Peter A. Ward, M.D.
Godfrey D. Stobbe Professor,
Department of Pathology

pward@umich.edu

Research Interests:

Regulation and role of complement activation products, adhesion-promoting molecules and cytokines in the inflammatory response and in sepsis; signaling pathways in phagocytes

The main focus of our laboratory is the regulation of the inflammatory response. An in vivo model of acute lung injury induced by the intrapulmonary deposition of IgG immune complexes in rats has been developed. The role of various adhesion molecules (e.g. ICAM-1, VCAM-1), cytokines (e.g. TNFa), chemokines (e.g. MIP-2, CINC), anti-inflammatory interleukins (e.g. IL-10, IL-13), complement factors (e.g. C5a), and endogenous protease inhibitors (e.g. TIMP-2 and SLPI) are studied in this model as well as in vitro.

A second area of research is sepsis. Major features of sepsis are the systemic responses (e.g. failing blood pressure, etc.) and the susceptibility to intrapulmonary infection. In an effort to understand this process, rats develop sepsis by cecal ligation/puncture and are then evaluated for increased susceptibility to injury after a direct pulmonary insult (airway instillation lipopolysaccharide or IgG immune complex deposition). We find that adhesion molecules, cytokines, and especially the complement factor C5a contribute to the enhanced lung injury in the state of sepsis. Currently, the role of IL-17A in sepsis is being investigated.

In addition, we study some of the signaling molecules such as MAP -kinases and the transcription factor NF-kB involved in the inflammatory response. Our laboratory routinely uses some of the standard cellular and molecular biological techniques such as cloning, RT- PCR , Southern, Western and Northern blot analysis, ELISA, chemotaxis, antibody production, bacterial and mammalian expression of proteins, transfections etc.

Representative Publications:

Ward, P.A.: The curiosity of IL-15.  Nat Med.  2007 13(8):903-904.  PMID: 17680000.

Flierl, M.A., Rittirsch, D., Nadeau, B.A., Chen, A.J., Sarma, J.V., Zetoune, F.S., McGuire, S.R., List, R.P., Day, D.E., Hoesel, L.M., Gao, H., Van Rooijen, N., Huber-Lang, M.S., Neubig, R.R., Ward, P.A.: Phagocyte-derived catecholamines enhance acute inflammatory injury.  Nature 2007 449:721-725.  PMID: 17914358.

Flierl, M.A., Rittirsch, D., Huber-Lang, M.S., Sarma, J.V., and Ward, P.A.: Molecular events in the cardiomyopathy of sepsis.  Mol Med 2008, 14:327-336.  PMID: 18256728.

Flierl, M.A., Rittirsch, D., Gao, H., Hoesel, L.M., Nadeau, B.A., Day, D.E., Zetoune, F.S., Sarma, J.V., Huber-Lang, M.S., Ferrara, J.L.M., and Ward, P.A.:  Adverse functions of IL-17A in experimental sepsis.  FASEB J. 2008 22:2198-2205.  PMID: 18299333.

Flierl, M.A., Rittirsch, D., Nadeau, B.A., Day, D.E., Zetoune, F.S., Sarma, J.V., Huber-Lang, M.S. and Ward, P.A. Functions of the complement components C3 and C5 during sepsis.  FASEB J.  2008 22:3483-3490.  PMID: 18587006.

Rittirsch, D., Flierl, M.A., and Ward, P.A.: Harmful molecular mechanisms in sepsis.  Nat Rev Immun.  2008 8:776-787.  PMID: 18802444.

Rittirsch, D., Huber-Lang, M., Flierl, M., and Ward, P.A.: Immunodesign of experimental sepsis by cecal ligation and puncture.  Nat Protoc. 2009 4:31-36.  PMID: 19131954.

Flierl, M.A., Stahel, P.F., Rittirsch, D., Huber-Lang, M., Niederbichler, A.D., Hoesel, L.M., Touban, B.M., Morgan, S.J., Smith, W.R., Ward, P.A., and Ipaktchi, K.: Inhibition of complement C5a prevents breakdown of the blood-brain barrier and pituitary dysfunction in experimental sepsis.  Crit Care, 2009 Feb 5 13:R12 [Epub ahead of print].  PMID: 19196477.

Ward, P.A.: Functions of C5a receptors.  J. Mol Med.  2009 87:375-378.  PMID: 19189071.

Flierl, M.A., Rittirsch, D., Nadeau, B.A., Sarma, J.V., Day, D.E., Lentsch, A.B., Huber-Lang, M.S., and Ward, P.A.:  Upregulation of phagocyte-derived catecholamines augments the acute inflammatory response.  PLoS One.  2009 4(2):e4414. [Epub 2009 Feb 12]  PMID: 19212441.

Ward, P.A.: The sepsis seesaw: seeking a heart salve.  Nature Medicine Bench to Bedside.  2009 15:497-498.  PMID: 19424210.

Rittirsch, D., Flierl, M.A., Day, D.E., Nadeau, B.A., Zetoune, F.S., Sarma, J.V., Werner, C.M., Wanner, G.A., Simmen, H.P., Huber-Lang, M.S., and Ward, P.A.:  Cross-talk between TLR4 and Fcγ receptor III (CD16) pathways.  PLoS Pathogens.  Epub 2009 Jun 5, 5(6):e10000464.  PMID:  19503602.