Postdoctoral Position Available

Evelyn Kurt-Jones, Ph.D.

Academic Role: Professor

Faculty Appointment(s) In:
   Medicine

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

Signaling by receptors on monocytes and macrophages that mediate the innate immune response to bacterial and viral infection.

Research in the laboratory is focused on the role of receptor- mediated events  in the pathogenesis of infectious and inflammatory processes.  In particular, the role of CD14 and Toll-like receptors in the development of an innate immune response is being investigated.  These studies have led to the observation that CD14 and Toll-like receptors mediate responses to a range of pathogens including bacteria, viruses and fungi. Heat shock proteins which are produced by damaged tissues also trigger innate immunity by a CD14-dependent mechanism.

Our studies include the investigation of the signaling pathways utilized by CD14 and Toll-like receptors. We have demonstrated that CD14, which is linked to the outer leaflet of the cell membrane by a lipid-anchor, is physically and functionally linked to heterotrimeric G proteins. Toll-like receptors are linked to the NF-kB signaling pathway. Our studies suggest that CD14 and Toll-like receptors are components of a multimeric receptor complex that is activated by protein and lipid components of pathogens leading to the production of inflammatory cytokines.

Rotation Project Background

Innate immunity and Toll-like receptors. We study the role of Toll-like receptors (TLRs) in the activation of monocyte/macrophage innate immunity and cytokine secretion in response to infection. The innate immune response is triggered when microbial products interact with pattern recognition receptors. Two important members of this receptor group are CD14, the high affinity LPS receptor of monocytes, and the Toll-like receptors (TLRs), an ancient family of pathogen recognition receptors. CD14 and TLRs are receptors for an array of microbial products, including lipopolysaccharide (LPS) from gram-negative bacteria , peptidoglycan from gram-positive bacteria, lipoarabinomannan from mycobacteria and the fusion protein of paramyxoviruses. These receptors are also activated by heat shock proteins and, thus, may play an important role in the recognition of damaged (or infected) tissues.

Representative Publications

Solomon, KR¹, Kurt-Jones, EA¹, Saladino, RA, Stack, AM, Dunn, IF, Ferretti, M, Golenbock, D, Fleisher, GR, Finberg, RW. ¹co-first authors. (1998) Heterotrimeric G Proteins Physically Associated with the Lipopolysaccharide Receptor CD14 Modulate both In Vivo and In Vitro Responses to Lipopolysaccharide. J Clin Invest 102(11): 2019-27.

Kol, A., Lichtman, AH, Finberg, RW, Libby, P, Kurt-Jones, EA. (2000) Cutting Edge: Heat Shock Protein 60 Activates the Innate Immune Response; CD14 is an Essential Receptor for HSP60 Activation of Mononuclear Cells. J Immunol 164:13-17.

Asea, A, MA, Kraeft, SK, Kurt-Jones, EA, Stevenson, Chen, LB, Finberg, RW, Koo, GC, Calderwood, SK. (2000) HSP70 stimulates cytokine production through a CD14-dependant pathway, demonstrating its dual role as a chaperone and cytokine. Nature Medicine 6:435-442

Potential Rotation Projects

1. Expression of Toll-like receptors: Patterns of TLR expression in normal cells. Control of TLR receptor expression by environmental factors and cytokines. TLR expression in diseased tissues.



2. Role of TLRs in disease pathogenesis: Use of knockout and genetically defined animals to study the role of TLRs in the control of bacterial or viral diseases.



3. Structure-function studies of TLR signaling: Assessing the signaling activity of wild type and mutant TLRs (altered by site-directed mutageneis) using transient transfection and luciferase reporter gene analysis.

Office: LRB 226
Phone: 508-856-3531
Fax: 508-856-6176
E-mail: Evelyn.Kurt-Jones@umassmed.edu
Keywords: Immunology, Virology, Signal Transduction

More on Evelyn Kurt-Jones' Research Research | Publications | Rotations View All Sections on One Page

Postdoctoral Position Available We are seeking a post-doctoral fellow to study toll/interleukin 1 receptors and their role in inflammatory disease pathogenesis using human cells and mouse models. Candidates should have a Ph.D. or M.D. degree, or have completed degree requirements. Experience in immunology, molecular biology and/or biochemistry and publication of papers in the areas of cytokine biology, receptor biochemistry and/or cell signaling required.