Philip C. Andrews, Ph.D.

Professor, Biological Chemistry

 1198 300 NIB

734-763-3130

Appointments

Biological Chemistry, Medical School
Computational Medicine and Bioinformatics, Medical School
Chemistry, College of LSA

Areas of Interest

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 Rutolo).   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. 

Laboratory Members:

Hye Kyong Kweon, Postdoctoral Fellow

hkweon@umich.edu

Angela Walker, Research Laboratory Specialist

mailto:akwalker@umich.edu

(734) 615-4864

Lolit Piersimoni, Research Associate

mailto:lolitap@umich.edu

(734) 615-4864

Honors & Awards

1993 Alan McCall Award in Mass Spectrometry for best paper in journal Organic Mass Spectrometry

1998 Inventor Recognition University of Michigan Technology Management office

1998 Faculty Recognition Award

Published Articles or Reviews

Our research is funded through the generosity of The National Cancer Institute, The National Human Genome Research Institute, and The Merck Genome Research Institute. Please visit http://www.proteome.med.umich.edu

1. Falkner J, Andrews P. Fast tandem mass spectra-based protein identification regardless of the number of spectra or potential modifications examined. Bioinformatics. 2005 May 15; 21(10):2177-84. Ulintz PJ, Zhu J, Qin ZS, Andrews PC. Improved classification of mass spectrometry database search results using newer machine learning approaches. Mol Cell Proteomics. 2006 Mar;5(3):497-509. Epub 2005 Nov 30.

2. Falkner JA, Falkner JW, Andrews PC. ProteomeCommons.org JAF: reference information and tools for proteomics. Bioinformatics. 2006 Mar 1;22(5):632-3. Epub 2006 Jan 24.

3. Ostrom, PH, Gandhi, H, Strahler, JR, Walker, AK, Andrews, PC, Leykam, J, Stafford, TW, Kelly, RK, Walker, DN, Buckley, M and Humpula,J.: Unraveling the sequence and structure of the protein osteocalcin from a 42 ka fossil horse. Geochimica et Cosmochimica Acta. (in press)

4. Garcia BA, Joshi S, Thomas CE, Chitta RK, Diaz RL, Busby SA, Andrews PC, Ogorzalek Loo RR, Shabanowitz J, Kelleher NL, Mizzen CA, Allis CD, Hunt DF. Comprehensive Phosphoprotein Analysis of Linker Histone H1 from Tetrahymena thermophila.Mol Cell Proteomics. 2006 Sep;5(9):1593-1609. Epub 2006 Jul 10.

5. Ulintz PJ, Zhu J, Qin ZS, Andrews PC. Improved classification of mass spectrometry database search results using newer machine learning approaches. Mol Cell Proteomics. 2006 Mar;5(3):497-509. Epub 2005 Nov 30.

6. Jagtap P, Michailidis G, Zielke R, Walker AK, Patel N, Strahler JR, Driks A, Andrews PC, Maddock JR. Early events of Bacillus anthracis germination identified by time-course quantitative proteomics.
Proteomics. 2006 Aug 23; [Epub ahead of print]

7. Jiang M, Datta K, Walker A, Strahler J, Bagamasbad P, Andrews PC, Maddock JR. The Escherichia coli GTPase CgtAE Is Involved in Late Steps of Large Ribosome Assembly. J Bacteriol. 2006 Oct;188(19):6757-70.

8. Kozarova A, Sliskovic I, Mutus B, Vacratsis PO, Simon ES, Andrews PC. Identification of Redox Sensitive Thiols of Protein Disulfide Isomerase Using Isotope Coded Affinity Technology and Mass Spectrometry. J Am Soc Mass Spectrom. 2006 Oct 27; [Epub ahead of print]

9. Falkner JA, Falkner JW, Andrews PC. ProteomeCommons.org IO Framework: reading and writing multiple proteomics data formats. Bioinformatics. 2007 Jan 15;23(2):262-3.

10. Falkner JA, Kachman M, Veine DM, Walker A, Strahler JR, Andrews PC. Validated MALDI-TOF/TOF Mass Spectra for Protein Standards. J Am Soc Mass Spectrom. 2007 May;18(5):850-5. PMID: 17329120

11. Jiang M, Sullivan SM, Walker AK, Strahler JR, Andrews PC, Maddock JR. Identification of novel Escherichia coli ribosome-associated proteins using isobaric tags and multidimensional protein identification techniques. J Bacteriol. 2007 May;189(9):3434-44. PMID: 17337586

12. Jayapandian M, Chapman A, Tarcea VG, Yu C, Elkiss A, Ianni A, Liu B, Nandi A, Santos C, Andrews P, Athey B, States D, Jagadish HV. Michigan Molecular Interactions (MiMI): putting the jigsaw puzzle together. Nucleic Acids Res. 2007 Jan;35(Database issue):D566-71. Epub 2006 Nov 27.

13. Parrish JR, Yu J, Liu G, Hines JA, Chan JE, Mangiola BA, Zhang H, Pacifico S, Fotouhi F, Dirita VJ, Ideker T, Andrews P, Finley RL Jr. A proteome-wide protein interaction map for Campylobacter jejuni. Genome Biol. 2007 Jul 5;8(7):R130

14. Mathivanan S, et al. Human Proteinpedia enables sharing of human protein data. Nat Biotechnol. 2008 Feb;26(2):164-7. PMID: 18259167

15. Leichert LI, Gehrke F, Gudiseva HV, Blackwell T, Ilbert M, Walker AK, Strahler JR, Andrews PC, Jakob U. Quantifying changes in the thiol redox proteome upon oxidative stress in vivo. Proc Natl Acad Sci U S A. 2008 Feb 14; [Epub ahead of print] PMID: 18287020

16. Ulintz PJ, Bodenmiller B, Andrews PC, Aebersold R, Nesvizhskii AI. Investigating MS2/MS3 matching statistics: a model for coupling consecutive stage mass spectrometry data for increased peptide identification confidence. Mol Cell Proteomics. 2008 Jan;7(1):71-87. Epub 2007 Sep 13. PMID: 17872894

For a complete list of this person’s publications, click HERE