Biochemistry and Molecular Biophysics Graduate Group

BMB Home » Academics » BMB Courses » BMB 598

BMB 598 - Tutorials

Course Director: Aaron Gitler
Assistant Professor of Cell and Developmental Biology
1109 Biomedical Research Bldg (BRB) II/III
Office: 215-573-8251
Lab: 215-898-9487
Fax: 215-898-9871
Email: gitler@mail.med.upenn.edu

Description of course:
The tutorial course is designed to provide students with an in-depth appreciation of a specific subject, and present their knowledge orally. A tutorial can be used to enable students to become more deeply acquainted with the literature of a particular field or experimental approach related to their thesis project. The tutorial can also be used to better prepare students for their Candidacy Exam. Students are encouraged to select a tutorial with faculty mentors other than their thesis advisor.

Upon completion of the tutorial, students must prepare a written description of the area studied (1-2 single spaced pages) and present a short seminar (25 minutes, with 5 minutes for discussion) on the specific topic. Students will be graded on both the written and oral presentations. Graduate Group faculty and students are invited to attend these talks.

 

Charles S. Abrams, M.D.
Professor of Medicine
912 BRB II/III
Tel: 215-898-1058
Email: abrams@mail.med.upenn.edu

Tutorial Topics: 1) phospholipid second messenger signaling; 2) actin assembly in platelets and lymphocytes; 3) protein-lipid interactions

References:

  1. Volpicelli-Daley, LA, L Lucast, L-W Gong, L Liu, J Sasaki, T Sasaki, CS Abrams, Y Kanaho, P De Camilli (2010) Phosphatidylinositol 4-phosphate 5-kinases (PIPKIs) and phosphatidylinositol 4,5 bisphosphate [PI(4,5)P2] synthesis in the brain. J. Biologic Chemistry (in press).
  2. Min, SH, CS Abrams (2009) Why do phosphatidylinositol kinases have so many isoforms? Biochemical J 423(1):99-108.
  3. Mao, YS, M Yamaga, X Zhu, M Wei, H-Q Sun, J Wang, M Yun, Y Wang, G Di Paolo, M Bennett, IS Mellman, CS Abrams, PV De Camilli, CY Lu, and HL Yin (2009) Essential and unique roles of PIP5Kg and a in Fcg receptor-mediated phagocytosis. J. Cell Biology 184:281-296.
  4. Lian, L, W Wang, M Flick, J Choi, E. Scott, J Degen, MA Lemmon, CS Abrams (2009) Loss of pleckstrin defines a novel pathway for PKC-mediated exocytosis. Blood 113(15):3577-3584.
  5. Pan, W, S-C Choi, H Wang, Y Qin, L Volpicelli-Daley, L Swan, L Lucast, C Khooo, X Zhang, L Li, CS Abram., SY Sokol, D Wu (2008) Wnt3a-mediated formation of phosphatidylinositol 4,5-bisphosphate regulates LRP6 phosphorylation. Science (2008) 321:1350-1353.
  6. Wang, Y, X Chen, L Lian, T Tang, TJ Stalker, T Sasaki, LF Brass, JK Choi , JH Hartwig, and CS Abrams (2008) Loss of PIP5KIb demonstrates that rapid PIP2 synthesis is required for IP3 formation. Proceedings of the National Academy of Science (USA) 105:14064-14069.
  7. Bezman, N, L Lian, CS Abrams, LF Brass, ML Kahn, MS Jordan, GA Koretzky (2008) : Requirements of SLP-76 tyrosines in ITAM and integrin receptor signaling and in platelet function in vivo. Journal of Experimental Medicine 205:1775 – 1788.


Yair Argon, Ph.D.
Professor of Pathology & Laboratory Medicine
816B Abramson Research Center
Tel: 267-426-5131
Fax: 267-426-5165
E-mail: yargon@mail.med.upenn.edu

Tutorial Topics: 1) protein folding in the cell; 2) the unfolded protein response; 3) protein conformation diseases

References:

  1. Elkabetz, Y, Y Argon and S Bar-Nun (2005) Cysteines in the CH1 domain underlie retention of unassembled Ig heavy chains. J. Biol. Chem. (Feb 10, e-publication)
  2. Gidalevitz, T, C Biswas, H Ding, D Schneidman-Duhovny, HJ Wolfson, F Stevens, S Radford and Y Argon (2003) Identification of the N-terminal peptide binding site of GRP94. J. Biol. Chem. 279:16543-52
  3. Vogen, SM, T Gidalevitz, C Biswas, BS Simen, E Stein, F Gulmen, and Y Argon. (2002) Radicicol-sensitive peptide binding to the N-terminal portion of GRP94. J. Biol. Chem., 277:40742-40750.
  4. Davis, DP, G Gallo, SM Vogen, JL Dul, KL Sciarretta, A Kumar, R Raffen, FJ Stevens and Y Argon (2001) Both the environment and somatic mutations govern the aggregation pathway of pathogenic immunoglobulin light chain. J. Mol. Biol. 313:1023-1036.
  5. Dul, JL, PD Davis, EK Williamson, FJ Stevens and Y Argon (2001) Hsp70 and antifibrillogenic peptides promote degradation and inhibit intracellular aggregation of amyloidogenic light chains. J. Cell Biol. 152:705-715.
  6. Davis, D, R Raffen, JL Dul, S Vogen, EK Williamson, FJ Stevens, and Y. Argon (2000) Inhibition of amyloid fiber assembly by both BiP and its target peptide. Immunity 13:433-442.

Paul H. Axelsen, M.D.
Professor of Pharmacology, Biochemistry & Biophysics, and Medicine
105 Johnson Pavilion
Tel: (215) 898-9238
Email: axe@upenn.edu

Tutorial topics: 1) membrane protein folding and oxidative stress (various forms of optical spectroscopy and mass spectrometry); 2) structure-based rational drug design (only for students with advanced computer skills)

References:

  1. Kim, YS, Liu, L, Axelsen, PH, and Hochstrasser, RM (2008) Two dimensional infrared spectra of isotopically diluted amyloid fibrils from Ab40. Proceedings of the National Academy of Sciences USA 105:7720-7725.
  2. Liu, L, Komatsu, H, Murray, IVJ, and Axelsen, PH (2008) Promotion of amyloid x protein misfolding and fibrillogenesis by a lipid oxidation product. Journal of Molecular Biology 377:1236-1250.
  3. Murray, IVJ, L Liu, H Komatsu, K Uryu, G Xiao, JA Lawson, and PH Axelsen, (2007) Membrane mediated amyloidogenesis and the promotion of oxidative lipid damage by amyloid x proteins. Journal of Biological Chemistry 282:9335-9345.
  4. MacDonald, ML, IVJ Murray, and PH Axelsen (2007) Mass spectrometric analysis demonstrates that BODIPY 581/591 C11 overestimates and inhibits oxidative lipid damage. Free Radical Biology and Medicine 42:1392-1397.
  5. Murray, IVJ, ME Sindoni, and PH Axelsen (2005) Promotion of oxidative lipid membrane damage by amyloid x proteins. Biochemistry 44:12606-12613.
  6. Schneeweis, LA, V Koppaka, S Lund-Katz, MC Phillips, and PH Axelsen (2005) Structural analysis of lipoprotein E particles. Biochemistry 44:12525-12534.
  7. Jusuf, S and PH Axelsen (2004) Synchronized conformational fluctuations and binding site desolvation during molecular recognition. Biochemistry 43:15446-15452.
  8. Paul, C, J Wang, WC Wimley, RM Hochstrasser, and PH Axelsen (2004) Vibrational coupling, isotopic editing, and x sheet structure in a membrane bound polypeptide. Journal of the American Chemical Society 126:5843-5850.
  9. Koppaka, V, C Paul, IVJ Murray, and PH Axelsen. (2003) Early synergy between A beta 42 and oxidatively damaged membranes in promoting amyloid fibril formation by A beta 40. Journal of Biological Chemistry 278:36277-36284.

Joseph A. Baur, Ph.D.
Assistant Professor of Physiology
728 Clinical Research Building
Tel: 215-746-4585
Fax: 215-898-5408
Email: baur@mail.med.upenn.edu

Tutorial topics: 1) sirtuin deacetylases; 2) molecular mechanisms of caloric restriction

References:

  1. Baur, JA (2009) Metabolic effects of caloric restriction. In Encyclopedia of Life Sciences, John Wiley & Sons, Ltd, Chichester, UK. (in press)
  2. Pearson, KJ, JA Baur, KN Lewis, L Peshkin, NL Price, N Labinsky, WR Swindell, D Kamara, RK Minor, E Perez, HA Jamieson, Y Zhang, SR Dunn, K Sharma, N Pleshko, LA Woolett, A Csiszar, Y Ikeno, D Le Couteur, PJ Elliott, KG Becker, P Navas, DK Ingram, NS Wolf, Z Ungvari, DA Sinclair, and R de Cabo (2008) Resveratrol delays age-related deterioration and mimics transcriptional aspects of dietary restriction without extending life span. Cell Metabolism 8(2):157-168.
  3. Yang, H., T Yang, JA Baur, E Perez, T Matsui, JJ Carmona, DW Lamming, NC Souza-Pinto, VA Bohr, A Rosenzweig, R de Cabo, AA Sauve, DA Sincalir (2007) Mitochondrial NAD+ levels are regulated and promote cell survival via SIRT3 and SIRT4. Cell 130(6):1095-1107.
  4. Baur, JA, KJ Pearson, NL Price, HA Jamieson, C Lerin, A Kalra, VV Prabhu, JS Allard, G Lopez-Lluch, K Lewis, PJ Pistell, S Poosala, KG Becker, O Boss, D Gwinn, M Wang, S Ramaswamy, KW Fishbein, RG Spencer, EG Lakatta, D Le Couteur, RJ Shaw, P Navas, P Puigserver, DK Ingram, R de Cabo, DA Sinclair. (2006) Resveratrol improves health and survival of mice on a high-calorie diet. Nature 444(7177):337-342.
  5. Yang, H, JA Baur, A Chen, C Miller, DA Sinclair (2006) Design and synthesis of compounds the extend yeast replicative lifespan. Aging Cell 6(1):35-43.
  6. Baur, JA, DA Sinclair (2006) Therapeutic potential of resveratrol: the in vivo evidence. Nature Reviews in Drug Discovery 5(6): 337-342.
  7. Baur, JA, JW Shay, and WE Wright (2004) Spontaneous reactivation of a silent telomeric transgene. Chromosoma 112:240-246.
  8. Baur, JA, Y Zou, JW Shay, and WE Wright (2001) Telomere position effect in human cells. Science 292:2075-2077.

Morris J. Birnbaum, M.D., Ph.D.
Professor of Medicine, and Cell & Developmental Biology
Howard Hughes Medical Institute Investigator
322 Clinical Research Building
Tel: 215-898-5001
Fax: 215-573-9138
email: birnbaum@mail.med.upenn.edu

Tutorial Topics: 1) the mechanism of insulin signaling; 2) the regulation of metabolism

References:

  1. Leavens, KF, Easton, RM, Shulman, GI, Previs, SF and Birnbaum, MJ (2009) Akt2 is required for hepatic lipid accumulation in models of insulin resistance. Cell Metab. 10:405-418.
  2. DiAngelo, JR and Birnbaum MJ (2009) The regulation of fat cell mass by insulin in Drosophila melanogaster. Mol. Cell. Biol. 29:6431-6452.
  3. Gross, DN, van den Heuvel, AP, and Birnbaum, MJ (2008) The role of FoxO in the regulation of metabolism. Oncogene 27:2320-2336.
  4. Li, X, Monks, B, Ge, Q, and Birnbaum, MJ (2007) Akt/PKB regulates hepatic metabolism by directly inhibiting PGC-1a. Nature 447:1012-1016.
  5. Gleason, CE, Lu, D, Witters, LA, Newgard, CB, and Birnbaum, MJ (2007) The role of AMPK and mTOR in nutrient sensing in pancreatic β-cells. J. Biol. Chem. 282:10341-10351.
  6. Easton, RM, Cho, H, Roovers, K, Shineman, DW, Mizrahi, M, Forman, MS, Lee, V M-Y, Szabolcs, M, de Jong, R, Oltersdorf, T, Ludwig, T, Efstratiadis, A, and Birnbaum, MJ (2005) Role for Akt3/PKBg in attainment of normal brain size. Mol. Cell. Biol. 25:1869-1878.
  7. Bae, SS, Cho, H, Mu, J and Birnbaum, MJ (2003) Isoform-specific regulation of insulin-dependent glucose uptake by Akt/Protein Kinase B. J. Biol. Chem. 278:49530.
  8. Cho, H, Mu, J, Kim, JK, Thorvaldson, JL, Chu, Q, Crenshaw, EB, Kaestner, KH, Bartolomei, MS, Shulman, GI, and Birnbaum, MJ (2001) Insulin resistance and diabetes mellitus in mice lacking Akt2/PKB. Science 292:1728-1731. 

Ben E. Black, Ph.D.
Assistant Professor of Biochemistry and Biophyiscs
913A Stellar-Chance Labs
Tel: 215-898-5039
Email: blackbe@mail.med.upenn.edu 

Tutorial Topics: 1) mechanisms for assuring accurate chromosome segregation; 2) epigenetic versus genetic determinants for centromere identity; 3) chromosome "compartments" and nuclear architecture

References:

  1. Foltz, DR, LET Jansen, BE Black, AO Bailey, JR Yates III, and DW Cleveland (2006) The human CENP-A centromeric nucleosome-associated complex. Nat. Cell Biol. 8:458-469.
  2. Black, BE, DR Foltz, S Chakravarthy, K Luger, VL Woods Jr., and DW Cleveland (2004) Structural determinants for generating centromeric chromatin.  Nature 430:578-582.
  3. Cleveland, DW, Y Mao, and KF Sullivan (2003) Centromeres and kinetochores: from epigenetics to mitotic checkpoint signaling. Cell 112:407-421.

Kathleen Boesze-Battaglia, Ph.D.
Associate Professor
Department of Biochemistry, School of Dental Medicine
520 Leon Levy Building
Tel: 215-898-9167
Email: battagli@biochem.dental.upenn.edu

Tutorial Topics: 1) membrane dynamics and fusion; 2) membrane protein reconstitution; 3) lipid-protein interactions

References:

  1. Damek-Poprawa, M, E Golub, L Otis, G Harrison, C Phillips and K Boesze-Battaglia (2006)  Chondrocytes utilize a cholesterol dependent lipid translocator to externalize phosphatidylserine. Biochemistry 45:3325-3336.
  2. Boesze-Battaglia, K, D Besack, T McKay, A Zekavat, L Otis, K Jordan-Sciutto and BJ Shenker (2006) Cholesterol-rich membrane microdomains mediate cell cycle arrest induced by Actinobacillus actinomycetemcomitans cytolethal distending toxin. Cellular Microbiology 8:823-836.
  3. Damek-Poprawa, M, J Krouse, C Gretzula and K Boesze-Battaglia (2005)  A novel tetraspanin fusion protein, peripherin-2, requires a region upstream of the fusion domain for activity. J. Biol. Chem. 280:9217-24.
  4. Boesze-Battaglia, K, J Dispoto and MA Kahoe (2002) Association of a photoreceptor specific tetraspanin protein, ROM-1 with triton X-100 resistant membrane rafts from rod outer segment disk membranes. J. Biol. Chem. 277:41843-41849.
  5. Albert, A and K Boesze-Battaglia (2005) The role of cholesterol in rod outer segment membranes. Progress in Lipid Research 44:99-124.
  6. Boesze-Battaglia, K and AFX Goldberg (2002) Photoreceptor renewal: a role for peripherin/RDS.  International Reviews in Cytology 217:183-225.

Ari Borthakur, Ph.D.
Assistant Professor, Department of Radiology
Associate Director,Center for Magnetic Resonance & Optical Imaging
B1 Stellar-Chance Labs
Tel: 215-573-8482
Fax: 215-573-2113
Email: borthaku@mail.med.upenn.edu

Tutorial Topics: 1) MRI of degenerative diseases; 2) measurement of tissue perfusion and oxygen metabolism using MRI; 3) design of novel pulse sequences for clinical applications

References:

  1. Clark CM, Davatzikos C, Borthakur A, Newberg A, Leight S, Lee VMY, Trojanowski JQ. (2008) Biomarkers for early detection of Alzheimer pathology. Neurosignals 16(1):11-18.
  2. Borthakur A, Sochor M, Davatzikos C, Melhem ER, Trojanowski JQ, Clark CM. (2008) T1rho of Alzheimer's Disease. Neuroimage 41:1199–1205.
  3. Mellon EA, Beesam RS, Kasam M, Baumgardner JE, Borthakur A, Witschey WR, Jr., Reddy R. (2009) Single shot T1rho magnetic resonance imaging of metabolically generated water in vivo. Adv Exp Med Biol 645:279-286.
  4. Witschey WRT, Borthakur A, Elliott MA, Fenty M, Sochor M, Wang C, Reddy R. (2008) T1ρ-prepared balanced gradient echo for rapid 3D T1r MRI. Journal of Magnetic Resonance Imaging 28(3):744-754.
  5. Mellon EA, Pilkinton DT, Clark CM, Witschey WRT, Reddy R, Borthakur A (2009) Sodium MRI detection of mild Alzheimer Disease. American Journal of Neuroradiology.

Christopher G. Burd, Ph.D.
Associate Professor of Cell and Developmental Biology
1001 BRB II/III
Tel: 215-573-5158
Email: cburd@mail.med.upenn.edu

Tutorial Topics: 1) protein sorting in secretory and endocytic pathway; 2) molecular cell biology of Golgi and endosomal organelles; 3) protein-lipid interactions

References:

  1. Shin, ME, KE Ogburn, PM Gilbert, OA Varban and CG Burd (2001) FYVE domain targets Pib1p ubiquitin ligase to endosome and vacuolar membranes. J. Biol. Chem. 276:41388-41393.
  2. Gilbert, PM and CG Burd (2001) GDP dissociation inhibitor domain II required for Erab GTPase recycling. J. Biol. Chem. 265:8014-8020.
  3. Luan, PSD Emr, WE Balch and CG Burd (1999) Molecular dissection of guanine nucleotide dissociation inhibitor function in vivo. Rab-independent binding to membranes and role of Rab recycling factors. J. Biol. Chem. 274:14806-14817.
  4. Kutateladze, T, KD Ogburn, WT Watson, T de Beer and CG Burd (1999) Phospatidylinositol 3-phosphate recognition by the FYVE domain. Mol. Cell. 3:805-811.
  5. Burd, CG. and SD. Emr (1998) Phosphatidylinositol(3)-phosphate signaling mediated by specific binding to RING FYVE domains. Mol. Cell 2:157-162.

Theresa Busch, Ph.D.
Research Associate Professor of Radiation Oncology
B13 Anatomy-Chemistry Building
Tel: 215-573-3168
Fax: 215-898-0090
Email: buschtm@mail.med.upenn.edu

Tutorial topics: 1) photodynamic therapy of solid tumors; 2) dose rate effects in light delivery to tissue; 3) tumor vascularization/microenvironment

References:

  1. Wang H.W., Rickter E., Yuan M., Wileyto E.P., Glatstein E., Yodh A., Busch T.M. (2007) Effect of photosensitizer dose on fluence rate responses to photodynamic therapy. Photochemistry and Photobiology 83:1040-1048.
  2. Hahn S.M., Putt M.E., Metz J., Shin D.B., Rickter E., Menon C., Smith D., Glatstein E., Fraker D.L., Busch T.M. (2006) Photofrin uptake in the tumor and normal tissues of patients receiving intra-peritoneal photodynamic therapy. Clinical Cancer Research 12:5464-5470.
  3. Yu G., Durduran T., Zhou C., Wang H.W., Putt M.E., Saunders M., Sehgal C.M., Glatstein E., Yodh A.G., Busch T.M. (2005) Noninvasive monitoring of murine tumor blood flow during photodynamic therapy provides early assessment of treatment efficacy. Clinical Cancer Research 11:3543-3552.
  4. Wang H.W., Putt M.E., Emanuele M.J., Shin D.B., Glatstein E., Yodh A.G., Busch T.M. (2004) Treatment-induced changes in tumor oxygenation predict photodynamic therapy outcome. Cancer Research 64(20):7553-7561.
  5. Busch T.M., Wileyto E.P., Emanuele M.J., Del Piero F., Marconat, L., Glatstein E., Koch C.J. (2002) Photodynamic therapy creates fluence rate dependent gradients in the intra-tumoral spatial distribution of oxygen  Cancer Research 62:7273-7279.

Fevzi Daldal, Ph.D.
Professor of Biology
103B Carolyn Lynch Building
Tel: 215-898-8780
Email: fdaldal@sas.upenn.edu

Tutorial Topics: 1) cofactor addition to apoproteins and protein maturation; genomic and proteomic approaches; 2) membrane proteins involved in biological energy transduction

References:

  1. O’Brian, M.R. and L. Thony-Meyer (2002) Biochemistry, regulation and genomics of haem biosynthesis in prokaryotes. Adv. Microb. Physiol. 46:257-318.
  2. Kranz, R.G., C.S. Beckett and B.S. Goldman (2002) Genomic analyses of bacterial respiratory and cytochrome c assembly systems: Bordetella as a model for the system II cytochrome c biogenesis pathway. Res. Microbiol. 153:1-2.
  3. Saraste, M. (1999) Oxidative phosphorylation at the fin de siecle. Science 283:1488-1493.
  4. Darrouzet, E., C.C. Moser, P.L. Dutton and F. Daldal (2001) Large scale domain movement in cytochrome bc1; a new device for electron transfer in proteins. Trends. Biochem. Sci. 26:445-451.

William F. DeGrado, Ph.D.
George W. Raiziss Professor of Biochemistry and Biophysics
1009B Stellar-Chance Labs
Tel: 215-898-4590
Email: wdegrado@mail.med.upenn.edu

Tutorial Topics: 1) metalloproteins; 2) protein folding; 3) protein design; 4) membrane protein folding.

References:

  1. Yin, H, Slusky, JS, Berger, BW, Walters, RS, Vilair, G, Litinov, RI, Lear, JD, Caputo, GA, Bennett, JS, DeGrado, WF (2007) Computational design of peptides that target transmembrane helices Science 315:1817-1823.
  2. Wade, H, Stayrook, SE, and DeGrado, WF (2006) The structure of a designed diiron(III) protein: implications for cofactor stabilization and catalysis. Angew Chem Int Ed Engl 45:4951-4954.
  3. Walters, RF and DeGrado, WF (2006) Helix-packing motifs in membrane proteins. Proc Natl Acad Sci USA 103:13658-13663.
  4. Stouffer, AL, Nanda, V, Lear, JD and DeGrado, WF (2005) Sequence determinants of a transmembrane proton channel: an inverse relationship between stability and function. J Mol Biol 347:169-179.
  5. Cochran, FV, Wu, SP, Wang, W, Nanda, V, Saven, JG, Therien, MJ, and DeGrado, WF (2005) Computational de novo design and characterization of a four-helix bundle protein that selectively binds a nonbiological cofactor. J Am Chem Soc 127:1346-1347.
  6. Kaplan, J and DeGrado, WF (2004) De novo design of catalytic proteins. Proc Natl Acad Sci USA 101:11566-11570.
  7. Liu, D, Choi, S, Chen, B, Doerksen, RJ, Clements, DJ, Winkler, JD, Klein, ML and DeGrado, WF (2004) Nontoxic membrane-active antimicrobial arylamide oligomers. Angew Chem Int Ed Engl 43:1158-1162.
  8. Li, R, Mitra N, Gratkowski H, Vilaire G, Litvinov R, Nagasami C, Weisel JW, Lear JD, DeGrado WF, Bennett JS (2003) Activation of integrin alphaIIbbeta3 by modulation of transmembrane helix associations. Science 300:795-798.

Roberto Dominguez, Ph.D.
Professor of Physiology
A507 Richards Building
Tel: 215-573-4559
Fax: 215-573-5851
E-mail: droberto@mail.med.upenn.edu

Tutorial Topic: Mechanisms linking cellular membranes and cytoskeleton dynamics

References:

  1. Dominguez, R (2009) Actin filament nucleation and elongation factor - stucture-function relationships. Crit Rev Biochem Mol Biol 44(6):351-366
  2. Shvetsov A, Berkane E, Dominguez R and Reisler E (2009) The actin-binding domain of cortactin is dynamic and unstructed and affects lateral and longitudinal contacts in F-actin. Cell Motility and the Cytoskeleton 66:90-98.
  3. Lee SH, Baek K and Dominguez R (2008) Large nucleotide-dependent conformational change in Rab28. FEBS Letters 582:4107-4111.
  4. Baek K, Liu X, Ferron F, Shu S, Korn ED and Dominguez R (2008) Modulation of actin structure and function by phosphorylation of Tyr-53 and profilin binding. PNAS 105:11748–11753.
  5. Rebowski G, Boczkowska M, Hayes DB, Guo L, Irving TC and Dominguez R (2008) X-ray scattering study of actin polymerization nuclei assembled by tandem W domains. PNAS 105:10785-10790.
  6. Boczkowska M, Rebowski G, Petoukhov MV, Hayes DB, Svergun DI and Dominguez R (2008) X-ray scattering study of activated Arp2/3 complex with bound actin-WCA. Structure 16:695-704.
  7. Chereau D, Boczkowska M, Skwarek-Maruszewska A, Fujiwara I, Hayes DB, Rebowski G, Lappalainen P, Pollard TD and Dominguez R (2008) Leiomodin is an actin filament nucleator in muscle cells. Science 320:239-243.
  8. Lee SH, Weins A, Hayes DB, Pollak, MR and Dominguez R (2008) Crystal structure of the actin-binding domain of α-actinin-4 Lys255Glu mutant implicated in focal segmental glomerulosclerosis. J. Mol. Biol. 376:317-324.
  9. Ferron F, Rebowski G, Lee SH and Dominguez R. (2007) Structural basis for the recruitment of profilin–actin complexes during filament elongation by Ena/VASP. EMBO J. 26:4597-4606.
  10. Lee SH, Hayes DB, Rebowski G, Tardieux I, Dominguez R (2007) Toxofilin from Toxoplasma gondii forms a ternary complex with an antiparallel actin dimer. PNAS 104:16122-16127.

Gideon Dreyfuss, Ph.D.
Isaac Norris Professor of Biochemistry and Biophysics
Investigator, Howard Hughes Medical Institute
328 Clinical Research Building
Tel: 215-898-0398
Email: gdreyfuss@hhmi.upenn.edu

Tutorial Topics: 1) protein-protein interactions and the control of actin cytoskeleton dynamics; 2) At the interface between the actin cytoskeleton and the cell membrane.

References:

  1. Mourelatos, Z, Dostie J, Paushkin S, Sharma A, Charroux B, Abel L, Rappsilber J, Mann M and Dreyfuss G (2002) miRNPs: a novel class of ribonucleoproteins containing numerous microRNAs. Genes and Dev. 16:720-728.
  2. Pellizzoni, L, Yong, J, and Dreyfuss, G (2002) The SMN complex is a specificity factor essential for snRNP assembly. Science 298:1775-1779.
  3. Dreyfuss, G, Kim VN, and Kataoka, N (2002) mRNA-binding proteins and the messages they carry. Nature Reviews: Molecular Cell Biology 3:195-205.
  4. Kim, VN, Kataoka, N, and Dreyfuss, G (2001) Role of nonsense-mediated decay factor, hUpf3, in the splicing-dependent exon-exon junction complex. Science 293:1832-1836.
  5. Nakielny, S and G Dreyfuss (1999) Transport of proteins and RNAs in and out of the nucleus. Cell 99:677-690.
  6. Pellizzoni, L, N. Kataoka, B Charroux and G Dreyfuss (1998) A novel function for SMN, the spinal muscular atrophy disease gene product, in pre-mRNA splicing. Cell 95:615-624.
  7. Fischer, U, Liu Q and Dreyfuss G(1997) A complex containing SMN and SIP1 has an essential role in spliceosomal snRNPs biogenesis. Cell 90:1023-1029.

Hua-Ying Fan, Ph.D.
Assistant Professor of Biochemistry and Biophyiscs
564 Clinic Research Building
Tel: 215-573-5705
Email: hfan@mail.med.upenn.edu

Tutorial Topics: 1) regulation of chromatin structure; 2) regulation of ATP-dependent chromatin remodeling; 3) misregulation of chromatin structure and human diseases.

References:

  1. Lake, RJ, A Geyko, G Hemashettar, Y Zhao, H-Y Fan (2010) UV-induced association of the CSB remodeling protein with chromatin requires ATP-dependent relief of N-terminal autorepression. Molecular Cell 37(2):235-246.
  2. Fan, H-Y, K Trotter, T Archer, R Kingston (2005) Swapping function of two chromatin remodeling complexes. Molecular Cell 17:805-815.
  3. Fan, H-Y, X He, RE Kingston, GJ Narlikar (2003) Distinct strategies to make nucleosomal DNA accessible. Molecular Cell 11:1311-1322.

Kathryn M. Ferguson, Ph.D.
Associate Professor of Physiology,
D505 Richards Building
Tel: 215-573-1207
Email: ferguso2@mail.med.upenn.edu

Tutorial Topics: 1) dimerization of receptor tyrosine kinases; 2) molecular interactions in signal transduction pathways; 3) assembly of complexes that control intracellular traffic; 4) X-ray crystallography

References:

  1. Li, S, K. Schmitz, PD Jeffrey, J Wiltzius, P Kussie, and KM Ferguson (2005) Structural basis for inhibition of the Epidermal Growth Factor Receptor by cetuximab. Cancer Cell 7:301-311.
  2. Dawson, JP, MB Berger, C-C Lin, J Schlessinger, MA Lemmon, and KM Ferguson (2005) Epidermal Growth Factor Receptor dimerization and activation require ligand-induced conformational changes in the dimer interface. Mol. Cell Biol. 25:7734-7742.
  3. Ferguson KM, MB Berger, JM Mendrola, HS Cho, DJ Leahy, and MA Lemmon (2003)  EGF activates its receptor by removing interactions that auto-inhibit ectodomain dimerization. Molecular Cell 11:507-517.

Aaron D. Gitler, Ph.D.
Assistant Professor of Cell and Developmental Biology
1109 Biomedical Research Building II/III
Tel: 215-573-8251
Email: gitler@mail.med.upenn.edu

Tutorial Topics: 1) the role of protein misfolding in neurodegenerative disease 2) genetic models of human disease 3) genome-wide approaches to cell biology and human disease

References:

  1. Cooper, AA, AD Gitler, A Cashika, CM Haynes, KJ Hill, B Bhullar, K Liu ,K Xu , KE Strathearn, F Liu, et al. (2006) Alpha-synuclein blocks ER-Golgi traffic and Rab1 rescues neuron loss in Parkinson's models. Science 313:324-328.
  2. Auluck, PK, HY Chan, JQ Trojanowski, VM Lee, and NM Bonini (2002). Chaperone suppression of alpha-synuclein toxicity in a Drosophila model for Parkinson's disease. Science 295:865-868.
  3. Johnson, BS, JM McCaffery, S. Lindquist, S., and AD Gitler. (2008). A yeast TDP-43 proteinopathy model: Exploring the molecular determinants of TDP-43 aggregation and cellular toxicity. Proc Natl Acad Sci USA 105:6439-6444.
  4. Schuldiner, M., SR Collins, NJ Thompson, V Denic, A Bhamidipati,T Punna, J Ihmels, B Andrews, C Boone, JF Greenblatt, et al. (2005). Exploration of the function and organization of the yeast early secretory pathway through an epistatic miniarray profile. Cell 123:507-519.
  5. Tong, AH, M Evangelista, AB Parsons, H Xu, GD Bader, N Page, M Robinson, S Raghibizadeh, CW Hogue, H Bussey et al. (2001) Systematic genetic analysis with ordered arrays of yeast deletion mutants. Science 294:2364-2368.

Yale E. Goldman, M.D., Ph.D.
Professor of Physiology
Director, Pennsylvania Muscle Institute
D-700 Richards Building
Tel: 215-898-4017
Email: goldmany@mail.med.upenn.edu

Tutorial Topics: 1) motor proteins, structural biology and energy transduction; 2) ribosomal protein biosynthesis; 3) single molecule manipulation and optical spectroscopy.

References:

  1. Forkey, JN, ME Quinlan, AM Shaw, JE Corrie and YE Goldman (2003) Three-dimensional structural dynamics of myosin V by single-molecule fluorescence polarization. Nature 422:399-404.
  2. Rodnina, MA, T Pape, A Savelsbergh, D Mohr, NB Matassva and M Wintermeyer (2000) Mechanisms of partial reactions of the elongation cycle catalyzed by elongation factors Tu and G. In: The Ribosome: Structure, Function, Antibiotics, and Cellular Interactions (Garrett, R.A., S.R. Douthwaite, A. Lijias, A.T. Matheson, P.B. Moore and H.F. Noller, eds.), ASM Press, Washington DC 25:301-317.
  3. Forkey, JN, ME Quinlan and YE Goldman (2000) Protein structural dynamics by single molecule fluorescence polarization. Prog. Biophys. Mol. Biol. 74:1-35.
  4. Taylor, KA, H Schmitz, MC Reedy, YE Goldman, C Franzini-Armstrong, H Sasaki, RT Tregear, K Poole, C Lucaveche, RJ Edwards, LF Chen, H Winkler and MK Reedy (1999) Tomographic 3-D reconstruction of quick-frozen, Ca2+-activated contracting insect flight muscle. Cell 99:421-431.
  5. Corrie, JET, BD Brandmeier, RE Ferguson, DR Trentham, J Kendrick-Jones, SC Hopkins, UA van der Heide, YE Goldman, C Sabido-David, RE Dale, S Criddle and M Irving (1999) Dynamic measurement of myosin light-chain-domain tilt and twist in muscle contraction. Nature 400:425-430.
  6. Goldman, YE (1998) Wag the tail: structural dynamics of actomyosin. Cell 93:1-4.
  7. Hopkins, SC, C Sabido-David, JE Corrie, M Irving and YE Goldman (1998) Fluorescence polarization transients from rhodamine isomers on the myosin regulatory light chain in skeletal muscle fibers. Biophys. J. 74:3093-3110.
  8. Dantzig, JA, H Higuchi and YE Goldman (1998) Studies of molecular motors using caged compounds. Methods in Enzymol 291:307-348.
  9. Smith, CA and I Rayment (1996) Active site comparisons highlight structural similarities between myosin and other P-loop proteins. Biophys J. 70:1590-1602.
  10. Nyborg, J and A Liljas (1998) Protein biosynthesis: structural studies of the elongation cycle. FEBS Letters 430:95-109.

Mark Goulian, Ph.D.
Associate Professor of Biology, and Physics and Astronomy
204F Carolyn Lynch Laboratory
Tel: 215-573-6991
Fax: 215-898-2010
Email: goulian@sas.upenn.edu

Tutorial Topics: 1) modeling and design principles of bacterial regulatory circuits; 2) directed evolution of bacterial regulatory circuits

References:

  1. Miyashiro, T and M Goulian (2008) High stimulus unmasks positive feedback in an autoregulated bacterial signaling circuit. Proc. Natl. Acad. Sci. 105:17457-17462.
  2. Siryaporn, A and M Goulian (2008) Cross-talk suppression between the CpxA-CpxR and EnvZ-OmpR two-component systems in E. coli. Mol Microbiol. 70:494-506.
  3. Skerker, JM, BS Perchuk, A Siryaporn, EA Lubin, O Ashenberg, M Goulian, and M Laub (2008) Rewiring the specificity of two-component signal transduction systems. Cell 133:1043-1054.
  4. Miyashiro, T, and M Goulian (2007) Stimulus-dependent differential regulation in the Escherichia coli PhoQ PhoP system. Proc. Nat. Acad. Sci. 104:16305-16310.
  5. Derr, P, E Boder, and M Goulian (2006) Changing the specificity of a bacterial chemoreceptor. J. Mol. Biol. 355:923-932.
  6. Goulian, M (2004) Robust control in bacterial regulatory circuits. Curr. Opin. Microbiol. 7:198-202.
  7. Batchelor, E, TJ Silhavy and M Goulian (2004) Continuous control in bacterial regulatory circuits. J. Bacteriol. 186:7618-7635.
  8. Batchelor, E and M Goulian (2003) Robustness and the cycle of phosphorylation and dephosphorylation in a two-component regulatory system. Proc. Nat. Acad. Sci. 100:691-696.

Doron Greenbaum, Ph.D.
Assistant Professor of Pharmacology
304G Carolyn Lynch Laboratory
Tel: 215-746-2992
Fax:  215-573-9004
Email: greenbaum@pharm.med.upenn.edu

Tutorial Topics: 1) protease biochemistry, function and inhibition; 2) invasion strategies of malaria parasites; 3)  chemical biology techniques to study enzyme function

References:

  1. Joyce J, A Baruch, K Chehade, N Meyer-Morse, E Giraudo, F Tsai, DC Greenbaum, J Hager, M Bogyo, D Hanahan (2004) Cathepsin cysteine proteases are effectors of invasive tumor growth and angiogenesis during multistage tumorigenesis.  Cancer Cell 5: 443-453.
  2. Yasothornsrikul, S, DC Greenbaum, K Medzihradszky, T Toneff, R Bundey, R Miller, B Schilling, I Petermann, J Dehnert, A Logvinova, P Goldsmith, J Neveu, W Lane, B Gibson, T Reinheckel, C Peters, M Bogyo, V Hook (2003) Cathepsin L in secretory vesicles functions as a prohormone-processing enzyme for production of the enkephalin peptide neurotransmitter. PNAS 100: 9590-9595.
  3. Greenbaum DC, A Baruch, M Grainger, Z Bozdech, K Medzihradszky, J Engel, A Holder, J DeRisi, M Bogyo (2002) A role for the protease falcipain 1 in host cell invasion by the human malaria parasite.  Science 298:2002-2006.
  4. Greenbaum D, W Arnold, F Lu, L Hayrapetian, D Bromme, I Kuntz, M Bogyo (2002) Small molecule affinity fingerprinting: a tool for enzyme family subclassification, target identification, and inhibitor design. Chem. Biol. 9: 1085-1094.
  5. Greenbaum DC, KF Medzihradszky, A Burlingame, M Bogyo (2002) Epoxide electrophiles as activity-dependent cysteine protease profiling and discovery tools.  Chem. Biol. 7:569-581.

Harry Ischiropoulos, Ph.D.
Gisela and Dennis Alter Research Professor of Pediatrics and Pharmacology
417 Abramson Research Center
Tel: 215-90-5320
Email: ischirop@mail.med.upenn.edu

Tutorial Topics: 1) biological chemistry of nitric oxide; 2) oxidative chemistry and detection of reactive species; 3) protein aggregation

References:

  1. Parastatidis, I, LM Thomson, A Burke, I Chernysh, C Nagaswam., J Visser, S Stamer, DC Liebler, G Koliakos, HFG Heijnen, GA FitzGerald, JW Weisel, and H Ischiropoulos (2008) Fibrinogen x-chain tyrosine nitration is a prothrombotic risk factor.  J. Biol. Chem. Sep 25. [Epub ahead of print] PMID: 18818200.
  2. Parastatidis, I., LM Thomson, DM Fries, RE Moore, J Tohyama, X Fu, SL Hazen, HFG Heijnen, MK Dennehy, DC Liebler, DJ Rader, and H Ischiropoulos (2007) Increased protein nitration burden in the atherosclerotic lesions and plasma of apolipoprotein A-I deficient mice. Circ. Res. 101:368-376.
  3. Greco, TM, R Hodara, I Parastatidis, HFG Heijnen, MK Dennehy, DC Liebler, and H Ischiropoulos (2006) Identification of S-nitrosylation motifs by site-specific mapping of the S-nitrosocysteine proteome in human vascular smooth muscle cells. Proc. Natl. Acad. Sci. USA 103:7420-7425.
  4. Mazzulli, JR, AJ Mishizen, BI Giasson, DR Lynch, SA Thomas, A Nakashima, T Nagatsu, A Ot., and H Ischiropoulos (2006) Cytosolic catechols inhibit alpha-synuclein aggregation and facilitate the formation of intracellular soluble oligomeric intermediates. J. Neurosci. 26:10068-10078.
  5. Hodara, R, EH Norris, BI Giasson, AJ Mishizen-Eberz, DR Lynch, V M-Y Lee, and H Ischiropoulos (2004) Functional consequences of x-synuclein tyrosine nitration: diminished binding to lipid vesicles and increased fibril formation. J. Biol. Chem. 279:47746-47753.

Roland G. Kallen, M.D., Ph.D.
Professor of Biochemistry and Biophysics
913B Stellar-Chance Labs
Tel: 215-898-5184
Email: rgk@mail.med.upenn.edu

Tutorial Topic: Ion channel structure and function

References:

  1. Kallen, RG, SA Cohen and RL Barchi (1993) Structure, function and expression of voltage-dependent sodium channels. Molecular Neurobiol. 7:383-428.
  2. Horn, R. (2002) Coupled movements in voltage-gated ion channels. J. Gen. Physiol. 120:449-53.
  3. Bezanilla, F (2002) Voltage sensor movements. J. Gen. Physiol. 120:465-473.
  4. Gandhi, CS and EY Isacoff (2002) Molecular models of voltage sensing. J. Gen. Physiol. 120:455-63.
  5. Larsson, HP (2002) The search is on for the voltage sensor-to-gate coupling. J. Gen. Physiol. 120:475-481.

Rahul M. Kohli, M.D., Ph.D.
Assistant Professor of Medicine, and Biochemistry & Biophysics
502B Johnson Pavilion
Tel: 215-662-2359
Email: rkohli@upenn.edu

Tutorial Topics: 1) SOS pathways and multidrug resistance in pathogens; 2) adaptive and innate defense by cytidine deaminase enzymes

References:

  1. Smith PA, Romesberg FE. (2007) Combating bacteria and drug resistance by inhibiting mechanisms of persistence and adaptation. Nature Chem. Biol. 3:549-556.
  2. Cirz RT, Romesberg FE. (2007) Controlling Mutation: Intervening in Evolution as a Therapeutic Strategy. Critical Revs. Biochem. Mol. Biol. 42:341-354.
  3. Peled JU, Kuang FL, Iglesias-Ussel MD, Roa S, Kalis SL, Goodman MF, Matthew D Scharff MD. (2008) The biochemistry of somatic hypermutation. Annu. Rev. Immunol. 26:481-511.
  4. Rosenberg BR, Papavasiliou FN. (2007) Beyond SHM and CSR: AID and related cytidine deaminases in the host response to viral infection. Adv. Immun. 94:215-44.
  5. Kohli RM, Abrams SR, Gajula KS, Maul RW, Gearhart PJ, Stivers JT. (2009) A portable hotspot recognition loop transfers sequence preferences from APOBEC family members to activation-induced cytidine deaminase. J. Biol. Chem. 284:22898-22904.

Todd Lamitina, Ph.D.
Assistant Professor of Physiology
613 Goddard Labs
Tel: 215-898-3223 (office)
Tel: 215-898-0566 (lab)
Email: lamitina@mail.med.upenn.edu

Tutorial topics: 1) cellular osmoregulation; 2) molecular mechanisms of environmental stress responses

References:

  1. Lamitina, T (2006) Functional genomic approaches in C. elegans. Methods Mol Biol 351:127-138.
  2. Lamitina, T, CG Huang and K Strange (2006) Genome-wide RNAi screening identifies protein damage as a regulator of osmoprotective gene expression. Proc Natl Acad Sci USA 103:12173-12178.
  3. Yan X, J Xing, C Lorin-Nebel, AY Estevez, K Nehrke, T Lamitina and K Strange (2006) Function of a STIM1 homologue in C. elegans: evidence that store-operated Ca2+ entry is not essential for oscillatory Ca2+ signaling and ER Ca2+ homeostasis. J Gen Physiol.
  4. Huang, CG, P Agre, K Strange and T Lamitina (2006) Isolation of C. elegans deletion mutants following ENU mutagenesis and thermostable restriction enzyme PCR screening. Mol Biotechnol 32:83-86.
  5. Lamitina, ST and K Strange (2004) Transcriptional targets of the DAF-16 insulin signaling pathwayprotect C. elegans from extreme hypertonic stress. Am J Physiol Cell Physiol.
  6. Lamitina, ST, R Morrison, GW Moeckel and K Strange (2004) Adaptation of the nematode Caenorhabditis elegans to extreme osmotic stress. Am J Physiol Cell Physiol 286:C785-C791.

Michael Lampson, Ph.D.
Assistant Professor of Biology
204-I Carolyn Lynch Laboratory
Tel: 215-746-3040
Email: lampson@sas.upenn.edu

Tutorial topics: 1) kinetochore-microtubule interactions; 2) mitotic kinases at the kinetochore; 3) Mechanisms of chromosome cohesion in  meiosis

References:

  1. Liu D, M Vleugel, CB Backer, T Hori, T Fukagawa., IM Cheeseman, MA Lampson (2010) Regulated targeting of protein phosphatase 1 to the outer kinetochore by KNL1 opposes Aurora B kinase.  Journal of Cell Biology (in press).
  2. Liu D, G Vader, MJ Vromans, MA Lampson, SM Lens (2009) Sensing chromosome bi-orientation by spatial separation of Aurora B kinase from kinetochore substrates. Science 323:1350-1353.
  3. Kapoor TM, MA Lampson, P Hergert., L Cameron, D Cimini, ED Salmon, BF McEwen, A Khodjakov. (2006) Chromosomes can congress to the metaphase plate prior to bi-orientation. Science 311:388-391.
  4. Lampson MA, K Renduchitala, A Khodjakov, TM Kapoor (2004) Correcting improper chromosome–spindle attachments during cell division. Nature Cell Biology 6:232-237.

Matthew J. Lazzara, Ph.D.
Assistant Professor of Chemical and Biomolecular Engineering
371 Towne Building
Tel: 215-746-2264
Fax: 215-573-2093
Email: mlazzara@seas.upenn.edu

Tutorial Topics: 1) cell signaling by the ErbB receptors; 2) modeling receptor-mediated processes; 3) transport phenomena in physiology

References:

  1. Lazzara, MJ, K Lane, R Chan, P Jasper, M Yaffe, PK Sorger, T Jacks, BG Neel, and DA Lauffenburger (2010) Incomplete activation of ERK in EGFR-mutant lung cancer cells contributes to increased cellular sensitivity to gefitinib. Cancer Res 70:3843-385.
  2. Lazzara, MJ and DA Lauffenburger (2009) Quantitative modeling perspectives on the ErbB system of cell regulatory processes. Exp Cell Res 315:717-725.
  3. Lazzara, MJ and WM Deen (2007) Model of albumin reabsorption in the proximal tubule. Am J Physiol Renal Physiol 292:F430-439.
  4. Lazzara, MJ and WM Deen (2004) Effects of concentration on the partitioning of macromolecule mixtures in agarose gels. J Colloid Interface Sci 272:288-297.

Mark A. Lemmon, Ph.D.
Professor of Biochemistry and Biophysics
809C Stellar-Chance Labs
Tel: 215-898-3072
Email: mlemmon@mail.med.upenn.edu

Tutorial Topics: 1) membrane targeting by specific and not-so-specific phospholipid recognition; 2) signaling by the EGF receptor family of receptor tyrosine kinases; 3) scaffolding proteins that direct the specificity of cellular signaling pathways: 4) molecular mechanisms in reeptor-mediated endocytosis.

References:

  1. Yu, JW and MA Lemmon (2001) All phox homology (PX) domains from Saccharomyces cerevisiae specifically recognize phosphatidylinositol-3-phosphate. J. Biol. Chem. 276:44179-44184.
  2. Sankaran, VG, DE Klein, MM Sachdeva and MA Lemmon (2001) High-affinity binding of FYVE domains to phosphatidylinositol-3-phosphate requires intact phospholipid, but not FYVE domain oligomerization. Biochemistry 40:8581-8587.
  3. Ferguson, KM, JM Kavran, VG Sankaran, E Fournier, SJ Isakoff, EY Scolnick and MA Lemmon (2000) Structural basis for discrimination of 3-phosphoinositides by pleckstrin homology domains. Molecular Cell 6:373-384.
  4. Ferguson, KM, PJ Darling, TL Macatee, M Mohan and MA Lemmon (2000) Extracellular domains drive homo-but not hetero-dimerization of ErbB receptors. EMBO J. 19:4632-4643.
  5. Lee, A, DW Frank, MS Marks and MA Lemmon (1999) Dominant-negative inhibition of receptor-mediated endocytosis by dynamin-1 with a defective PH domain. Current Biol. 9:261-264.

Mitchell Lewis, D. Phil.
Professor of Biochemistry and Biophysics
813A Stellar-Chance Labs
Tel: 215-898-0949
Email: lewis@mail.med.upenn.edu

Tutorial Topics: 1) protein-DNA interactions; 2) protein folding; 3) protein modelling; 4) x-ray diffraction; 5) genetic algorithms.

References:

  1. Lewis, M and DC Rees (1985) Fractal surfaces of proteins. Science 230:1163-1165.
  2. Lewis, M, G Chang, N Horton, MA Kercher, H Pace, MA Schumacher, RG Brennan and P Lu (1996) Crystal structure of the lactose operon repressor and its complexes with DNA and inducer. Science 271:1247-1254.
  3. Chang, G and M Lewis (1996) Molecular replacement using genetic algorithms. Acta Cryst. 53:544-558.
  4. Bennett, MJ, RH Albert, JM Jez, H Ma, TM Penning and M Lewis (1997) Steroid recognition and regulation of hormone action: crystal structure of testosterone and NADP bound to 3α-hydroxysteroid/dihydrodiol dehydrogenase. Structure 5:779-811.

Kristen W. Lynch, Ph.D.
Associate Professor of Biochemistry and Biophysics
909B Stellar-Chance Labs
Tel: 215-573-7749 (office)
Tel: 215-573-7756 (lab)
Email: klync@mail.med.upenn.edu

Tutorial Topics: 1) combinatorial control of alternative splicing; 2) specificity in protein-RNA interactions; 3) regulation and consequences of alternative splicing in T cells.

References:

  1. House, AE and KW Lynch (2008) Regulation of alternative splicing: more than just the ABCs. J. Biol. Chem. 18:1217-1221.
  2. Ip, J, A Tong, Q Pan, J Topp, BJ Blencowe and KW Lynch (2007) Global analysis of alternative splicing during T cell activation. RNA 13:563-572.
  3. House, AE and KW Lynch (2006) An exonic splicing silencer represses spliceosome assembly after ATP-dependent exon recognition. Nat. Struct. Mol. Biol. 13:937-944.
  4. Lynch, KW (2004) Consequences of regulated pre-mRNA splicing in the immune system. Nat Rev Immunol. 4:931-940.
  5. Rothrock, C, B Cannon, B Hahm and KW Lynch (2003) A conserved signal-responsive sequence mediates activation-induced alternative splicing of CD45. Mol. Cell 12:1317-1324.
  6. Hertel, KJ, KW Lynch and T Maniatis (1997) Common themes in the function of transcription and splicing enhancers. Curr Opin Cell Biol. 9:350-357.
  7. Lynch, KW and T Maniatis (1996) Assembly of specific SR protein complexes on distinct regulatory elements of the Drosophila doublesex splicing enhancer. Genes & Dev. 10:2089-2101.

Michael S. Marks, Ph.D.
Professor of Pathology and Laboratory Medicine
513 Stellar-Chance Labs
Tel: 215-898-3204
Email: marksm@mail.med.upenn.edu

Tutorial Topics: 1) molecular regulation of protein transport to endosomes and lysosomes; 2) molecular mechanisms of organelle biogenesis; 3) endosomal assembly of amyloid fibrils

References:

  1. Setty, S.R.G., D. Tenza, E.V. Sviderskaya, D.C. Bennett, G. Raposo and M.S. Marks (2008) Cell-specific ATP7A transport sustains copper-dependent tyrosinase activity in melanosomes. Nature 454:1142-1146.
  2. Setty, S.R.G., D. Tenza, S.T. Truschel, E.M. Chou, E.V. Sviderskaya, A.C. Theos, M.L. Lamoreux, S.M. Di Pietro, M. Starcevic, D.C. Bennett, E.C. Dell'Angelica, G. Raposo and M.S. Marks (2007) BLOC-1 is required for cargo-specific sorting from vacuolar early endosomes toward lysosome-related organelles. Mol. Biol. Cell 18:768-780.
  3. Hurbain I., W.J.C. Geerts, T. Boudier, S. Marco, A.J. Verkleij, M.S. Marks and G. Raposo (2008) Electron tomography of early melanosomes: implications for melanogenesis and the generation of fibrillar amyloid sheets. Proc. Natl. Acad. Sci. U.S.A. 105:19726-19731.
  4. Theos, A.C., S.T. Truschel, D.C. Harper, J.F. Berson, D. Tenza, P.C. Thomas, G. Raposo and M.S. Marks (2006) A novel pathway for sorting to intralumenal vesicles of multivesicular endosomes involved in organelle morphogenesis. Dev. Cell 10:343-354. (see preview by Katzmann, DJ (2006) Dev. Cell 10:278-280).
  5. Fowler D.M., A.V. Koulov, C. Alory-Jost, M.S. Marks, W.E. Balch and J.W. Kelly (2006) Functional amyloid formation within mammalian tissue. PLoS Biol. 4:e6.
  6. Theos, A.C., D. Tenza, J.A. Martina, I. Hurbain, A.A. Peden, E.V. Sviderskaya, A. Stewart, M.S. Robinson, D.C. Bennett, D.F. Cutler, J.S. Bonifacino, M.S. Marks and G. Raposo (2005) Functions of AP-3 and AP-1 in tyrosinase sorting from endosomes to melanosomes. Mol. Biol. Cell. 16:5356-5372.

Ronen Marmorstein, Ph.D.
Wistar Institute Professor of Biochemistry and Biophysics
327 Wistar Institute
Tel.: (215) 898-5006
Email: marmor@wistar.org

Tutorial Topics: 1) chromatin regulation; 2) structure-based design; 3) structural basis for cancer

References:

  1. Liu, X., Wang, L., Zhao, K., Thompson, P.R. Hwang, Y., Marmorstein, R. and Cole, P.A. (2008) The structural basis of protein acetylation by the p300/CBP transcriptional coactivator. Nature 451:846-850.
  2. Xie, P., Williams, D.S., Atilla-Gokcumen, G.E., Milk, L., Xiao, M., Smalley, K.S.M., Herlyn, M., Meggers, E., and Marmorstein, R. (2008) Structure-based design of an organoruthenium Phosphatidyl-Inositol-3-Kinase inhibitor reveals a switch governing lipid kinase potency and selectivity. ACS Chem. Biol. 3:305-316.
  3. Tang, Y., Holbert, M.A., Wurtele, H., Meeth, K., Rocha, W., Gharib, M., Jiang, E., Thibault, P., Verreault, A., Cole, P.A. and Marmorstein, R. (2008) Fungal Rtt109 histone acetyltransferase is an unexpected structural homolog of metazoan p300/CBP. Nature Struc. Mol. Biol. 15:738-745.
  4. Tang, Y., Meeth, K., Jiang, E., Luo, C. and Marmorstein, R. (2008) Structure of Vps75 and implications for histone chaperone function. Proc. Natl. Acad. Sci. 105:12206-12211.
  5. Malecka, K.A., Ho, W.C. and Marmorstein, R. (2009) Crystal structure of a p53 core domain tetramer bound to DNA. Oncogene 28:325-333.
  6. Xie, P., Streu, G., Qin, J., Bregman, H., Pagano, N., Meggers, E., Marmorstein, R. (2009) Crystal structure of BRAF in complex with an organoruthenium inhibitor reveals a mechanism for inhibition of an active form of BRAF kinase. Biochemistry 48:5187-5198.
  7. Brent, M.M., Iwata, A., Carten, J., Zhao, K. and Marmorstein, R. (2009) Structure and biochemical characterization of protein acetyltransferase (PAT) from Sulfolobus Solfataricus J. Biol. Chem. In press

E. Michael Ostap, Ph.D.
Professor of Physiology
B40 Anatomy-Chemistry Building
Tel: 215-573-9758
Email: ostap@mail.med.upenn.edu

Tutorial Topics: 1) molecular motors; 2) mechanisms of myosin processivity; 3) cytoskeletal dynamics

References:

  1. Tang, N. and E.M. Ostap (2001) Motor domain dependent localization of Myo1b. Current Biol. 11:1131-1135.
  2. De La Cruz, E.M., A.L. Wells, H.L. Sweeney and E.M. Ostap (2000) Actin and light chain isoform dependence of myosin V kinetics. Biochemistry 39:14196-14202.
  3. De La Cruz, E.M., E.M. Ostap and H.L. Sweeney (2001) Kinetic mechanism and regulation of myosin-VI. J. Biol. Chem. 276:32373-32381.
  4. Veigel, C., F. Wang, M.L. Bartoo, J.R. Sellers and J.E. Molloy (2002) The gated gait of the processive molecular motor, myosin V. Nature Cell Biol. 4:59-65.
  5. Rief, M., M.S. Rock, A.D. Mehta, M.S. Mooseker, R.E. Cheney and J.A. Spudich (2000) Myosin-V stepping kinetics: a molecular model for processivity. Proc. Natl. Acad. Sci USA 97:9482-9486.

Ravi Radhakrishnan, Ph.D.
Associate Professor of Bioengineering
540 Skirkanich Hall
210 S. 33rd Street
Tel: 215-898-0487
Fax: 215-573-2071
Email: rradhak@seas.upenn.edu

Tutorial Topics: 1) Transition path sampling; 2) Mixed QM/MM simulations; 3) Monte Carlo simulations; 4) CPMD simulations

References:

  1. Radhakrishnan, R. and T. Schlick (2004) Orchestration of cooperative events in DNA synthesis and repair mechanism unraveled by transition path sampling of DNA polymerase b’s closing. Proc. Nat. Acad. Sci. 101: 5970-5975. (Pubmed ID: 15069184).
  2. Venkatramani, R, R Radhakrishnan (2010) Computational delineation of the catalytic step of a high fidelity DNA polymerase. Protein Science (A Protein Society Journal) 19(4):815-825. PDF (Pubmed: 20162624)
  3. Agrawal, NJ, R Radhakrishnan, P Purohit (2007) Coarse-grained model for DNA curvature and flexibility in the presence of DNA-binding proteins. Biophysical J 94:3150-3158 (Pubmed ID: 18192346).
  4. Agrawal, NJ and R Radhakrishnan (2007) Role of glycocalyx in mediating nanocarrier cell adhesion explored using a thermodynamic model and Monte Carlo Simulation. J. Phys. Chem. C 111:15848 - 15856. (Pubmed ID: 19081797).
  5. Shi, F, SE Telesco, Y Liu, R Radhakrishnan*, MA Lemmon* (2010) The ErbB3/HER3 intracellular domain is competent to bind ATP and catalyze autophosphorylation. Proceedings of the National Academy of Sciences ( in press) *Co-corresponding authors. (Pubmed: 20351256).

Arjun Raj, Ph.D.
Assistant Professor of Bioengineering
240 Skirkanich Hall
210 S. 33rd Street
Tel: 215-821-7394
Philadelphia, PA 19104
Email: arjunraj@seas.upenn.edu

Tutorial topics: 1. Non-coding RNA identification and function; 2. Randomness and robustness in gene expression and development

References:

  1. Raj, A*, SA Rifkin*, E Andersen, A van Oudenaarden (2010) Gene expression variability underlies incompletely penetrant phenotypes. Nature 463:913-918. (* equal contributions)
  2. Wilusz JE, H Sunwoo, DL Spector (2009) Long noncoding RNAs: functional surprises from the RNA world [Review article]. Genes and Development 23:1494-1504.
  3. Raj, A, A van Oudenaarden (2008) Nature, nurture or chance: stochastic gene expression and its consequences [Review article]. Cell 135(2):216-226.
  4. Maamar, H*, A Raj*, D Dubnau (2007) Noise in gene expression determines cell fate in Bacillus subtilis. Science 317(5837): 526-529 (*equal contributions).
  5. Raj, A, CS Peskin, D Tranchina, DY Vargas, S Tyagi (2006) Stochastic mRNA Synthesis in mammalian cells. PLoS Biol 4(10): e309.

Ravinder Reddy, Ph.D.
Professor of Radiology
Science Director, CMROI
B1 Stellar-Chance Labs
Tel: 215-898-5708
Fax: 215-573-2113
Email: krr@mail.med.upenn.edu

Tutorial Topics: 1) Oriented macromolecules and MR image contrast; 2) Polarization transfer in the rotating frame; 3) MRI of oxidative metabolism

References:

  1. Witschey, WR, A Borthakur, MA Elliott, E Mellon, S Niyogi, DJ Wallman, C Wang, R Reddy (2007) Artifacts in T1r weighted imaging: Compensation for B1 and B0 field imperfections. J. Magn. Reson. (Epub).
  2. Witschey, WR, A Borthakur, MA Elliott, E Mellon, S Niyogi, C Wang, R Reddy (2007) Compensation spin-lock artifacts using an off-resonance rotary echo in T1r off-weighted imaging. Magn. Reson. Med. 1:2-7.
  3. Borthakur, A, M Corbo, JQ Trojanowski, V M-Y Lee, R Reddy (2006) In vivo measurement of plaque burden in a mouse model of Alzheimer’s Disease. J. Magn. Reson. Imaging 24:1011-1017.
  4. Hulvershorn, J, A Borthakur, L Bloy, EE Gualtieri, R Reddy, JS Leigh, M Elliott (2005) T1r contrast in functional magnetic resonance imaging. Magn. Reson. Med. 54:1155-1162.
  5. Tailor, DR, JE Baumgardner, RR Regatte, AC McLaughlin, JS Leigh, R Reddy (2004) Proton MRI of metabolically produced H217O using an efficient 17O2 delivery system. Neuroimage 22:611.
  6. Akella, SVS., RR Regatte, AJ Wheaton, A Borthakur, R Reddy (2004) Reduction of residual dipolar interaction in cartilage by spin-lock technique. Magn. Reson. Med. 52:1103-1109.
  7. Wheaton AJ, A Borthakur, MT Corbi, G Moonis, E Melhem, R Reddy (2004) T2rho contrast in MR images of the human brain. Magn Reson Med. 52:1223.

Heinrich Roder, Ph.D.
Adjunct Professor of Biochemistry and Biophysics
Senior Member, Institute for Cancer Research
Fox Chase Cancer Center
Tel: 215-728-3123
Email: roder@fccc.edu

Tutorial Topics: 1) protein folding; 2) protein structure and dynamics; 3) amyloid formation; 4) NMR; 5) fast kinetics.

References:

  1. Latypov, RF, H Cheng, NA Roder, J Zhang, and H Roder (2006) Structural characterization of an equilibrium unfolding intermediate in cytochrome c. J. Mol. Biol. 357:1009-1025.
  2. Kurchan, E, H Roder and BE Bowler (2005) Kinetics of loop formation and breakage in the denatured state of Iso-1-cytochrome c. J. Mol. Biol. 353:730-743.
  3. Welker, E, K Maki, MC Shastry, D Juminaga, R Bhat, HA Scheraga and H Roder (2004) Ultrarapid mixing experiments shed new light on the characteristics of the initial conformational ensemble during the folding of ribonuclease A. Proc. Natl. Acad. Sci. USA 101:17681-17686.
  4. Roder, H, K Maki, H Cheng and MC Shastry (2004) Rapid mixing methods for exploring the kinetics of protein folding. Methods 34:15-27.
  5. Kuwata, K, T Matumoto, H Cheng, K Nagayama, TL James and H Roder (2003) NMR-detected hydrogen exchange and molecular dynamics simulations provide structural insight into fibril formation of prion protein fragment 106-126. Proc. Natl. Acad. Sci. USA 100:14790-14795.
  6. Teilum, K, K Maki, BB Kragelund, FM Poulsen and H Roder (2002). Early kinetic intermediate in the folding of acyl-CoA binding protein detected by fluorescence labeling and ultrarapid mixing. Proc. Natl. Acad. Sci. USA 99:9807-9812.
  7. Kuwata, K, R Shastry, H Cheng, M Hoshino, CA Batt, Y Goto and H Roder (2001). Structural and kinetic characterization of early folding events in beta-lactoglobulin. Nature Struct. Biol. 8:151-155.

Brian M. Salzberg, Ph.D.
Professor of Neuroscience & Physiology
234 Stemmler Hall
Tel: 215-898-2441
Email: bmsalzbe@mail.med.upenn.edu

Tutorial Topics: 1) Optical measurement of membrane potential; 2) multiple-site optical recording; 3) light scattering measurements of excitation-secretion coupling at mammalian nerve terminals; 4) optical studies of neural nets.

References:

  1. Muschol, M, BR Dasgupta and BM Salzberg (1999) Caffeine interaction with fluorescent calcium indicator dyes. Biophys. J. 77:577-586.
  2. Obaid, AL, T Koyano, J Lindstrom, T Sakai and BM Salzberg (1999) Spatio-temporal patterns of activity in an intact mammalian network with single cell resolution: optical studies of nicotinic activity in an enteric plexus. J. Neurosci. 19:3073-3093.
  3. Rohr, S and BM Salzberg (1994) Characterization of impulse propagation at the microscopic level across geometrically defined expansions of excitable tissue: multiple site optical recording of transmembrane voltage (MSORTV) in patterned growth heart cell cultures. J. Gen. Physiol. 104:287-309.
  4. Obaid, AL, R Flores and BM Salzberg (1989) Calcium channels that are required for secretion from intact nerve terminals of vertebrates are sensitive to w-conotoxin and relatively insensitive to dihydropyridines: optical studies with and without voltage-sensitive dyes. J. Gen. Physiol. 93:715-729.
  5. Salzberg, BM, AL Obaid and H Gainer (1985) Large and rapid changes in light scattering accompany secretion by nerve terminals in the mammalian neurohypophysis. J. Gen. Physiol. 86:395-411.
  6. Salzberg, BM, AL Obaid, DM Senseman and H Gainer (1983) Optical recording of action potentials from vertebrate nerve terminals using potentiometric probes provides evidence for sodium and calcium components. Nature 306:36-40.

Casim A. Sarkar, Ph.D.
Associate Professor of Bioengineering, and Chemical & Biomolecular Engineering
373 Towne Building
Tel: 215-573-4072
Fax: 215-573-2071
E-mail: casarkar@seas.upenn.edu

Tutorial Topics: 1) protein design; 2) modeling cell-fate decisions

References:

  1. Sarkar*,CA, I Dodevski*, M Kenig, S Dudli, A Mohr, E Hermans, and A Plückthun. (2008) Directed evolution of a G-protein coupled receptor for expression, stability, and binding selectivity. Proceedings of the National Academy of Sciences USA 105:14808-14813. (*contributed equally)
  2. Palani, S. and CA Sarkar (2008) Positive receptor feedback during lineage commitment can generate ultrasensitivity to ligand and confer robustness to a bistable switch. Biophysical Journal 95:1575-1589.
  3. Kubetzko*, S, CA Sarkar*, and A Plückthun. (2005) Protein PEGylation decreases observed target association rates via a dual blocking mechanism. Molecular Pharmacology 68:1439-1454. (*contributed equally)
  4. Sarkar, CA, K Lowenhaupt, T Horan, TC Boone, B Tidor, and DA Lauffenburger (2002) Rational cytokine design for increased lifetime and enhanced potency using pH-activated histidine switching. Nature Biotechnology 20:908-913. (2002)

Jeffery G. Saven, Ph.D.
Associate Professor of Chemistry
266 Cret Wing, Department of Chemistry
Tel: 215-573-6062
Email: saven@sas.upenn.edu

Tutorial Topics: 1) molecular simulation and modeling; 2) biomolecular design and engineering

References:

  1. J. Tang, S.-G. Kang, J. G. Saven and F. Gai. (2009) Characterization of cofactor-induced folding mechanism of a zinc binding peptide using computationally designed mutants. Journal of Molecular Biology 389:90-102.
  2. Bender, G.M., A. Lehmann, H. Zou, H. Cheng, H. C. Fry, D. Engel, M.J. Therien, J. K. Blasie, H. Roder, J.G. Saven, and W.F. DeGrado (2007) de novo design of a single chain diphenylporphyrin metalloprotein. Journal of the American Chemical Society 129:10732-10740.
  3. C. A. Butts, J. Swift, S.-G. Kang, L. Di Costanzo, D. W. Christianson, J. G. Saven, and I. J. Dmochowski (2008) Directing noble metal ion chemistry within a designed ferritin protein. Biochemistry 47:12729–12739.

Kim A. Sharp, Ph.D.
Associate Professor of Biochemistry and Biophysics
236 Anatomy-Chemistry Building
Tel: 215-573-3506
Email: sharpk@mail.med.upenn.edu

Tutorial Topics: 1) protein-ligand binding – theory and applications; 2) macromolecular electrostatics – theory and applications; 3) electron and proton transfer in proteins.

References:

  1. Sharp, K (2001) Entropy-enthalpy compensation: fact or artifact? Protein Sci. 10:661-667

James Shorter, Ph.D.
Assistant Professor of Biochemistry and Biophysics
805B Stellar-Chance Labs
Tel: 215-573-4256
Email: jshorter@mail.med.upenn.edu

Tutorial Topics: 1) Are prions invariably pathogenic? 2) How can aggregated proteins be returned to function? 3) How are yeast prions inherited?

References:

  1. Doyle, S. M., Shorter, J., Zolkiewski, M., Hoskins, J. R., Lindquist, S., and Wickner, S. (2007). Asymmetric deceleration of ClpB or Hsp104 ATPase activity unleashes protein-remodeling activity. Nat. Struct. Mol. Biol. 14:114-122.
  2. Shorter, J., and Lindquist, S. (2006). Destruction or potentiation of different prions catalyzed by similar Hsp104 remodeling activities. Mol. Cell 23:425-438.
  3. Shorter, J., and Lindquist, S. (2005). Prions as adaptive conduits of memory and inheritance. Nat. Rev. Genetics 6:435-450.
  4. Shorter, J., and Lindquist, S. (2005). Navigating the ClpB channel to solution. Nat. Struct. Mol. Biol. 12: 4-6.
  5. Shorter, J., and Lindquist, S. (2004). Hsp104 catalyzes formation and elimination of self-replicating Sup35 prion conformers. Science 304:1793-1797.

Emmanuel Skordalakes, Ph.D.
Wistar Institute Assistant Professor of Biochemistry and Biophysics
320 Wistar Institute
Tel: 215-495-6884 (office) 215-898-2202 (lab)
Email: skorda@wistar.org

Tutorial Topics: We use biophysical and biochemical techniques to understand the mechanism of telomere replication and maintenance.

References:

  1. Mitchell, M, J Smith, M Mason, S Harper, DW Speicher, FB Johnson and E Skordalakes (2010) Cdc13 N-terminal dimerization, DNA binding and telomere length regulation. Molecular and Cell Biology (Accepted)
  2. Mitchell M, Gillis A, Futahashi M, Fujiwara H, Skordalakes E. (2010) Structural basis for telomerase catalytic subunit TERT binding to RNA template and telomeric DNA. Nature Structural & Molecular Biology 17(4):513-518. 2010 2035777
  3. Gillis AJ, Schuller AP, Skordalakes E. (2008) Structure of the Tribolium castaneum telomerase catalytic subunit TERT. Nature 455:(7213):633-637. 18758444
  4. Rouda, S and E Skordalakes (2007) Structure of the RNA-binding domain of telomerase: implications for RNA recognition and binding. Structure 15:1403-1412.

David W. Speicher, Ph.D.
Wistar Institute Professor of Biochemistry and Biophysics
151 Wistar Institute/4268
Tel: 215-898-3972
Email: speicher@wistar.org

Tutorial Topics: 1) validation of molecular models using chemical crosslinking and MS; 2) probing surface accessibility of amino acid side chains in vitro and in vivo; 3) systems analysis of cancer metastasis; 4) discovery and validaton of serological disease biomarkers

References:

  1. Gaetani, M., Mootien, S, Harper, S, Gallagher, PG., and Speicher, D.W. (2008) Structural and functional effects of hereditary hemolytic anemia-associated point mutations in the alpha spectrin tetramer site. Blood 111:5712-5720. PMID: 18218854
  2. Li, D., Tang, H.-Y, and Speicher, D.W. (2008) A structural model of the erythrocyte spectrin heterodimer initiation site determined using homology modeling and chemical crosslinking. J. Biol. Chem. 283:1553-1562. PMID: 17977835
  3. Li, D., Harper, S. and Speicher, D.W. (2007) Initiation and propagation of spectrin heterodimer assembly involves distinct energetic processes. Biochemistry 46:10585-10594. PMID: 17713925
  4. Johnson, C.P., Tang, H-Y., Carag, C., Speicher, D.W. and Discher, D.E. (2007) Forced unfolding of proteins within cells. Science 317:663-666. PMID: 17673662
  5. Hoffman, S.A., Joo, W-A., Echan, L.A. and Speicher, D.W. (2007) Higher dimensional (Hi-D) separation strategies dramatically improve the potential for cancer biomarker detection in serum and plasma. Journal of Chromatography B 849:43-52. PMID: 17140865
  6. Johnson, C.P., Gaetani, M., Ortiz, V., Bhasin, N., Harper, S., Gallagher, P.G.., Speicher, D.W. and Discher, D. (2007) Pathogenic proline mutation in linker between spectrin repeats: disease caused by spectrin unfolding. Blood 109:3538-3543. PMID: 17192394
  7. Tang, H-Y., Ali-Khan, N., Echan, L.A., Levenkova, N., Rux, J.J. and Speicher, D.W. (2005) A novel 4-dimensional strategy combining protein and peptide separation methods enables detection of low abundance proteins for comprehensive profiling in human plasma and serum proteomics. Proteomics 5:3329-3342. PMID: 16052622

Cecilia Tommos, Ph.D.
Research Assistant Professor of Biochemistry and Biophysics
905 Stellar-Chance Labs
Tel: 215-746-2444
Email: tommos@mail.med.upenn.edu

Tutorial Topics: 1) Photosynthetic water oxidation; 2) biological energy transduction; 3) amino-acid radical enzymes and model systems

References:

  1. Westerlund, K., B.W. Berry, H. Privett and C. Tommos (2005) De novo designed radical proteins. Biochim. Biophys. Acta 1707:103-116.
  2. Hoganson, C.W. and C. Tommos (2004) Tyrosine redox chemistry in biocatalysis. Biochim. Biophys. Acta 1655:116-122.
  3. Gibney, B.R. and C. Tommos (2005) De novo protein design. In Photosystem II: The Light-Driven Water: Plastoquinone Oxidoreductase. T. Wydrzynski and K. Satoh (Eds.), Springer, Dordrecht, 729-751.
  4. Tommos, C. (2002) Electron, proton and hydrogen-atom transfers in photosynthetic water oxidation. Phil. Trans. Roy. Soc. 357:1383-1394.
  5. Tommos, C. and G.T. Babcock (2000) Proton and hydrogen currents in photosynthetic water oxidation, Biochim. Biophys. Acta 1458:199-219.
  6. Tommos, C. and G.T. Babcock (1998) Oxygen production in nature: a light-driven metalloradical enzyme process. Acc. Chem. Res. 31:18-25.

Phong T. Tran, Ph.D.
Associate Professor of Cell and Developmental Biology
1009 BRB II/III
Tel: 215-746-2755
Email: tranp@mail.med.upenn.edu

Tutorial Topics: 1) microtubule biopolymers and their function; 2) mechanism of force production by microtubules; 3) fluorescence imaging of living cells.

References:

  1. Tran, P.T., L. Marsh, V. Doye, S. Inoué and F. Chang (2001) A mechanism for nuclear positioning in fission yeast based upon microtubule pushing. J. Cell Biol. 153:397-411.
  2. Tran, P.T., R.A. Walker and E.D. Salmon (1997) A metastable intermediate state of microtubule dynamic instability that differs significantly between plus and minus ends. J. Cell Biol. 138:105-117.
  3. Tran, P.T., P. Joshi and E.D. Salmon (1997) How tubulin subunits dissociate from the shortening ends of microtubules. J. Struct. Biol. 118:107-118.

Sergei Vinogradov, Ph.D.
Associate Professor of Biochemistry and Biophysics
317 Anatomy-Chemistry Building
Tel: 215-573-7524
Email: vinograd@mail.med.upenn.edu

Tutorial Topics: 1) advanced optical probes for oxygen and pH; 2) photophysics of porphyrin molecules; 3) phosphorescence lifetime microscopy and tomography.

References:

  1. Finikova, O. S., Lebedev, A. Y., Aprelev, A. V., Troxler, T., Gao, F., Garnacho, C., Muro-Galindo, S., Hochstrasser, R. M., Vinogradov, S. A. (2008) Oxygen microscopy by two-photon-excited phosphorescence. ChemPhysChem 9:1673-1679.
  2. Finikova, O.S., Troxler, T., Senes, A., DeGrado, W.F., Hochstrasser, R.M., Vinogradov, S.A. (2007) Tuning energy and electron transfer rates in Pt-tetrabenzoporphyrin-rhodamine assemblies for two-photon imaging of oxygen. J. Phys. Chem. A 111:6977-6990.
  3. Apreleva, S.V., Wilson, D.F., Vinogradov, S.A. (2006) Tomographic imaging of oxygen by phosphorescence lifetime. Applied Optics 45:8547-8559.
  4. Brinas, R.P., Troxler, T., Hochstrasser, R.M., Vinogradov, S.A. (2005) Phosphorescent oxygen sensor with dendritic protection and two-photon absorbing antenna. J. Am. Chem. Soc. 127:11851-11862.
  5. Percec, V., Dulcey, A. E., Balagurusamy, V. S. K., Miura, Y., Smidrkal, J., Peterca, M., Nummelin, S., Edlund, U., Hudson, S. D., Heiney, P. A., Duan, Hu, Magonov, S. N., Vinogradov, S.A. (2004) Self-assembling amphiphilic dendritic dipeptides that mimic helical protein pores. Nature 430:764-768.

A. Joshua Wand, Ph.D.
Benjamin Rush Professor of Biochemistry and Biophysics
905 Stellar-Chance Labs
Tel: 215-573-7288
Email: wand@mail.med.upenn.edu

Tutorial Topics: 1) protein structure, dynamics and stability; 2) protein-protein recognition; 3) high resolution NMR methods.

References:

  1. Lee, A.L., S.A. Kinnear and A.J. Wand (2000) Redistribution and loss of side-chain entropy upon formation of a calmodulinopeptide complex. Nature Struct. Biol. 7:72-77.
  2. Wand, A.J. (2001) Dynamic activation of protein function: a view emerging from NMR spectroscopy Nature Struct. Biol. 8:926-993.
  3. Fuentes, E.J. and A.J. Wand (1998) The local stability and dynamics of apocytochrome b562 examined by the dependence of hydrogen exchange on hydrostatic pressure. Biochemistry 37:9877-9883.
  4. Lee, A.L. and A.J. Wand (2001) Microscopic origins of entropy, heat capacity and the glass transition in proteins. Nature 411:501-504.
  5. Babu, C.R., P.F. Flynn and A.J. Wand (2001) Validation of protein structure from preparations of encapsulated proteins dissolved in low viscosity fluids. J. Am. Chem. Soc. 123:2691-2692.

John W. Weisel, Ph.D.
Professor of Cell and Developmental Biology
1054 BRB II/III
Tel:215-898-3573
Email: weisel@mail.med.upenn.edu

Tutorial Topics: 1) molecular mechanisms of platelet aggregation; 2) molecular mechanisms of fibrin assembly and fibrinolysis; 3) interactions of individual ligand-receptor pairs in vivo and on cells; 4) thrombus formation

References:

  1. Standeven, K.F., R.S. Ariens, P. Whitaker, A.E. Ashcroft, J.W. Weisel and P.J. Grant (2002) The effect of dimethylbiguanide on thrombin activity, FXIII activation, fibrin polymerization and fibrin clot formation. Diabetes 51:189-197.
  2. Hantgan, R.R., M. Rocco, C. Nagaswami and J.W. Weisel (2001) Binding of a fibrinogen mimetic stabilizes integrin allbb3’s open conformation. Protein Sci. 10:1614-1626
  3. Weisel, J.W., C. Nagaswami, J.L. Woodhead, A.A.-R. Higazi, W.J. Cain, S.M. Marcovina, M.L. Koschinsky, D.B. Cines and K. Bdeir (2001) The structure of lipoprotein(a) and ligand-induced conformational changes. Biochemistry 40:10424-10435.
  4. Collet, J.-P., D. Park, C. Lesty, J. Soria, C. Soria, G. Montalescot and J.W. Weisel (2000) Influence of fibrin network, conformation and fibrin fiber diameter on fibrinolysis speed: dynamic and structural approaches by confocal microscopy Arteriosclerosis, Thromb. Vasc. Biol. 20:1354-1361.
  5. Ariäns, R.A.S., H. Philippou, C. Nagaswami, J.W. Weisel, D.A. Lane and P.J. Grant (2000) The factor XIII Val34Leu polymorphism accelerates thrombin activation of factor XIII and affects crosslinked fibrin structure. Blood 96:988-995.
  6. Murthy, S.N.P., J.H. Wilson, T.J. Lukas,Y. Veklich, J.W. Weisel and L. Lorand (2000) Transglutaminase-catalyzed crosslinking of the Aa and g constituent chains in fibrinogen. Proc. Natl. Acad. Sci USA 97:44-48.

X. Long Zheng, M.D., Ph.D.
Assistant Professor of Pathology and Laboratory Medicine
816G Abramson Research Building
Tel: 215-590-3565 (office) 215-590-3890 (lab)
Fax: 267-426-5165
Email: zheng@email.chop.edu

Tutorial topics: 1) Pathogenesis of thrombotic thrombocytopenic purpura; 2) ADAMTS13 and microvacular thrombosis; 3) Cofactor dependent regulation of ADAMTS13 function

References:

  1. Laje P., Shang D., Cao W., Niiya M., Endo M., Radu A., DeRagotis N., Scheiflinger F., Zoltick P.W., Flake A.W., and Zheng X.L. (2009) Correction of murine ADAMTS13 deficiency by hematopoietic progenitor cell-mediated gene therapy. Blood : DOI 10.1182/blood-2008-08-17302.
  2. Niiya M., Endo M., Shang D., Zoltick P.W., Muvarak N.E., Cao W.J., Jin S-Y., Skipwith C.G., Motto,D.G., Flake A.W. and Zheng X.L.(2009) Correction of ADAMTS13 deficiency by in utero gene transfer of lentiviral vector encoding ADAMTS13 genes. Mol. Ther. 17(1): 34-41.
  3. Cao W.J., Krishnaswamy S., Camire R.M., Lenting P.J., Zheng X.L. (2008) Factor VIII accelerates proteolytic cleavage of von Willebrand factor by ADAMTS13. Proc. Natl. Acad. Sci. USA. 105(21):7416-7421.
  4. Cao W.J., Niiya M., Zheng X.W., Shang D., Zheng X.L. (2008) Inflammatory cytokines inhibit synthesis of ADAMTS13 metalloprotease in hepatic stellate cells and endothelial cells. J. Thromb. Hemost. 6:1233-1235.
  5. Zheng X.L., Sadler J.E.(2008) Pathogenesis of thrombotic microangiopathies. Ann. Rev. Pathol. Mech. Dis. 3:249-277.
  6. Zhang P., Pan W., Rux A.H., Sachais B.S., Zheng X.L. (2007) The cooperative activity between the carboxyl-terminal TSP1 repeats and the CUB domains of ADAMTS13 is crucial for recognition of von Willebrand factor under flow. Blood 110(6):1887-1894.
  7. M. Niiya, M. Uemura, X.W. Zheng, M. Dockal, E. Pollak, F. Scheiflinger, R. Wells, Zheng X.L.(2006) Increased ADAMTS13 proteolytic activity in rat hepatic stellate cells upon activation in vitro and in vivo. J. Thromb. Hemost. 4(5):1063-1070.
  8. Shang D., X. W. Zheng, M. Niiya, Zheng X.L.(2006) Apical sorting of ADAMTS13 in human vascular endothelial cells and Madin-Darby canine kidney cells depend on CUB domains and their association with lipid rafts. Blood 108(7):2209-2217.
  9. Shelat S., Smith P., Ai J., Zheng X.L. (2006) Inhibitory autoantibodies against ADAMTS13 in patients with thrombotic thrombocytopenic purpura bind ADAMTS13 protease and may accelerate its clearance in vivo. J. Thromb. Hemost. 4:1707-1717.
  10. Ai J., Smith P., Wang S., Zhang P., Zheng X.L.(2005) The proximal carboxyl terminal domains of ADAMTS13 determine substrate specificity and are all required for cleavage of Von Willebrand factor. J. Biol. Chem. 280(33):29428-29234.
  11. Zheng X.L., Kaufman RM, Goodnough LT, Sadler JE. (2004) Effect of plasma exchange on plasma ADAMTS13 metalloprotease activity, inhibitor level, and clinical outcome in patients with idiopathic and nonidiopathic thrombotic thrombocytopenic purpura. Blood 103(11):4043-4049.
  12. Zheng X.L., Nishio K, Majerus EM, Sadler JE. (2003) Cleavage of von Willebrand factor requires the spacer domain of the metalloprotease ADAMTS13. J Biol Chem. 278(32):30136-30141.
  13. Zheng X.L., Pallera AM, Goodnough LT, Sadler JE, Blinder MA. (2003) Remission of chronic thrombotic thrombocytopenic purpura after treatment with cyclophosphamide and rituximab. Ann Intern Med. 138(2):105-108.
  14. Zheng X.L., Majerus EM, Sadler JE. ADAMTS13 and TTP. (2002) Curr Opin Hematol. 9(5):389-394. Review.
  15. Zheng X.L., Chung D, Takayama TK, Majerus EM, Sadler JE, Fujikawa K. (2001) Structure of von Willebrand factor-cleaving protease (ADAMTS13), a metalloprotease involved in thrombotic thrombocytopenic purpura. J Biol Chem. 276(44):41059-41063.

updated 08/10