Section: Research

Douglas Golenbock, M.D.

Academic Role: Professor

Faculty Appointment(s) In:
   Infectious Diseases and Immunology
   Medicine
   Molecular Genetics and Microbiology

Other Affiliation(s):
   Center for AIDS Research
   Program in Immunology and Virology

Toll receptors, sepsis and malaria.

Dr Douglas Golenbock is a Professor of Medicine and Infectious Diseases and Chief of the Division of Infectious Diseases and Immunology at the University of Massachusetts Medical School.  The principal goal of Dr Golenbock´s laboratory is to characterize the receptors used by phagocytic leukocytes to respond to the presence of microbial products, thus resulting in acute and chronic inflammatory diseases. These include septic shock, pyogenic pneumonia, fatal viral infections and malaria.  A major focus of the laboratory is the effect of bacterial lipopolysaccharide (LPS) and the study of the family of its receptors, including the LPS binding proteins LBP and CD14, the Toll-like receptors (TLRs), and the TLR4 co receptor, MD-2.  Other microbial products of more recent interest to our group include bacterial and viral nucleic acid, malarial hemozoin and lipopeptides produced by Gram-positive bacteria.  The Golenbock laboratory uses a variety of approaches to study cellular activation by microbial products. Most of these involve modern molecular genetic techniques, and include the construction of heterologously expressing cell lines, both in established cell lines (e.g., CHO and HEK293) as well as immortalized macrophages.  Once these lines are constructed, we use them in biochemical, immunological and imaging studies to ask questions about how ligand induced signal transduction begins.  Using this approach, the lab has characterized LPS signal transduction, helping to define the TLR4/MD-2 complex as a central LPS recognition molecule. Furthermore, we have identified TLR2 as a central pattern recognition protein for a large variety of important immunostimulatory substances from pyogenic bacteria, fungi, mycoplasma and mycobacteria. We are particularly interested in how receptors change from being inactive to active, and have recently focused on the induced change in conformation and activity of TLR9 after it binds stimulatory DNA.  We believe that such approaches provide us with new insights into the molecular basis of infectious illness, as well as a variety of sterile inflammatory illnesses such as Systemic Lupus Erythematosis and Atherosclerosis, that are mechanistically similar to infectious diseases.  

Office: LRB 208
Phone: 508-856-5980
Fax: 508-856-5463
E-mail: Douglas.Golenbock@umassmed.edu

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