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.
de Jong NWM, Ramyar KX, Guerra FE, Nijland R, Fevre C, Voyich JM, McCarthy AJ, Garcia BL, van Kessel KPM, van Strijp JAG, Geisbrecht BV, Haas PA. Immune evasion by a staphylococcal inhibitor of myeloperoxidase. Proc Natl Acad Sci U S A. 2017 Aug 29;114(35):9439-9444. doi: 10.1073/pnas.1707032114. Epub 2017 Aug 14. PMID: 28808028.
Woehl JL, Ramyar KX, Katz BB, Walker JK, Geisbrecht BV. The structural basis for inhibition of the classical and lectin complement pathways by S. aureus extracellular adherence protein. Protein Sci. 2017 Aug;26(8):1595-1608. doi: 10.1002/pro.3195. Epub 2017 May 31. PMID: 28512867.
Garcia BL, Skaff DA, Chatterjee A, Hanning A, Walker JK, Wyckoff GJ, Geisbrecht BV. Identification of C3b-Binding Small-Molecule Complement Inhibitors Using Cheminformatics. J Immunol. 2017 May 1;198(9):3705-3718. doi: 10.4049/jimmunol.1601932. Epub 2017 Mar 15. PMID: 28298523.
Papanastasiou M, Koutsogiannaki S, Sarigiannis Y, Geisbrecht BV, Ricklin D, Lambris JD. Structural Implications for the Formation and Function of the Complement Effector Protein iC3b. J Immunol. 2017 Apr 15;198(8):3326-3335. doi: 10.4049/jimmunol.1601864. Epub 2017 Mar 3. PMID: 28258193.
Garcia BL, Zwarthoff SA, Rooijakkers SH, Geisbrecht BV. Novel Evasion Mechanisms of the Classical Complement Pathway. J Immunol. 2016 Sep 15;197(6):2051-60. doi: 10.4049/jimmunol.1600863. Review. PMID: 27591336.
Georgoutsou-Spyridonos M, Ricklin D, Pratsinis H, Perivolioti E, Pirmettis I, Garcia BL, Geisbrecht BV, Foukas PG, Lambris JD, Mastellos DC, Sfyroera G. Attenuation of Staphylococcus aureus-Induced Bacteremia by Human Mini-Antibodies Targeting the Complement Inhibitory Protein Efb. J Immunol. 2015 Oct 15;195(8):3946-58. doi: 10.4049/jimmunol.1500966. Epub 2015 Sep 4. PMID: 26342032.
Stapels DA, Geisbrecht BV, Rooijakkers SH. Neutrophil serine proteases in antibacterial defense. Curr Opin Microbiol. 2015 Feb;23:42-8. doi: 10.1016/j.mib.2014.11.002. Epub 2014 Nov 18. Review. PMID: 25461571.
Woehl JL, Stapels DAC, Garcia BL, Ramyar KX, Keightley A, Ruyken M, Syriga M, Sfyroera G, Weber AB, Zolkiewski M, Ricklin D, Lambris JD, Rooijakkers SHM, Geisbrecht BV. The extracellular adherence protein from Staphylococcus aureus inhibits the classical and lectin pathways of complement by blocking formation of the C3 proconvertase. J Immunol. 2014 Dec 15;193(12):6161-6171. doi: 10.4049/jimmunol.1401600. Epub 2014 Nov 7. PMID: 25381436
Stapels DA, Ramyar KX, Bischoff M, von Köckritz-Blickwede M, Milder FJ, Ruyken M, Eisenbeis J, McWhorter WJ, Herrmann M, van Kessel KP, Geisbrecht BV, Rooijakkers SH. Staphylococcus aureus secretes a unique class of neutrophil serine protease inhibitors.Proc Natl Acad Sci U S A. 2014 Sep 9;111(36):13187-92. doi: 10.1073/pnas.1407616111. Epub 2014 Aug 26. PMID: 25161283