Immunobiology
Herr Lab

Herr Research Lab

Our laboratory is interested in mechanistic studies of cellular adhesion and receptor-mediated signaling in immunology and microbiology. The biological processes we are interested in include formation of biofilms by Staphylococcus aureus and S. epidermidis, activation of immune responses by IgA and IgG antibodies, and adhesion of platelets to collagen. Each of these processes is dependent upon specific interactions between proteins on different cells, or between soluble proteins and cell-surface receptors.

We are interested in understanding the specific details of these macromolecular interactions, both in terms of the atomic structures of the proteins involved and the thermodynamics of binding. To study these interactions, we use protein x-ray crystallography to gain structural insight and various biophysical techniques such as analytical ultracentrifugation, surface plasmon resonance, circular dichroism spectroscopy, or isothermal titration calorimetry to study the binding interactions and stoichiometries of protein-protein complexes. Understanding these processes at the molecular level will be crucial for the development of novel therapies. For example, biofilms are bacterial communities encased in a polysaccharide slime that are resistant to antibiotic treatment and host immune response.

Our lab discovered novel approaches to inhibit biofilm formation that are being developed as a therapeutic approach. Although IgA and IgG antibodies are critical for host immune responses to infection, formation of antibody immune complexes can lead to pathology in many autoimmune diseases. Finally, platelet adhesion to collagen is the first step in thrombus formation, normally responsible for limiting blood loss but potentially leading to heart attack and stroke.

Publications

Yarawsky, AE; Hopkins, JB; Chatzimagas, L; Hub, JS; Herr, AB. Solution Structural Studies of Pre-amyloid Oligomer States of the Biofilm Protein Aap. Journal of Molecular Biology. 2022; 434:167708.

Erickson, JJ; Archer-Hartmann, S; Yarawsky, AE; Miller, JL C; Seveau, S; Shao, TY; Severance, AL; Miller-Handley, H; Wu, Y; Pham, G; et al. Pregnancy enables antibody protection against intracellular infection. Nature. 2022; 606:769-775.

Gonzalez, T; Stevens, ML; Kyzy, AB; Alarcon, R; He, H; Kroner, JW; Spagna, D; Grashel, B; Sidler, E; Martin, LJ; et al. Biofilm propensity of Staphylococcus aureus skin isolates is associated with increased atopic dermatitis severity and barrier dysfunction in the MPAACH pediatric cohort. Allergy: European Journal of Allergy and Clinical Immunology. 2021; 76:302-313.

Yarawsky, AE; Herr, AB. The staphylococcal biofilm protein Aap forms a tetrameric species as a necessary intermediate before amyloidogenesis. The Journal of biological chemistry. 2020; 295:12840-12850.

Yarawsky, AE; Johns, SL; Schuck, P; Herr, AB. The biofilm adhesion protein Aap from Staphylococcus epidermidis forms zinc-dependent amyloid fibers. The Journal of biological chemistry. 2020; 295:4411-4427.

Posgai, MT; Tonddast-Navaei, S; Jayasinghe, M; Ibrahim, GM; Stan, G; Herr, AB. FcαRI binding at the IgA1 CH2-CH3 interface induces long-range conformational changes that are transmitted to the hinge region. Proceedings of the National Academy of Sciences of USA. 2018; 115:E8882-E8891.

Shelton, CL; Conrady, DG; Herr, AB. Functional consequences of B-repeat sequence variation in the staphylococcal biofilm protein Aap: deciphering the assembly code. The Biochemical journal. 2017; 474:427-443.

Zhou, L; Hinerman, JM; Blaszczyk, M; Miller, JL C; Conrady, DG; Barrow, AD; Chirgadze, DY; Bihan, D; Farndale, RW; Herr, AB. Structural basis for collagen recognition by the immune receptor OSCAR. Blood. 2016; 127:529-537.

Strait, RT; Posgai, MT; Mahler, A; Barasa, N; Jacob, CO; Koehl, J; Ehlers, M; Stringer, K; Shanmukhappa, SK; Witte, D; et al. IgG1 protects against renal disease in a mouse model of cryoglobulinaemia. Nature. 2015; 517:501-504.

Conrady, DG; Wilson, JJ; Herr, AB. Structural basis for Zn2+-dependent intercellular adhesion in staphylococcal biofilms. Proceedings of the National Academy of Sciences of USA. 2013; 110:E202-E211.

Conrady, DG; Brescia, CC; Horii, K; Weiss, AA; Hassett, DJ; Herr, AB. A zinc-dependent adhesion module is responsible for intercellular adhesion in staphylococcal biofilms. Proceedings of the National Academy of Sciences of USA. 2008; 105:19456-19461.

Horii, K; Kahn, ML; Herr, AB. Structural basis for platelet collagen responses by the immune-type receptor glycoprotein VI. Blood. 2006; 108:936-942.

Herr, AB; Ballister, ER; Bjorkman, PJ. Insights into IgA-mediated immune responses from the crystal structures of human FcalphaRI and its complex with IgA1-Fc. Nature. 2003; 423:614-620.

ORNITZ, DM; HERR, AB; NILSSON, M; WESTMAN, J; SVAHN, CM; WAKSMAN, G. FGF binding and FGF receptor activation by synthetic heparan-derived di- and trisaccharides. Science. 1995; 268:432-436.

Smith, CA; Sonneson, GJ; Hoey, RJ; Hinerman, JM; Sheehy, K; Walter, R; Herr, AB; Horn, JR. Molecular recognition requires dimerization of a VHH antibody. mAbs. 2023; 15:2215363.

Yarawsky, AE; Ori, AL; English, LR; Whitten, ST; Herr, AB. Convergent behavior of extended stalk regions from staphylococcal surface proteins with widely divergent sequence patterns. Protein Science. 2023; 32:e4707.

Yarawsky, AE; Dinu, V; Harding, SE; Herr, AB. Strong non-ideality effects at low protein concentrations: considerations for elongated proteins. European Biophysics Journal. 2023; 52:427-438.

Yadav, R; Shaikh, T; Tikole, S; Herr, AB; Fitzkee, NC. 1H, 15N, and 13C chemical shift backbone resonance NMR assignment of the accumulation-associated protein (Aap) lectin domain from Staphylococcus epidermidis. Biomolecular NMR Assignments. 2023; 17:95-99.

Kleven, RT; Huang, S; Ford, SM; Sakthivel, K; Thomas, SR; Zuccarello, M; Herr, AB; Holland, CK. Effect of Recombinant Tissue Plasminogen Activator and 120-kHz Ultrasound on Porcine Intracranial Thrombus Density. Ultrasound in Medicine and Biology. 2023; 49:539-548.

Kappes, EC; Kattamuri, C; Czepnik, M; Yarawsky, AE; Brûlé, E; Wang, Y; Ongaro, L; Herr, AB; Walton, KL; Bernard, DJ; et al. Follistatin Forms a Stable Complex With Inhibin A That Does Not Interfere With Activin A Antagonism. Endocrinology. 2023; 164:bqad017.

Wang, C; Chantraine, C; Viljoen, A; Herr, AB; Fey, PD; Horswill, AR; Mathelié-Guinlet, M; Dufrêne, YF. The staphylococcal biofilm protein Aap mediates cell-cell adhesion through mechanically distinct homophilic and lectin interactions. Editor, Yooseph S. 2022; 1:pgac278.

Yarawsky, AE; Hopkins, JB; Chatzimagas, L; Hub, JS; Herr, AB. Solution Structural Studies of Pre-amyloid Oligomer States of the Biofilm Protein Aap. Journal of Molecular Biology. 2022; 434:167708.

Erickson, JJ; Archer-Hartmann, S; Yarawsky, AE; Miller, JL C; Seveau, S; Shao, TY; Severance, AL; Miller-Handley, H; Wu, Y; Pham, G; et al. Pregnancy enables antibody protection against intracellular infection. Nature. 2022; 606:769-775.

Locker, KC S; Kachapati, K; Wu, Y; Bednar, KJ; Adams, D; Patel, C; Tsukamoto, H; Heuer, LS; Aronow, BJ; Herr, AB; et al. Endosomal Sequestration of TLR4 Antibody Induces Myeloid-Derived Suppressor Cells and Reverses Acute Type 1 Diabetes. Diabetes. 2022; 71:470-482.

Borowska, MT; Drees, C; Yarawsky, AE; Viswanathan, M; Ryan, SM; Bunker, JJ; Herr, AB; Bendelac, A; Adams, EJ. The molecular characterization of antibody binding to a superantigen-like protein from a commensal microbe. Proceedings of the National Academy of Sciences of USA. 2021; 118:e2023898118.

Zamakhaeva, S; Chaton, CT; Rush, JS; Ajay Castro, S; Kenner, CW; Yarawsky, AE; Herr, AB; van Sorge, NM; Dorfmueller, HC; Frolenkov, GI; et al. Modification of cell wall polysaccharide guides cell division in Streptococcus mutans. Nature Chemical Biology. 2021; 17:878-887.

Locker, KC S; Herr, AB. Binding Proteins | Antibodies: Structure and Immune Effector Functions. Encyclopedia of Biological Chemistry III. : Elsevier; Elsevier; 2021.

Davis, G; York, AJ; Bacon, WC; Lin, SC; McNeal, MM; Yarawsky, AE; Maciag, JJ; Miller, JL C; Locker, KC S; Bailey, M; et al. Seroprevalence of SARS-CoV-2 infection in Cincinnati Ohio USA from August to December 2020. Editor, Kumar B. PloS one. 2021; 16:e0254667.

Slater, A; Di, Y; Clark, JC; Jooss, NJ; Martin, EM; Alenazy, F; Thomas, MR; Ariëns, RA S; Herr, AB; Poulter, NS; et al. Structural characterization of a novel GPVI-nanobody complex reveals a biologically active domain-swapped GPVI dimer. Blood. 2021; 137:3443-3453.

Khodoun, MV; Morris, SC; Shao, WH; Potter, C; Angerman, E; Kiselev, A; Yarawsky, AE; Herr, AB; Klausz, K; Otte, A; et al. Suppression of IgE-mediated anaphylaxis and food allergy with monovalent anti-FcεRIα mAbs. Journal of Allergy and Clinical Immunology. 2021; 147:1838-1854.e4.

Gonzalez, T; Stevens, ML; Kyzy, AB; Alarcon, R; He, H; Kroner, JW; Spagna, D; Grashel, B; Sidler, E; Martin, LJ; et al. Biofilm propensity of Staphylococcus aureus skin isolates is associated with increased atopic dermatitis severity and barrier dysfunction in the MPAACH pediatric cohort. Allergy: European Journal of Allergy and Clinical Immunology. 2021; 76:302-313.

Stevens, ML; Gonzalez, T; Schauberger, E; Baatyrbek kyzy, A; Andersen, H; Spagna, D; Kalra, MK; Martin, LJ; Haslam, D; Herr, AB; et al. Simultaneous skin biome and keratinocyte genomic capture reveals microbiome differences by depth of sampling. Journal of Allergy and Clinical Immunology. 2020; 146:1442-1445.

DeVore, SB; Gonzalez, T; Sherenian, MG; Herr, AB; Khurana Hershey, GK. On the surface: Skin microbial exposure contributes to allergic disease. Annals of Allergy, Asthma, and Immunology. 2020; 125:628-638.

Yarawsky, AE; Herr, AB. The staphylococcal biofilm protein Aap forms a tetrameric species as a necessary intermediate before amyloidogenesis. The Journal of biological chemistry. 2020; 295:12840-12850.

Liu, S; Refaei, M; Liu, S; Decker, A; Hinerman, JM; Herr, AB; Howell, M; Musier-Forsyth, K; Tsang, P. Hairpin RNA-induced conformational change of a eukaryotic-specific lysyl-tRNA synthetase extension and role of adjacent anticodon-binding domain. The Journal of biological chemistry. 2020; 295:12071-12085.

Herr, AB. Secret(ory) revealed: the long-awaited structures of secretory IgA. Cell Research. 2020; 30:558-559.

Myers, JM B; Sherenian, MG; Kyzy, AB; Alarcon, R; An, A; Flege, Z; Morgan, D; Gonzalez, T; Stevens, ML; He, H; et al. Events in Normal Skin Promote Early-Life Atopic Dermatitis-The MPAACH Cohort. Journal of Allergy and Clinical Immunology: In Practice. 2020; 8:2285-2293.e6.

Yarawsky, AE; Johns, SL; Schuck, P; Herr, AB. The biofilm adhesion protein Aap from Staphylococcus epidermidis forms zinc-dependent amyloid fibers. The Journal of biological chemistry. 2020; 295:4411-4427.

Khodoun, MV; Morris, SC; Angerman, E; Potter, C; Schuman, R; Wunderlich, M; Maciag, JJ; Locker, KC S; Mulloy, JC; Herr, AB; et al. Rapid desensitization of humanized mice with anti-human FcεRIα monoclonal antibodies. Journal of Allergy and Clinical Immunology. 2020; 145:907-921.e3.

Myers, JB; Sherenian, M; Kyzy, AB; Alarcon, R; An, A; Flege, Z; Morgan, D; Gonzalez, T; Stevens, M; He, H; et al. The Mechanisms of Atopic Dermatitis to Asthma in Children (MPAACH) Cohort: Novel Atopic Dermatitis Endotypes. Journal of Allergy and Clinical Immunology. 2020; 145:ab337.

Sliz, A; Locker, KC S; Lampe, K; Godarova, A; Plas, DR; Janssen, EM; Jones, H; Herr, AB; Hoebe, K. Gab3 is required for IL-2- and IL-15-induced NK cell expansion and limits trophoblast invasion during pregnancy. Science Immunology. 2019; 4:eaav3866.

Grants

R01 GM094363 (Herr PI) (2011-2015), Studies of metal-dependent intercellular adhesion in Staphylococcal biofilms.

R01 GM098539 (Renfrow PI, Herr sub-contract PI) (2011-2015) Analytical tools for the analysis of clustered O-glycans in clinical samples.

Research Innovation and Pilot grant, Cincinnati Children's (Strait PI, Herr Co-PI) (2015) Characterization of IgG1 inhibition of inflammatory arthritis.

American Heart Association Predoctoral Award, Great Rivers Affiliate (Shelton PI, Herr sponsor) (2013-2015), Clues into preventing persistent cardiovascular infections by targeting the biofilm protein Aap from S. epidermidis.

Fulbright-Nehru Doctoral Research Fellowship, (Prakash PI, Herr Sponsor) (2014-2015) Development of an in-vitro mixed biofilm model to understand the drug resistance nature in device associated Staphylococci.

Contact Us

A photo of Andrew Herr.

Andrew B. Herr, PhD

Phone: 513-803-7490
Email: andrew.herr@cchmc.org

Herr Lab at a hockey game.