Brian Geisbrecht, Ph.D., University Distinguished 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.
Herdendorf TJ, Stapels DAC, Rooijakkers SHM, Geisbrecht BV. Local structural plasticity of the Staphylococcus aureus evasion protein EapH1 enables engagement with multiple neutrophil serine proteases.J Biol Chem. 2020 May 29;295(22):7753-7762. doi: 10.1074/jbc.RA120.013601. Epub 2020 Apr 17. PMID: 32303641; PMCID: PMC7261791.
Herdendorf TJ, Geisbrecht BV. Staphylococcus aureus evasion proteins EapH1 and EapH2: Residue-level investigation of an alternative binding motif for human neutrophil elastase.Arch Biochem Biophys. 2019 Nov 15;676:108140. doi: 10.1016/j.abb.2019.108140. Epub 2019 Oct 14. PMID: 31622584; PMCID: PMC6938032.
Herdendorf TJ, Geisbrecht BV. Investigation of Human Neutrophil Elastase Inhibition by Staphylococcus aureus EapH1: The Key Role Played by Arginine 89.Biochemistry. 2018 Dec 18;57(50):6888-6896. doi: 10.1021/acs.biochem.8b01134. Epub 2018 Nov 30. PubMed PMID: 30461258; PMCID: PMC6347974.
Ploscariu NT, de Jong NWM, van Kessel KPM, van Strijp JAG, Geisbrecht BV. Identification and structural characterization of a novel myeloperoxidase inhibitor from Staphylococcus delphini.Arch Biochem Biophys. 2018 May 1;645:1-11. doi: 10.1016/j.abb.2018.03.007. Epub 2018 Mar 7. PubMed PMID: 29524428; PMCID: PMC5899673.
de Jong NWM, Vrieling M, Garcia BL, Koop G, Brettmann M, Aerts PC, Ruyken M, van Strijp JAG, Holmes M, Harrison EM, Geisbrecht BV, Rooijakkers SHM. Identification of a staphylococcal complement inhibitor with broad host specificity in equid Staphylococcus aureus strains.J Biol Chem. 2018 Mar 23;293(12):4468-4477. doi: 10.1074/jbc.RA117.000599. Epub 2018 Feb 5. PubMed PMID: 29414776; PMCID: PMC5868266.
de Jong NWM, Ploscariu NT, Ramyar KX, Garcia BL, Herrera AI, Prakash O, Katz BB, Leidal KG, Nauseef WM, van Kessel KPM, van Strijp JAG, Geisbrecht BV. A structurally dynamic N-terminal region drives function of the staphylococcal peroxidase inhibitor (SPIN). J Biol Chem. 2018 Feb 16;293(7):2260-2271. doi: 10.1074/jbc.RA117.000134. Epub 2018 Jan 5. PubMed PMID: 29306874; PMCID: PMC5818189.
Stapels DAC, Woehl JL, Milder FJ, Tromp AT, van Batenburg AA, de Graaf WC, Broll SC, White NM, Rooijakkers SHM, Geisbrecht BV. Evidence for multiple modes of neutrophil serine protease recognition by the EAP family of Staphylococcal innate immune evasion proteins.Protein Sci. 2018 Feb;27(2):509-522. doi: 10.1002/pro.3342. Epub 2017 Nov 21. PubMed PMID: 29114958; PMCID: PMC5775164.
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; PMCID: PMC5584439.
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; PMCID; PMC5521547.
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; PMCID: PMC5417336.
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; PMCID: PMC5478675.
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; PMCID: PMC5012295.