Text Image: UM Medical School: Graduate Program in Immunology
Text Image: Faculty


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; role of complement in sepsis.

The main focus of our laboratory is the regulation of the inflammatory response. An in vivo model of acute lung injury has been developed in mice. 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. Our earlier studies have shown that sepsis developing in rodents after cecal ligation and puncture (CLP) is associated with activation of complement and generation of the anaphylatoxin, C5a, which then interacts with its receptors (C5aR, C5L2) present on a variety of cells, both myeloid and myeloid-derived cells.  Such interactions appear to be associated with the multiorgan failure of sepsis.  Currently, we have a focus on C5a being able to interact with cardiomyocytes, resulting in heart failure.  Cardiac dysfunction is a major complication of sepsis, resulting in septic shock.  Currently, two of my former postdoctoral fellows at the University of Jena, Germany, are making plans to initiate Phase II Clinical Trials in humans with sepsis, using a “humanized’ version of a mouse antibody that neutralizes C5a.

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, Western and Northern blot analysis, ELISA, antibody production, bacterial and mammalian expression of proteins, transfections, etc.


Representative Publications

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.

Rittirsch, D., Flierl, M.A., and Ward, P.A.: Harmful molecular mechanisms in sepsis.  Nat Rev Immun.  2008 8:776-787.  PMID: 18802444.  PMCID: PMC2786961.

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.  PMCID: PMC2636885

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.  PMCID: PMC2685003.

Hemmila, M.R., Mattar, A., Taddonio, M.A., Arbabi, S., Hamouda, T., Ward, P.A., Wang, S.C., Baker, J.R., Jr.:  Topical nanoemulsion therapy reduces bacterial wound infection and inflammation after burn injury.  Surgery. 2010 Feb 26. [Epub ahead of print]  PMID: 20189619.  NIHMSID170651

Ward, P.A., Zetoune, F.S., and Sarma, J.V: Defective innate immunity and hyper-inflammatory responses in sepsis.  Proceedings of the 8th World Congress on Trauma, Shock, Inflammation and Sepsis, TSIS 2010, March 9-13th, pp. 9-12.

Ward, P.A.: The harmful role of C5a on innate immunity in sepsis.  J. Innate Immun. (DOI:10.1159/000317194) Published Online: June 26, 2010.

Speyer, C.L. and Ward, P.A.: Role of endothelial chemokines and their receptors during inflammation.  J. Invest. Surg.  2011;24:18-27.  PMID: 21275526. 

Atefi, G., Zetoune, F.S., Herron, T.J., Jalife, J., Bosmann, M., Al-Aref, R., Sarma, J.V., and Ward, P.A.: Complement dependency of cardiomyocyte release of mediators during sepsis.  FASEB J. 2011 Jul;25(7):2500-2508.

Bosmann, M., Russkamp, N.F., Patel, V.R., Zetoune, F.S., Sarma, J.V., and Ward, P.A.: The outcome of polymicrobial sepsis is independent of T and B cellsSHOCK 2011 36(4):396-401.  PMID: 21701414.

Flierl, M.A., Rittirsch, D., Weckbach, S., Huber-Lang, M., Ipaktchi, K., Ward, P.A. and Stahel, P.F.: Disturbances of the hypothalamic-pituitary-adrenal axis and plasma electrolytes during experimental sepsis.  Ann of Intensive Care, 2011, 1:53. PMID: 22208725.

Bosmann, M., and Ward, P.A.:  Role of C3, C5 and anaphylatoxin receptors in acute lung injury and in sepsis.  Adv Exp Med Biol.  2012;946:147-159.

Bosmann, M., Sarma, J.V., Atefi, G., Zetoune, F.S., and Ward, P.A.:  Evidence for anti-inflammatory effects of C5a on the innate IL-17A/IL-23 axis.  FASEB J. 2012 26:1640-1651.

Ward, P.A.: Immunosuppression in sepsis.  JAMA. 2011 Dec 21;306(23):2618-9.  PMID: 22187286. 

Bosmann, M., Grailer, J.J., Zhu, K., Matthay, M.A., Sarma, J.V., Zetoune, F.S. and Ward, P.A.: Anti-inflammatory effects of β2 adrenergic receptor agonists in experimental acute lung injury.   FASEB J. 2012 26:2137-2144. 

Ward, P.A., Guo, R.F., and Riedemann,N.C.: Manipulation of the complement system for benefit in sepsis.  Crit Care Res Pract. 2012 Epub 2012 Mar 5.  PMID: 22482043.

Bosmann, M., Haggadone, M., Hemmila, M., Zetoune, F., Sarma, J.V. and Ward, P.A.:  Complement activation product C5a is a selective suppressor of TLR4-induced, but not TLR3-induced, production of IL-27 (p28) from macrophages.  J. Immunol. 2012;188;5086-5093.  PMCID:PMC3345104.

Bosmann, M., and Ward, P.A.: Therapeutic potential of targeting IL-17 and IL-23 in sepsis.  Clinical and Translational Medicine. DOI:10.1186/2001-1326-1-4. 2012;1:4. PMCID: PMC3552565.

Sarma, J.V., and Ward, P.A.: New developments in C5a receptor signaling.  Cell Health and Cytoskeleton.  2012:4;73-82.  PMID: 23576881.  PMCID:PMC3619443.

Bosmann, M., and Ward, P.A.:  Fingerprinting of the TLR4-induced acute inflammatory response.  Festschrift in Experimental and Molecular Pathology–Julius M. Cruse.  2012. 93:319-323.  PMCID:PMC3518574.

Wang, XD, and Ward, P.A.:  Opportunities and challenges of disease biomarkers: a new section in the journal of translational medicine.  Journal of Translational Medicine 2012, 10:240 PMCID:PMC3543303.

 

 



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