Brian Geisbrecht, Ph.D.
University Distinguished Professor
Undergraduate Advisor
Contact information
Office: 176 Chalmers Hall
Phone: 785-532-3154
Fax: 785-532-7278
E-mail: geisbrechtb@ksu.edu
Education
B.S. 1996, Saint Vincent College, Latrobe, PA
Ph.D. 2000, The Johns Hopkins University School of Medicine, Baltimore, MD.
Research video
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.
Selected publications
Geisbrecht BV, Lambris JD, Gros P. Complement component C3: A structural perspective and potential therapeutic implications. Semin Immunol. 2022 Jun 24:101627. doi: 10.1016/j.smim.2022.101627. Epub ahead of print. PMID: 35760703.
Xu X, Lewis Marffy AL, Keightley A, McCarthy AJ, Geisbrecht BV. Group B Streptococcus Surface Protein β: Structural Characterization of a Complement Factor H-Binding Motif and Its Contribution to Immune Evasion. J Immunol. 2022 Mar 1;208(5):1232-1247. doi: 10.4049/jimmunol.2101078. Epub 2022 Feb 2. PMID: 35110419; PMCID: PMC8881398.
Savitt AG, Manimala S, White T, Fandaros M, Yin W, Duan H, Xu X, Geisbrecht BV, Rubenstein DA, Kaplan AP, Peerschke EI, Ghebrehiwet B. SARS-CoV-2 Exacerbates COVID-19 Pathology Through Activation of the Complement and Kinin Systems. Front Immunol. 2021 Nov 12:767347. doi: 10.3389/fimmu.2021.767347. PMID: 34804054; PMCID: PMC8602850.
Xu X, Zhang C, Denton DT, O'Connell D, Drolet DW, Geisbrecht BV. Inhibition of the Complement Alternative Pathway by Chemically Modified DNA Aptamers That Bind with Picomolar Affinity to Factor B. J Immunol. 2021 Feb 15;206(4):861-873. doi: 10.4049/jimmunol.2001260. Epub 2021 Jan 8. PMID: 33419768; PMCID: PMC7851746.
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.
Peerschke EI, Stanchina E, Chang Q, Manova-Todorova K, Barlas A, Savitt AG, Geisbrecht BV, Ghebrehiwet B. Anti gC1qR/p32/HABP1 Antibody Therapy Decreases Tumor Growth in an Orthotopic Murine Xenotransplant Model of Triple Negative Breast Cancer. Antibodies (Basel). 2020 Oct 6;9(4):51. doi: 10.3390/antib9040051. PMID: 33036212; PMCID: PMC7709104.
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.
Mastellos DC, Blom AM, Connolly ES, Daha MR, Geisbrecht BV, Ghebrehiwet B, Gros P, Hajishengallis G, Holers VM, Huber-Lang M, Kinoshita T, Mollnes TE, Montgomery RA, Morgan BP, Nilsson B, Pio R, Ricklin D, Risitano AM, Taylor RP, Mantovani A, Ioannidis JPA, Lambris JD. 'Stealth' corporate innovation: an emerging threat for therapeutic drug development. Nat Immunol. 2019 Nov;20(11):1409-1413. doi: 10.1038/s41590-019-0503-1. Erratum in: Nat Immunol. 2019 Oct 11;: PMID: 31562490; PMCID: PMC7368001.
Ghebrehiwet B, Geisbrecht BV, Xu X, Savitt AG, Peerschke EIB. The C1q Receptors: Focus on gC1qR/p33 (C1qBP, p32, HABP-1). Semin Immunol. 2019 Oct;45:101338. doi: 10.1016/j.smim.2019.101338. Epub 2019 Nov 16. PMID: 31744753.
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.