A.B. in Chemistry and Mathematics, Vassar College. PIs: Prof. Miriam Rossi and Prof. Joseph Tanski
PhD. in Biological Chemistry, Massachusetts Institute of Technology. PIs: Prof. Catherine L. Drennan and Prof. Collin M. Stultz.
Postdoctoral Research Assistant, University of California, Berkeley and The Scripps Research Institute. PI: Prof. Michael A. Marletta.
Work in my lab uses a variety of biochemical techniques to understand protein function and X-ray crystallography to analyze protein structure. In general, I am interested in the utilization of non-canonical or unnatural amino acids to study protein structure and function, and more broadly how cells sense and respond to their environment.
Non-canonical amino acids to study protein structure and tune protein function
Amino acids can be thought of as the building blocks of life—they can be put together to form unique peptides or proteins with distinct structures and functions. There are 20 naturally occurring amino acids and a few additional amino acid variants that our cells are able to make by modifying the initial 20 amino acids. Scientists continue to expand the alphabet of amino acids by chemically synthesizing amino acids that are not made in nature—these are often called non-canonical amino acids (ncAAs) or unnatural amino acids (UAAs). This expanded alphabet provides biochemists with additional tools to both explore protein structure and tune protein function. A large portion of the work in my lab focuses on the development, characterization, and utilization of ncAAs to do exactly this – better understand protein structures (Area A) and alter protein functions (Area B). I also have an interest in small molecule and ion sensing proteins (Area C). Areas A and B are largely done in collaboration with my colleagues Prof. Scott Brewer and Prof. Edward Fenlon Central to all of this scholarship is the mentoring of and collaboration with undergraduate researchers.
Area A: Develop, characterize, and utilize ncAAs or other small molecules with vibrational reporters to study protein structure. Vibrational reporters in protein systems are functional groups made of a few atoms (e.g. nitriles CN or azides N3) whose infrared (IR) spectroscopic signals are outside the range of the normal functional groups present in a protein (e.g. carbonyls C=O, amides NH, and alcohols OH) (Figure 3). The exact location or frequency of the IR signals for these reporters will change according to local solvation, hydrogen bonding, and electrostatic environments. Using protein-binding small molecules or ncAAs with vibrational reporter functional groups attached, local environments in proteins can be explored site-specifically.
Area B: Using ncAAs to investigate and tune protein function. In addition to using ncAAs to study protein structure, we are utilizing them to tune the functionality of a number of protein systems. Using a variety of phenylalanine-derived ncAAs we have altered the photophysical properties of GFP. We are currently working to tune the oxygen binding affinity of the heme nitric oxide and/or oxygen binding (H-NOX) protein using a variety of tyrosine-derived ncAAs.
Area C: Sensing of small molecules and ions. All organisms have mechanisms to sense their environment and relay that signal to cause an appropriate response (e.g., altered metabolism or gene expression, movement away from a toxin or towards nutrients). The goals in these projects are to biochemically and structurally characterize proteins involved in sensing and signaling pathways.
Grants & Awards
NSF CAREER Award entitled: "Probing Structure and Expanding Function with Genetically Encoded Non Canonical Amino Acids." 2019 - 2024
NIH R15 Academic Research Enhancement Award Grant entitled: "Monitoring and Tuning a Gas-Binding Heme Protein with Unnatural Amino Acids." 2016 - 2019
Research Corporation Cottrell College Science Award for our project entitled: "Sensing of Halogenated Pollutants by Dehalococcoides mccartyi." 2014 - 2016
NIH Ruth L. Kirschstein NRSA Postdoctoral Fellowship (F32) (declined)
Chair of 2011 Bioinorganic Chemistry Gordon Graduate Research Seminar, Ventura, CA
Sigma Xi, Vassar College Chapter
Chemistry Department Award to Graduating Senior, Vassar College
ACS College Recognition Award, Vassar College
F&M Undergraduate co-authors are in bold and corresponding authors are indicated with an asterisk.
Lee, B. L.; Papoutsis, B. M.; Wong, N. Y.; Piacentini, J.; Kearney, C.; Huggins, N. A.; Cruz, N.; Ng, T. T.; Hao, K. H.; Kramer, J. S.; Fenlon, E. E.; Nerenberg, P. S.; Phillips-Piro, C. M.; Brewer, S. H. Unraveling Complex Local Protein Environments with 4-Cyano-L-phenylalanine. Journal of Physical Chemistry B, 2022, 126, 8957-8969.
Olenginski, G.M., Piacentini, J., Harris, D., Runko, N., Papoutsis, B.M., Alter, J., Hess, K.R., Brewer, S.H.*, and Phillips-Piro, C.M.* Structural and spectrophotometric investigation of two unnatural amino acid altered chromophores in the superfolder green fluorescent protein. Acta Crystallographica D, 2021, D77, 1010-1018.
Luo, M., Eaton, C., Hess, K.R., Phillips-Piro, C.M.*, Brewer, S.H.*, and Fenlon, E.E.* Paired Spectroscopic and Crystallographic Studies of Protease Active Sites. Chemistry Select, 2019, 4, 9836-9843
Maurici, N., Savidge, N., Lee, B., Brewer, S.H., and Phillips-Piro, C.M.* Crystal structures of GFP with unnatural amino acid 4-nitro-L-phenylalanine. Acta Crystallographica F, 2018, F74, 650-655.
Kearney, C.; Olenginski, L. T., Hirn, T. D.; Fowler, G. D.; Tariq, D.; Brewer, S. H.*; Phillips-Piro, C. M.* Exploring Local Solvation Environments of a Heme Protein using the Spectroscopic Reporter 4-Cyano-L-phenylalanine. RSC Advances, 2018, 8, 13503-13512.
Hespen, C.W.; Bruegger, J.J.; Phillips-Piro, C. M.; Marletta, M. A.* Structural and Functional Evidence Indicates Selective Oxygen Signaling in Caldanaerobacter subterraneus H NOX. ACS Chemical Biology, 2016, DOI: 10.1021/acschembio.6boo431.
Dippel, A.B.; Olenginski, G.M.; Maurici, N.; Liskov, M. T.; Brewer, S. H.*; and Phillips-Piro, C.M.* Probing the effectiveness of spectroscopic reporter unnatural amino acids: a structual study. Acta Cryst. D. 2016, D72, 121-130.
Tookmanian, E.M.; Phillips-Piro, C.M.*; Fenlon, E.E.*; and Brewer, S.H.* Azidoethoxyphenylalanine as a Vibrational Reporter and Click Chemistry Partner in Proteins. Chemistry–A European Journal. 2015, 21, 19096-19103.
Weinert, E.E.; Phillips-Piro, C. M.; Marletta, M. A. Porphyrin pi-Stacking in a Heme Protein Scaffold Tunes Gas Ligand Affinity. J. Inorg. Biochem. 2013, 127, 7-12.
Winter, M. B.; Klemm, P. J.; Phillips-Piro, C. M.; Raymond, K. N.; Marletta, M. A. Porphyrin Substituted H-NOX Proteins as High Relaxivity MRI Contrast Agents. Inorg. Chem. 2013 52 (5), 2277-2279.
Weinert, E. E.; Phillips-Piro, C. M.; Tran, R.; Mathies, R. A.; Marletta, M. A. Controlling Conformational Flexibility of an O2-Binding H-NOX Domain. Biochemistry 2011, 50, 6832-6840.
Phillips, C. M.; Stultz, C. M.; Drennan, C. L. Search for the nik Operon: How a Ligand-Responsive Transcription Factor Hunts for its DNA Binding Site. Biochemistry 2010, 49, 7757-7763.
Phillips, C. M.; Schreiter, E. R.; Stultz, C. M.; Drennan, C. L. Structural Basis of Low Affinity Nickel-Responsive Transcription Factor NikR from Escherichia coli. Biochemistry 2010, 49, 7830-7838.
Phillips, C. M.; Nerenberg, P. S.; Drennan, C. L.; Stultz, C. M. The Physical Basis for Metal Selectivity in Escherichia coli NikR. Journal of the American Chemical Society 2009, 131, 10220-10228.
Phillips, C. M.; Drennan, C. L. Nickel Regulatory Transcription Factor, NikR. Handbook of Metalloproteins; Messerschmidt, A., Ed.; John Wiley & Sons, Ltd. 2008.
Bohon, J.; Jennings, L. D.; Phillips, C. M.; Licht, S.; Chance, M. R. The Conformation of Functional Domains in the ClpA Hexamer : A Synchrotron Footprinting Study. Structure 2008, 16, 1157-1165.
Phillips, C. M.; Schreiter, E. R.; Guo, Y.; Wang, S. C.; Zamble, D. B.; Drennan, C. L. Structural Basis of the Metal Specificity for Nickel Regulatory Protein NikR. Biochemistry 2008, 47 (7), 1938-1946.
Caruso, F.; Pettinari, C.; Marchetti, F.; Natanti, P.; Phillips, C.; Tanski, J.; Rossi, M. Synthesis, Molecular Structure (X-ray and DFT), and Solution Behavior of Titanium 4-Acyl-5-pyrazolonates. Correlations with Related Antitumor b-Diketonato Derivatives. Inorganic Chemistry 2007, 46, 7553-7560.
Pettinari, C.; Caruso, F.; Zaffaroni, N.; Villa, R.; Marchetti, F.; Pettinari, R.; Phillips, C.; Tanski, J.; Rossi, M. Synthesis, Spectroscopy (IR, multinuclear NMR, ESI-MS), Diffraction, Density Functional Study and in vitro Antiproliferative Activity of Pyrazole-beta-diketone Dihalotin(IV) Compounds on 5 Melanoma Cell Lines. Journal of Inorganic Biochemistry 2006, 100, 58-69.
Pettinari, C.; Marchetti, F.; Pettinari, R.; Cingolani, A.; Rivarola, E.; Phillips, C.; Tanski, J.; Rossi, M.; Caruso, F. Tin(II) and Lead(II) 4-Acyl-5-pyrazolonates: Synthesis, Spectroscopy (IR, 1H, 13C, and 119Sn NMR, 119Sn Mossbauer and ESI-MS) and X-ray Structural Characterization. European Journal of Inorganic Chemistry 2004, 17, 3484-3497.
2022 - Nathan Wong, Muya Li
2021 - Angelica Camilo, Brianna Papoutsis, Christian Bogardus, Lea Dungan
2020 - Darcy Harris, Nicolette Runko
2019 - ByungUk (Mike) Lee
2018 - Trexler Hirn, Maggie Luo
2017 - Caroline Kearney, Juliana Piacentini, Nicole Savidge
2016 - Nicole Maurici, Daniyal Tariq, Jordan Alter, Carolina Giraldo
2015 - Gregory Olenginski, Lukasz Olenginski, Elise Tookmanian
2014 - Andrew Dippel, Austin Zimmet
2013 - Brittany Sembler, Melanie Liskov
CNX164 - #Science: Engaging the Public
CHM111 and CHM112 - General Chemistry I and II with labs
CHM351 - Introductory Biochemistry with lab
CHM451 - Advanced Biochemistry
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