• Christine Piro
Associate Professor of Chemistry



Office: HAC416

Office: HAC 416
Lab: HAC 417 

Fall 2023 Office Hours: TBD or by appointment on Prof. Piro's Google Calendar


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 B2022126, 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. 2013127, 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.

Student Collaborations

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

Course Information

Courses Taught:

CNX164 - #Science: Engaging the Public

CHM111 and CHM112 - General Chemistry I and II with labs

CHM351 - Introductory Biochemistry with lab

CHM451 - Advanced Biochemistry

In the News

Story 7/16/2021

Student Researcher Helps Develop Tool for Biochemists

In her research with Chemistry Professor Christine Phillips-Piro, rising senior Sarah Schick is at work in the laboratory on a technique that would allow scientists to better understand how proteins...

Read More
Story 11/10/2016

Grant-Funded Chemistry Research Could Lead to Synthetic...

The research work of a Franklin & Marshall College professor and her students could one day lead to such developments as a blood substitute. 

Read More
Story 6/2/2016

Welcome Oliver Piro!

Assistant Professor Christine Phillips-Piro, and her husband, Nick, welcomed their second son, Oliver Piro!

Read More
Story 4/22/2014

F&M Chemistry Professor Developing Toxin-Sensing System

A Franklin & Marshall College science professor, with assistance from her students, is working to perfect a procedure that could one day identify pollutants that are difficult to detect. Assistant...

Read More