Division Chief and Professor of Pediatric Infectious Disease Affiliate Investigator, Fred Hutchinson Cancer Research Center Medical Director of Infection Prevention, Seattle Children’s Hospital
The Division of Infectious Disease includes 31 faculty members, including 12 Professors, 9 Associate Professors, 6 Assistant professors and 4 Acting Instructors. The Division is committed to conducting cutting-edge research on infectious diseases relevant to children, delivering the highest quality of clinical care in the area of infectious diseases, and providing world-class education to trainees in pediatric infectious diseases.
The Infectious Diseases Division currently has over 50 active grants. Our faculty are affiliated with the Center for Global Infectious Disease Research and the Center for Clinical and Translational Research at Seattle Children’s Research Institute.
Investigators in CGIDR have made significant contributions to understanding viral and bacterial pathogenesis in children and adults. Most notable findings:
- Dr. Grundner discovered new functions for hundreds of proteins in the dark genomes of Plasmodium falciparum and Mycobacterium tuberculosis using chemical proteomics (Mol Cell Proteomics 2018, Cell Chem Bio 2016).
- Dr. Sodora found that SIV infection results in immune changes and inflammation in the livers of nonhuman primates, these findings provide insights regarding how to treat liver dysfunction in HIV infected patients (PLoS Pathogens, 2018).
- The Kappe and Vaughan group has developed genetically engineered whole cell vaccine strains designed to protect against malaria parasite infection and has shown their safety, immunogenicity and efficacy in controlled human malaria infection trials (Science Transl Med. 2017, Jan 4;9(371). PMID: 28053159 and unpublished).
- The Frenkel group found that during effective antiretroviral therapy (ART) a subset of HIV infected clonal cell populations produce virions at low-levels persistently over years, and when ART is stopped these clones contribute to viral rebound, indicating that despite production of viral antigens HIV infected cell clones comprising the persistent reservoir escape immune surveillance (PLoS Pathogens 2000; https://pubmed.ncbi.nlm.nih.gov/32841299/).
- Drs. Bull and Frenkel found that during ART-suppression discordant shedding of HIV RNA shedding from the genital tract arises from HIV-infected cells producing virions near the limit-of-quantification in association with infected cell proliferation, with no evidence of HIV replication.
- Dr. Smith and Dr. Ying Zheng’s group (UW, Department of Bioengineering) used bioengineered human 3D microvessels to study how Plasmodium falciparum infected red blood cells adhere within the brain microcirculation (Science Advances; 2020 Jan 17;6(3):eaay7243. doi: 10.1126/sciadv.aay7243. eCollection 2020 Jan. PMC6968943 and mBio; 2019. May 28;10(3). pii: e00420-19. doi:10.1128/mBio.00420-19. PMC6538777 )
- Drs. Vaughan and Kappe showed that malaria parasite progeny fight for survival and drive out their parents during competitive blood stage growth (PLoS Genet 2019; 15(10): e1008453).
- Dr. Rajagopal’s group found that the pigment toxin exacerbates infection due to Group B Streptococcus (GBS) and lipid analogs attenuates GBS infection (Sci Immunol 2016;1(4):aah4576; Nat Commun 2020 Mar 20;11(1):1502).
- The Aitchison group, in collaboration with the Sherman lab at UW Microbiology, developed a novel method for single cell analysis of Mycobacterium tuberculosis, which was used to rapidly detect drug resistance in clinical isolates and will be instrumental in understanding the emergence of drug resistance in TB (Elife. 2020 May 13;9:e56613. doi: 10.7554/eLife.56613.)
- The Urdahl lab developed a new mouse tuberculosis (TB) model that reflects key features of human disease, providing new avenues to study TB and to test novel vaccines and therapies (Cell Host Microbe, 2020, in press).
- The Stuart lab identified gene expression changes in response to human infection by or vaccination against malaria, including those associated with immune protection [Rothen J. et al. (2018) PLoS One, PMCID: PMC6007927] and determined the functions of potential drug targets in multiprotein RNA processing complexes [McDermott S.M., et al. (2019) RNA, PMCID: PMC6800513] and of enzymes that control antigenic variation and coordinate numerous cellular processes in lethal trypanosome parasites. [Cestari I. et al. MCB, PMCID: PMC6336139, and Cestari, I. and Stuart, K. PLoS NTD in press}.
- Dr. Harrington found that malaria infection during pregnancy resulted in more maternal cells (maternal microchimerism) trafficking into the fetus and that these cells were associated with increased susceptibility to malaria infection but protection from malaria disease in the offspring (Journal of Infectious Disease, 2017).
- Scientists in the laboratory of Dr. Kaushansky has have developed and adapted new technologies for identifying key host regulators of malaria infection (Arang et al, Nature communications, Glennon et al, Cell Reports). These approaches are currently being applied to investigate regulators of the blood brain barrier (with the laboratory of Dr. Smith), viral infections (with the laboratory of Dr. Aitchison) and mediators of bacterial infections (with the laboratory of Dr. Rajagopal).
Center for Clinical and Translational Research (CCTR):
Divisional investigators in the CCTR have made significant contributions to defining the epidemiology and clinical impact of viral and bacterial pathogens in children and adults. Notable findings:
- Danielle Zerr, Aaron M Milstone, Christopher C Dvorak, Amanda L Adler, Lu Chen, Doojduen Villaluna, Ha Dang, Xuan Qin, Amin Addetia, Lolie C Yu, Mary Conway Keller, Adam J Esbenshade, Keith J August, Brian T Fisher, and Lillian Sung published “Chlorhexidine Gluconate Bathing in Children with Cancer or Receiving Hematopoietic Cell Transplantation: A Double-blinded Randomized Controlled Trial from the Children’s Oncology Group” in Cancer, 2020, under revision
- Dr. Kronman studies antimicrobial stewardship in both inpatient and outpatient settings to identify both ways to improve antibiotic use and unintended harms of antibiotic use. Examples include demonstrating that early life antibiotic use is associated with the development of inflammatory bowel disease (Pediatrics 2012;130(4):e794-e803), describing adverse events associated with prolonged antibiotic use (J Pediatric Infect Dis Soc 2015; 4(2): 119-125), demonstrating that outcomes of appendicitis treatment are equivalent with narrow-spectrum antibiotic therapy (Pediatrics 2016 Jul;138(1)) and involvement in a multi-site randomized trial evaluating a distance learning intervention to reduce antibiotic prescribing for outpatient acute respiratory infections (Pediatrics 2020 Sep 146 (3).
- Dr. Englund, working with Dr. Helen Chu in UW Dept. of Medicine, has studied the diagnosis and transmission of SARS-CoV-2 in the community (Chu et al NEJM 2020; McCulloch et al JAMA Network Open) and in children (Dingens et al Nature Communication 2020 in press). She has worked with obstetrical colleagues to study a novel nanoparticle RSV vaccine in pregnant women (Madhi et al, NEJM in press 2020). She also studies respiratory viral infections in transplant patients and in the community, including studies of community coronaviruses in transplant patients (Ogimi et al, JID 2020), and in infants in Nepal (Uddin CID 2018). She is interested in other viral infections in transplant recipients, pregnant women and infants in studies in Seattle (Murray et al Am J Trop Med, Nepal (Steinhoff et al, Lancet ID 2017; and Alaska (Chu et al JPIDS 2020).
- Drs. Zerr, Kronman and Weissman described the molecular and clinical epidemiology of multi-drug resistant Enterobacteriaceae in US pediatric hospitals and identified that many infections with multi-drug resistant E. coli were community associated (J Ped Inf Dis Soc 2017; Epub ahead of print) and have collaborated on additional epidemiologic studies of antimicrobial stewardship (Pediatr Emerg Care 2018 Jan 2. doi: 10.1097).
- Dr. Melvin demonstrated the safety and efficacy of atorvastatin for treatment of hyperlipidemia in HIV-infected children and youth. Pediatr Infect Dis J 2017; 36:53-60.
The ID division provides an inpatient consultation service and an ambulatory clinic. The clinical team includes 18 faculty members and three advanced practice providers. We have special clinical programs in pediatric HIV and pediatric transplant infectious diseases.
The Pediatric HIV program at Seattle Children's Hospital cares for HIV-infected children and adolescents from all over the state of Washington as well as from eastern Idaho. We also provide consultation to providers in Alaska caring for HIV-infected children. We collaborate with the Maternal Infant Care Center at UWMC in caring for HIV-exposed but uninfected infants. We have been a part of the International Maternal Pediatric Adolescent AIDS Clinical Trials network (previously known as the Pediatric AIDS Clinical Trials Group) funded by the NIH since 1989.
The Pediatric Infectious Disease section works on transplant-related disease prevention and treatment in collaboration with the Fred Hutchinson Cancer Research Center and pediatric transplant services at Seattle Children’s Hospital. Joint efforts in establishing guidelines, protocols, and individualized antibiotic plans are developed and reviewed with multiple services and divisions, including: Pediatric Hematology/Oncology, Immunology, Solid Organ Transplant services (Cardiology, Nephrology, Liver, and Surgery services), and Pharmacy, as well as Antimicrobial Stewardship and Infection Control. A guidebook for approaches to the prevention and treatment of infections in this high-risk population has been developed with the cooperation of these services and made available to the ID service and all health care providers participating in the care of these patients .Pediatric Transplant ID collaborates with the transplant services through direct patient care, discussions, lectures, and patient care conferences.
First formed in 1979, the University of Washington’s Pediatric Infectious Diseases fellowship training program has had a consistent record of success in training leaders focused on basic or translational research pertaining to diseases that affect children, and has graduated a number of fellows who subsequently took on academic leadership positions at their institution such as Division Chief of Pediatric Infectious Diseases or Department Chair of Pediatrics. Approximately 85% of our graduates have remained in academic medicine or worked with governmental institutions including the Centers for Disease Control and Prevention or the National Institutes of Health.
Our three-year program trains approximately 2 fellows per year in clinical pediatric infectious diseases and basic or translational research, with the goal of helping fellows launch academic research careers. Our fellows can select research mentorship from among the many outstanding researchers across the University of Washington, including in the Departments of Internal Medicine, Global Health, or Immunology. Further details on the program can be found here.
John Aitchison, PhD
Co-Director, Center for Global Infectious Disease Research, Seattle Children’s Research Institute, Professor, Pediatrics, Adjunct Professor, Biochemistry, University of Washington.
Dr. Aitchison combines the fields of systems cell biology and infectious disease research to understand fundamental aspects of cellular organization and function and how pathogens disrupt and control these cellular behaviors. His earlier work focused on the development of systems biology approaches that included high throughput ‘omics approaches and computational biology to integrate and interpret large-scale data. His more recent work builds on these advances in the context of infectious diseases to understand the battle between pathogens and host cells and systems, and mechanisms by which pathogens evade host defense. Pathogens under study include yeasts, Mycobacterium tuberculosis, Plasmodium falciparum causing malaria, and viruses.
Marta Bull, PhD
Research Associate Professor of Pediatrics, University of Washington School of Medicine, Seattle Children’s Research Institute.
Persistence of HIV at mucosal sites may provide a significant HIV reservoir even in patients undergoing antiretroviral therapy (ART), and might pose a barrier to a cure. Dr. Bull has been studying factors that promote persistence and replenishment of tissue reservoir that includes defining immunological microenvironments at mucosal sites, assessing viral dynamics, and the contribution of chronic herpes viruses to the maintenance of HIV reservoirs. Co-infection with other chronic viruses, particularly herpesviruses (HSV-1, HSV-2, CMV and EBV) are very common in HIV-infected individuals. Much of Dr. Bull’s work has focused on HIV in the female genital tract where she investigates whether the immune response to these infections maintains HIV tissue reservoirs due to antigen-specific CD4+ T cell proliferation with a subsequent increase in reservoir size. Her 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. 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.
Horacio Duarte, MD
Acting Instructor of Pediatrics, University of Washington, Seattle Children’s Hospital.
Dr. Duarte’s research focuses on improving HIV treatment and prevention efforts in sub-Saharan Africa for children and adults through the use of decision analysis, health economics, and infectious disease modeling methods. To date, this research has focused on evaluating strategies to address HIV drug resistance in resource-limited settings. He is also interested in using value of information analysis to inform the prioritization and design of potential HIV clinical research studies. Dr. Duarte graduated from Harvard College, where he studied biological anthropology, and the University of Texas Medical School at Houston. He completed his pediatric residency and pediatric infectious disease fellowship at the University of Washington/Seattle Children’s Hospital..
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 viruses such as SARS-CoV-2 with the Seattle Flu Study, as well as respiratory vaccines and novel methods of antiviral therapy for respiratory viruses including influenza and respiratory syncytial virus (RSV). Dr. Englund has been a coinvestigator in maternal immunization studies with influenza vaccines in Nepal 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, Chikara Ogimi, 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 since 2010, participating in respiratory and gastrointestinal viral surveillance in collaboration with Dr. Eileen Klein, Pediatric Emergency Department. Dr. Englund and her research team are actively involved in studies of new respiratory vaccines and vaccine effectiveness, including vaccines for the prevention of RSV in infants, children, and pregnant women. Her group is also studying new methods to diagnose and characterize viral respiratory diseases including SARS-CoV-2, including novel types of specimen collection and serological evaluation in collaboration with the CDC-sponsored New Vaccine Surveillance Network, the Seattle Flu Study/SCAN study at the University of Washington, and with Dr. Jesse Bloom’s Laboratory at Fred Hutch. Dr. Englund is a frequent speaker at national and international meetings, and has been active in national and international organizations. 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 and SARS-CoV-2 Diagnosis Working Group of the Infectious Disease Society of America.
Lisa M. Frenkel, MD
Professor, Pediatrics and Laboratory Medicine, Adjunct Professor, Global Health and Medicine
The Frenkel Group performs translational and basic laboratory research focused on HIV drug resistance (DR), HIV persistence and SARS-CoV-2.
Our group’s research on HIV DR aims to understand the establishment and dynamics of DR reservoirs and whether testing for HIV DR prior to antiretroviral therapy (ART) modifies outcomes (Lancet HIV, 2020; https://pubmed.ncbi.nlm.nih.gov/31818716/). Our participation in the NIH International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) since 1989 and expertise in HIV DR has led to us serving as the primary HIV-DR genotyping lab for all US sites and the reference lab for international IMPAACT studies, providing CLIA-certified assays for more than a decade, and consulting work with the CDC and UNAIDS. With UW Bioengineers, our laboratory focuses on developing and validating inexpensive methods to assess HIV drug resistance (EBioMedicine 2019; https://pubmed.ncbi.nlm.nih.gov/31767540/). Our research on mother-to-child transmitted HIV DR uncovered a series of errors across institutions that refuted the concept of transient infant HIV infection (Science 1998; https://pubmed.ncbi.nlm.nih.gov/9582120/) and cemented our insistence on meticulous laboratory quality assurance. Current projects focus on: (1) HIV DR of non-B subtypes to the globally recommended ART (tenofovir + lamivudine + dolutegravir (TLD)), and with abacavir instead of tenofovir in young children; and (2) the development of a economical assay to rapidly detect “virologic failure” (i.e., HIV RNA load >500-1000 copies/mL plasma), and in specimens with failure, detect HIV DR at cost of reagents ≤$10.00/test in <2 hours; supported by two R01 and an IMPAACT award.
Our research on mechanisms underlying HIV persistence despite effective ART has introduced novel concepts to the field: (1) That low-level viremias during ART are primarily comprised of virions with identical env and pol sequences suggesting production by clones of infected cells (Journal Virology, 2005; http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1181593/); (2) That cells with identical viral sequences appear to increase during ART, further supporting clonal proliferation of cells with provirus (Journal Virology, 2013; http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3554159/); (3) That multiple cells have proviruses with identical HIV integration sites into genes, proof of clonal cell populations, which increase during suppressive ART and which tend to persist in genes that control immune functions, the cell cycle or cancers (Science, 2014; http://www.ncbi.nlm.nih.gov/pubmed/25011556); and (4) That during effective ART a subset of HIV infected clones persistently produce virions at low-levels, including variants that contribute to viral rebound when ART is stopped, suggesting that clones that actively produce virus escape immune surveillance and serve as HIV reservoir of persistent infection capable of repopulating the host if ART is suspended (PLoS Pathogens 2000; https://pubmed.ncbi.nlm.nih.gov/32841299/). Current projects include studies of: (1) HIV effects on the outcome of human papilloma virus infections in Ugandan women with uterine cervical dysplasia; (2) differences in HIV reservoirs of South African children and their mothers; and (3) identification of HIV reservoirs that rebound upon suspension of ART and the factors that select for persistence of these reservoirs; supported by three R01 awards.
Along with colleagues in the Center for Infectious Disease Research, our group is conducting studies to discover and validate biomarkers that can be used to identify people prior to infection who upon later infection are likely to experience asymptomatic SARS-CoV-2 infection vs. severe COVID-19 (project financed by Seattle Children’s, with NIH application pending review).
Benjamin Gern, MD
Acting Instructor of Pediatrics, University of Washington School of Medicine, Seattle Children’s Hospital.
Dr. Gern’s research focuses on the spatial organization of the immune response to Mycobacterium tuberculosis (Mtb), the leading cause of infectious mortality. He uses advanced quantitative imaging approaches and more-physiologic murine models to characterize the factors dictating T cell function and trafficking within the context of the pulmonary granuloma. His work has identified the highly-localized role of TGFβ in the inhibition of T cell persistence and function, specifically within Mtb-infected tissues. These concepts learned from mouse models are subsequently tested in non-human primates. With recently developed collaborations, he plans to validate these findings in human tissues, with the ultimate goal of identifying targets for host-directed therapy and informing vaccine design.
Christoph Grundner, PhD
Research Associate Professor, University of Washington School of Medicine, Seattle Children’s Research Institute
Mycobacterium tuberculosis (Mtb) remains the most deadly bacterial pathogen, and rampant drug resistance requires renewed efforts to find new and better therapies. At the core of Mtb’s success as a pathogen lies its ability to sense and adapt to host cues, in particular through sensor protein kinase signaling. The Grundner lab maps these signaling pathways and determines their role in Mtb physiology. These studies provide fundamental insight into Mtb biology and identify new targets for therapeutic interference. Because the Mtb Ser/Thr kinases are related to eukaryotic kinases, we repurpose the extensive pharmaceutical resources developed for targeting human kinases for use against Mtb. A major bottleneck in Mtb research on every level is the large number of genes with unknown function in the Mtb genome. Determining protein function is currently exceedingly slow and proceeds one protein at a time. To scale functional annotation to the level of other -omics approaches, we use activity-based protein profiling combined with mass spectrometry towards high-throughput identification of functions for these unknown proteins. These new tools allow probing of even the most divergent enzyme space and provide a more complete understanding of the genomic dark matter of Mtb.
Whitney Harrington, MD, PhD
Assistant Professor of Pediatrics, University of Washington School of Medicine; Principal Investigator, Center for Global Infectious Diseases, Seattle Children’s Research Institute.
Dr. Harrington’s research focuses on intergenerational immune interactions and their effect on susceptibility to infection during pregnancy and infection. In particular, her lab investigates the role of maternal microchimerism (maternal cells acquired by the fetus in utero) in fetal and infant immune development, early vaccine responses, and susceptibility to infection. She previously demonstrated that maternal malaria was associated with an increase in the number of cells that trafficked to the fetus and that these cells affected later malaria susceptibility in the infant. Current projects in her lab include isolating and phenotyping the maternal cells, determining whether infants acquire a maternal graft with immunologic memory, and whether the maternal cells affect the development of immune responses against malaria, HIV, and CMV in the infant. She collaborates with Drs. Aitchison, Frenkel, Jaspan, Sather, and Sodora within the division.
Rafael E. Hernandez, MD, PhD
Assistant Professor of Pediatrics, University of Washington School of Medicine, Seattle Children’s
Dr. Rafael Hernandez’s research focuses on understanding the pathogenesis of mycobacteria, including both Mycobacterium tuberculosis (MTB) and nontuberculous mycobacteria. His focus is on developing better treatment strategies for both tuberculosis and NTM infections. One aim of his work is to understand how mycobacteria interact with cells of the immune system to promote their own survival and how this interaction induces drug tolerance in mycobacteria, making them more resistant to killing by antibiotics. Recent work has also focused on developing better treatment strategies for NTM. One of these projects uses a modeling approach to identify multidrug regimens which are more effective against NTM, which can be especially problematic in patients with cystic fibrosis or other underlying medical conditions. To conduct these investigations Dr. Hernandez employs a combination of bacterial genetics, microbiology, cellular in vitro and zebrafish animal models. This work will help to facilitate the identification and subsequent development of more effective and shorter treatments for both tuberculosis and NTM disease. Dr. Hernandez works closely with Dr. Sherman in the UW department of microbiology. He also serves as the director of the Cystic Fibrosis (CF) Isolate Core at Seattle Children’s Hospital, which distributes bacterial isolates and performs microbiology testing to facilitate CF research both locally and nationally.
Heather Jaspan, MD, PhD
Associate Professor of Pediatrics, University of Washington School of Medicine; Adjunct Associate Professor, Global Health, Seattle Children’s Hospital, Seattle Children’s Research Institute.
Dr. Jaspan’s research group has a major focus on development of immunity from fetal life until adolescence, with the ultimate goal to design new or improved preventive measures for infectious diseases. in addition to studying infant vaccine-induced immunity, the lab is interested in the interplay between mucosal and systemic immunity and the mucosal microbiome, including that of the infant gut and adolescent genital tract. To this end, the group utilizes a translational approach, combining epidemiological, molecular microbiological, immunological and bioinformatic methods, and supplements this work with mechanistic studies in in vitro and animal models. Dr. Jaspan also has a research team in Cape Town, South Africa where several clinical and translational studies are ongoing.
Stefan Kappe, Ph.D.
Professor and Associate Vice Chair for Basic Research, Department of Pediatrics, University of Washington School of Medicine; Adjunct Professor, Department of Global Health, University of Washington School of Medicine. Associate Director, Center for Global Infectious Disease Research, Seattle Children’s Research Institute.
Dr. Kappe’s research focuses on the biology, immunology and vaccinology of obligate intracellular Plasmodium parasites, which cause malaria, and on the development of interventions that prevent malaria infection. Dr. Kappe is particularly interested in the parasites mosquito stages and pre-erythrocytic stages including sporozoite and liver stage biology, immunology and vaccine design. Both, the sporozoite stage but particularly the elusive liver stage, are challenging to work with and have remained poorly studied. The Kappe laboratory has pioneered functional genomics studies of both sporozoites and liver stages and has thus laid the groundwork for a systems approach to their analysis. The lab works with rodent malaria models and the human malaria parasites Plasmodium falciparum and Plasmodium vivax. Dr. Kappe have made major contributions to the field by elucidating the molecular underpinnings that regulate sporozoite infectivity for the mammalian host, factors that are critical for parasite liver infection and key parasite and host factors that are critical for intrahepatocytic liver stage growth. He has also more recently contributed major findings in the area of host responses to liver stage infection and immunity to malaria parasite liver infection. Finally, Dr. Kappe has pioneered the design of genetically engineered, attenuated parasites for vaccination, which are tested in animal models but also in early phase human clinical studies called controlled human malaria infections. Dr. Kappe partners with biotech for manufacturing of these attenuated vaccine strains and further clinical development.
Alexis Kaushansky, PhD
Associate Professor of Pediatrics, University of Washington School of Medicine; Adjunct Associate Professor, Global Health; Principal Investigator, Seattle Children’s Research Institute; Member Brotman Baty Institute; Member Center for Stem Cell and Regenerative Medicine
Dr. Kaushansky’s research focus is host responses to infection. Her laboratory is particularly interested in how pathogens of global importance alter the biology of their hosts to ensure their own survival. One major effort in the Kaushansky laboratory focuses on how Plasmodium parasites, the causative agent of malaria, alter two major environments after infection: (1) the liver, which is the site of asymptomatic infection and (2) the blood brain barrier, whose breakdown causes the most severe form of malaria pathogenesis, cerebral malaria. By identifying key host regulators of infection and pathogenesis, the Kaushansky lab has identified targeted interventions that can eliminate infection. In addition to uncovering key regulators of malaria infection, research from the Kaushansky lab has also highlighted similarities and differences between the host response to infection by the divergent parasites Toxoplasma gondii and Trypanosoma cruzi. A better understanding of these similarities and differences could lead to broadly applicable interventions that target multiple infections with a single regimen. Acknowledging that the “right tools for the job” are often not available when studying infectious disease, the Kaushansky lab has ongoing efforts that aim to develop technologies that overcome barriers to studying infectious disease. These tools include (1) computational tools to model host and drug responses to infection, (2) robotic systems to automate laborious laboratory tasks and, (3) the development of organs-on-chip systems in collaboration with bioengineers to study infections in vitro in a realistic environment. She collaborates broadly with scientists throughout the University of Washington and internationally. Within the division, she has ongoing research projects with Drs. Sather, Smith, Aitchison and Rajagopal. A list of research 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 Principal 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 infection prevention and antimicrobial stewardship. Outside the Division, he collaborates with researchers 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, Professor of Pediatrics, University of Washington School of Medicine, Seattle Children’s Hospital
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, Englund and Vora.
Peter J Myler, Ph.D.
Professor of Pediatrics, University of Washington School of Medicine, Seattle Children’s Research Institute and Director of the Seattle Structural Genomics Center for Infectious Disease (SSGCID).
The Myler laboratory makes extensive use of genome-scale approaches, such as for genome (re-)sequencing, mRNA profiling (RNA-seq) and chromatin immunoprecipitation using sequencing (ChIP-seq), to investigate the molecular mechanisms underlying transcription and regulation of gene expression during Leishmania differentiation. We are particularly interested in elucidating the role of epigenomic histone and DNA modifications (including the novel DNA base J) in these processes. For the past 20 years, we have been actively involved in structural genomics and Dr. Myler is currently PI and director of the Seattle Structural Genomics Center for Infectious Disease (SSGCID), which is funded under a contract from the National Institute of Allergy and Infectious Diseases (NIAID). The mission of SSGCID is to use X-ray crystallography, Cryo-electron microscopy and NMR spectroscopy to solve the structure of proteins targets in emerging and re-emerging infectious disease organisms, primarily to facilitate development of new therapeutics using structure-based drug design.
Chikara Ogimi, MD
Assistant Professor of Pediatrics, University of Washington School of Medicine, Seattle Children’s Hospital; Research Associate, Fred Hutchinson Cancer Research Center
Dr. Ogimi’s research interests include the study of diagnostic, therapeutic and preventive strategies for respiratory viral infections in children and immunocompromised hosts. Dr. Ogimi’s research has contributed to assessing the clinical impact of seasonal human coronavirus, one of the most common respiratory viruses for these populations. Currently, he is investigating the disease burden of a wider spectrum of respiratory viruses, establishing new endpoints, and evaluating the interaction between respiratory viral infections and antibiotic use in transplant recipients. Dr. Ogimi works closely with Drs. Janet Englund, Alpana Waghmare and Michael Boeckh.
Lakshmi Rajagopal, PhD
Professor of Pediatrics, Adjunct Associate Professor of Microbiology and Global Health, University of Washington School of Medicine, Seattle Children’s Research Institute
Dr. Rajagopal is a Professor of Pediatrics, Adjunct Professor of Microbiology and Global Health at the University of Washington in Seattle, WA. Her laboratory is located at Seattle Children’s Research Institute. Her research interest is to understand virulence mechanisms of human pathogens and their interactions with the host. Her laboratory currently focuses on understanding how virulence factors of Group B Streptococcus (GBS) contribute to stillbirth, preterm birth and neonatal infections. Studies from her laboratory showed that the molecular basis for GBS hemolysis is the ornithine rhamnolipid pigment and increased pigment expression exacerbates GBS virulence. Dr. Rajagopal has received multiple grants from the National Institutes of Health for her GBS research and serves as a permanent member of the Bacterial Pathogenesis Study Section. Recently, Dr. Rajagopal is also involved in efforts to understand how the Zika virus causes fetal injury during pregnancy. The goal of the research in the Rajagopal laboratory is to ultimately translate the research findings into therapeutic measures that can prevent infections during pregnancy.http://www.ncbi.nlm.nih.gov/sites/myncbi/lakshmi.rajagopal.1/bibliography/41150840/public/?sort=date&direction=descending
Jennifer Rathe, MD, PhD
Acting Instructor of Pediatrics, University of Washington School of Medicine, Seattle Children’s Hospital.
I am a Pediatric Infectious Disease physician scientist who evaluates patients with complicated infections and investigates respiratory viral infections. My research focuses on understanding the key interactions of the host-viral interface in pediatric rhinovirus infections in ex-vivo human airway models. With these and future studies, I hope to identify highly impactful therapeutic targets that guide development of treatments to benefit vulnerable populations. I am a recipient of the Stanley and Susan Plotkin / Sanofi Pasteur fellowship Award providing invaluable support of my research.
D. Noah Sather, Ph.D.
Associate Professor, University of Washington School of Medicine, Seattle Children’s Research Institute.
Dr. Sather’s research focuses on the development of vaccines to induce protective antibody responses against disease causing pathogens. A guiding principle of this work is to understand infection-induced antibody responses to serve a natural prototype to guide vaccine development. The two main areas for research are HIV-1 and malaria. His HIV-1 work has helped to define how broadly neutralizing antibodies develop during infection, and his current efforts are focused on understanding the kinetics, dynamics, and evolution of B cell responses to vaccination with HIV-1 Envelope proteins. His malaria work spans two species of malaria-causing parasites: Plasmodium falciparum and Plasmodium vivax. The major areas of this work include identification of new vaccine candidates, optimization of protective responses, and understanding how pre-existing immunity influences vaccine outcomes. Publications: https://pubmed.ncbi.nlm.nih.gov/?term=noah+sather&sort=date
Sherilyn Smith, MD
Professor of Pediatrics, 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 Clinical Skills Learning Specialist at the University of Washington and Aquifer Chief Academic Officer (an educational not for profit). Her research focuses on innovations in medical education.
Joseph D. Smith, PhD
Professor of Pediatrics, University of Washington School of Medicine, Seattle Children’s Research Institute
Dr. Smith’s research is focused on understanding malaria pathogenesis and new approaches to treat vascular dysfunction from hyperinflammatory injury. One focus in his laboratory is to understand how Plasmodium falciparum-infected red blood cells bind to the endothelial lining of different microvascular beds and how this interaction leads to vascular inflammation and leak. His laboratory uses a combination of field-based and laboratory studies to investigate severe malaria. Another research focus is using systems-based approaches to investigate host signaling mechanisms that regulate endothelial barrier properties and evaluating new therapeutic approaches to treat vascular injury. A complete list of Smith lab publications can be found here.
Donald Sodora, PhD
Professor, Center for Global Infectious Disease Research, Seattle Children’s Research Institute, Professor, Pediatrics, Adjunct Professor, Dept. Global Health, University of Washington.
Dr. Sodora’s studies have evaluated the interplay between the host and viral infections. Over the past 20 years the focus of the laboratory has primarily been on understanding transmission and disease progression during HIV infection. These studies have included infants, identifying changes within the infant immune system that may influence whether an exposure to HIV results in a successful infection. More recently, the laboratory has begun to assess host-virus interactions during SARS-CoV-2 (Covid-19) infections. The long-term goal of the ongoing studies is to identify novel approaches for development of vaccines or therapeutic approaches to prevent the spread and disease complications resulting from a viral infection.
Studies in the Sodora laboratory include both animal models and human cohort studies.
Caleb Stokes, MD, PhD
Acting Instructor of Pediatrics, University of Washington School of Medicine, Seattle Children’s Hospital
I am interested in the mechanisms of brain injury caused by infection or inflammation within the central nervous system (CNS). My undergraduate and graduate training was in basic and developmental neurosciences; understanding neural circuits and nervous system dysfunction are some of my primary scientific motivations. As an infectious diseases clinician and translational researcher my career goal is to find ways of enhancing immune protection and limiting the detrimental effects of inflammation in neuronal circuits. I am currently studying how the innate immune system helps control Zika virus infection, using induced neural progenitor cells which are derived from human induced pluripotent stem cells (iPSCs). Using this system, we are able to derive all of the major cell types present in the developing brain, which has allowed us to identify differences in the ways that neural progenitors, neurons and glia respond to viral infection. I am actively engaged in teaching and mentoring activities through Seattle Children’s hospital and my basic science work. I am firmly committed to increasing the number and impact of underrepresented minorities and women in biomedical research and improving equity in medicine.
NIH bibliography: https://www.ncbi.nlm.nih.gov/myncbi/1t3Q9m88doE56/bibliography/public/
Ken Stuart, PhD
Professor, Department of Pediatrics, University of Washington School of Medicine, Seattle Children’s Research Institute
Dr. Stuart’s research is focused on protozoan pathogens and the diseases that they cause. These include malaria which is caused by Plasmodium parasites and three diverse diseases caused by related Trypanosomatid and Leishmanial parasites. His lab investigates Human immune responses to malaria vaccination and infection in order to aid vaccine development. He also investigates fundamental molecular and cellular processes of trypanosomatid parasites in order to elucidate novel molecular functions and identify potential drug targets. Dr. Stuart is well known for his groundbreaking studies of RNA editing, a novel fundamental genetic process. He also led parasite genomics and drug discovery consortia and currently leads a multi-institution U19 research program on human immune responses to HIV, malaria and TB, which is part of the NIH Human Immunology Project Consortium. He has served on NIH study sections and USAID and WHO advisory groups and currently serves on the NIAID council.
Kevin Urdahl, MD, PhD
Professor of Pediatrics and Immunology, University of Washington School of Medicine, Seattle Children’s Research Institute.
Dr. Urdahl’s research is focused on understanding the immunity against Mycobacterium tuberculosis (Mtb) and seeks to inform the rational design of an effective vaccine. He uses advanced immunologic approaches in the mouse Mtb model to identify innate and adaptive mechanisms that promote immunity against Mtb, as well as those that restrict immunity. Recently, his lab has developed a new mouse model, in which mice are infected with an ultra-low dose of Mtb (1-3 founding bacteria), that better recapitulates several features of human TB. They are currently using this model to gain new insights into Mtb immunity and pathogenesis, and also hope to develop this model further as a platform for pre-clinical testing of TB vaccine and therapeutic candidates. Dr. Urdahl is the PI of Cascade IMPAc-TB, a large NIH consortium that seeks to identify mechanisms of immunity against Mtb by integrating animal and human studies. Through this consortium, he collaborates with three clinical sites in Africa and his research in mice is shaped by this crosstalk with human TB research.
Ashley Vaughan, BSc, PhD
Research Assistant Professor, University of Washington School of Medicine; Seattle Children’s Research Institute
Ashley received his PhD from the London School of Hygiene and Tropical Medicine and studies the disease malaria, caused by Plasmodium parasites. He has showed the importance of the parasite’s fatty acid synthetic pathway for sporozoite and liver stage maturation. He also researches how to elicit the most protective immune response after vaccination with genetically attenuated parasites. Ashley has led significant advances in the use of human-liver chimeric mouse models in studying malaria. This includes complete liver stage development and the transition to blood stage malaria in the mouse for the human malarias Plasmodium falciparum and Plasmodium vivax. He has also used this mouse model for the creation of experimental Plasmodium falciparum genetic crosses, a significant advance that will aid in our understanding of Plasmodium falciparum drug resistance. Ashley continues to be fascinated by basic parasite pre-erythrocytic biology and uses rodent malaria and parasite transgenesis to understand how the parasite interacts with its vector and host during sporozoite and liver stage development. Ashley collaborates with Drs. Sather, Kappe and Aitchison.
Surabhi (Sara) Vora, MD, MPH
Associate 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 CAR T-cell and HCT patients. She is an investigator for the International Pediatric Fungal Network as well as the Pediatric Infectious Diseases Transplant Network and involved in multidisciplinary efforts to develop local and national guidance for pediatric patients with COVID-19 infections. Her clinical time is split between the inpatient infectious diseases service and outpatient clinic. 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. Dr. Vora 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
Assistant Professor, Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center
Dr. Waghmare’s research is focused on respiratory viral infections in immunocompetent and immunocompromised adults and children. She is interested in the factors that influence disease severity and progression, with the intent to identify diagnostic, prevention, and treatment strategies. Dr. Waghmare’s focus to date has been 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 and 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’s group is investigating similar markers of disease progression for other respiratory viruses, including parainfluenza viruses and respiratory syncytial virus. Since the onset of the SARS-CoV-2 pandemic, Dr. Waghmare has been evaluating the natural history of infection in a longitudinal surveillance cohort study of individuals at high risk of infection. The goals of the study include understanding the incidence rate, viral shedding duration and re-infection rates as well as defining the kinetics of antibody and T-cell responses in infected individuals.
Dr. Waghmare is also involved in clinical trials for novel antivirals and immune based therapies for the treatment of respiratory viral infections in children and adults.
Thor Wagner, MD
Associate Professor of Pediatrics, University of Washington School of Medicine, Seattle Children’s Hospital
Dr. Wagner’s research is focused on understanding and treating chronic viral infections. His primary focus is pediatric HIV, which accounts for 10% of all HIV deaths. Dr. Wagner has been focused on the mechanisms that allow HIV to persist despite prolonged antiretroviral treatment. This research led Dr. Wagner to focus on treatment strategies that target HIV-infected cells. 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 cells in small and large animal models. His lab has also started to explore cell therapy for other chronic viral infections.
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 Pediatrics, 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 recently led a trial through Children’s Oncology Group to determine whether bathing with chlorhexidine gluconate reduces central line-associated bloodstream infections in children with cancer.
Her clinical time includes inpatient Infectious Diseases consultations and the outpatient Infectious Diseases clinic. In addition, she is the Medical Director for the Infection Prevention Program at Seattle Children’s Hospital. Outside the hospital, she enjoys hiking and cross-country skiing whenever she can find someone to go along. She also loves spending time with her young adult children, spouse, and pups.
The overall goal of our training programs is to train individuals for careers in academic pediatrics who will be skilled investigators and clinical subspecialists. Clinical training is intensive during the first year; our institutions have large patient bases, providing a rich clinical exposure over the six-twelve months of intensive clinical training. Subsequent years are devoted primarily to investigation, with clinics at sufficient frequency to develop a longitudinal perspective on patient management and to maintain clinical skills.
For more information, please visit the Pediatrics Infectious Disease Fellowship webpage
Seattle Children's Research Institute
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