Kevin H. Gardner

Biochemistry/Structural Biology

(he/his/him)

Areas of Expertise/Research

  • Biochemistry
  • Biotechnology
  • Cancer Biology
  • Drug Development

Building

CUNY Advanced Science Research Center

Office

ASRC 3.322

Phone

212-413-3220

picture of Kevin Gardner

Kevin H. Gardner

Profile

Kevin H. Gardner received his B.S. in Biochemistry from UC Davis (1989) and his Ph.D. in Molecular Biophysics & Biochemistry from Yale University (1995), where he developed NMR methods to study metalloprotein structure.  He continued his training in structural biology with a postdoctoral fellowship with Lewis Kay at the University of Toronto, developing novel isotopic labeling and other methods for the study of large protein complexes with solution NMR.  Dr. Gardner began his independent academic career at the UT Southwestern Medical Center in Dallas, where he established a structural biology research group within the Departments of Biophysics and Biochemistry, exploring regulatory mechanisms of several classes of sensory proteins and discovering ways which these may be controlled by natural or artificial stimuli in the process.
 
Dr. Gardner now serves as the inaugural director of the Structural Biology Initiative of the CUNY Advanced Science Research Center (ASRC) and as the Einstein Professor of Chemistry & Biochemistry at City College.  The ASRC, a new 200,000 ft2 interdisciplinary research enterprise built by CUNY, assembles teams of scientists in fields that are often separated within most academic centers – structural biology, photonics, nanotechnology, neuroscience and environmental sciences – to catalyze novel collaborative interactions among experts in these fields.
 

Education

Postdoctoral research, University of Toronto; advisor: Lewis E. Kay, Ph.D. (1995-1998)
 
Ph.D., Molecular Biophysics & Biochemistry, Yale University; advisor: Joseph E. Coleman, M.D., Ph.D. (1989-1995)
 
B.S., Biochemistry, University of California, Davis (1985-1989) 

Research Interests

Environmentally-regulated protein/protein interactions

Environmental cues regulate many biological processes, controlling pathways used by cells to respond to changing conditions.  Such regulation is often initiated by sensory protein domains that use internally-bound ligands to convert environmentally-triggered changes into altered protein/protein interactions.  Several families of these domains have evolved with remarkable diversity in the stimuli they sense and outputs that they control.  Combining biophysics, biochemistry and cell biology in our group – and critically collaborating with labs in related areas – we seek insights into the signaling mechanisms of proteins used by cells to sense and respond to the environment around them.  In doing so, we aim to decipher how proteins use common sensory mechanisms despite tremendous diversity in their functions and biological settings – for example, revealing how a cancer-related transcription factor in human cells senses natural metabolites similarly to a photosensory protein looking for blue light within marine bacteria.  Such studies lay the foundation for both understanding the natural regulation of these systems and artificially controlling them, leading to first-in-class anti-cancer drugs (Merck's belzutifan) and optogenetic tools for biotechnology.

Selected Publications

Dikiy, I.*, Swingle, D.*, Toy, K., Edupuganti, U.R., Rivera-Cancel, G. and Gardner K.H. (2023) Conservation of function with diversification of higher-order structure within sensor histidine kinase.  J. Biol. Chem., 299: 104934.

Berlew, E.E., Yamada, K., Rand, E.A., Kuznetsov, I.A., Ochs, C., Jaber, Z., Gardner, K.H. and Chow, B.Y. (2022) Designing single-component optogenetic membrane recruitment systems: The Rho-family GTPase signaling toolbox.  ACS Synthetic Biology, 11: 515-521.

Hart, J.E. and Gardner, K.H.  (2021)  Lighting the way: Recent progress on the structure and function of phototropin blue light receptors.  J. Biol. Chem., 296: 100594.

Xu, X., Dikiy, I., Evans, M.R., Marcelino, L.P. and Gardner, K.H.  (2021)  Fragile protein folds: Sequence and environmental factors affecting the equilibrium of two interconverting, stably folded protein conformations.  Magn. Reson., 2: 63-76.

Xu, X., Gagné, D., Aramini, J.M. and Gardner, K.H.  (2021)  Volume and compressibility differences between protein conformations revealed by high-pressure NMR.  Biophys J., 120: 924-935.

Dikiy, I. and Gardner, K.H.  (2019). Shining light on the Alphaproteobacterial general stress response.  Mol Micro, 112: 438-441.

Dikiy, I., Edupuganti, U.R., Abzalimov, R.R., Borbat, P.B., Srivastava, M., Freed, J.H., and Gardner, K.H.  (2019)  Insights into histidine kinase activation mechanisms from the monomeric blue light sensor EL346. Proc Natl Acad Sci, 116: 4963-4972.

Glantz, S.T., Berlew, E.E., Jaber, Z., Schuster, B.S., Gardner, K.H. and Chow, B.Y.  (2018)  Directly light-regulated binding of RGS-LOV photoreceptors to anionic membrane phospholipids.  Proc Natl Acad Sci, 115: E7720-E7727.

Losi, A., Gardner, K.H. and Möglich, A.  (2018)  Blue-light receptors for optogenetics.  Chem Res, 118: 10659-10709.

Clark, L.*, Dikiy, I.*, Chapman, K., Rödström, K.E., Aramini, J., LeVine, M., Khelashvili, G., Rasmussen, S.G.F., Gardner, K.H. and Rosenbaum, D.M.  (2017)  Ligand modulation of sidechain dynamics in a wild-type human GPCR.  eLife, 6: e28505. (*:equal contributors).

Chen, W., Hill, H., Christie, A., Kim, M.S., Holloman, E., Pavía-Jiménez, A., Homayoun, F., Ma, Y., Patel, N., Yell, P., Hao, G., Yousuf, Q., Joyce, A., Pedrosa, I., Geiger, H., Zhang, H., Chang, J. Gardner, K.H., Bruick, R.K., Reeves, C., Hwang, T.H., Courtney, K., Frenkel, E., Sun, X., Zojwalla, N., Wong, T., Rizzi, J.P., Wallace, E.M., Josey, J.A., Xie, Y., Xie, X.-J., Kapur, P., McKay, R.M. and Brugarolas, J.  (2016)  Targeting renal cell carcinoma with a HIF-2 antagonist.  Nature, 539: 112-117

Motta-Mena, L.B., Reade, A., Mallory, M.J., Glantz, S., Weiner, O.D., Lynch, K.W. and Gardner, K.H.  (2014)  An optogenetic gene expression system with rapid activation and deactivation kinetics.  Nat Chem Biol, 10: 196-202.

Scheuermann, T.H., Li, Q., Ma, H.-W., Key, J., Zhang, L., Chen, R., Garcia, J.A., Naidoo, J., Longgood, J., Frantz, D.E., Tambar, U.K., Gardner, K.H.† and Bruick, R.K.†  (2013)  Allosteric inhibition of Hypoxia Inducible Factor 2 with small molecules.  Nat Chem Biol, 9: 271-276. (†: corresponding authors).

Nash, A.I.*, McNulty, R.*, Shillito, M.E., Swartz, T.E., Bogomolni, R.A., Luecke, H.† and Gardner, K.H.† (2011)  Structural basis of photosensitivity in a bacterial LOV-HTH DNA binding protein.  Proc Natl Acad Sci, 108: 9449-9454. (*: equal contributors, †: corresponding authors)

Harper, S.M., Neil, L.C. and Gardner, K.H.  (2003)  Structural basis of a phototropin light switch.  Science, 301: 1541-1544.

Amezcua, C.A., Harper, S.M., Rutter J. and Gardner, K.H.  (2002)  Structure and interactions of PAS kinase N-terminal PAS domain: Model for intramolecular kinase regulation.  Structure, 10: 1349-1361. 

Selected Honors

Stein and Moore Award 2023, Protein Society
Award for the Biophysics of Health and Disease 2023, Biophysical Society
Einstein Professor of Chemistry and Biochemistry 2013-present, City College of New York
Excellence in Education Awards 2010, 2012 UT Southwestern Medical Center
Excellence in Postdoctoral Mentoring Award 2011, UT Southwestern Postdoctoral Association
Virginia Lazenby O'Hara Chair in Biochemistry 2006-2013, UT Southwestern Medical Center
Outstanding Teacher Award 2004-2005, Dept. of Biochemistry, UT Southwestern
Searle Scholar 1999-2002, The Chicago Community Trust
W.W. Caruth, Jr. Scholar in Biomedical Research 1998-2013, UT Southwestern Medical Center
Helen Hay Whitney Postdoctoral Fellow 1996-1998, Helen Hay Whitney Foundation
NIH/NRSA Postdoctoral Fellow 1995-1996, National Institutes of Health
HHMI Predoctoral Fellow 1989-1994, HHMI
B.S. with Highest Honors (Biochemistry) 1989, UC Davis
Departmental Citation for Excellence 1989, UC Davis, Department of Biochemistry
Phi Beta Kappa 1989, UC Davis