Philip C. Andrews, Ph.D.

Professor, Biological Chemistry
Professor, Computational Medicine and Bioinformatics
Professor, Chemistry

Office: 1198 NIB
Lab: 1100, 1195 NIB
300 N. Ingalls Street
Ann Arbor, MI 48109-5404


(734) 763-3130

Areas of Interest

Our laboratory is very interested in understanding the functional and organizational patterns underlying complex systems with our major emphasis being on protein interactions and the role of post-translational modifications in controlling those interactions. We rely primarily on mass spectrometry and protein chemistry techniques to address problems in these areas.

A major focus has been to map changes in post-translational modifications during shifts in biological processes, notably the relative roles of phosphorylation and protein expression in the budding to filamentous growth shift in yeast (collaboration with Anuj Kumar), the self-assembly of the Golgi apparatus in cell division (with Yanzhuang Wang), and the organization of mitochondrial membrane protein complexes during metabolic changes (with Brandon Ruotolo). We also pursued the interdependencies of post-translational modifications in histones and their general relationships to cell functions (with Yifan Liu). 

To further these studies we are developing new technologies for global quantitative analysis of protein interactions in vivo and linking these interactions to the accompanying post-translational modifications. To this end, we have developed a series of new chemical crosslinkers and tagging reagents that are compatible with mass spectrometry and have a number of other useful properties. The ultimate aim of this research is to identify and quantify protein interactions in vivo that differentiate physiological states. These methods are currently being applied to the Golgi and mitochondrial membrane projects mentioned above. The latter project is intended to provide a molecular architecture for mitochondrial membrane proteins and to quantify changes in these structures during oxidative and anoxic metabolism. The goal for the Golgi project is similar in the sense that we have mapped the dramatic changes in phosphorylation status of Golgi and Golgi matrix proteins during the Golgi disassembly process that occurs during normal mitosis and we will link those phosphorylations to the protein interactions.

These reagents also have considerable utility in the field of structural mass spectrometry where they can be applied to the many solution-phase structures of proteins and protein complexes not amenable to X-ray crystallography or NMR. Our aims in structural mass spectrometry are to accurately map distance constraints between amino acid residues, identify flexible domains, and quantify changes in protein structures. These reagents are being applied to several large, isolated complexes, among them Hsp70 and Hsp90 complexes with a variety of proteins (collaboration with Dan Southworth and Jason Gestwicki).

Finally, our reagents, by introducing fixed charges on the surfaces of protein complexes have proven to be quite useful for top-down analysis of protein complexes and we expect them to have a major impact in this regard. 

All these applications generate large, complex data sets that require development of new computational tools which we are pursuing in our lab and in collaboration with Alexey Nesvizhskii. 

Honors & Awards

Faculty Recognition Award, University of Michigan, 1998
Inventor Recognition Award, University of Michigan Technology Management Office, 1998
Alan McCall Award in Mass Spectrometry for best paper in the journal Organic Mass Spectrometry, 1993

Published Articles or Reviews

Recent Publications

Structures of rhodopsin in complex with G-protein-coupled receptor kinase 1.
Chen Q, Plasencia M, Li Z, Mukherjee S, Patra D, Chen CL, Klose T, Yao XQ, Kossiakoff AA, Chang L, Andrews PC, Tesmer JJG.
Nature. 2021; 595: 600–5.

Hyperphosphorylation Renders Tau Prone to Aggregate and to Cause Cell Death.
Liu M, Sui D, Dexheimer T, Hovde S, Deng X, Wang KW, Lin HL, Chien HT, Kweon HK, Kuo NS, Ayoub CA, Jimenez-Harrison D, Andrews PC, Kwok R, Bochar DA, Kuret J, Fortin J, Tsay YG, Kuo MH.
Mol Neurobiol. 2020; 57: 4704–19.

Pervasive Charge Solvation Permeates Native-like Protein Ions and Dramatically Influences Top-down Sequencing Data.
Polasky DA, Dixit SM, Keating MF, Gadkari VV, Andrews PC, Ruotolo BT.
J Am Chem Soc. 2020; 142: 6750–60.

Structural analysis of lecithin:cholesterol acyltransferase bound to high density lipoprotein particles.
Manthei KA, Patra D, Wilson CJ, Fawaz MV, Piersimoni L, Shenkar JC, Yuan W, Andrews PC, Engen JR, Schwendeman A, Ohi MD, Tesmer JJG.
Commun Biol. 2020; 3: 28.

Altered Domain Structure of the Prion Protein Caused by Cu2+ Binding and Functionally Relevant Mutations: Analysis by Cross-Linking, MS/MS, and NMR.
McDonald AJ, Leon DR, Markham KA, Wu B, Heckendorf CF, Schilling K, Showalter HD, Andrews PC, McComb ME, Pushie MJ, Costello CE, Millhauser GL, Harris DA.
Structure. 2019; 27: 907–22.

Synthesis of CID-cleavable protein crosslinking agents containing quaternary amines for structural mass spectrometry.
Hagen SE, Liu K, Jin Y, Piersimoni L, Andrews PC, Showalter HD.
Org Biomol Chem. 2018; 16: 6867–70.

For a list of publications at Google Scholar, click HERE

Web Sites