Brian Geisbrecht, Ph.D., Professor
Office: 101B Burt Hall
B.S. 1996, Saint Vincent College, Latrobe, PA
Areas of specialty
- Innate Immunity
- Molecular Basis of Infectious Diseases and Host-Pathogen Interactions
- Structural Biology and Molecular Recognition
My laboratory is taking a multidisciplinary approach toward a better understanding of the events which lay the foundation for initiation and propagation of staphylococcal disease. The ultimate goals of this research program are two-fold. The first is to use a structure-based approach to expand our basic knowledge of the various host/pathogen interactions that occur between S. aureus and human physiological systems. As multiple antibiotic-resistant strains of this pathogen have emerged and disseminated throughout the public and health care setting, the number of therapies that effectively combat S. aureus infection has grown dangerously low. Consequently, if we are to provide sufficient measures against S. aureus infection in the future, we need to further our basic understanding of this how it interacts with and defends itself against the human body. Our second goal is to capitalize upon the information obtained from analysis of these host/pathogen interactions toward developing new treatments for human inflammatory diseases. For example, it is now understood that the complement system lies at the heart of a wide-range of inflammatory and vascular disorders in humans. Because studies from the last decade have shown that S. aureus is particularly adept at evading complement attack, we believe that naturally-occurring staphylococcal complement inhibitor proteins may be useful templates for new types of anti-inflammatory drugs. Other work has also shown that S. aureus actively blocks a number of other disease-associated defense and repair processes, including coagulation, neutrophil transmigration, and angiogenesis. All of this suggests that important breakthroughs for treating a number of non-infectious human diseases may actually be found by studying the biology of this important pathogen.
Garcia BL, Summers BJ, Ramyar KX, Tzekou A, Lin Z, Ricklin D, Lambris JD, Laity JH, Geisbrecht BV. A structurally dynamic N-terminal helix is a key functional determinant in staphylococcal complement inhibitor (SCIN) proteins. J Biol Chem. 2013 Jan 25;288(4):2870-81. doi: 10.1074/jbc.M112.426858. Epub 2012 Dec 11. PubMed PMID: 23233676; PubMed Central PMCID: PMC3554951.
Garcia BL, Summers BJ, Lin Z, Ramyar KX, Ricklin D, Kamath DV, Fu ZQ, Lambris JD, Geisbrecht BV. Diversity in the C3b [corrected] contact residues and tertiary structures of the staphylococcal complement inhibitor (SCIN) protein family.J Biol Chem. 2012 Jan 2;287(1):628-40. doi: 10.1074/jbc.M111.298984. Epub 2011 Nov 15. Erratum in: J Biol Chem. 2012 Mar 16;287(12):9329. PubMed PMID: 22086928; PubMed Central PMCID: PMC3249117.
Garcia BL, Ramyar KX, Ricklin D, Lambris JD, Geisbrecht BV. Advances in understanding the structure, function, and mechanism of the SCIN and Efb families of Staphylococcal immune evasion proteins. Adv Exp Med Biol. 2012;946:113-33. doi: 10.1007/978-1-4614-0106-3_7. Review. PubMed PMID: 21948365; PubMed Central PMCID: PMC3422867.
Chen H, Ricklin D, Hammel M, Garcia BL, McWhorter WJ, Sfyroera G, Wu YQ, Tzekou A, Li S, Geisbrecht BV, Woods VL Jr, Lambris JD. Allosteric inhibition of complement function by a staphylococcal immune evasion protein. Proc Natl Acad Sci U S A. 2010 Oct 12;107(41):17621-6. doi: 10.1073/pnas.1003750107. Epub 2010 Sep 27. PubMed PMID: 20876141; PubMed Central PMCID: PMC2955122.
Garcia BL, Ramyar KX, Tzekou A, Ricklin D, McWhorter WJ, Lambris JD, Geisbrecht BV. Molecular basis for complement recognition and inhibition determined by crystallographic studies of the staphylococcal complement inhibitor (SCIN) bound to C3c and C3b. J Mol Biol. 2010 Sep 10;402(1):17-29. doi: 10.1016/j.jmb.2010.07.029. Epub 2010 Jul 21. PubMed PMID: 20654625; PubMed Central PMCID: PMC2930029.
Ricklin D, Tzekou A, Garcia BL, Hammel M, McWhorter WJ, Sfyroera G, Wu YQ, Holers VM, Herbert AP, Barlow PN, Geisbrecht BV, Lambris JD. A molecular insight into complement evasion by the staphylococcal complement inhibitor protein family. J Immunol. 2009 Aug 15;183(4):2565-74. doi: 10.4049/jimmunol.0901443. Epub 2009 Jul 22. PubMed PMID: 19625656; PubMed Central PMCID: PMC2881335.
Ricklin D, Ricklin-Lichtsteiner SK, Markiewski MM, Geisbrecht BV, Lambris JD. Cutting edge: members of the Staphylococcus aureus extracellular fibrinogen-binding protein family inhibit the interaction of C3d with complement receptor 2. J Immunol. 2008 Dec 1;181(11):7463-7. PubMed PMID: 19017934; PubMed Central PMCID: PMC2673544.
Lambris JD, Ricklin D, Geisbrecht BV. Complement evasion by human pathogens. Nat Rev Microbiol. 2008 Feb;6(2):132-42. doi: 10.1038/nrmicro1824. Review. PubMed PMID: 18197169; PubMed Central PMCID: PMC2814840.
Hammel M, Sfyroera G, Ricklin D, Magotti P, Lambris JD, Geisbrecht BV. A structural basis for complement inhibition by Staphylococcus aureus. Nat Immunol. 2007 Apr;8(4):430-7. Epub 2007 Mar 11. PubMed PMID: 17351618.