
Brian F. Volkman, PhD
Director, Program in Chemical Biology; Professor, Biochemistry
Locations
- Biochemistry
TBRC C3815
Contact Information
Education
BS, Butler University, 1989
Biography
Dr. Volkman obtained his Bachelor of Science degree in Chemistry and Physics from Butler University in 1989 and his Doctorate degree from The University of California at Berkeley. The latter was awarded in 1994 for structural studies on proteins involved in bacterial gene regulation using NMR spectroscopy. Dr. Volkman's postdoctoral training was in the Department of Biochemistry at the University of Wisconsin-Madison. In 2000, Dr. Volkman started at the Medical College of Wisconsin where he is Professor in the Biochemistry Department. Dr. Volkman's work focuses on the structural biology of immunological signaling molecules and the use of NMR spectroscopy in structural proteomics.
Research Experience
- Amino Acid Sequence
- Binding Sites
- Chemokine CCL21
- Chemokine CXCL12
- Chemokines
- Chemokines, C
- Chemokines, CXC
- Chemotaxis
- Computational Biology
- Crystallography, X-Ray
- Dimerization
- Drug Design
Research Interests
Our goal is to invent new ways to treat cancer and other ailments by examining the three-dimensional architecture of proteins involved in disease and synthesizing new drug candidate molecules. This research links the expertise of chemists, structural biologists, and clinician-scientists who collaborate in the design and testing of potential therapies. Graduate students in my group have invented and patented new compounds that show promise as treatments for cancer and psoriasis. Your donation helps us accelerate the drug development process by paying for preclinical studies that most research grants simply won’t support - bridging the gap between our basic science discoveries and clinical trials.
We use NMR spectroscopy and many other techniques to (1) understand the transmission of biological signals in terms of molecular structure, recognition and dynamics and (2) exploit this knowledge for the design and discovery of new molecules with practical utility as research tools, bioactive nanomaterials, or new drugs.
Dynamics and folding. Protein function is exquisitely dependent on compactly folded structures that combine energetic stability with intrinsic flexibility. Our work has revealed surprising new examples of conformational variability and altered the established paradigm for protein folding to include the new category of ‘metamorphic’ proteins. We are now trying to define the thermodynamic and evolutionary origins of metamorphic folding using the divergence of human lymphotactin from the rest of the chemokine family as a prototypical example. Other projects analyze novel modes of conformational switching that control cell polarity and enzyme activity.
Molecular recognition. Biological signals are often controlled by promoting or disrupting the interaction between two proteins. Many chemokines have been directly implicated in human diseases. Compounds that block chemokine signaling might function as inhibitors of inflammation, cancer progression, viral infection or autoimmune disease. We recently used NMR to solve the structure of the first chemokine-receptor complex, and subsequently used the details of this interface to search for small molecule ligands that bind the chemokine and block its activity. A hybrid in silico/NMR approach to inhibitor screening is now being used to target multiple chemokines with the ultimate goal of drug discovery to treat metastatic cancer and psoriasis.
Lab Photo
Back Row L. to R.: Chris Veldkamp, Francis Peterson, Rob Tyler, Anthony Getschman (hands), Austin Jiang,
Alex Chadwick, Davin Jensen, Dustin Whitney and Josh Weiner
Middle Row L. to R.: Chad Koplinski, Amanda Nevins
First Row L. to R.: Dr. Brian Volkman, Echo the dog, Jamie Wieting, Becky Holme
Publications
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(Luís R, Volkman BF, Szpakowska M, Chevigné A.) J Leukoc Biol. 2025 Feb 04 PMID: 39903605 02/04/2025
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The multifaceted role of XCL1 in health and disease.
(Syed M, Dishman AF, Volkman BF, Walker TL.) Protein Sci. 2025 Feb;34(2):e70032 PMID: 39840812 PMCID: PMC11751857 SCOPUS ID: 2-s2.0-85215400606 01/22/2025
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(Zhang BB, Harrison K, Zhong Y, Maxwell JWC, Ford DJ, Calvey LP, So SS, Peterson FC, Volkman BF, Stone MJ, Bhusal RP, Kulkarni SS, Payne RJ.) J Am Chem Soc. 2024 Dec 18;146(50):34253-34259 PMID: 39629944 SCOPUS ID: 2-s2.0-85211025577 12/04/2024
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Molecular basis for chemokine recognition and activation of XCR1.
(Zhang X, Schlimgen RR, Singh S, Tomani MP, Volkman BF, Zhang C.) Proc Natl Acad Sci U S A. 2024 Nov 26;121(48):e2405732121 PMID: 39565315 PMCID: PMC11621518 SCOPUS ID: 2-s2.0-85210106138 11/20/2024
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Constitutive activity of an atypical chemokine receptor revealed by inverse agonistic nanobodies.
(Perez Almeria CV, Otun O, Schlimgen R, Lamme TD, Crudden C, Youssef N, Musli L, Jenjak S, Bobkov V, Drube J, Hoffmann C, Volkman BF, Granier S, Bechara C, Siderius M, Heukers R, Schafer CT, Smit MJ.) bioRxiv. 2024 Nov 04 PMID: 39574661 PMCID: PMC11580867 11/22/2024
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(Xu T, Schou AS, Lackman JJ, Barrio-Calvo M, Verhallen L, Goth CK, Jensen BAH, Veldkamp CT, Volkman BF, Peterson FC, Hjortø GM.) Int J Mol Sci. 2024 Oct 09;25(19) PMID: 39409188 PMCID: PMC11477141 SCOPUS ID: 2-s2.0-85206465330 10/16/2024
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(Pontejo SM, Martinez S, Zhao A, Barnes K, de Anda J, Alimohamadi H, Lee EY, Dishman AF, Volkman BF, Wong GCL, Garboczi DN, Ballesteros A, Murphy PM.) bioRxiv. 2024 Jul 25 PMID: 39091850 PMCID: PMC11291121 08/02/2024
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Structural basis for selectivity and antagonism in extracellular GPCR-nanobodies.
(Schlimgen RR, Peterson FC, Heukers R, Smit MJ, McCorvy JD, Volkman BF.) Nat Commun. 2024 May 30;15(1):4611 PMID: 38816420 PMCID: PMC11139983 SCOPUS ID: 2-s2.0-85194992751 05/31/2024
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(Zhang BB, Harrison K, Zhong Y, Maxwell JWC, Ford DJ, Calvey LP, So SS, Peterson FC, Volkman BF, Stone MJ, Bhusal RP, Kulkarni SS, Payne RJ.) Journal of the American Chemical Society. 18 December 2024;146(50):34253-34259 SCOPUS ID: 2-s2.0-85211025577 12/18/2024
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An orthogonalized PYR1-based CID module with reprogrammable ligand-binding specificity.
(Park SY, Qiu J, Wei S, Peterson FC, Beltrán J, Medina-Cucurella AV, Vaidya AS, Xing Z, Volkman BF, Nusinow DA, Whitehead TA, Wheeldon I, Cutler SR.) Nat Chem Biol. 2024 Jan;20(1):103-110 PMID: 37872402 PMCID: PMC10746540 SCOPUS ID: 2-s2.0-85174576715 10/24/2023
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(Jorge SD, Chi YI, Mazaba JL, Haque N, Wagenknecht J, Smith BC, Volkman BF, Mathison AJ, Lomberk G, Zimmermann MT, Urrutia R.) Front Genet. 2023;14:1291307 PMID: 38090150 PMCID: PMC10715303 SCOPUS ID: 2-s2.0-85179362461 12/13/2023
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(Chi YI, Jorge SD, Jensen DR, Smith BC, Volkman BF, Mathison AJ, Lomberk G, Zimmermann MT, Urrutia R.) Comput Struct Biotechnol J. 2023;21:5249-5258 PMID: 37954151 PMCID: PMC10632586 11/13/2023