BMB 598 Tutorial

Course Director: Ben E. Black, Ph.D.
Assistant Professor of Biochemistry and Biophysics
913A Stellar-Chance Laboratories
Email: blackbe@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 related to their thesis project. The tutorial can also be used to better prepare students for their Preliminary Exam.

Upon completion of the tutorial, students must prepare a written description of the area studied (3-5 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.
Associate 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. Abrams, C.S. and M.A. Lemmon (2002) Pleckstrin homology domains and the cytoskeleton. FEBS Letters (in press)
  2. Chatah, N.H. and C.S. Abrams (2001) G-protein coupled receptors regulate the membrane association of PIP5K through a pathway dependent on both Rac and Rho. J. Biol. Chem. 276:34059-34065.
  3. Roll, R.L., E.M. Bauman, J.S. Bennett and C.S. Abrams (2000) Phosphorylated plekstrin induces cell signaling via an integrin-dependent pathway. J. Cell Biol. 150:1461-1466.
  4. Ma, A., A. Metjian, S. Bagrodia, S.J. Taylor and C.S. Abrams (1998) Cytoskeletal reorganization by G protein-coupled receptors, via a pathway dependent on PI3-Kg, a Rac GEF, and Rac. Mol. & Cell. Biol. 18:4744-4751.

 

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, H.J. 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, S.M., T. Gidalevitz, C. Biswas, B.S. 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, D.P., G. Gallo, S.M. Vogen, J.L. Dul, K.L Sciarretta, A. Kumar, R. Raffen, F.J. 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, J.L., P. D. Davis, E.K. Williamson, F.J. 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, J.L. Dul, S. Vogen, E.K. Williamson, F.J. 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.
Associate Professor of Pharmacology, Biochemistry & Biophysics, and Medicine
105 Johnson Pavilion
Tel.: (215) 898-9238
Email: axe@pharm.med.upenn.edu

Tutorial topics:

1) Membrane protein folding and oxidative stress (various forms of spectroscopy and mass spectrometry); 2) Structure-based rational drug design (only for students with advanced computer skills).

References:

  1. Murray, I.V.J., L. Liu, H. Komatsu, K. Uryu, G. Xiao, J.A. Lawson, and P.H. Axelsen, (2007) Membrane mediated amyloidogenesis and the promotion of oxidative lipid damage by amyloid β proteins. Journal of Biological Chemistry (in press)
  2. MacDonald, M.L., I.V.J. Murray, and P.H. Axelsen (2007) Mass spectrometric analysis demonstrates that BODIPY 581/591 C11 overestimates and inhibits oxidative lipid damage. Free Radical Biology and Medicine (in press)
  3. Murray, I.V.J., M. E. Sindoni, and P. H. Axelsen (2005) Promotion of oxidative lipid membrane damage by amyloid β proteins. Biochemistry 44:12606-12613.
  4. Schneeweis, L.A., V. Koppaka, S. Lund-Katz, M.C. Phillips, and P.H. Axelsen (2005) Structural analysis of lipoprotein E particles. Biochemistry 44:12525-12534.
  5. Jusuf, S. and P.H. Axelsen (2004) Synchronized conformational fluctuations and binding site desolvation during molecular recognition. Biochemistry 43:15446-15452.
  6. Paul, C., J. Wang, W.C. Wimley, R.M. Hochstrasser, and P.H. Axelsen (2004) Vibrational coupling, isotopic editing, and β sheet structure in a membrane bound polypeptide. Journal of the American Chemical Society 126:5843-5850.
  7. Koppaka, V., C. Paul, I.V.J. Murray, and P.H. 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.

 

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, D.R., L.E.T. Jansen, B.E. Black, A.O. Bailey, J.R. Yates III, and D.W. Cleveland (2006) The human CENP-A centromeric nucleosome-associated complex. Nat. Cell Biol. 8:458-469.
  2. Black, B.E., D.R. Foltz, S. Chakravarthy, K. Luger, V.L. Woods Jr., and D.W. Cleveland (2004) Structural determinants for generating centromeric chromatin.  Nature 430:578-582.
  3. Cleveland, D.W., Y. Mao, and K.F. 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 B.J. Shenker (2006) Cholesterol-rich membrane microdomains mediate cell cycle arrest induced by Actinobacillus actinomycetemcomitans cytolethal distending toxin. Cellular Microbiology 8:823-36.
  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 M.A. 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 A.F.X. Goldberg (2002) Photoreceptor renewal: a role for peripherin/RDS.  International Reviews in Cytology 217:183-225.

 

Ari Borthakur, Ph.D.
Assistant Professor of Radiology
B1 Stellar-Chance Labs
Tel: 215-898-2045, 898-9357
Fax: 215-573-2113
Email: ari@mail.mmrrcc.upenn.edu

Tutorial Topics:
1) T1ρ 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. Borthakur A., T. Gur, A.J. Wheaton, M. Corbo, J.Q. Trojanowski, V.M. Lee, R. Reddy (2006) In vivo measurement of plaque burden in a mouse model of Alzheimer’s Disease. Journal of Magnetic Resonance Imaging (in press).
  2. Auerbach J.D., W. Johannessen, A. Borthakur, A.J. Wheaton, C.A. Dolinskas, R.A. Balderston, R. Reddy, D.M. Elliott (2006) Quantitative in vivo assessment of human lumbar disc degeneration using T1ρ-weighted magnetic resonance imaging. European Spine Journal (in press).
  3. Hulvershorn J., A. Borthakur, L. Bloy, E.E. Gualtieri, R. Reddy, J.S. Leigh, M.A. Elliott (2005) T1ρ contrast in functional magnetic resonance imaging. Magnetic Resonance in Medicine 54(5):1155-1162.

 

Christopher G. Burd, Ph.D.
Assistant 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, M.E., K.E. Ogburn, P.M. Gilbert, O.A. Varban and C.G. Burd (2001) FYVE domain targets Pib1p ubiquitin ligase to endosome and vacuolar membranes. J. Biol. Chem. 276:41388-41393.
  2. Gilbert, P.M. and C.G. Burd (2001) GDP dissociation inhibitor domain II required for Erab GTPase recycling. J. Biol. Chem. 265:8014-8020.
  3. Luan, P. S.D. Emr, W.E. Balch and C.G. 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., K.D. Ogburn, W.T. Watson, T. de Beer and C.G. Burd (1999) Phospatidylinositol 3-phosphate recognition by the FYVE domain. Mol. Cell. 3:805-811.
  5. Burd, C.G. and S.D. Emr (1998) Phosphatidylinositol(3)-phosphate signaling mediated by specific binding to RING FYVE domains. Mol. Cell. 2:157-162.

 

Fevzi Daldal, Ph.D.
Professor of Biology
103B 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.
Associate Professor of Physiology
A507 Richards Bldg.
Tel: 215-573-4559
Fax: 215-573-5851
E-mail: droberto@mail.med.upenn.edu

Tutorial Topics:
1) Protein-protein interactions and the control of actin cytoskeleton dynamics; 2) Ser/Thr protein phosphate 1 targeting and regulation.

  1. Chereau D., Boczkowska M., Skwarek-Maruszewska A., Fujiwara I., Hayes D.B., Rebowski G., Lappalainen P., Pollard T.D. & Dominguez R. (2008). Leiomodin is an actin filament nucleator in muscle cells. Science 320:239-243.
  2. Boczkowska M., Rebowski G., Petoukhov M.V., Hayes D.B., Svergun D.I. & Dominguez R. (2008). X-ray scattering study of activated Arp2/3 complex with bound actin-WCA. Structure [in press.]
  3. Lee S.H., Weins A., Hayes D.B., Pollak M.R. & 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.
  4. Ferron F., Rebowski G., Lee S.H. & Dominguez R. (2007). Structural basis for the recruitment of profilin–actin complexes during filament elongation by Ena/VASP. EMBO J. 26:4597-4606.
  5. Lee S.H., Hayes D.B., Rebowski G., Tardieux I., Dominguez R. (2007). Toxofilin from Toxoplasma gondii forms a ternary complex with an antiparallel actin dimer. PNAS 104:16122-16127.
  6. Dominguez R. (2007). The β-thymosin/WH2 Fold: Multifunctionality and structure. Ann N Y Acad Sci. 1112:86-94.
  7. Lee S.H., Kerff F., Chereau D., Ferron F., Klug A., Dominguez R. (2007). Structural basis for the actin-binding function of Missing-in-Metastasis. Structure 15:145-55.

 

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., V.N. Kim, and Kataoka, N. (2002) mRNA-binding proteins and the messages they carry. Nature Reviews: Molecular Cell Biology 3:195-205.
  4. Kim, V.N., 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., Q. Liu and G. Dreyfuss (1997) A complex containing SMN and SIP1 has an essential role in spliceosomal snRNPs biogenesis. Cell 90:1023-1029.

 

Wafik S. El-Deiry, M.D. Ph.D.
Professor of Medicine, Genetics, and Pharmacology
437 Clinical Research Building;
Tel: 215-909-9015
Email: wafik@mail.med.upenn.edu

Tutorial Topics:
1) Tumor suppressor genes; 2) apoptosis; 3) signal transduction in cancer; 4) drug development in cancer

References:

  1. El-Deiry, W.S., ed.(2003) Tumor Suppressor Genes, Vols 1 and 2, Humana Press.
  2. Burns, T.F. and W.S. El-Deiry (2003) Cell death signaling in malignancy. Cancer Treat. Res. 115:319-43, 2003.
  3. Sax, J.K. and W.S. El-Deiry (2003) p53 downstream targets and chemosensitivity. Cell Death Diff. 10:413-417.
  4. Ozoren, N. and W.S. El-Deiry (2003) Cell surface death receptor signaling in normal and cancer cells. Semin. Cancer Biol. 13:135-147.
  5. Wang, W., R. Takimoto, F. Rastinejad and W.S. El-Deiry (2003) Stabilization of p53 by CP-31398 inhibits ubiquitination without altering phosphorylation at serine 15 or 20 or MDM2 binding. Mol. Cell. Biol. 23:2171-2181.
  6. Fei, P., E.J. Bernhard and W.S.El-Deiry (2002) Tissue-specific induction of p53 targets in vivo. Cancer Res. 62:7316-7327.
  7. Sax, J.K., P. Fei, M.E. Murphy, E. Bernhard, S.J. Korsmeyer and W.S. El-Deiry (2002) BID regulation by p53 contributes to chemosensitivity. Nat. Cell Biol. 4:842-849.
  8. MacLachlan, T.K. and W.S. El-Deiry (2002) Apoptotic threshold is lowered by p53 transactivation of caspase-6. Proc. Natl. Acad. Sci. USA 99:9492-9497.
  9. MacLachlan, T.K., R, Takimoto and W.S. El-Deiry (2002) BRCA1 directs a selective p53-dependent transcriptional response towards growth arrest and DNA repair targets. Mol. Cell Biol. 22:4280-4292.

 

Kathryn M. Ferguson, Ph.D.
Assistant 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, P.D. Jeffrey, J. Wiltzius, P. Kussie, and Ferguson, K.M. (2005) Structural basis for inhibition of the Epidermal Growth Factor Receptor by cetuximab. Cancer Cell 7:301-311.
  2. Dawson, J.P., M.B. Berger, C.-C. Lin, J. Schlessinger, M.A. Lemmon, and K.M. 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 K.M., M.B. Berger, J.M. Mendrola, H.S. Cho, D.J. Leahy, and M.A. Lemmon (2003)  EGF activates its receptor by removing interactions that auto-inhibit ectodomain dimerization. Molecular Cell 11:507-517.

 

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, J.N., M.E. Quinlan, A.M. Shaw, J.E.Corrie and Y.E. Goldman (2003) Three-dimensional structural dynamics of myosin V by single-molecule fluorescence polarization. Nature 422:399-404.
  2. Rodnina, M.A., T. Pape, A. Savelsbergh, D. Mohr, N.B. 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, J.N., M.E. Quinlan and Y.E. Goldman (2000) Protein structural dynamics by single molecule fluorescence polarization. Prog. Biophys. Mol. Biol. 74:1-35.
  4. Taylor, K.A., H. Schmitz, M.C. Reedy, Y.E. Goldman, C. Franzini-Armstrong, H. Sasaki, R.T. Tregear, K. Poole, C. Lucaveche, R.J. Edwards, L.F. Chen, H. Winkler and M.K. Reedy (1999) Tomographic 3-D reconstruction of quick-frozen, Ca2+-activated contracting insect flight muscle. Cell 99:421-431.
  5. Corrie, J.E.T., B.D. Brandmeier, R.E. Ferguson, D.R. Trentham, J. Kendrick-Jones, S.C. Hopkins, U.A. van der Heide, Y.E. Goldman, C. Sabido-David, R.E. 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, Y.E. (1998) Wag the tail: structural dynamics of actomyosin. Cell 93:1-4.
  7. Hopkins, S.C., C. Sabido-David, J.E. Corrie, M. Irving and Y.E. 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, J.A., H. Higuchi and Y.E. Goldman (1998) Studies of molecular motors using caged compounds. Methods in Enzymol 291:307-348.
  9. Smith, C.A. 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
Associate Professor of 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. Derr, P., E. Boder, and M. Goulian (2006) Changing the specificity of a bacterial chemoreceptor. J. Mol. Biol. 355:923-932.
  2. Goulian, M. (2004) Robust control in bacterial regulatory circuits. Curr. Opin. Microbiol. 7:198-202.
  3. Batchelor, E., T.J. Silhavy and M. Goulian (2004) Continuous control in bacterial regulatory circuits. J. Bacteriol. 186:7618-7635.
  4. 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
805 BRB II/III
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, D.C. 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, D.C. 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, K.F. Medzihradszky, A. Burlingame, M. Bogyo (2002) Epoxide electrophiles as activity-dependent cysteine protease profiling and discovery tools.  Chem. Biol. 7:569-581.

 

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, R.G., S.A. Cohen and R.L. 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, C.S. and E.Y. Isacoff (2002) Molecular models of voltage sensing. J. Gen. Physiol. 120:455-63.
  5. Larsson, H.P. (2002) The search is on for the voltage sensor-to-gate coupling. J. Gen. Physiol. 120:475-481.

 

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

  1. Lamitina, T. (2006) Functional genomic approaches in C. elegans. Methods Mol Biol 351:127-138.
  2. Lamitina, T., C.G. 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, A.Y. 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, C.G., 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, S.T. 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, S.T., R. Morrison, G.W. Moeckel and K. Strange (2004) Adaptation of the nematode Caenorhabditis elegans to extreme osmotic stress. Am J Physiol Cell Physiol 286:C785-C791.

 

Mark A. Lemmon, Ph.D.
Associate 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, J.W. and M.A. Lemmon (2001) All phox homology (PX) domains from Saccharomyces cerevisiae specifically recognize phosphatidylinositol-3-phosphate. J. Biol. Chem. 276:44179-44184.
  2. Sankaran, V.G., D.E. Klein, M.M. Sachdeva and M.A. 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, K.M., J.M. Kavran, V.G. Sankaran, E. Fournier, S.J. Isakoff, E.Y. Scolnick and M.A. Lemmon (2000) Structural basis for discrimination of 3-phosphoinositides by pleckstrin homology domains. Molecular Cell 6:373-384.
  4. Ferguson, K.M., P.J. Darling, T.L. Macatee, M. Mohan and M.A. Lemmon (2000) Extracellular domains drive homo-but not hetero-dimerization of ErbB receptors. EMBO J. 19:4632-4643.
  5. Lee, A., D.W. Frank, M.S. Marks and M.A. 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 D.C. Rees (1985) Fractal surfaces of proteins. Science 230:1163-1165.
  2. Lewis, M., G. Chang, N. Horton, M.A. Kercher, H. Pace, M.A. Schumacher, R.G. 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, M.J., R.H. Albert, J.M. Jez, H. Ma, T.M. Penning and M. Lewis (1997) Steroid recognition and regulation of hormone action: crystal structure of testosterone and NADP bound to 3a-hydroxysteroid/dihydrodiol dehydrogenase. Structure 5:779-811.

 

Michael S. Marks, Ph.D.
Associate 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, SRG, D Tenza, ST Truschel, EM Chou, EV Sviderskaya, AC Theos, ML Lamoreux, SM Di Pietro, M Starcevic, DC Bennett, EC Dell'Angelica, G Raposo and MS Marks (2007) BLOC-1 is required for cargo-specific sorting from vacuolar early endosomes toward lysosome-related organelles.  Mol. Biol. Cell 18:768-780.
  2. Di Pietro, SM, JM Falcón-Pérez, D Tenza, SRG Setty, MS Marks, G Raposo and EC Dell'Angelica (2006) BLOC-1 interacts with BLOC-2 and the AP-3 complex to facilitate protein trafficking on endosomes. Mol. Biol. Cell 17: 4027-4038.
  3. Theos, AC, JF Berson, SB Cromer, DC Harper, KE Herman, EV Sviderskaya, ML Lamoreux, DC Bennett, G Raposo and MS Marks (2006) Dual loss of ER export and endocytic signals with altered melanosome morphology in the silver mutation of Pmel17.  Mol. Biol. Cell 17:3598-3612.
  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.
  7. Theos, A.C., S.T. Truschel, G. Raposo and M.S. Marks (2005) The Silver locus product Pmel17/ gp100/ Silv/ ME20: controversial in name and in function. Pigment Cell Res. 18:322-336.
  8. Berson, J.F., A.C. Theos, D.C. Harper, D. Tenza, G. Raposo and M.S. Marks (2003) Proprotein convertase cleavage liberates a fibrillogenic fragment of a resident glycoprotein to initiate melanosome biogenesis. J. Cell Biol. 161:521-533.

 

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. 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. (in press)
  2. 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.
  3. Brent, M.M. and Marmorstein, R. (2008) Ankyrin for methylated lysines. Nature Struc. Mol. Biol. 15:221-222.
  4. Liu, X. and Marmorstein, R. (2007) Structure of the retinoblastoma protein bound to adenovirus E1A reveals the molecular basis for viral oncoprotein inactivation of a tumor suppressor. Genes Dev. 21:2711-2716.
  5. Ho, W.C., Luo, C., Zhao, K., Chai, X., Fitzgerald, M.X. and Marmorstein, R. (2006) High resolution structure of the p53 core domain: implications for binding small molecule stabilizing compounds. Acta Cryst. 62:1484-1493.

 

Hillary C.M. Nelson, Ph.D.
Associate Professor of Biochemistry and Biophysics
813 Stellar-Chance Labs/6059
Tel: 215-573-7473
Email: hnelson@mail.med.upenn.edu;

Tutorial Topic:

Physiological role of trehalose during adverse environmental conditions

References:

  1. Dashnau, J.L., Conlin, L.K., Nelson, H.C., and Vanderkooi, J.M.  (2008) Water structure in vitro and within Saccharomyces cerevisiae yeast cells under conditions of heat shock. Biochimica et Biophysica Acta 1780:41-50.
  2. Conlin, L.C. and Nelson, H.C.M. (2007) Trehalose affects the transcriptional activity of yeast heat shock transcription factor. Mol. Cell. Biol. 27:1505-1515.

 

E. Michael Ostap, Ph.D.
Associate 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.

 

Ravinder Reddy, Ph.D.
Professor of Radiology & Science Director, MMRRCC
B1-Stellar-Chance Labs
Tel: 215-898-5708
Fax: 215-573-2113
Email: ravi@mail.mmrrcc.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, Borthakur A, Elliott MA, Mellon E, Niyogi S, Wallman DJ, Wang C, Reddy R.  (2007) Artifacts in T1r weighted imaging: Compensation for B1 and B0 field imperfections. J. Magn. Reson. (Epub).
  2. Witschey WR, Borthakur A, Elliott MA, Mellon E, Niyogi S, Wang C, Reddy R. (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, Corbo M, Trojanowski JQ, Lee Virginia MY, Reddy R. (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, Borthakur A, Bloy L, Gualtieri EE, Reddy R, Leigh JS, Elliott M., T1r (2005) Contrast in functional magnetic resonance imaging. Magn. Reson. Med. 54:1155-1162.
  5. Tailor, D. R., Baumgardner, J. E., Regatte, R. R., McLaughlin, A. C., Leigh, J. S., Reddy, R. (2004) Proton MRI of metabolically produced H217O using an efficient 17O2 delivery system. Neuroimage 22:611.
  6. Akella S.V.S., Regatte R. R., Wheaton A.J., Borthakur A., Reddy R. (2004) Reduction of residual dipolar interaction in cartilage by spin-lock technique. Magn. Reson. Med. 52:1103-1109.
  7. Wheaton AJ, Borthakur A, Corbi MT, Moonis G, Melhem E, Reddy R. (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, R.F., H. Cheng, N.A. Roder, J. Zhang, J. 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 B.E. 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, M.C. Shastry, D. Juminaga, R. Bhat, H.A. 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 M.C. 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, T.L. 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, B.B. Kragelund, F.M. 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, C.A. 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., B.R. Dasgupta and B.M. Salzberg (1999) Caffeine interaction with fluorescent Calcium indicator dyes. Biophys. J. 77:577-586.
  2. Obaid, A.L., T. Koyano, J. Lindstrom, T. Sakai and B.M. 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 B.M. 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, A.L., R. Flores and B.M. 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, B.M., A.L. 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, B.M., A.L. Obaid, D.M. 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.

 

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

Tutorial Topics:
1) biomolecular simulation and modeling; 2) protein folding; 3) protein design; 4) membrane proteins; 5) combinatorial libraries and directed evolution; 6) synthetic folding molecules.

References:

  1. J. Zou and J. G. Saven (2003) Using self-consistent fields to bias Monte Carlo methods with applications to designing and sampling protein sequences. The Journal of Chemical Physics 118:3843–3854.
  2. W. Wang and J. G. Saven (2002) Designing gene libraries from protein profiles for combinatorial protein experiments. Nucleic Acids Research 30:120.
  3. J. G. Saven (2002) Combinatorial protein design. Current Opinion in Structural Biology 12:453-458.
  4. J. G. Saven (2001) Designing protein energy landscapes. Chemical Reviews 101:3113-3130.

 

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 Laboratories
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. Skordalakes, E and JM Berger (2006) Structural insights into RNA-dependent ring closure and motor domain activation by the Rho transcription termination factor. Cell 127(3):553-564.
  2. Skordalakes E, AP Brogan, SB Park, H Kohn, and JM Berger (2005) Structural mechanism of inhibition of the Rho transcription termination factor by the antibiotic bicyclomycin. Structure 13:99-109.
  3. Daganzo, SM, JP Erzberger, WM Lam, E Skordalakes, R Zhang, AA Franco, SJ Brill, PD Adams, JM Berger, PD Kaufman (2003) Structure and function of the conserved core of histone deposition protein Asf1 Curr Biol. 13(24):2148-2158.
  4. Skordalakes E, and JM Berger (2003) Structure of the Rho transcription terminator: mechanism of mRNA recognition and helicase loading. Cell 114(1):135-146. (Accompanying Minireview, Cell 114:157-159).
  5. Hansen CL, E Skordalakes, JM Berger, SR Quake (2002) A robust and scalable microfluidic metering method that allows protein crystal growth by free interface diffusion. Proc Natl Acad Sci USA 99(26):16531-16536.
  6. Skordalakes E, GG Dodson, DS Green, CA Goodwin, MF Scully, HR Hudson, VV Kakkar, JJ Deadman (2001) Inhibition of human alpha-thrombin by a phosphonate tripeptide proceeds via a metastable pentacoordinated phosphorus intermediate. J Mol Biol 311(3):549-555.
  7. Skordalakes E, S Elgendy, CA Goodwin, D Green, MF Scully, VV Kakkar, JM Freyssinet, G Dodson, JJ Deadman (1998) Bifunctional peptide boronate inhibitors of thrombin: crystallographic analysis of inhibition enhanced by linkage to an exosite 1 binding peptide. Biochemistry 37(41):14420-14427.

 

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) proteomics (protein profiling) of cancer metastasis; 2) discovery of serological disease biomarkers; 3) characterization of posttranslational modifications using MS; 4) thermodynamics of protein-protein interactions

References:

  1. Zuo, X. and D.W. Speicher (2002)  Comprehensive analysis of complex proteomes using microscale solution isoelectrofocusing and slightly overlapping narrow range two-dimensional gels.  Proteomics 2:58-68.
  2. Zuo, X., Hembach, P., Echan, L., and Speicher D.W. (2002)  Enhanced analysis of human breast cancer proteomes using micro-scale solution isoelectrofocusing combined with high resolution 1-D and 2-D gels.  Journal of Chromatography B 782:253-265.
  3. Speicher, D.W., Lee, K., Tang, H.-Y., Echan, L., Ali-Khan, N., Zuo, X., and Hembach, P. (2004) Current challenges in proteomics: Mining low abundance proteins and expanding protein profiling capacities. In: Advances in Mass Spectrometry, Vol. 16 (Ashcroft, A.E., Brenton, G, and Monaghan, J.J., ed.) pp. 37-57.
  4. Chong, J.M., A. Uren, J.S. Rubin and D.W. Speicher (2002)  Disulfide bond assignments of secreted frizzled related protein-1 provide insights about frizzled homology and netrin module.  J. Biol. Chem. 277:5134-5144.
  5. Tang, H.-Y., Speicher, D.W. (2004) In vivo phosphorylation of human erythrocyte spectrin occurs in a sequential manner.  Biochemistry 43:4251-4262.
  6. Harper, S.L., G.E. Begg and D.W Speicher (2001)  Role of terminal non-homologous domains in initiation of human red cell spectrin dimerization.  Biochemistry 40:9935-9943.

 

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.
Assistant 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.

 

 

Jane M. Vanderkooi, Ph.D.
Professor of Biochemistry and Biophysics
909C Stellar-Chance Labs
Tel.: 215-898-8783
Email: vanderko@mail.med.upenn.edu

Tutorial Topics:
How do proteins protect cells against extreme conditions? A survey of water protein interactions. Or a survey of techniques used to study this problem.

References:

  1. Dashnau, Jennifer L., Nathaniel V. Nucci, Kim A. Sharp, and Jane M. Vanderkooi (2006) Hydrogen bonding and the cryoprotective properties of glycerol/water mixtures. J. Phys. Chem. 110(27):13670-13677.
  2. Nucci, Nathaniel V. and Jane M. Vanderkooi (2005) Temperature dependence of hydrogen bonding and freezing behavior of water in reverse micelles. J. Phys. Chem. 109:18301-18309.

 

A. Joshua Wand, Ph.D.
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.cellbio.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
e-mail: zheng@email.chop.edu

Tutorial topics:

1) ADAMTS (A disintegrin and metalloprotease with thrombospondin type 1 repeats) superfamily and human diseases; 2) sorting of membrane and secretory proteins in polarized cells; 3) ADAMTS13 in regulation of thrombosis.

References:

  1. Nishio K, Anderson PJ, Zheng X, Sadler JE. (2004) Binding of platelet glycoprotein Ibalpha to von Willebrand factor domain A1 stimulates the cleavage of the adjacent domain A2 by ADAMTS13. Proc Natl Acad Sci USA. 101(29):10578-83.
  2. Zheng X, 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):4043-9.
  3. Majerus EM, Zheng X, Tuley EA, Sadler JE. (2003) Cleavage of the ADAMTS13 propeptide is not required for protease activity. J Biol Chem. 278(47):46643-8.
  4. Zheng X, 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):30136-41.
  5. Zheng X, 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):105-8.
  6. Zheng X, Majerus EM, Sadler JE. ADAMTS13 and TTP. (2002) Curr Opin Hematol. 9(5):389-94. Review.
  7. Zheng X, Sadler JE. (2002) Mucin-like domain of enteropeptidase directs apical targeting in Madin-Darby canine kidney cells. J Biol Chem. 277(9):6858-63.
  8. Zheng X, 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):41059-63. 

updated 04/08