Brian F. Volkman, PhD
BS, Butler University, 1989
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.
- Amino Acid Sequence
- Binding Sites
- Chemokine CCL21
- Chemokine CXCL12
- Chemokines, C
- Chemokines, CXC
- Computational Biology
- Crystallography, X-Ray
- Drug Design
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.
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
Mechanistic Insight into the Suppression of Polyglutamine Aggregation by SRCP1.
(Haver HN, Wedemeyer M, Butcher E, Peterson FC, Volkman BF, Scaglione KM.) ACS Chem Biol. 2023 Mar 17;18(3):549-560 PMID: 36791332 PMCID: PMC10023506 SCOPUS ID: 2-s2.0-85148304370 02/16/2023
Fragment-based drug discovery of small molecule ligands for the human chemokine CCL28.
(Zhou AL, Jensen DR, Peterson FC, Thomas MA, Schlimgen RR, Dwinell MB, Smith BC, Volkman BF.) SLAS Discov. 2023 Feb 23 PMID: 36841432 SCOPUS ID: 2-s2.0-85149845436 02/26/2023
DPP4-Truncated CXCL12 Alters CXCR4/ACKR3 Signaling, Osteogenic Cell Differentiation, Migration, and Senescence.
(Elmansi AM, Eisa NH, Periyasamy-Thandavan S, Kondrikova G, Kondrikov D, Calkins MM, Aguilar-Pérez A, Chen J, Johnson M, Shi XM, Reitman C, McGee-Lawrence ME, Crawford KS, Dwinell MB, Volkman BF, Blumer JB, Luttrell LM, McCorvy JD, Hill WD.) ACS Pharmacol Transl Sci. 2023 Jan 13;6(1):22-39 PMID: 36659961 PMCID: PMC9844133 01/21/2023
DPP4-Truncated CXCL12 Alters CXCR4/ACKR3 Signaling, Osteogenic Cell Differentiation, Migration, and Senescence
(Elmansi AM, Eisa NH, Periyasamy-Thandavan S, Kondrikova G, Kondrikov D, Calkins MM, Aguilar-Pérez A, Chen J, Johnson M, Shi XM, Reitman C, McGee-Lawrence ME, Crawford KS, Dwinell MB, Volkman BF, Blumer JB, Luttrell LM, McCorvy JD, Hill WD.) ACS Pharmacology and Translational Science. 13 January 2023;6(1):22-39 SCOPUS ID: 2-s2.0-85143982229 01/13/2023
Rapid biosensor development using plant hormone receptors as reprogrammable scaffolds.
(Beltrán J, Steiner PJ, Bedewitz M, Wei S, Peterson FC, Li Z, Hughes BE, Hartley Z, Robertson NR, Medina-Cucurella AV, Baumer ZT, Leonard AC, Park SY, Volkman BF, Nusinow DA, Zhong W, Wheeldon I, Cutler SR, Whitehead TA.) Nat Biotechnol. 2022 Dec;40(12):1855-1861 PMID: 35726092 PMCID: PMC9750858 SCOPUS ID: 2-s2.0-85132543880 06/22/2022
Selective and Cell-Active PBRM1 Bromodomain Inhibitors Discovered through NMR Fragment Screening.
(Shishodia S, Nuñez R, Strohmier BP, Bursch KL, Goetz CJ, Olp MD, Jensen DR, Fenske TG, Ordonez-Rubiano SC, Blau ME, Roach MK, Peterson FC, Volkman BF, Dykhuizen EC, Smith BC.) J Med Chem. 2022 Oct 27;65(20):13714-13735 PMID: 36227159 PMCID: PMC9630929 SCOPUS ID: 2-s2.0-85140311972 10/14/2022
Conformational selection guides β-arrestin recruitment at a biased G protein-coupled receptor.
(Kleist AB, Jenjak S, Sente A, Laskowski LJ, Szpakowska M, Calkins MM, Anderson EI, McNally LM, Heukers R, Bobkov V, Peterson FC, Thomas MA, Chevigné A, Smit MJ, McCorvy JD, Babu MM, Volkman BF.) Science. 2022 Jul 08;377(6602):222-228 PMID: 35857540 PMCID: PMC9574477 SCOPUS ID: 2-s2.0-85133822505 07/21/2022
Defining the Mutational Landscape That Affects the Histone Demethylase KDM6A/UTX in Human Cancer.
(Chi YI, Stodola TJ, de Assuncao TM, Volkman B, Smith B, Mathison AJ, Lomberk G, Zimmermann MT, Urrutia R.) FASEB J. 2022 May;36 Suppl 1 PMID: 35555661 SCOPUS ID: 2-s2.0-85130046941 05/14/2022
A new obligate CXCL4–CXCL12 heterodimer for studying chemokine heterodimer activities and mechanisms
(Nguyen KTP, Volkman B, Dréau D, Nesmelova IV.) Scientific Reports. December 2022;12(1) SCOPUS ID: 2-s2.0-85139877877 12/01/2022
Conformational selection guides β-arrestin recruitment at a biased G protein–coupled receptor
(Kleist AB, Jenjak S, Sente A, Laskowski LJ, Szpakowska M, Calkins MM, Anderson EI, McNally LM, Heukers R, Bobkov V, Peterson FC, Thomas MA, Chevigné A, Smit MJ, McCorvy JD, Babu MM, Volkman BF.) Science. 8 July 2022;377(6602):222-228 SCOPUS ID: 2-s2.0-85133822505 07/08/2022
The Extended N-Terminal Domain Confers Atypical Chemokine Receptor Properties to CXCR3-B.
(D'Uonnolo G, Reynders N, Meyrath M, Abboud D, Uchański T, Laeremans T, Volkman BF, Janji B, Hanson J, Szpakowska M, Chevigné A.) Front Immunol. 2022;13:868579 PMID: 35720349 PMCID: PMC9198273 SCOPUS ID: 2-s2.0-85132304428 06/21/2022
Structural bioinformatics enhances the interpretation of somatic mutations in KDM6A found in human cancers.
(Chi YI, Stodola TJ, De Assuncao TM, Leverence EN, Smith BC, Volkman BF, Mathison AJ, Lomberk G, Zimmermann MT, Urrutia R.) Comput Struct Biotechnol J. 2022;20:2200-2211 PMID: 35615018 PMCID: PMC9111933 SCOPUS ID: 2-s2.0-85130080827 05/27/2022