Chemical Biology

Benjamin Garcia

Photo: 
First Name: 
Benjamin
Last Name: 
Garcia
Official Title: 
Presidential Professor of Biochemistry and Biophysics
Contact Information
Office Location: 
9-124 Smilow Center for Translational Research
Email: 
bgarci@mail.med.upenn.edu
Phone: 
215-573-9423
Education: 

B.S. University of California, Davis (2000) Chemistry

Ph.D. University of Virginia (2005) Chemistry

NIH NRSA Postdoctoral Fellow, Institute for Genomic Biology Postdoctoral Fellow, University of Illinois, Urbana-Champaign (2008)

Research Interests: 

The Garcia Lab utilizes high-resolution mass spectrometry to explore cellular signaling, epigenetic mechanisms and chromatin regulation. We are especially interested in understanding how protein and nucleic acid modifications mediate their canonical functions and regulate nuclear processes. Mass spectrometry has become an unparalleled tool in the analysis of these biological molecules and allows us to obtain quantitative information about modifications as well as their co-occurrence. These modifications are critical for nuclear stability and transcription; and dysregulation of these pathways underlie several human diseases such as cancer. Our work aims to reveal the roles of these modifications in the cell cycle, proliferation, differentiation, signaling pathways and metabolism, to consequently help elucidate the mechanisms of various diseases.

Selected Publications: 

Characterization of histone acylations links chromatin modifications with metabolism. Simithy J, Sidoli S, Yuan ZF, Coradin M, Bhanu NV, Marchione DM, Klein BJ, Bazilevsky GA, McCullough CE, Magin RS, Kutateladze TG, Snyder NW, Marmorstein R, Garcia BA. Nat Commun. 2017 Oct 26;8(1):1141. doi: 10.1038/s41467-017-01384-9.

 

The nucleosomal surface is the main target of histone ADP-ribosylation in response to DNA damage. Karch KR, Langelier MF, Pascal JM, Garcia BA. Mol Biosyst. 2017 Nov 21;13(12):2660-2671.

 

Proteome-wide acetylation dynamics in human cells. Kori Y, Sidoli S, Yuan ZF, Lund PJ, Zhao X, Garcia BA. Sci Rep. 2017 Aug 31;7(1):10296.

 

Metabolic labeling in middle-down proteomics allows for investigation of the dynamics of the histone code. Sidoli S, Lu C, Coradin M, Wang X, Karch KR, Ruminowicz C, Garcia BA. Epigenetics Chromatin. 2017 Jul 6;10(1):34.

 

Differential quantification of isobaric phosphopeptides using data-independent acquisition mass spectrometry. Sidoli S, Fujiwara R, Kulej K, Garcia BA. Mol Biosyst. 2016 Jul 19;12(8):2385-8.

 

Preferential Phosphorylation on Old Histones during Early Mitosis in Human Cells. Lin S, Yuan ZF, Han Y, Marchione DM, Garcia BA. J Biol Chem. 2016 Jul 15;291(29):15342-57.

 

A Novel Quantitative Mass Spectrometry Platform for Determining Protein O-GlcNAcylation Dynamics. Wang X, Yuan ZF, Fan J, Karch KR, Ball LE, Denu JM, Garcia BA. Mol Cell Proteomics. 2016 Jul;15(7):2462-75.

 

Histone H4 acetylation and the epigenetic reader Brd4 are critical regulators of pluripotency in embryonic stem cells. Gonzales-Cope M, Sidoli S, Bhanu NV, Won KJ, Garcia BA. BMC Genomics. 2016 Feb 4;17:95.

 

Bioorthogonal Chemistry for the Isolation and Study of Newly Synthesized Histones and Their Modifications. Arnaudo AM, Link AJ, Garcia BA. ACS Chem Biol. 2016 Mar 18;11(3):782-91.

 

Monitoring Cellular Phosphorylation Signaling Pathways into Chromatin and Down to the Gene Level. Han Y, Yuan ZF, Molden RC, Garcia BA. Mol Cell Proteomics. 2016 Mar;15(3):834-53.

 

Low Resolution Data-Independent Acquisition in an LTQ-Orbitrap Allows for Simplified and Fully Untargeted Analysis of Histone Modifications. Sidoli S, Simithy J, Karch KR, Kulej K, Garcia BA. Anal Chem. 2015 Nov 17;87(22):11448-54.

 

Sequential Window Acquisition of all Theoretical Mass Spectra (SWATH) Analysis for Characterization and Quantification of Histone Post-translational Modifications. Sidoli S, Lin S, Xiong L, Bhanu NV, Karch KR, Johansen E, Hunter C, Mollah S, Garcia BA. Mol Cell Proteomics. 2015 Sep;14(9):2420-8.

 

Characterization of histone post-translational modifications during virus infection using mass spectrometry-based proteomics. Kulej K, Avgousti DC, Weitzman MD, Garcia BA. Methods. 2015 Nov 15;90:8-20.

Megan L. Matthews

Photo: 
First Name: 
Megan L.
Last Name: 
Matthews
Official Title: 
Assistant Professor of Chemistry
Contact Information
Office Location: 
2003 Vagelos
Email: 
megamatt@sas.upenn.edu
Phone: 
215-746-4738
Twitter: 
@MegaMatthewsLab
Admin Support: 
Education: 

B.S., Chemistry, Miami University (2005)

 

Ph.D., Chemistry, The Pennsylvania State University (2011)

 

Merck Helen Hay Whitney Postdoctoral Fellow (2012–2015) and postdoctoral associate (2015–2017), Department of Molecular Medicine, The Scripps Research Institute

Research Interests: 

Research in the Matthews group unites enzymology and chemical biology to develop novel chemical proteomics technologies for the discovery of enzyme cofactors and regulatory post-translational modifications that cannot readily be predicted by gene or protein sequence.

 

Intrinsic nucleophiles abound among the proteinogenic amino acids, but, interestingly, reactive electrophiles are essentially absent. Therefore, the majority of chemical probes target nucleophilic sites to discover enzymes, inhibitors and drug therapies. However, by acquiring them through post-translational modifications, enzymes do indeed exploit diverse classes of protein-bound electrophiles for catalysis and other essential functions. Owing to this mode of acquisition, functional electrophiles are not generally predictable from sequence; thus, their breadth and prevalence remain to be found. Our group is exploring this unknown to understand the functions of reactive modifications that we have found unexpectedly on drug targets implicated in cancer and Alzheimer’s disease. Such discoveries can be uncovered using the ‘reverse-polarity’ chemical probes that we develop. We expect that this largely un-profiled half of the reactive proteome – the covalent ‘electrophilome’ – will be found to rival its 'nucleophilome' counterpart in functional diversity and disease relevance.

Selected Publications: 

The Scripps Research Institute

17.    Matthews ML*, He L, Olson EJ, Horning BD, Correia BE, Yates JR, III, Dawson PE & Cravatt BF*. “Chemoproteomic profiling and discovery of protein electrophiles in human cells.” Nat. Chem. 9, 234–243 (2017).

16.    Horning BD, Suciu RM, Ghadiri D, Ulanovskaya O, Matthews ML, Lum KM, Backus KM, Brown SJ, Rosen H & Cravatt BF. “Chemical proteomic profiling of human methyltransferases.” J. Am. Chem. Soc. 138, 13335–13343 (2016).

15.    Rajagopalan S, Wang C, Yu K, Kuzin AP, Richter F, Lew S, Miklos AE, Matthews ML, Seetharaman J, Su M, Hunt JF, Cravatt BF & Baker D. “Design of activated serine-containing catalytic triads with atomic-level accuracy.” Nat. Chem. Biol. 10, 386-391 (2014).

14.    Chang JW, Niphakis MJ, Lum KM, Cognetta AB, Wang C, Matthews ML, Niessen S, Buczynski MW, Parsons LH & Cravatt BF. “Highly selective inhibitors of monoacylglycerol lipase bearing a reactive group that is bioisosteric with endocannabinoid substrates.” Chem. Biol. 19, 579-588 (2012).

The Pennsylvania State University

13.    Srnec M, Wong SD, Matthews ML, Krebs C, Bollinger JM, Jr. & Solomon EI. “Electronic structure of the ferryl intermediate in the a-ketoglutarate dependent non-heme iron halogenase SyrB2: Contributions to H-atom abstraction reactivity.” J. Am. Chem. Soc. 138, 5110-5122 (2016). 

12.    Matthews ML*, Chang WC, Layne AP, Miles LA, Krebs C & Bollinger JM, Jr.* “Direct nitration and azidation of aliphatic carbons by an iron-dependent halogenase.” Nat. Chem. Biol. 10, 209-215 (2014).  

11.    Wong SD, Srnec M, Matthews ML, Liu LV, Kwak Y, Park K, Bell CB, Alp EE, Zhao JY, Yoda Y, Kitao S, Seto M, Krebs C, Bollinger JM, Jr. & Solomon EI. “Elucidation of the Fe(IV)=O intermediate in the catalytic cycle of the halogenase SyrB2.” Nature 499, 320-323 (2013).

10.    Krebs C, Dassama LMK, Matthews ML, Jiang W, Price JC, Korboukh V, Li N & Bollinger JM, Jr. “Novel approaches for the accumulation of oxygenated intermediates to multi-millimolar concentrations.” Coord. Chem. Rev. 257, 234-243 (2013).

9.      Hollenhorst MA, Bumpus SB, Matthews ML, Bollinger JM, Jr. Kelleher NL & Walsh CT. “The nonribosomal peptide synthetase enzyme DdaD tethers N(b)-fumaramoyl-L-2,3-diaminopropionate for Fe(II)/a-ketoglutarate-dependent epoxidation by DdaC during dapdiamide antibiotic biosynthesis.” J. Am. Chem. Soc. 132, 15773-15781 (2010).

8.      Bollinger JM, Jr. & Matthews ML. “Remote enzyme microsurgery.” Science 327, 1337-1338 (2010).

7.      Matthews ML, Neumann CS, Miles LA, Grove TL, Booker SJ, Krebs C, Walsh CT & Bollinger JM, Jr. “Substrate positioning controls the partition between halogenation and hydroxylation in the aliphatic halogenase, SyrB2.” Proc. Natl. Acad. Sci. USA 106, 17723-17728 (2009).

6.      Matthews ML, Krest CM, Barr EW, Vaillancourt FH, Walsh CT, Green MT, Krebs C & Bollinger JM, Jr. “Substrate-triggered formation and remarkable stability of the C–H bond-cleaving chloroferryl intermediate in the aliphatic halogenase, SyrB2.” Biochemistry 48, 4331-4343 (2009).

5.      Bollinger JM, Jr., Diao Y, Matthews ML, Xing G & Krebs C. “Myo-inositol oxygenase: a radical new pathway for O2 and C-H activation at a nonheme diiron cluster.” Dalton Trans. 905-914 (2009).

4.      Krebs C, Matthews ML, Jiang W & Bollinger JM, Jr. “AurF from Streptomyces thioluteus and a possible new family of manganese/iron oxygenases.” Biochemistry 46, 10413-10418 (2007).

3.      Fujimori DG, Barr EW, Matthews ML, Koch GM, Yonce JR, Walsh CT, Bollinger JM, Jr., Krebs C & Riggs-Gelasco PJ. “Spectroscopic evidence for a high-spin Br-Fe(IV)-oxo intermediate in the a-ketoglutarate-dependent halogenase CytC3 from Streptomyces.”  J. Am. Chem. Soc. 129, 13408-13409 (2007).

 

Miami University, 2001–2005

2.      Matthews ML, Periyannan G, Hajdin C, Sidgel TK, Bennett B & Crowder MW. “Probing the reaction mechanism of the D-ala-D-ala dipeptidase, VanX, by using stopped-flow kinetic and rapid-freeze quench EPR studies on the Co(II)-substituted enzyme.” J. Am. Chem. Soc. 128, 13050-13051 (2006).

1.      Breece RM, Costello A, Bennett B, Sigdel TK, Matthews ML, Tierney DL & Crowder MW. “A five-coordinate metal center in Co(II)-substituted VanX.” J. Biol. Chem. 280, 11074-11081 (2005).

Chemistry Biophysics Mini-Symposium

Fri, 2016-12-09 (All day)
Speaker: 
TBA
Location: 
TBA

Sergei Vinogradov

Photo: 
First Name: 
Sergei
Last Name: 
Vinogradov
Official Title: 
Professor of Biochemistry and Biophysics

Biophysical Chemistry, Photochemistry/Photophysics

Contact Information
Email: 
vinograd.upenn@gmail.com
Phone: 
215-573-7524
Education: 

M.S. (Chemistry) Moscow State University, Russia, 1988.

Ph.D. (Organic Chemistry) Moscow State University, Russia, 1995.

Research Interests: 
Dr. Vinogradov's research is focused on the development of advanced probes for microscopy and imaging applications. On the fundamental level our interests encompass chemistry of porphyrins and other pyrrolic dyes, energy and electron transfer in multichromophoric systems, spectroscopy and imaging. Essentially, we are a group of synthetic and physical chemists developing new techniques for biomedical research. Over the past years the main focus of the lab has been optical imaging of oxygen in biological systems, including chemistry of imaging probes, phosphorescence lifetime imaging instrumentation, image reconstruction methods and a variety of applications of phosphorescence. Other bio-analytes of interests have been pH and metal ions. Currently the laboratory also pursues interests in optical energy upconversion and magnetic field effects on luminescence in view of their applications in imaging. Dr. Vinogradov collaborates broadly with laboratories across the world whose interests include basic studies of cellular metabolism and applications in neuroscience, stem cell biology, cancer therapy, tissue engineering and ophthalmology.
Selected Publications: 

Esipova, T. V., Ye, X. C., Collins, J. E., Sakadzic, S., Mandeville, E. T., Murray, C. B., Vinogradov, S. A.: Dendritic upconverting nanoparticles enable in vivo multiphoton microscopy with low-power continuous wave sources. PNAS 109(51): 20826-20831, 2012.

 

Mani, T., Tanabe, M., Yamauchi, S., Tkachenko, N. V., Vinogradov, S. A.: Modulation of Visible Room Temperature Phosphorescence by Weak Magnetic Fields. Journal of Physical Chemistry Letters 3(21): 3115-3119, 2012.

 

Mani, T., Niedzwiedzki, D.M., Vinogradov, S.A.: Generation of Phosphorescent Triplet States via Photoinduced Electron Transfer: Energy and Electron Transfer Dynamics in Pt Porphyrin-Rhodamine B Dyads. J. Phys. Chem. A. 116: 3598−3610, 2012.

 

Vinogradov, S.A., Wilson, D.F. : Porphyrin-dendrimers as biological oxygen sensors. Designing dendrimers. Wiley, 2012.

 

Esipova, T. V., Karagodov, A., Miller, J., Wilson, D. F., Busch, T. M., Vinogradov, S. A.: Two new "protected" oxyphors for biological oximetry: properties and application in tumor imaging. Analytical Chemistry 83(22): 8756-8765, 2011.

 

Lecoq, J., Parpaleix, A., Roussakis, E., Ducros, M., Houssen, Y. G., Vinogradov, S. A.*, Charpak, S.*: Simultaneous two-photon imaging of oxygen and blood flow in deep cerebral vessels. Nature Medicine 17(7): 893-U262, 2011 Notes: Note that postdoc E. Roussakis is a co-first author and I am one of the two senior corresponding authors. My lab is entirely responsible for the new oxygen microscopy technology and worked with the collaborator to implement it in the brain.

 

Finikova, O. S., Lebedev, A. Y., Aprelev, A., Troxler, T., Gao, F., Garnacho, C., Muro, S., Hochstrasser, R. M., Vinogradov, S. A.: Oxygen microscopy by two-photon-excited phosphorescence. ChemPhysChem 9(12): 1673-1679, 2008.

 

Apreleva, S. V., Wilson, D. F., Vinogradov, S. A.: Tomographic imaging of oxygen by phosphorescence lifetime. Applied Optics 45(33): 8547-8559, 2006.

Hirschmann Visiting Professor - Lecture III (Sam Gellman, Wisconsin)

Thu, 2016-04-07 12:00 - 13:00
Speaker: 

Prof. Sam Gellman

University of Wisconsin, Madison

 

Location: 

Lynch Lecture Hall

 

Lecture II

Hirschmann Visiting Professor - Lecture II (Sam Gellman, Wisconsin)

Wed, 2016-04-06 13:00 - 14:00
Speaker: 

Prof. Sam Gellman

University of Wisconsin, Madison

Location: 

Lynch Lecture Hall

Lecture II

Special Biophysical Chemistry Seminar: Christy Landes, Rice

Wed, 2016-01-20 13:00 - 14:00
Speaker: 

Prof. Christy Landes

Rice University

Location: 
Lynch Lecture Hall
Attached Document: 

Single molecule dynamics at soft interfaces: from basic science to a $100,000,000,000 problem

 

Abstract

Special Seminar: Andrew Lee (Northwestern)

Tue, 2014-07-08 15:30 - 16:30
Speaker: 
Dr. Andrew Lee Northwestern University
Location: 
Lynch Lecture Hall
Attached Document: 
Interaction of Nanoparticle-Oligonucleotide Conjugates with Serum Nucleases

Joachim Frank Sympsoium

Wed, 2014-04-23 08:30 - 15:00
Speaker: 

The Ribosome: Structure and Function

 

Research Symposium Honoring 2014 Franklin Medal Laureate Joachim Frank

Location: 

Smilow Center for Translational Research

Attached Document: 

Speakers

 

Peter B. Moore, Ph.D.

Sterling Professor of Chemistry, Professor of Molecular Biophysics and Biochemistry, Yale University

 

Barry S. Cooperman, Ph.D.

Professor of Chemistry and Biological Chemistry, University of Pennsylvania

 

Christian Spahn, Ph.D.

Director, Institute for Medical Physics and Biophysics, Charité-Universitätsmedizin, Berlin

 

Yifan Cheng, Ph.D.

Research Professor of Biochemistry and Biophysics, University of California San Francisco

Department of Chemistry

231 S. 34 Street, Philadelphia, PA 19104-6323

215.898.8317 voice | 215.573.2112 fax | web@chem.upenn.edu

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