Infectious Disease
Seattle Children's Research Institute1900 9th Ave.
Seattle, WA 98101
(206) 987-2073
Interim Division Chief
Contents
About the Division
The Division of Infectious Disease is committed to providing quality care at Seattle Children's in the area of infectious diseases.
Clinical Programs
The Infectious Disease division provides diagnostic and therapeutic services for children with proven or suspected infectious diseases and treats complicated, chronic or recurrent infections.
Research Programs
Jane L. Burns, MD
Chief, Division of Pediatric Infectious Diseases, Seattle Children’s Hospital
Professor of Pediatrics, University of Washington School of Medicine
Dr. Burns’ primary area of research for many years has been cystic fibrosis (CF) microbiology, including antibiotic resistance and bacterial pathogenesis. Her studies have used both in vitro and in vivo models of infection. Novel methods of in vitro susceptibility testing have been established, including testing drug activity against bacteria grown in biofilms and examining drug bioactivity in the presence of CF sputum. She has worked with both primary CF cells and immortalized cell lines in tissue culture to examine bacterial pathogenesis including attachment, invasion and apoptosis. In vivo experiments use a mouse model of chronic bacterial infections with Pseudomonas aeruginosa and Burkholderia cepacia complex. Recent work is examining the phenotypic and genotypic adaptations of both organisms to growth within the CF airway. Dr. Burns frequently collaborates with clinical and basic science CF researchers at Seattle Children’s Hospital and the University of Washington. In addition, she directs the Center for CF Microbiology at Seattle Children’s Hospital, which is a core laboratory for the CF Foundation Therapeutics Development Network.
Lawrence Corey, MD
Professor, Laboratory Medicine and Medicine
Co-Director, Vaccine & Infectious Disease Institute
Head, Program in Infectious Diseases, 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.
Lisa M. Frenkel, MD
Professor of Pediatrics and Laboratory Medicine
Director of Virology Clinic
Our research focuses on practical questions related to the prevention of HIV-1 infection in infants, mechanisms leading to shedding of virus in adults and treatment of drug-resistant virus in children and adults. Several projects, detailed below, evaluate the selection and dynamics of drug-resistant HIV-1 mutants during antiretroviral therapy (ART) and as a result of peripartum chemoprophylaxis given to women and infants. Our group is also keenly interested in the implementation of interventions to prevent mother-to-child-transmission in resource-strapped communities, and understanding the mechanisms that cause some adults but not others to shed HIV-1 from their in their breast milk or from their genital tract. In addition, we aim to develop and transfer practical and economical assays for HIV-1 detection in infants, and for monitoring treatment and drug-resistant mutants in these communities. Our projects include collaborative studies with colleagues in India, Kenya, Mozambique, Peru, Thailand, the USA and Zimbabwe.
Soren Gantt, MD, PhD
Assistant Professor
One focus of Dr. Gantt’s research is human herpesvirus 8 (HHV-8), the cause of Kaposi's sarcoma (KS). KS is the most common cancer in many parts of Africa, including Uganda, where nearly everyone is infected with HHV-8 by adulthood. Dr. Gantt, along with Dr. Corey Casper and colleagues, is following Ugandan children from birth to determine when HHV-8 infection is acquired. The natural history of primary HHV-8 infection is then evaluated in these children with respect to clinical illness, viral replication patterns, and the development of immune responses. In addition, Dr. Gantt has shown that some drugs used to suppress HIV infection have previously unrecognized activity against HHV-8 replication in vitro. As such, Dr. Gantt is investigating the ability of specific antiretroviral therapy regimens to inhibit HHV-8 replication and their potential to reduce KS incidence among people co-infected with HIV and HHV-8.
In collaboration with Dr. Lisa Frenkel, Dr. Gantt is studying the mechanisms by which infants become infected with HIV through breast milk in Zimbabwe. Breastfeeding now accounts for the majority of mother-to-child HIV transmission, a problem that is complicated by the lack of safe infant feeding options in much of Africa, where HIV prevalence is highest. Drs. Gantt and Frenkel have shown that mastitis, or inflammation of the breast, markedly increases the amount of HIV in breast milk. Furthermore, they discovered that HIV in breast milk is strongly correlated with replication of cytomegalovirus and Epstein-Barr virus, two ubiquitous human herpes group viruses. Ongoing studies are aimed at understanding the role of the infant immune response in the risk of HIV acquisition during breastfeeding.
Lucas Hoffman, MD, PhD
Assistant Professor
We are working to understand why children with chronic lung infections don’t improve with antibiotics as predicted based on our knowledge of the microbes involved. As a paradigm for this problem, we focus on the chronic lung infections in people with the genetic disease cystic fibrosis (CF), infections that usually respond incompletely to antibiotics predicted to be effective against the bacteria we know to be present. They exhibit several other characteristics common to many difficult to treat, chronic lung infections, including the following:
- They frequently include multiple microbial species infecting together, which makes it difficult to know which of these species impact lung disease, either by themselves or by interacting with other, pathogenic microbes.
- The chemical and microbial environment in which these infections occur is probably different from that used in laboratory microbial tests, including the availability of nutrients that impact microbial behavior.
Currently, our laboratory studies the behavior of the microbes causing CF and other chronic lung infections in models that attempt to more closely reflect the airway environment, which includes multiple microbial species, antibiotics, and specific nutrients. We hope to identify new and more effective treatments for children with chronic, polymicrobial lung infections, starting with CF.
Rachel Adria Katzenellenbogen, MD
Assistant Professor
Human papillomavirus (HPV) is the most common sexually transmitted infection, affecting more than 75% of the adult population. HPV is categorized as high-risk or low-risk, based on its association with cancer. Through dysregulation of normal cellular function, high-risk HPV blocks signals for DNA damage, programmed cell death, and cellular arrest, all as a part of its viral life cycle. I am studying the mechanism by which high-risk HPV activates telomerase, and enzyme found normally in stem cells and almost categorically activated in cancers, in order to understand how HPV drives cells to become malignant.
Lakshmi Rajagopal, PhD
Assistant Professor
Our research interest is to understand signaling events that occur during bacterial disease pathogenesis. The human pathogens that we study are Group B Streptococcus (GBS) and Staphylococcus aureus.
GBS is a Gram-positive bacteria that causes invasive infections in human newborns and certain adult populations. Our studies on GBS focus on elucidating the role of a serine/threonine kinase in regulation of adaptive responses and virulence of the organism. We have shown that a serine/threonine kinase called Stk1 regulates de novo purine biosynthesis and toxin expression and is important for virulence of GBS (Rajagopal, et al., J Biol Chem 2003;278:14429-14441; Rajagopal, et al., Mol Microbiol 2005;56:1329-1346; Rajagopal, et al., Mol Microbiol 2006;62:941-957). In recent studies, we have shown that phosphorylation of the two-component regulator CovR by Stk1 eliminates CovR regulation of the GBS toxins. Current studies are focused toward identifying extracellular signals that dictate toxin expression of GBS (Lin, et al., Mol Microbiol 2009;71:1477-1495.
Like GBS, S. aureus is also Gram-positive cocci that can cause severe invasive disease in humans. We have recently begun to explore the role of a serine/threonine kinase homolog in virulence of S. aureus.
Timothy Rose, PhD
Professor
Our 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, we 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. Our research focuses on the Kaposi's sarcoma-associated herpesvirus (KSHV) and its homologs in non-human primates. We 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. We 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.
Craig E. Rubens, MD, PhD
Professor of Pediatrics/Microbiology
Executive Director, Global Alliance to Prevent Prematurity and Stillbirth
Dr. Rubens has a long-standing research program on the molecular pathogenesis of bacterial perinatal infections. Group B streptococci (GBS) are a major cause of perinatal infections, including intrauterine infections, and pneumonia, sepsis and meningitis in newborn infants. Using this organism, he has explored how this pathogen causes disease using molecular techniques, cell, and animal models that emulate human reproductive infections during pregnancy and infection of the neonate during parturition. Molecular approaches are used to identify the genetic and biochemical basis of specific bacterial virulence traits—such as epithelial/endothelial cell entry and transcytosis, evasion of innate immune mechanisms by inhibiting complement activation and phagocytic uptake, and microbial survival in various host environments (bloodstream, reproductive system, and neonatal lung). His laboratory pioneered genetic techniques to identify the genes and biosynthetic mechanisms important for the production of capsular polysaccharide and other virulence traits by GBS. Projects also include characterizing the early stages of bacterial pneumonia by investigating the host/pathogen interactions using genomic and proteomic techniques. This project characterizes the bacterial response to the lung airway, specific traits critical for microbial persistence in the face of lung innate immunity, and has begun to characterize the host airway proteome for the proteins and other factors that contribute to innate immune mechanisms. Recently, his laboratory is developing a model to understand the mechanisms of infection-induced preterm labor and premature birth. This model explores how bacteria ascend in the female reproductive track to incite inflammation during pregnancy that leads to preterm labor and intra-amniotic infection. Insights from the above studies have begun to identify new means of preventing or treating pneumonia, preterm labor, perinatal bacterial infections, and improving reproductive outcomes.
Arnold L. Smith, MD
Professor
Interim Director of the Center for Childhood Infections & Prematurity Research.
The Smith lab seeks to understand the biology of Haemophilus influenzae, a ubiquitous bacterium in humans and the mechanisms it uses in producing mucosal disease of the respiratory tract and sporadic invasive disease. The current focus is on regulation of gene expression, which differs from strain-to-strain and is both stochastic and directed; the role of intermediary metabolism in virulence is emphasized. A wide variety of model systems and techniques is used to gain insight into this bacterium.
Kevin Urdahl, MD, PhD
Assistant Professor
Dr. Urdahl is an attending physician in Pediatric Infectious Diseases at Seattle Children’s Hospital and an Assistant Professor at the University of Washington School of Medicine. He earned his MD and his PhD in Microbiology/Immunology at the University of Minnesota. He completed both his pediatric residency and his Infectious Diseases fellowship at Seattle Children’s Hospital and the University of Washington. Dr. Urdahl’s laboratory is applying recently-developed immunologic tools to the study of tuberculosis in order to gain a better understanding of T lymphocyte-mediated mechanisms that promote protection against tuberculosis and also mechanisms that suppress immunity and help facilitate persistence of the pathogen. The overall goal of this research is to identify strategies that could contribute to the development of an effective vaccine. Recently, his laboratory defined a role for a suppressive subset of T lymphocytes that dampens immunity and prevents the immune system from effectively eradicating the bacteria that causes tuberculosis. Dr. Urdahl is the recipient of a Burroughs Wellcome Fund Career Award in the Biological Sciences.
Thor Wagner, MD
Acting Instructor
My research is focused on pediatric HIV infection, which accounts for 15% of all HIV deaths. I have two specific research questions:
Despite excellent drugs, why can’t we cure HIV? HIV-infected children currently face a lifetime of complicated daily therapy. I hypothesize that there is persistent low-level replication of HIV, especially at peripheral sites where the immune system is most active, such as mucosal surfaces. Specifically, I am looking at HIV in the sputum of children who are receiving state-of-the-art HIV treatment in order to see if there is evidence of ongoing viral replication. I am also exploring whether HIV is propagated within lymphocytes as the cells replicate. Determining how HIV persists despite therapy is a critical first step in developing new strategies to eradicate the virus.
In low-resource settings, why aren’t more children being treated? Effective HIV drugs are increasingly available worldwide, but children are often not started on therapy. A major reason is that there are no simple tests available to diagnose infants with HIV. Existing tests are extremely expensive and can only be done in sophisticated laboratories. As a result, 50% of all HIV-infected children die before they are diagnosed. I am collaborating with a biotechnology company to develop promising new technology that would enable inexpensive “point-of-care” infant HIV testing.
Scott Weissman, MD
Clinical Assistant Professor
Despite being one of the most exhaustively studied free-living organisms in biology, the Escherichia coli bacterium continues to produce a massive burden of disease, including extraintestinal syndromes such as urinary tract infections (UTI) and bloodstream infections. Since the initiation of intrapartum antimicrobial prophylaxis for group B streptococcus during pregnancy, E. coli has become the leading bacterial cause of early-onset sepsis (EOS) in newborns. Now, with ampicillin-resistant rates >80% among E. coli isolates, it remains unclear whether contemporary EOS isolates represent antibiotic-resistant derivatives of the traditional K1-encapsulated clones described in the 1970’s (which would facilitate rapid point-of-care screening tests) or a more diverse array of novel antibiotic-resistant clones like those that have complicated empiric treatment of community-acquired UTI (e.g., Bactrim-resistant ‘clonal group A’).
My lab uses PCR- and sequence-based molecular typing techniques to characterize clinical isolate collections gathered through active and passive surveillance by the NICHD Neonatal Research Network and the Minnesota Department of Health. With the appearance of EOS-associated clones resistant to standard ampicillin/gentamicin combination therapy, this project will inform guidelines for the empiric treatment of early-onset sepsis.
My lab is also using molecular techniques to characterize the spread of plasmid-borne extended-spectrum beta-lactamase (ESBL) enzymes among Enterobacteriaceae. 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). Our molecular typing methods will characterize the dynamics of antibiotic resistance, to distinguish epidemics of resistance genes that spread between plasmids, plasmids that spread between strains, and strains that spread across continents.
Training Programs
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 Training Program website.
Related Links
Contact List
| Name | Title | |
|---|---|---|
| Burns, Jane, MD | Professor and Interim Division Chief | jane.burns@seattlechildrens.org |
| Campbell, Angela, MD | Assistant Professor | angela.campbell@seattlechildrens.org |
| Englund, Janet, MD | Professor | janet.englund@seattlechildrens.org |
| Frenkel, Lisa, MD | Professor | lfrenkel@u.washington.edu. |
| Gantt, Soren, MD, PhD | Assistant Professor | sgantt@u.washington.edu |
| Melvin, Ann, MD | Associate Professor | ann.melvin@seattlechildrens.org |
| Rajagopal, Lakshmi, PhD | Assistant Professor | lakshmi.rajagopal@seattlechildrens.org |
| Rose, Lynn, PhD | Research Associate Professor | lynn.rose@seattlechildrens.org |
| Rose, Timothy M., PhD | Professor | timothy.rose@seattlechildrens.org |
| Rubens, Craig, MD, PhD | Professor; Executive Director, Global Alliance to Prevent Prematurity and Stillbirth | craig.rubens@seattlechildrens.org |
| Smith, Arnold, MD | Professor; Interim Director of the Center for Childhood Infections & Prematurity Research | arnold.smith@seattlechildrens.org |
| Smith, Sherilyn, MD | Associate Professor | ssmit1@u.washington.edu |
| Tamura, Glen, MD | Assistant Professor | gtamura@u.washington.edu |
| Urdahl, Kevin, MD, PhD | Assistant Professor | kurdah@u.washington.edu |
| Van Voorhis, Wesley C., MD, PhD | Associate Professor, Adjunct Associate Professor | wesley@u.washington.edu |
| Wagner, Thor, MD | Acting Instructor | thor.wagner@seattlechildrens.org |
| Weissman, Scott, MD | Clinical Assistant Professor | weissman@u.washington.edu |
| Zerr, Danielle, MD | Associate Professor | danielle.zerr@seattlechildrens.org |