Inflammation Research Unit
Dept. of Physiology
Puskin u. 9, 1088 Budapest,
+36(1) 266-2755 x4053
Website: Semmelweis University
Our group analyzes the molecular mechanisms of phagocyte function and its role in various disease states such as autoimmune inflammation or osteoporosis. Ongoing projects in the lab include:
1) Signal transduction mechanisms in neutrophils. Using a gene-targeting approach, we are currently testing the role of various kinases (Src-family kinases, Syk, etc.) and other intracellular signaling molecules (e. g. PLCg2, p190RhoGAP) in integrin- and Fc-receptor-mediated neutrophil functions. These studies will reveal novel receptor-proximal signal transduction processes likely involved in neutrophil-mediated inflammation.
2) Molecular mechanisms of osteoclast differentiation and function. In these studies, the development and bone-resorbing function of osteoclasts is being studied in the absence of various intracellular signaling molecules (Syk, PLCg2, etc). We also attempt to associate these signaling molecules with specific cell surface receptors such as RANK, c-fms or b3-integrins. These studies will reveal novel aspects of osteoclast-mediated bone resorption, likely involved in pathological bone loss during osteoporosis or autoimmune arthritis.
3) Molecular players of in vivo autoimmune inflammation During this series of experiments, we test the contribution of the above signal transduction molecules (Src-family kinases, Sy, PLCg2, etc.) to the development of autoimmune inflammatory diseases in vivo. We currently focus on autoantibody-induced arthritis but will extend these studies to other arthritis and glomerulonephritis models.
Our research activity will likely provide significant novel information on the molecular mechanisms of phagocyte-mediated inflammatory and bone diseases and will likely point to novel targets of pharmacological therapy.
Zoltán Jakus, MD, PhD
Tamás Németh, MD
Jakus Z, Németh T, Verbeek JS and Mócsai A: Critical But Overlapping Role of FcgRIII and FcgRIV in Activation of Murine Neutrophils by Immobilized Immune Complexes. J Immunol 2008, 180: 618-629.
Jakus Z, Fodor S, Abram CL, Lowell CA and Mócsai A: Immunoreceptor-Like Signaling by b2 and b3 Integrins. Trends Cell Biol 2007, 17: 493-501.
Mócsai A, Abram CL, Jakus Z, Hu Y, Lanier LL, Lowell CA: Integrin Signaling in Neutrophils and Macrophages Uses Adaptors Containing Immunoreceptor Tyrosine-Based Activation Motifs. Nat Immunol 2006, 7: 1326-1333.
Jakus Z, Berton G, Ligeti E, Lowell CA and Mócsai A: Responses of Neutrophils to Anti-Integrin Antibodies Depends on Costimulation through Low-Affinity FcgRs: Full Activation Requires Both Integrin and Nonintegrin Signals. J Immunol 2004, 173: 2068-2077.
Mócsai A, Humphrey MB, Van Ziffle JAG, Hu Y, Burghardt A, Spusta SC, Majumdar S, Lanier LL, Lowell CA and Nakamura MC: The Immunomodulatory Adapter Proteins DAP12 and Fc-receptor g-chain (FcRg) Regulate Development of Functional Osteoclasts Through the Syk Tyrosine Kinase. Proc Natl Acad Sci USA 2004, 101: 6158-6163.