Andrew Kleist, PhD

Signal transduction, G protein-coupled receptors (GPCRs), protein dynamics, molecular bioinformatics, disease polymorphisms, pharmacogenomics and genomic medicine

Research Experience

Medical College of Wisconsin, 2014-2019
Advisor: Brian Volkman, PhD
Project: Signal discrimination and signal transduction at chemokine G protein-coupled receptors (F30CA196040)

Laboratory of Molecular Biology, Cambridge UK, 2018-2019
Advisor: Madan Babu, PhD
Project: Structural bioinformatics of chemokine-GPCR interactions

Duke University, 2010-2012
Advisor: Robert Lefkowitz, MD
Project 1: Identification of ligand bias at G protein-coupled receptors using a novel, cell-free approach
Project 2: Identification of β-arrestin-biased ligands at G protein-coupled receptors from chemical and virtual compound libraries

Publications

Kleist, A.B., Peterson, F., Tyler, R.C., Gustavsson, M., Handel, T.M., and Volkman, B.F. (2019). Solution NMR spectroscopy of GPCRs: Residue-specific labeling strategies with a focus on (13)C-methyl methionine labeling of the atypical chemokine receptor ACKR3. Methods Cell Biol 149, 259-288.

Thomas, M.A., *Kleist, A.B., and Volkman, B.F. (2018). Decoding the chemotactic signal. J Leukoc Biol 104, 359-374. *Equal contribution

Szpakowska, M., Nevins, A.M., Meyrath, M., Rhainds, D., D'Huys, T., Guite-Vinet, F., Dupuis, N., Gauthier, P.A., Counson, M., Kleist, A., et al. (2018). Different contributions of chemokine N-terminal features attest to a different ligand binding mode and a bias towards activation of ACKR3/CXCR7 compared with CXCR4 and CXCR3. Br J Pharmacol 175, 1419-1438.

Ziarek, J.J., Kleist, A.B., London, N., Raveh, B., Montpas, N., Bonneterre, J., St-Onge, G., DiCosmo-Ponticello, C.J., Koplinski, C.A., Roy, I., et al. (2017). Structural basis for chemokine recognition by a G protein-coupled receptor and implications for receptor activation. Sci Signal 10.

Kleist, A.B., Getschman, A.E., Ziarek, J.J., Nevins, A.M., Gauthier, P.A., Chevigne, A., Szpakowska, M., and Volkman, B.F. (2016). New paradigms in chemokine receptor signal transduction: Moving beyond the two-site model. Biochem Pharmacol 114, 53-68.

Strachan, R.T., Sun, J.P., Rominger, D.H., Violin, J.D., Ahn, S., Rojas Bie Thomsen, A., Zhu, X., Kleist, A., Costa, T., and Lefkowitz, R.J. (2014). Divergent transducer-specific molecular efficacies generate biased agonism at a G protein-coupled receptor (GPCR). J Biol Chem 289, 14211-14224.

Weiss, D.R., Ahn, S., Sassano, M.F., Kleist, A., Zhu, X., Strachan, R., Roth, B.L., Lefkowitz, R.J., and Shoichet, B.K. (2013). Conformation guides molecular efficacy in docking screens of activated beta-2 adrenergic G protein coupled receptor. ACS Chem Biol 8, 1018-1026.

Meeting Abstracts

Kleist, A., R. Tyler, F.C. Peterson, T.M. Handel, and B.F. Volkman. 2015. Surveying conformational landscapes at chemokine receptors using Nuclear Magnetic Resonance spectroscopy. Abstract for poster presentation. Membrane Protein Structures Meeting, Argonne National Laboratory, Lemont, Illinois, April 2015.

General Interests

Ice hockey, reading, saxophone, NPR