LABORATORY ROTATION (BMB 699)

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

 

  1. The purpose of the Lab Rotation is to provide the student with the opportunity to experience different laboratory environments and different experimental approaches and in so doing, assist him or her in choosing a laboratory for thesis work.
  2. A student is required to do a rotation in three different laboratories. The rotations should be with a member of the Graduate Group; the Chair of the Graduate Group must approve any rotations in a laboratory outside of the Graduate Group. The Chair of the Graduate Group must also approve in writing any exemptions from the three required lab rotations.
  3. In general, all rotations are to be completed by the end of the first year, enabling the student to select a research lab by the beginning of the second year.

    Time schedule for rotations:
    Rotation 1: Fall semester.
    Rotation 2: Spring semester
    Rotation 3: Summer I semester

    An incoming student may take Rotation 1 in the summer prior to the Fall semester. The date for the start of the lab rotation is different every year, but is usually the first or second week of June.
  4. Students should begin to search for a Faculty Supervisor about one month before the beginning of the proposed rotation. An appointment to discuss possible projects should be arranged with the potential Faculty Supervisor. Students are encouraged to talk with several faculty, and to discuss with the Course Director the choice of Faculty Supervisor and other options, prior to making a commitment to a specific laboratory.
  5. The rotation is under the supervision and guidance of the Faculty Supervisor. At the beginning of a lab rotation, the Faculty Supervisor and student are encouraged to discuss and clearly define the goals of the project. A "Lab Rotation Approval Form" with project title must be signed by both the student and the Faculty Supervisor, approved by the Course Director, and returned to the Academic Office for placement in the student's file. The Course Director should be notified in case of difficulties or shortcomings that may jeopardize the expeditious and satisfactory progression of the proposal.
  6. Upon completion of the rotation, the Faculty Supervisor must submit a grade and a written evaluation of the student's performance for inclusion in the student's file. A copy of this evaluation may be given to the student upon request. Students are encouraged to discuss the contents of the written evaluation with their Faculty Supervisor. The student will also be asked to provide a confidential evaluation of the lab rotation experience.
  7. At the end of each semester (fall, spring and summer), all students participating in rotations that semester will be scheduled to present a talk to the Graduate Group faculty and students (Lab Rotation Talks). This is a requirement for completion of the course.  Anyone who fails to give a presentation at the scheduled time will obtain an incomplete for the course and will be scheduled to present on that rotation during the Lab Rotation Talks in the following semester (giving two talks if also registered in the class for that semester). Under exceptional circumstances, and subject to approval by the Course Director and the Faculty Supervisor for the rotation, a paper may be accepted in lieu of the presentation. The Faculty Supervisor may also require a student to prepare a short report or paper at the completion of the rotation.
  8. Attendance at the Lab Rotation Talks is required. Unexcused absence from all or part of the session will result in reduction of the grade submitted by the Faculty Supervisor by one half grade.

  9. After completing the three rotations, students should be able to make an informed choice as to a Thesis Advisor. If a student is not able to find a suitable lab after three rotations, he or she can petition the Course Director for permission to do an additional rotation or independent study to find a Thesis Advisor.

 
 

LABORATORY ROTATION OFFERINGS

(Note: number of openings indicated in parentheses)

 

Charles S. Abrams, M.D.
Associate Professor of Medicine
912 BRB II/III
tel.: 215-898-1058
fax: 215-573-7400
e-mail: abrams@mail.med.upenn.edu

  1. Signaling events during T-cell chemotaxis.
  2. Structure function studies of the DEP domain.
  3. Studies of actin assembly in platelets and lymphocytes.

 

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

(1-2 students)

  1. Roles of the molecular chaperones BiP and GRP94 in protein folding in the cell.
  2. Identification of chaperone client proteins by proteomic methods.
  3. Prion-like polymerization of antibodies in systemic amyloidosis.

 

Paul H. Axelsen, M.D.
Associate Professor of Pharmacology
105 Johnson Pavilion
tel.: 215-898-9238
fax: 215-573-2236
e-mail: axe@pharm.med.upenn.edu

(2 students)

All rotation projects involve biophysical approaches aimed at understanding the mechanism of action of established drugs, unraveling pathophysiological processes to identify new drug targets, or the rational design of new drugs for known targets. Students may become involved in:

  1. Computational studies of molecular recognition – exploring structure-function relationships and rational drug design using molecular dynamics simulation, statistical thermodynamics, and computer graphics analysis.
  2. Molecular spectroscopy - UV-VIS, infrared, and fluorescence spectroscopy emphasizing internal reflection techniques, applied to understanding how membrane-bound targets are recognized by drugs and other molecules involved in various infectious, cardiovascular, and neurodegenerative diseases.

 

Shelley L. Berger, Ph.D.
Wistar Institute Hilary Koprowski Professor of Gene Expression and Regulation
Adjunct Professor of Genetics and Biology
389 Wistar Institute
tel.: 215-898-3922
fax: 215-898-0663
e-mail: berger@wistar.org

(1-2 students)

  1. Role of histone covalent modifications and chromatin remodeling in eukaryotic transcriptional regulation.
  2. Identification and structure/function/regulation studies of novel histone acetyltransferases and kinases.
  3. Transcriptional activation by the tumor suppressor p53, emphasizing the role of covalent modifications of both p53 and histones.

 

Ben E. Black, Ph.D.
Assistant Professor of Biochemistry and Biophysics
913A Stellar-Chance Labs
e-mail: blackbe@mail.med.upenn.edu

  1. Mechanisms to establish and maintain centromere identity
  2. Structure and function of a specialized histone, CENP-A, at the centromere
  3. Hydrogen/deuterium exchange on the proteins and supramolecular complexes directing accurate chromosome segregation

 

Kathleen Boesze-Battaglia, Ph.D.
Associate Professor
Department of Biochemistry
School of Dental Medicine
520 Leon Levy Building
Tel: 215-898-9167
Fax: 215-898-3695
Email: battagli@biochem.dental.upenn.edu

Tetraspanin membrane proteins and Intrinsically Disordered Protein (IDP) domains. Peripherin/rds a tetraspanin protein required for the formation of photoreceptor cells contains an intrinsically disordered C-terminal protein domain. Mutations in this domain diminish retinal function and contribute to retinal degenerative diseases. We propose that this C-terminus acts as a structural and functional scaffold and peripherin/rds function is regulated by protein binding partners.

  1. We will determine if disease associated mutations favor ordered structures that are unable to bind to regulatory partners of peripherin/rds including calmodulin using Surface Plasmon Resonance and Circular dichroism techniques.
  2. We will determine if phosphorylation of the C-terminus alters the binding kinetics of calmodulin and melanoregulin using surface plasmon resonance

Microbial Pathogenesis. The cytolethal distending toxins2 (Cdts) are a family of heat-labile protein cytotoxins produced by several different bacterial species including diarrheal disease-causing enteropathogens. Regardless of the microbial source of Cdt, the heterotrimeric holotoxin functions as an AB2 toxin where CdtB is the active (A) unit and the complex of CdtA and CdtC comprise the binding (B) unit.  Our data suggests that the toxin requires a cholesterol rich membrane micro-domain for function.

  1. We will assess how single point mutations of the active CdtB subunit alter CdtB-mediated toxicity using flow cytometry and confocal microscopy.
  2. We will determine if mutations in membrane recognition domain(s) of CdtC or CdtB alter subunit structure and holotoxin assembly using tryptophan fluorescence quenching studies and surface plasmon resonance (Biacore) analysis.

A second area of study seeks to identify unique structural domains of a leukotoxin, Ltx, involved in cell surface recognition and toxicity. Ltx is a member of the RTX family of cytolytic proteins that has a unique specificity for human immune cells.

  1. We will determine which Ltx domains associate with the cell membrane by generating and analyzing tryptophan substitution mutants using Circular dichroism (CD) and fluorescence quenching studies.

 

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

The goal of our research is to develop MRI-based techniques for the study of various degenerative diseases.

(2-3 students)

  1. Develop MRI image processing techniques
  2. Design pulse sequences
  3. Study tissue structure and biochemistry using MRI
  4. Develop clinical applications for the early diagnosis of disease e.g. Alzheimer’s Disease, arthritis

 

Lawrence (Skip) F. Brass, M.D., Ph.D.
Professor of Medicine and Pharmacology
915 BRB II/III
tel.: 215-573-3540
fax: 215-573-2189
e-mail: brass@mail.med.upenn.edu

(1-2 students)

  1. In vivo and in vitro consequences of aberrant signaling through G proteins and GPCRs using mouse models of platelet activation.
  2. Contact-dependent signaling mechanisms in the growth and stabilization of the platelet plug.

 

Christopher G. Burd, Ph.D.
Assistant Professor of Cell and Developmental Biology
Room 1010 BRB II/III
tel.: 215-573-5158
e-mail: cburd@mail.med.upenn.edu

(1-2 students)

  1. Genomics-and proteomics-based analysis of GTPase signaling.
  2. Regulation of protein sorting by phosphatidylinositol 3-kinase and PtdIns(3)P-binding
    proteins.
  3. Membrane targeting of small GTPases.


Barry S. Cooperman, Ph.D.
Professor of Chemistry
358 Chemistry Labs
tel.: 215-898-6330
fax: 215-898-2037
e-mail: cooprman@pobox.upenn.edu

(2 students)

  1. Studies on the structure and function of ribosomes, using fluorescent probes and advanced microscopy to study protein synthesis on single ribosomes and single turnover experiments to correlate structural change with specific kinetic steps.
  2. Studies on ribonucleotide reductase - its allosteric mechanism, its inhibition by peptides as a tool for designing of potential chemotherapeutic agents, and its catalytic mechanism, involving long-range electron transfer. Principal approaches involve kinetic measurements, chemical synthesis, site-specific mutagenesis and molecular modeling.
  3. Studies on serpin-serine proteinase interaction – the focus of these studies is the elucidation of the mechanism by which serpins (serine proteinase inhibitors), proteins that play a large role in modulating the inflammatory response, inhibit serine proteinases such as chymotrypsin, prostate specific antigen, and cathepsin G. Principal approaches involve rapid kinetics, site-specific mutagenesis, and fluorescence and Fourier transform IR spectroscopy.

 

Fevzi M. Daldal, Ph.D.
Professor of Biology
103B Lynch Laboratory
tel:215-898-4394
fax: 215-898-8780
e-mail: fdaldal@sas.upenn.edu

  1. Structure guided mutagenesis and spectroscopic analysis of bacterial cyt bc1 complex.
  2. Genome-wide search for bacterial mutants, genes, proteins of cytochrome c biogenesis.

 

William F. DeGrado, Ph.D.
George W. Raiziss Professor of Biochemistry and Biophysics
1009B Stellar-Chance Labs
tel.: 215-898-4590
fax: 215-573-7229
e-mail: wdegrado@mail.med.upenn.edu

(2 students)

  1. de novo protein design.
  2. Cellular adhesion.

 

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

(1 student)

Rotation projects involve structural and biophysical methods aimed at understanding protein-protein interactions in the regulation of actin cytoskeleton dynamics. Students will carry out protein expression, purification and characterization, protein crystallization, X-ray data collection and structure determination. Other methods will include ITC, MALS, bioinformatics and small- and wide-angle X-ray scattering.

 

Gideon Dreyfuss, Ph.D.
Isaac Norris Professor of Biochemistry and Biophysics
Investigator, Howard Hughes Medical Institute
328 Clinical Research Building
tel.: 215-898-0398
fax: 215-573-2000
e-mail: gdreyfuss@hhmi.upenn.edu

(2-3 students)

  1. The survival of motor neurons (SMN) protein complex.
  2. Robotic High-throughput screening of small molecules for potential therapeutics for Spinal Muscular Atrophy.
  3. RNA-binding proteins, hnRNP complexes, and mRNA processing.
  4. Nuclear export and import of proteins and RNAs.

 

Roland Dunbrack, Ph.D.
Adjunct Associate Professor of Biochemistry and Biophysics
Member, Fox Chase Cancer Center
tel.:215-728-2434
fax.: 215-728-2412
email: Roland.Dunbrack@fccc.edu

The Dunbrack group develops methods for protein structure prediction by comparative modeling, and applies these methods to proteins of biological and clinical interest. Rotation projects could involve:

  1. statistical analysis of protein structural features
  2. improvement of algorithms for loop and side-chain prediction
  3. applications to specific classes of proteins such as DNA repair proteins.

 

P. Leslie Dutton, Ph.D.
Eldridge Reeves Johnson Professor of Biochemistry and Biophysics
1005 Stellar-Chance Labs
tel.: 215-898-0991
fax: 215-573-2235
e-mail: dutton@mail.med.upenn.edu

  1. Coupling of electrons and protons in biological catalysis.
  2. Design and engineering of synthetic redox proteins.

 

Wafik S. El-Deiry, M.D. Ph.D.
Professor of Medicine, Genetics, and Pharmacology
tel: 215-898-9015
fax: 215-573-9139
email: Wafik@mail.med.upenn.edu

Reversing drug resistance in cancer represents a major driving force in the El-Deiry Lab. Major projects include:

  1. Understanding the mechanism of action of the p53 tumor suppressor, including its role in radiation and drug-induced apoptosis in vivo, identification of novel p53 target genes, and the identification and testing of drugs that can modulate p53 signaling including drugs that can alter a mutant p53 conformation to a wild-type conformation.
  2. Characterization of a novel family of apical caspase-interacting proteins.
  3. Characterization and therapeutic modulation of a p53-regulated mitotic checkpoint.
  4. Understanding of TRAIL (TNF-related Apoptosis Inducing Ligand) signaling including determinants of TRAIL sensitivity and resistance and the potential of TRAIL as a cancer therapy alone or in combination with other drugs.
  5. Understanding the relationship between BRCA1 and p53 signaling, including the contribution of BRCA1-mediated transcription to DNA repair and breast tumor suppression.
  6. Understanding the role of Myc in apoptotic signaling and drug sensitivity.
  7. Recent efforts in the lab have been employing in vivo molecular imaging strategies in the design of cell-based assays for chemical library screening, as well as the development of xenograft models to image tumor growth and determinants of therapeutic response.

 

S. Walter Englander, Ph.D.
Jacob Gershon-Cohen Professor of Medical Science
Department of Biochemistry and Biophysics
1009 Stellar-Chance Labs
tel.: 215-898-8042
fax: 215-898-2415
e-mail: engl@mail.med.upenn.edu

(2 students)

  1. Protein folding
  2. Fast reaction stopped flow
  3. Hydrogen exchange measured by NMR
  4. Hydrogen exchange analysis/literature/theory

 

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

(1-2 students)

  1. Structural basis of ligand binding specificity in the Epidermal Growth Factor (EGF) receptor family
  2. Mechanisms of antibody mediated inhibition of the EGF receptor
  3. Analysis of protein-protein interactions involved in regulation of clathrin mediated endocytosis and intracellular trafficking
  4. Biochemical and structural analysis of protein:protein interactions in innate immune signaling pathways

 

Feng Gai, Ph.D.
Associate Professor of Chemistry
254 Chemistry 73 Building
Tel: 215-573-6256
Fax: 215-573-2112
Email: gai@sas.upenn.edu

(1-2 students)

  1. Kinetics of  protein folding and aggregation
  2. Kinetics of peptide-membrane association
  3. Single-molecule study of peptide and protein conformational dynamics

 

Yale E. Goldman, M.D., Ph.D.
Professor of Physiology
D700 Richards Building
tel.: 215-898-4017
fax: 215-898-2653
e-mail: goldmany@mail.med.upenn.edu

(1 student)

  1. Single macromolecule structural dynamics.
  2. Internal motions of myosin in cell motility.
  3. Mechanism protein biosynthesis on individual ribosomes.

 

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

  1. Intracellular localization of two-component signaling proteins
  2. Rational design and directed evolution of bacterial signaling circuits.

  

Doron Greenbaum, Ph.D.
Assistant Professor of Pharmacology
304G Carolyn Lynch Laboratories
tel.: 215-746-2992
fax: 215-573-9004
e-mail: greenbaum@pharm.med.upenn.edu

  1. Role of cysteine proteases in the rupture of malaria parasites from host cells using cell biology and synthetic inhibitors
  2. Role of serine proteases in the invasion pathway of malaria parasites using cell biology and synthetic inhibitors
  3. Biological evaluation of novel malarial proteases during erythrocytic life cycle
  4. Synthesis of new activity-based probes for proteases

 

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

  1. High throughput RNAi screening to identify genes that regulate osmosensitive gene expression
  2. Phenotypic and cell biological studies to determine the effects of hypertonicity on protein folding and aggregation
  3. Microarray analysis of osmoregulatory mutants

 

Mark A. Lemmon, Ph.D.
Professor of Biochemistry and Biophysics
809C Stellar-Chance Labs
tel. 215-898-3072
fax: 215-573-4764
e-mail: mlemmon@mail.med.upenn.edu

(2 students)

  1. EGF receptor heterodimerization; studies of receptor extracellular domains using biophysical techniques.
  2. Molecular biological approaches to analysis of ligand specificity in the EGF receptor family.
  3. Lipid biding by Pleckstrin homology domains: structural and functional studies.
  4. Inter-domain cooperation in protein-protein interactions involved in cellular signaling.

 

Zhe Lu, M.D., Ph.D.
Professor of Physiology
D302A Richards Building
Tel.: 215-573-7711
Fax: 215-573-1940
Email: zhelu@mail.med.upenn.edu

(1 student)

The laboratory of Dr. Zhe Lu focuses on examining the molecular and biophysical mechanisms of ion channels, and developing inhibitors of specific channels:

  1. Using a combined approach of molecular biology, biochemistry and biophysics to study the structure and function relationship of ion channels.
  2. Developing novel channel inhibitors both through passive screening various natural sources and peptide libraries, and through active designing.

 

Michael S. Marks, Ph.D.
Associate Professor of Pathology and Laboratory Medicine
513 Stellar-Chance Labs
tel.: 215-898-3204
fax: 215-573-4345
e-mail: marksm@mail.med.upenn.edu

(1 student)

  1. Regulation of melanosome fibril formation induced by resident melanosomal proteins using recombinant proteins.
  2. Assess redox stability imparted by expression of resident melanosomal proteins in living cells and/or subcellular fractions.
  3. Development of an assay to reconstitute steps in melanosome biogenesis in vitro - particularly formation of multivesicular bodies.

 

Ronen Marmorstein, Ph.D.
Wistar Institute Professor of Biochemistry and Biophysics
Professor, The Wistar Institute
327 Wistar Institute
tel.: 215-898-5006
fax: 215-898-3868
e-mail: marmor@wistar.org

(2 students)

  1. Structure-based design of protein inhibitors and activators.
  2. Structure/function of chromatin regulatory enzymes.
  3. Structure/function of oncoproteins and tumor suppressors.

 

Jeanne C. Myers, Ph.D.
Associate Professor of Biochemistry and Biophysics
909A Stellar-Chance Labs
tel.: 215-898-0712
fax: 215-573-2085
e-mail: myers@mail.med.upenn.edu

(1 student)

  1. Biochemical and molecular characterization of collagen and myogenic transcription factors in a model of skeletal muscle differentiation.
  2. Construction of recombinant collagen proteins for biochemical and ultrastructural analysis of functional domains.

 

Tomoko Ohnishi, Ph.D.
Professor of Biochemistry and Biophysics
214A Anatomy-Chemistry Building
tel.: 215-898-8024
fax: 215-573-3748
e-mail: ohnishi@mail.med.upenn.edu

(1 student)

Spectroscopic characterization of redox centers in the NADH-quinone oxidoreductase in bacterial or mitochondrial system

 

E. Michael Ostap, Ph.D.
Associate Professor of Physiology
B40 Anatomy-Chemistry Building (office and lab)
B400 Richards Building (mail)
tel.: 215-898-3685
fax: 215-573-1171
e-mail: ostap@mail.med.upenn.edu

(1 student)

  1. Molecular motor biochemistry and regulation.
  2. Use of 2-hybrid screens to identify myosin-I receptors.
  3. Investigation of the assembly and orientation of lipid-bound myosin-I molecules.

 

Trevor M. Penning, Ph.D.
Professor of Pharmacology & Biochemistry and Biophysics
130C John Morgan Building
tel.: 215-898-9445
fax: 215-573-2236
e-mail: penning@pharm.med.upenn.edu

(1 student/semester)

  1. Structure-function of aldo-keto reductases that control ligand access to steroid hormone receptors.
  2. Steroid 5-beta-reductase and mutants responsible for bile-acid deficiency.
  3. Design, synthesis, and evaluation of inhibitors that block the production of steroid hormones in target tissues.
  4. Metabolic activation of polycyclic aromatic hydrocarbons (human carcinogens) in normal human lung cells.
  5. Mutation of Ras and p53 by reactive and redox-active o-quinones derived from polycyclic aromatic hydrocarbons.

 

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

(2-3 students)

  1. Multinuclear magnetic resonance (MR) methods for studying structure and function in biological systems.
  2. Polarization transfer and multiple quantum filters tailored for diagnostic imaging.
  3. Indirect MR methods for mapping oxygen consumption.
  4. Macromolecular order in biological tissues via dipolar and quadrupolar interaction.
  5. Rotating frame MR: Spin dynamics of slow molecular motions.

 

Brian M. Salzberg, Ph.D.
Professor of Neuroscience & Physiology
234 Stemmler Hall
tel.: 215-898-2441
fax: 215-573-2015
e-mail: bmsalzbe@mail.med.upenn.edu

(2-3 students)

  1. Light scattering changes during neuropeptide release from mammalian nerve terminals.
  2. Calcium dynamics in mammalian nerve terminals.

 

Jeffery G. Saven, Ph.D.
Assistant Professor of Chemistry
266 Cret Wing of Chemistry Complex, 34th & Spruce Streets
tel.: 215-573-6062
fax: 215-573-0980
e-mail: saven@sas.upenn.edu

Theory, simulation, combinatorial libraries

  1. Protein and foldamer design.
  2. Partial protein design via combinatorial libraries, theory and experiment.
  3. Macromolecular simulation.
  4. Bioinformatic and database studies.

 

Kim A. Sharp, Ph.D.
Associate Professor of Biochemistry and Biophysics
236 Anatomy-Chemistry Building
tel.: 215-573-3506
fax: 215-898-4217
e-mail: sharpk@mail.med.upenn.edu

(2 students)

  1. Calculation of antibody/antigen binding energies (electrostatic theory).
  2. Dynamics and calculation of spectral properties of cytochrome c (molecular dynamics).
  3. Theory of ligand binding to DNA (electrostatic, polyelectrolyte theory).
  4. Simulation of protein-substrate association (Brownian dynamics).
  5. Calculation of redox properties of proteins (electrostatic theory).

 

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

(2-3 students)

  1. Pathogenic Amyloid and Oligomer remodeling by Hsp104.
  2. Beneficial Amyloid and Prion remodeling by Hsp104.
  3. Protein-remodeling and disaggregation by AAA+ proteins and molecular chaperones.
  4. Sup35 prion structure.
  5. Small molecule antagonists of prionogenesis.

 

Emmanuel Skordalakes, Ph.D.
Assistant Professor, The Wistar Institute
320 Wistar Institute
tel: 215-495-6884 (office) 215-898-2202 (lab)
email: skorda@wistar.org

(1-2 students)

  1. Elucidation of the mechanism of telomere replication by the telomerase holenzyme.
  2. Understanding the mechanism of telomerase regulation and telomere maintenance by the sheltering complex.

 

David W. Speicher, Ph.D.
Wistar Institute Professor of Biochemistry and Biophysics
151 Wistar Institute
tel: 215-898-3972
fax: 215-898-0664
email: speicher@wistar.org

(2 students)

  1. Proteome analysis of molecular changes and cellular pathways implicated in breast cancer metastasis.
  2. Proteome analysis of novel serological markers and biosignatures of human cancers using mouse models.
  3. Development of novel high throughput protein profile analysis methods for human serum biomarker discovery.
  4. Proteome analysis of oxidative damage of proteins and protein profile changes associated with acute lung injury.
  5. Structure-function of EpCAM using ITC, analytical ultracentrifugation and protein biochemistry to develop improved colorectal cancer therapies.
  6. Structure-function of spectrin using mutagenesis and biophysical methods.

 

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

(1-2 students)

  1. Structural and electrochemical characterization of model radical proteins
  2. Forced folding and structural analysis of meta-stable proteins

 

Phong T. Tran, Ph.D.
Assistant Professor of Cell and Developmental Biology
1009 Biomedical Research Building II/III
tel.: 215-746-2755
fax: 215-898-9871
e-mail: tranp@mail.med.upenn.edu

(1-2 students)

  1. Cloning bulb1 through bulb10, genes whose mutations lead rod-shaped cells to become round or bulbous cells.
  2. 6D imaging (3D+timelapse+multicolors) of protein dynamics in living cells expressing fluorescent proteins.
  3. Molecular analysis of the microtubule and actin polymers in establishing cellular patterns such as nuclear positions and tip growth sites.

 

Jane M. Vanderkooi, Ph.D.
Professor of Biochemistry and Biophysics
909C Stellar-Chance Labs
tel. 215-898-8783
fax: 215-573-2042
e-mail: vanderko@mail.med.upenn.edu

(1 student)

  1. IR studies of proteins.
  2. Fluorescence and phosphorescence of proteins.
  3. Electric field calculations in proteins.

 

Gregory D. Van Duyne, Ph.D.
Professor of Biochemistry and Biophysics
809B Stellar-Chance Labs
tel.: 215-573-9730
fax: 215-573-4764
e-mail: vanduyne@mail.med.upenn.edu

(2 students)

  1. Probing the mechanism of site-specific DNA recombination using biochemical and biophysical approaches.
  2. Analyzing protein-protein interactions in the human SMN complex and the methylosome.
  3. Protein-protein and protein-RNA interactions in the human exon junction complex.
  4. \Structural biochemistry of chromosome organization.

 

A. Joshua Wand, Ph.D.
Professor of Biochemistry and Biophysics
905 Stellar-Chance Labs
tel.: 215-573-7288
fax: 215-573-7289
e-mail: wand@mail.med.upenn.edu

(1 student)

  1. Introduction to NMR: Collection of resonance assignment data for a small protein and its analysis. Likely candidates include a calmodulin-target domain complex or mutant protein. Can involve construction of target domain expression system.
  2. Membrane protein structure: Use of novel NMR-based approaches to characterize membrane protein structure. Involves preparation and initial characterization by NMR of membrane proteins.
  3. Mutational analysis of protein-protein and protein-prosthetic group interactions. Involves site specific mutagenesis, protein purification; biophysical characterization using CD, UV/Vis, fluorescence and NMR spectroscopy.
  4. Bioinformatics: Targeted application of knowledge-based algorithms for the NMR-based analysis of protein structure and dynamics. Computer programming oriented.
  5. Introduction to protein dynamics: Examination of protein dynamics using hydrogen exchange and NMR relaxation methods.

 

John W. Weisel, Ph.D.
Professor of Cell and Developmental Biology
1054 BRB II/III
tel.: 215-898-3573
fax: 215-898-9871
e-mail: weisel@anat3d2.anatomy.upenn.edu

(2 students)

  1. Molecular mechanisms of fibrin polymerization: structural studies are conducted to analyze the polymerization of naturally occurring and recombinant fibrinogen variants.
  2. Clots emulating aspects of physiological hemostasis and thrombosis: examination by electron microscopy of the structure of pathologic thrombi and whole blood clots and clots formed at low thrombin concentrations.
  3. Interactions of osteopontin with integrins in vitro and on cells; urokinase interactions with its cellular receptor; study of individual ligand/receptor interactions using optical tweezers
  4. Modulation of fibronolysis via interactions of defensin with plasminogen and Lp(a): studies of the structure and interactions of these proteins to determine molecular mechanisms involved.

 

David F. Wilson, Ph.D.
Professor of Biochemistry and Biophysics
901A Stellar-Chance Labs
tel.: 215-898-6382
fax: 215-573-3787
e-mail: wilsondf@mail.med.upenn.edu

(1 student)

  1. Instrumentation for measuring phosphorescence lifetimes and thereby oxygen concentration in fluids.
  2. Phosphorescence lifetime imaging for two and three-dimensional measurements of oxygen in vivo.
  3. Tumor oxygenation and radiation therapy in tumors.
  4. Brain neurotransmitter metabolism and ischemic/hypoxic injury.

 

Bryan A. Wolf, M.D., Ph.D.
Professor of Pathology and Laboratory Medicine
803 Abramson Research Center
tel.: 215-590-4446
fax: 215-590-1021
e-mail: wolfb@mail.med.upenn.edu

(1 student)

  1. Analysis of PANDER transgenic mouse
  2. Site-directed mutagenesis of PANDER
  3. siRNA approaches to downregulate PANDER
  4. Regulation of PANDER mRNA in beta-cells
  5. Secretory mechanisms of PANDER in beta-cells

 

John H. Wolfe, V.M.D., Ph.D.
Professor of Pathology and Medical Genetics, School of Veterinary Medicine
503 Abramson Research Center (CHOP)
tel.: 215-590-7028
fax: 215-590-3779
e-mail: jhwolfe@vet.upenn.edu

(1 student)

  1. Identification of molecules in degenerating neurons in a genetic disease model. The long-term goal is to understand the specific molecular events involved in inherited neurologic diseases of childhood.
  2. Characterization of a novel therapeutic protein engineered to target diseased neurons. This could involve further modification of the protein to alter its biodistribution, crystallization of the chimeric protein to understand its structure, or mapping the distribution in various areas of the brain. The long-term goal is to improve delivery of therapeutic proteins in the CNS.
  3. Engineering the expression systems of gene transfer vectors for improved delivery of therapeutic proteins. These studies involve manipulating promoters and other cis elements in gene transfer vectors that affect the expression of a foreign gene in specific cell types.
  4. Investigate specific molecular events controlling migration of neural stem cells in the brain after transplantation. The long-term goal is to better understand the potential of neural cell transplantation as a therapeutic modality.

 

Takashi Yonetani, Ph.D.
Professor of Biochemistry and Biophysics
220 Anatomy-Chemistry Building
tel.: 215-898-8787
fax: 215-898-8559
e-mail: yonetant@mail.med.upenn.edu

(1 student)

  1. Structure and function studies of allosteric mechanism of hemoglobin.
  2. Biochemical and biophysical studies of allosteric regulation of regulatory enzymes.
  3. Studies of blood substitutes

       

    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

    (1 student)

    Dr. Zheng's laboratory is focusing on the biology and biochemistry of ADAMTS13 metalloprotease that is associated with thrombosis. The rotation projects include:

    1. Structure and function relationship of ADAMTS13 metalloprotease.
    2. Biosynthesis and intracellular trafficking of ADAMTS13 in polarized epithelial and endothelial cells.
    3. Molecular interaction between von Willebrand factor and ADAMTS13 metalloprotease.
    4. Identification of the domains of ADAMTS13 interacting with anti-ADAMTS13 autoantibody.

    updated 04/08