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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(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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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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Development and validation of a purification system for functional full-length human SR-B1 and CD36.
(Powers HR, Jenjak SE, Volkman BF, Sahoo D.) J Biol Chem. 2023 Oct;299(10):105187 PMID: 37625590 PMCID: PMC10509710 SCOPUS ID: 2-s2.0-85171377774 08/26/2023
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(Chi YI, Jorge SD, Jensen DR, Smith BC, Volkman BF, Mathison AJ, Lomberk G, Zimmermann MT, Urrutia R.) bioRxiv. 2023 Sep 07 PMID: 37786696 PMCID: PMC10541560 10/03/2023
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Design of stimulus-responsive two-state hinge proteins.
(Praetorius F, Leung PJY, Tessmer MH, Broerman A, Demakis C, Dishman AF, Pillai A, Idris A, Juergens D, Dauparas J, Li X, Levine PM, Lamb M, Ballard RK, Gerben SR, Nguyen H, Kang A, Sankaran B, Bera AK, Volkman BF, Nivala J, Stoll S, Baker D.) Science. 2023 Aug 18;381(6659):754-760 PMID: 37590357 PMCID: PMC10697137 SCOPUS ID: 2-s2.0-85168284894 08/17/2023
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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
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Fragment-based screening by protein-detected NMR spectroscopy.
(Kerber PJ, Nuñez R, Jensen DR, Zhou AL, Peterson FC, Hill RB, Volkman BF, Smith BC.) Methods Enzymol. 2023;690:285-310 PMID: 37858532 PMCID: PMC10657026 SCOPUS ID: 2-s2.0-85166280504 10/20/2023
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(Ratnasinghe BD, Haque N, Wagenknecht JB, Jensen DR, Valdivia Esparza GK, Leverence EN, Milech De Assuncao T, Mathison AJ, Lomberk G, Smith BC, Volkman BF, Urrutia R, Zimmermann MT.) Comput Struct Biotechnol J. 2023;21:4790-4803 PMID: 37841325 PMCID: PMC10570560 10/16/2023
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(Shi ZR, Mabuchi T, Riutta SJ, Wu X, Peterson FC, Volkman BF, Hwang ST.) Journal of Psoriasis and Psoriatic Arthritis. July 2023;8(3):107-117 SCOPUS ID: 2-s2.0-85150743226 07/01/2023