Craig E Rubens, MD, PhD

Professional History

Board Certified:

Pediatrics

Medical/Professional School:

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

Residency:

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

Research Focus Area:

Host: Pathogen Interaction

Description of Research:

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.

Key Publications:

Rantanen MK, Lehtio L, Rajagopal L, Rubens CE, and Goldman A. 2006. Crystallization and preliminary crystallographic analysis of two Streptococcus agalactiae proteins, the family II inorganic pyrophosphatase, and the serine/threonine phosphatase. Acta Cryst F62:891-894.

Rubens C. 2006. Group B streptococcal infections in the postgenomic era: Interview. Future Microbiol 1:251-253.

Rajagopal L, Vo A, Silvestroni A, Rubens CE. 2006. Regulation of cytotoxin expression by converging eukaryotic-type and two-component signalling mechanisms in Streptococcus agalactiae. Mol Microbiol, 62:941-957. NIHMSID: NIHMS45491 (Supplemental Information NIHMS79452).

Braff MH, Jones AL, Skerrett SJ, Rubens CE. 2007. Staphylococcus aureus exploits cathelicidin antimicrobial peptides produced during early pneumonia to promote staphylokinase-dependent fibrinolysis. J Infect Dis, 195:1365-72.

Rantanen MK, Lehtio L, Rajagopal L, Rubens CE, and Goldman A. 2007. Structure of Streptococcus agalactiae serine/threonine phosphatase. The subdomain conformation is coupled to the binding of a third metal ion. FEBS J, 274:3128-3137.

Rantanen MK, Lehtio L, Rajagopal L, Rubens CE, and Goldman A. 2007. Structure of the Streptococcus agalactiae family II inorganic pyrophosphatase at 2.80 ? resolution. Acta Cryst, D63:738-743.

Jones AL, Mertz RH, Carl DJ, and Rubens CE. 2007. A streptococcal penicillin-binding protein is critical for resisting innate airway defenses in the neonatal lung. J Immuno, 179(5):3196-3202.

Aoyagi Y, Adderson EE, Rubens CE, Bohnsack JF, Min JG, Matsushita M, Fujita T, Okuwaki Y, Takahashi S. 2008. L-Ficolin/mannose-binding lectin-associated serine protease complexes bind to group B streptococci primarily through N-acetylneuraminic acid of capsular polysaccharide and activate the complement pathway. Infect Immun 76(1):179-188. PMCID: PMC2223634.

Ventura CL, Higdon R, Kolker E, Skerrett SJ, Rubens CE. 2008. Host airway proteins interact with Staphylococcus aureus during early pneumonia. Infect Immun, 76(3):888-898. PMCID: PMC2258841.

Ventura CL, Higdon R, Hohmann L, Martin D, Kolker E, Liggitt HD, Skerrett SJ, Rubens CE. 2008. Staphylococcus aureus elicits marked alterations in the airway proteome during early pneumonia. Infect Immun, 76(12):5862-5872. PMCID: PMC2583584.

Honors & Awards:

Children's Hospital Guild Association Endowed Chair for Pediatric Infectious Disease Research

Editorial Advisory Board, "Future Microbiology"

Clinical Infectious Disease Award for Outstanding Review

2006: Seattle Magazine Top Doctor

2006-07: Seattle Metropolitan Magazine Top Doctor

2007-Present: Executive Director, Global Alliance to Prevent Prematurity and Stillbirth.