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.
Clark, L., Dikiy, I., Rosenbaum, D.M. and Gardner, K.H. (2018) On the use of Pichia pastoris for isotopic labeling of human GPCRs for NMR studies. J. Biomol. NMR, 71: 203-211.
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., in press. DOI: 10.1021/acs.chemrev.8b00163
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).
Reade, A., Motta-Mena, L.B., Gardner, K.H., Stanier, D.Y., Weiner, O.D. and Woo, S. (2017) TAEL: A zebrafish-optimized optogenetic gene expression system with fine spatial and temporal control. Development, 144: 345-355.
Corrêa, F., Key, J., Kuhlman, B. and Gardner, K.H. (2016) Computational repacking of HIF-2a cavity replaces water-based stabilized core. Structure, 24: 1918-1927.
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.
Corrêa, F. and Gardner, K.H. (2016) Basis of mutual domain inhibition in a bacterial signaling switch. Cell Chem. Biol., 23: 945-954.
Glantz, S.T., Carpenter, E.J., Melkonian, M., Gardner, K.H., Boyden, E.S., Wong, G.K-S. and Chow, B.Y. (2016) Functional and topological diversity of LOV domain photoreceptors. Proc. Natl. Acad. Sci. USA, 113: E1442-E1451.
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. Nature 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).
Rivera-Cancel, G.*, Motta-Mena, L.B.* and Gardner, K.H. (2012) Identification of natural and artificial DNA substrates for the light-activated LOV-HTH transcription factor EL222. Biochemistry, 51: 10024-10034. (*: equal contributors)
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.
|Einstein Professor of Chemistry||2013-present, City College of New York|
|Excellence in Education Awards||2010, 2012 UT Southwestern Medical Center|
|GRC Chairs' Hall of Fame||2011, Gordon Research Conferences|
|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|
|Meloche Lecturer||2004, Dept. of Chemistry, University of Wisconsin|
|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|