole joined faculty in the Division of Pediatric Infectious Diseases in 2017. She earned an undergraduate degree at the University of Texas at Austin and then attended the University of Texas at Houston for medical school. Dr. Poole also earned a Masters of Public Health with a focus on Global Health Organizations at the University of Texas School of Public Health. She completed pediatric residency at the University of Chicago, and completed pediatric infectious disease fellowship training at the University of Washington.

Dr. Poole’s research area of interest is antimicrobial stewardship in ambulatory settings. Dr. Poole uses epidemiologic and quality improvement research methods to describe antibiotic prescribing patterns, identify targets for improvement, and study interventions to improve the quality of antibiotic use in children. She collaborates with Drs. Zerr, Kronman, and Weissman. Dr. Poole’s clinical time is spent on inpatient Infectious Disease consultations and the outpatient Infectious Disease clinic.

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 therapeutic 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 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, Dr. Rose studies the Kaposi’s sarcoma-associated herpesvirus/human herpesvirus 8 (KSHV/HHV8) and homologs in non-human primates and their transmission and pathogenic role in AIDS-related malignancies, such as Kaposi’s sarcoma.  His current research projects include the identification and characterization of cellular receptors mediating KSHV infection; cell-cell transmission of KSHV infections; the comparative analysis of KSHV and its simian homologs and their role in tumor induction associated with HIV-induced immunosuppression; the characterization of latency and the activating switch to herpesvirus replication; and the development of diagnostic tests for known and emerging viruses of global health importance.

Sherilyn Smith, MD
Professor of Pediatrics, Co-director Pediatric Clerkship, University of Washington School of Medicine, Seattle Children’s.

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 and mentoring for University of Washington medical students. Her research focuses on innovations in medical education. She cares for patients with infectious diseases in both the inpatient and outpatient settings.

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.

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 hematopoietic stem cell transplantation. She is an investigator for the International Pediatric Fungal Network as well as the Pediatric Infectious Diseases Transplant Network.  Her clinical interests include transplant infectious disease, HIV, travel medicine and tuberculosis.  In addition, she serves as a consultant to the Seattle Children’s Hospital Clinical Effectiveness (CE) Program, assisting with the development and implementation of standardized clinical pathways of care for inpatients at Seattle Children’s Hospital. She is Co-Director of the CE program’s Research and Writing Team which works to disseminate learnings from clinical pathways  to quality improvement literature.

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

Thor Wagner, MD
Associate Professor of Pediatrics, University of Washington School of Medicine, Seattle Children’s Hospital

Dr. Wagner’s research is focused on pediatric HIV, which accounts for 10% of all HIV deaths. One of the primary interests of his lab 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? This research compliments Dr. Wagner’s other primary research interest, which is engineering new treatment strategies more likely to cure HIV. Currently Dr. Wagner is developing anti-HIV chimeric antigen receptor (CAR) T cells, which are also resistant to HIV, as a potential strategy to cure HIV. The lab is currently optimizing this approach in vitro and testing CAR T cell sin small and large animal models.

Scott Weissman, MD
Associate Professor of Pediatrics, University of Washington School of Medicine; Medical Director, Antimicrobial Stewardship Program 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. Dr. Weissman currently focuses on leveraging clinical microbiology data to inform antimicrobial stewardship interventions.

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.

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