Profile

Craig E. Rubens, MD, PhD

Craig E. Rubens, MD, PhD

Infectious Disease

On staff since July 1984

Children's Title: Executive Director, Global Alliance to Prevent Prematurity and Stillbirth (GAPPS)

Academic Title: Affiliate Professor of Global Health, Affiliate Professor of Pediatrics, University of Washington School of Medicine

Research Center: Center for Global Infectious Disease Research

"When I had just started my pediatric residency, my first clinical rotation was in the neonatal intensive care unit. This was the same month my second child, Brandon, was born. I witnessed infants dying in their fathers' arms, due to infections and premature birth, and couldn’t help relate to the sense of loss and what it would mean to those families forever. I devoted my career at that point to understanding why infections during pregnancy and the first few months of life happened, how they led to disease like preterm birth and stillbirths, and set out to find out how best to stop these terrible outcomes from happening. Over the years, I have learned that the best solutions to provide outstanding patient care come from better knowledge generated by research and that answers to complex health issues rely on teamwork and collaboration at several levels to make an impact. "

Making A Difference

Overview

Board Certification(s)

Pediatrics

Medical/Professional School

University of South Carolina School of Medicine, Columbia, Immunology and Microbiology
University of Washington, Seattle

Residency

Pediatrics, Children's Hospital and Regional Medical Center, Seattle

Clinical Interests

Prevention of Prematurity

Research Description

I have 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, I have 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).

My 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, my 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.

Lab URL

http://www.gappsseattle.org/

Research Focus Area

Host: Pathogen Interaction

Awards and Honors

Award Name Award Description Awarded By Award Date
U.S. News Top Doctor U.S. News and World Report 2012

Publications

  • Lawn JE, Gravett MG, Nunes TM, Rubens CE, Stanton C
    Global report on preterm birth and stillbirth (1 of 7): definitions, description of the burden and opportunities to improve data.
    BMC pregnancy and childbirth , 2010 Feb. 23 : S1
  • Gravett MG, Rubens CE, Nunes TM
    Global report on preterm birth and stillbirth (2 of 7): discovery science.
    BMC pregnancy and childbirth , 2010 Feb. 23 : S2
  • Barros FC, Bhutta ZA, Batra M, Hansen TN, Victora CG, Rubens CE
    Global report on preterm birth and stillbirth (3 of 7): evidence for effectiveness of interventions.
    BMC pregnancy and childbirth , 2010 Feb. 23 : S3
  • Victora CG, Rubens CE
    Global report on preterm birth and stillbirth (4 of 7): delivery of interventions.
    BMC pregnancy and childbirth , 2010 Feb. 23 : S4
  • Sather M, Fajon AV, Zaentz R, Rubens CE
    Global report on preterm birth and stillbirth (5 of 7): advocacy barriers and opportunities.
    BMC pregnancy and childbirth , 2010 Feb. 23 : S5
  • Kelley M, Rubens CE
    Global report on preterm birth and stillbirth (6 of 7): ethical considerations.
    BMC pregnancy and childbirth , 2010 Feb. 23 : S6
  • Rubens CE, Gravett MG, Victora CG, Nunes TM
    Global report on preterm birth and stillbirth (7 of 7): mobilizing resources to accelerate innovative solutions (Global Action Agenda).
    BMC pregnancy and childbirth , 2010 Feb. 23 : S7
  • Ventura CL, Higdon R, Hohmann L, Martin D, Kolker E, Liggitt HD, Skerrett SJ, Rubens CE
    Staphylococcus aureus elicits marked alterations in the airway proteome during early pneumonia.
    Infection and immunity , 2008 Dec. : 5862-72
  • Siboo IR, Chaffin DO, Rubens CE, Sullam PM
    Characterization of the accessory Sec system of Staphylococcus aureus.
    Journal of bacteriology , 2008 Sept. : 6188-96
  • Ventura CL, Higdon R, Kolker E, Skerrett SJ, Rubens CE
    Host airway proteins interact with Staphylococcus aureus during early pneumonia.
    Infection and immunity , 2008 Mar. : 888-98
  • Jones AL, Mertz RH, Carl DJ, Rubens CE
    A streptococcal penicillin-binding protein is critical for resisting innate airway defenses in the neonatal lung.
    Journal of immunology (Baltimore, Md. : 1950) , 2007 Sept. 1 : 3196-202
  • Rantanen MK, Lehtiö L, Rajagopal L, Rubens CE, Goldman A
    Structure of the Streptococcus agalactiae family II inorganic pyrophosphatase at 2.80 A resolution.
    Acta crystallographica. Section D, Biological crystallography , 2007 June : 738-43
  • Rantanen MK, Lehtiö L, Rajagopal L, Rubens CE, Goldman A
    Structure of Streptococcus agalactiae serine/threonine phosphatase. The subdomain conformation is coupled to the binding of a third metal ion.
    The FEBS journal , 2007 June : 3128-37
  • Braff MH, Jones AL, Skerrett SJ, Rubens CE
    Staphylococcus aureus exploits cathelicidin antimicrobial peptides produced during early pneumonia to promote staphylokinase-dependent fibrinolysis.
    The Journal of infectious diseases , 2007 May 1 : 1365-72
  • Rajagopal L, Vo A, Silvestroni A, Rubens CE
    Regulation of cytotoxin expression by converging eukaryotic-type and two-component signalling mechanisms in Streptococcus agalactiae.
    Molecular microbiology , 2006 Nov. : 941-57
  • Rantanen MK, Lehtiö L, Rajagopal L, Rubens CE, Goldman A
    Crystallization and preliminary crystallographic analysis of two Streptococcus agalactiae proteins: the family II inorganic pyrophosphatase and the serine/threonine phosphatase.
    Acta crystallographica. Section F, Structural biology and crystallization communications , 2006 Sept. 1 : 891-4
  • Clancy A, Loar JW, Speziali CD, Oberg M, Heinrichs DE, Rubens CE
    Evidence for siderophore-dependent iron acquisition in group B streptococcus.
    Molecular microbiology , 2006 Jan. : 707-21
  • Tettelin H, Masignani V, Cieslewicz MJ, Donati C, Medini D, Ward NL, Angiuoli SV, Crabtree J, Jones AL, Durkin AS, Deboy RT, Davidsen TM, Mora M, Scarselli M, Margarit y Ros I, Peterson JD, Hauser CR, Sundaram JP, Nelson WC, Madupu R, Brinkac LM, Dodson RJ, Rosovitz MJ, Sullivan SA, Daugherty SC, Haft DH, Selengut J, Gwinn ML, Zhou L, Zafar N, Khouri H, Radune D, Dimitrov G, Watkins K, O'Connor KJ, Smith S, Utterback TR, White O, Rubens CE, Grandi G, Madoff LC, Kasper DL, Telford JL, Wessels MR, Rappuoli R, Fraser CM
    Genome analysis of multiple pathogenic isolates of Streptococcus agalactiae: implications for the microbial "pan-genome".
    Proceedings of the National Academy of Sciences of the United States of America , 2005 Sept. 27 : 13950-5
  • Cieslewicz MJ, Chaffin D, Glusman G, Kasper D, Madan A, Rodrigues S, Fahey J, Wessels MR, Rubens CE
    Structural and genetic diversity of group B streptococcus capsular polysaccharides.
    Infection and immunity , 2005 May : 3096-103
  • Clancy A, Lee MH, Jones AL, Rubens CE
    Construction and characterization of transposon TnphoZ for the identification of genes encoding exported proteins in Streptococcus agalactiae.
    FEMS microbiology letters , 2004 Dec. 15 : 257-64
  • Vann WF, Daines DA, Murkin AS, Tanner ME, Chaffin DO, Rubens CE, Vionnet J, Silver RP
    The NeuC protein of Escherichia coli K1 is a UDP N-acetylglucosamine 2-epimerase.
    Journal of bacteriology , 2004 Feb. : 706-12
  • Borchardt SM, Foxman B, Chaffin DO, Rubens CE, Tallman PA, Manning SD, Baker CJ, Marrs CF
    Comparison of DNA dot blot hybridization and lancefield capillary precipitin methods for group B streptococcal capsular typing.
    Journal of clinical microbiology , 2004 Jan. : 146-50
  • Shelver D, Rajagopal L, Harris TO, Rubens CE
    MtaR, a regulator of methionine transport, is critical for survival of group B streptococcus in vivo.
    Journal of bacteriology , 2003 Nov. : 6592-9
  • Jones AL, Needham RH, Rubens CE
    The Delta subunit of RNA polymerase is required for virulence of Streptococcus agalactiae.
    Infection and immunity , 2003 July : 4011-7
  • Rajagopal L, Clancy A, Rubens CE
    A eukaryotic type serine/threonine kinase and phosphatase in Streptococcus agalactiae reversibly phosphorylate an inorganic pyrophosphatase and affect growth, cell segregation, and virulence.
    The Journal of biological chemistry , 2003 Apr, 18 : 14429-41
  • Jones AL, Needham RH, Clancy A, Knoll KM, Rubens CE
    Penicillin-binding proteins in Streptococcus agalactiae: a novel mechanism for evasion of immune clearance.
    Molecular microbiology , 2003 Jan. : 247-56
  • Harris TO, Shelver DW, Bohnsack JF, Rubens CE
    A novel streptococcal surface protease promotes virulence, resistance to opsonophagocytosis, and cleavage of human fibrinogen.
    The Journal of clinical investigation , 2003 Jan. : 61-70
  • Chaffin DO, McKinnon K, Rubens CE
    CpsK of Streptococcus agalactiae exhibits alpha2,3-sialyltransferase activity in Haemophilus ducreyi.
    Molecular microbiology , 2002 July : 109-22
  • Beckmann C, Waggoner JD, Harris TO, Tamura GS, Rubens CE
    Identification of novel adhesins from Group B streptococci by use of phage display reveals that C5a peptidase mediates fibronectin binding.
    Infection and immunity , 2002 June : 2869-76