Biochemistry and Molecular Biophysics Graduate Group

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BMB 699 - Laboratory Rotation

Course Director: Rahul Kohli, M.D., Ph.D.
Assistant Professor of Medicine, and Biochemistry &  Biophysics
502 Johnson Pavilion
tel: 215-573-7523
rkohli@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.

    Rotation Start

    Form Due

    Rotation Ends

    Abstract Due

    Rotation Talks

    Rotation 1

    Sept

    Sept 20

    Nov/Dec

    Dec 1

    Early-Mid Dec

    Rotation 2

    Dec/Jan

    Jan 15

    March/April

    April 1

    Mid-April

    Rotation 3

    March/April

    April 15

    June

    June 15

    Early Sept*

    Rotation 4 (prn)

    June/July

    June 30

    Aug 30

    Aug 15

    Early Sept*

     

    * If a student does a 4th rotation, can choose to present on either Rotation 3 or Rotation 4.

    While there is flexibility in the start and end times of individual rotations, each rotation should be a minimum of 10 weeks in duration (or 8 weeks in the summer) and students should be actively in a rotation lab throughout their first year.

    An incoming student may take Rotation 1 in the summer prior to the Fall semester. The date for the start of the summer semester is different every year, but is usually the first or second week of June. This rotation would end at the end of August, with the abstract due August 15th, and the presentation in early September.

  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 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. For talks and poster presentations, one week prior to the presentations (see below), a 150-word abstract should be submitted to the Course Director and to the Academic Office. The abstract should describe the issue/question motivating the study, the approaches taken to address the issue/ question, and a synopsis of key findings, conclusions and future directions. Failure to submit the abstract in a timely manner will affect the rotation grade. Please also give your abstract a title (which does not count toward the word limit).

  8. End of the semester (fall, spring and summer) lab rotation presentation requirements will be in one of the following formats:

See Suggestions for Talk Preparation and Presentation (80 KB Word document) and attached article on "How to Give A Good Talk".

The talks, poster presentations, and written summaries are requirements for completion of the course. Anyone who fails to complete these requirements will obtain an incomplete for the course. The requirement must be completed by the end of the following semester.

Attendance at the Lab Rotation Talks and the Poster Presentations is required. Unexcused absence from all or part of these sessions will result in reduction of the grade submitted by the Faculty Supervisor by one half grade.

9. The Faculty Supervisor may also require a student to prepare a short report or paper at the completion of the rotation.

10. 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
 

Charles S. Abrams, M.D.
Professor of Medicine
912 BRB II/III
Tel: 215-898-1058
Fax: 215-573-7400
Email: 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
Email: yargon@mail.med.upenn.edu

1. Roles of the molecular chaperones BiP and GRP94 in protein folding in the cell
2. ldentification of chaperone client proteins by proteomic methods3.
3. Prion-like polymerization of antibodies in systemic amyloidosis

Paul H. Axelsen, M.D.
Professor of Pharmacology, Biochemistry & Biophysics, and Medicine
105 Johnson Pavilion
Tel.: 215-898-9238
Fax: 215-573-2236
Email: axe@upenn.edu

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. Experimental studies - Mass spectrometry, UV-VIS, fluorescence, and novel forms of infrared and infrared correlation spectroscopy applied to understanding critical protein-lipid interactions, and how these interactions are altered under conditions of oxidative stress and in Alzheimer's disease.

Joseph A. Baur, Ph.D.
Assistant Professor of Physiology
12-114 Smilow Center for Translational Research
Tel: 215-746-4585
Fax: 215-898-5408
Email: baur@mail.med.upenn.edu

  1. Functional consequences of changing mitochondrial mass
  2. Role of NAD concentration in metabolic regulation
  3. Regulation of mitochondrial mass by nitric oxid

Shelley L. Berger, Ph.D.
Daniel S. Och University Professor of Cell and Developmental Biology
9-125 Smilow Center for Translational Research
Tel: 215-898-3922 (office)
Fax: 215-746-8791
Email: bergers@upenn.edu

Rotations will encompass aspects of chromatin regulation, focusing on histone and factor post-translational modifications, in the following physiological pathways in cells and organisms: aging, gametogenesis, metabolic stress, DNA damage, viral infection, and ant behavioral caste specification.

Ben E. Black, Ph.D.
Associate Professor of Biochemistry and Biophysics
913A Stellar-Chance Labs
Email: 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 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.

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
Email: brass@mail.med.upenn.edu

  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
 

Theresa Busch, Ph.D.
Research Associate Professor of Radiation Oncology
8-126 Smilow Center for Translational Research,
Tel: 215-573-3168
Fax: 215-898-0090
Email: buschtm@mail.med.upenn.edu

  1. Investigation of the vascular mechanisms of tissue damage by photodynamic therapy
  2. Combined modality approaches to target tumor microenvironment
  3. Quantification of tumor cell kill by photodynamic therapy

Fevzi M. Daldal, Ph.D.
Professor of Biology
103B Carolyn Lynch Laboratory
Tel: 215-898-4394
Fax: 215-898-8780
Email: 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

Maya Capelson, Ph.D.
Assistant Professor of Cell & Developmental Biology
9-101 Smilow Center for Translational Research
Tel: 215-898-0550 (office) / 215-573-7548 (lab)
Email: capelson@mail.med.upenn.edu

1. Mapping chromatin binding of nuclear pore proteins in cell lines of distinct lineages
2. Characterization of the role of nuclear pore/matrix proteins in chromatin organization and structure
3. Functions of nuclear envelope proteins in deposition of histone modifications during development.

Bohdana M. Discher, Ph.D.
Research Assistant Professor of Biochemistry and Biophysics
901C Stellar-Chance Labs
Tel: 215-898-5668
Fax: 215-898-0465
Email: bohdana@mail.med.upenn.edu

1. Clickable Nanodiscs. "Nanodiscs" are membrane bilayers stabilized with membrane scaffold proteins (MSP). Nanodiscs provide a more natural environment for membrane proteins than do detergent micelles. The goal of this rotation project is to modify the membrane scaffold protein with azide or alkyne groups for click chemistry coupling. The modified MSP will serve as a platform attachment technology to study membrane protein-ligand interactions on field effect transistors (FETs) and on Quartz Crystal Microbalance with Dissipation (QCM-D) sensors.

2. Directional assembly of designed proteins into membranes. Our lab has designed and synthesized membrane proteins for electron transfer across membranes. The goal of this rotation project is to assemble the proteins into vesicles and to test the protein orientation using tryptophan fluorescence quenching.

Roberto Dominguez, Ph.D.
Professor of Physiology
728 Clinical Research Building
Tel: 215-573-4559
Fax: 215-573-5851
Email: droberto@mail.med.upenn.edu

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
Email: gdreyfuss@hhmi.upenn.edu

  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 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.
Professor of Biochemistry and Biophysics
1005 Stellar-Chance Labs
Tel: 215-898-0991
Fax: 215-573-2235
Email: dutton@mail.med.upenn.edu

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

S. Walter Englander, Ph.D.
Professor of Biochemistry and Biophysics
1009 Stellar-Chance Labs
Tel: 215-898-8042
Fax: 215-898-2415
Email: engl@mail.med.upenn.edu

  1. Protein folding
  2. Hydrogen exchange analysis/literature/theory
  3. NMR, mass spec, spectroscopy, fast reaction, stopped flow

Hua-Ying Fan, Ph.D.
Assistant Professor of Biochemistry and Biophysics
9-133 Smilow Center for Translational Research
Tel: 215-573-5705 (office) / 215-573-5713 (lab)
Email: hfan@mail.med.upenn.edu

  1. Determine how the ATP-dependent chromatin remodeling activity of the CSB remodeler is influenced by different nucleosomal substrates
  2. Dissect the functional interplay between the CSB remodeler and other epigenetic regulators
  3. Examine the mechanisms by which epigenetic factors impact cancer cell self-renewal and differentiation

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

  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.
Professor of Chemistry
254 Chemistry Building
Tel: 215-573-6256
Fax: 215-573-2112
Email: gai@sas.upenn.edu

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

Jerry D. Glickson, Ph.D.
Research Professor of Radiology
B6 Blockley Hall
Tel: 215-898-1805
Fax: 215-573-2113
Email: glickson@mail.med.upenn.edu

Opportunity for research on cancer pharmacology, metabolism and lactate/pyruvate. Our NIH proposal to delineate the Mechanism of Action of Lonidamine has been rated in the top 1% by the Medical Imaging Study Section (MEDI) and will be funded for five years starting July 1. This project focuses on NMR studies of melanoma cells in a bioreactor and in vivo. Our preliminary data indicates that this drug functions by inhibiting the monocarboxylate transporter (MCT) and the mitochondrial pyruvate carrier (MPC); this leads to selective acidification of tumor cells that are highly glycolytic, and it decreases levels of ATP in the tumors. These tumors exhibit increased response to chemotherapy with alkylating agents and anthracyclines, to radiation and to hyperthermia. The study involves studies with tumors in bioreactors and in mice as well as interactions with a leading laboratory at the University of Bristol in the UK on the MCT and MPC. Carbon-13 isotope exchange will be analyzed by fitting data to a mathematical algorithm that defines flux through the various pathways of tumor intermediary analysis. Expertise in cell biology, metabolism and mathematics is essential. We are looking for a special graduate student that could use this project as a launching pad to a productive career in academic medicine .

Yale E. Goldman, M.D., Ph.D.
Professor of Physiology
615B Clinical Research Building
Tel: 215-898-4017
Fax: 215-898-2653
Email: goldmany@mail.med.upenn.edu

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

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

  1. Bacterial signaling systems - network structure, single cell behavior, screens for novel regulators
  2. Directed evolution of regulatory circuits

Ekaterina Grishchuk, Ph.D.
Assistant Professor of Physiology
675 Clinical Research Building
Tel: 215-746-8178
Fax: 215-573-2273
Email: gekate@mail.med.upenn.edu

  1. in vitro motility of microtubule-dependent mechanochemical enzymes
  2. Single molecule analysis of kinetochore coupling proteins

Harry Ischiropoulos, Ph.D.
Gisela and Dennis Alter Research Professor of Pediatrics and Pharmacology
417 Abramson Research Center
Tel: 215-590-5320
Email: ischirop@mail.med.upenn.edu

  1. Proteomic analysis of proteins modified by S-nitrosation and nitration in human plasma and atherosclerotic lesions
  2. Development of unbiased complementary approaches for the proteomic evaluation of S-nitrosocysteine modified proteins in endothelial and vascular smooth muscle cells
  3. Mouse models of Parkinson’s disease
  4. Inventories of cellular secretomes that regulate neuron growth, differentiation and death. 

F. Bradley Johnson, M.D., Ph.D.
Associate Professor of Pathology & Laboratory Medicine
405A Stellar-Chance Laboratories
Tel: 215-573-5037
Fax: 215-573-6317
Email: johnsonb@mail.med.upenn.edu

1. Roles for chromatin in the regulation of gene expression in senescent cells.
2. DNA structures that form during replication of recalcitrant genomic regions.
3. Extracellular signals that regulate cell senescence

 

Rahul M. Kohli, M.D., Ph.D.
Assistant Professor of Medicine, and Biochemistry & Biophysics
502B Johnson Pavilion
Tel: 215-662-2359
Fax: 215-349-5111
Email: rkohli@upenn.edu

  1. Small molecules to prevent the evolution of Pseudomonas aeruginosa
  2. Harnessing the enzymes of antibody diversity for directed protein evolution
  3. The role of cytidine deamination in genomic plasticity
  4. Macromolecular interfaces of the anti-HIV innate defense factor, APOBEC3G

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

  1. Measure phosphorylation dynamics in living cells using FRET-based biosensors
  2. Model Aurora kinase signaling at centromeres to regulate microtubule attachments
  3. Analyze microtubule dynamics in meiotic spindles of mouse oocytes

Mitchell Lazar, M.D., Ph.D.
Sylvan Eisman Professor of Medicine
12-102 Smilov Center for Translational Research
Tel: 215-898-0198
Email: lazar@mail.med.upenn.edu

There are many potential rotation projects addressing the biochemistry, cellular biology, and physiology of nuclear receptors and the transcriptional regulation of circadian rhythms and metabolism. These change frequently as the science advances, so it is best to discuss these directly with Dr. Lazar.


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

  1. ErbB receptor trafficking and signaling in cancer
  2. Response of cancer cells to ErbB-receptor-targeted therapeutics
  3. Trafficking of Neph1 and Nephrin in glomerular podocytes and
    associated cell signaling processes

Mark A. Lemmon, Ph.D.
George W. Raiziss Professor of Biochemistry and Biophysics
322A Clinical Research Building
Tel: 215-898-3072
Fax: 215-573-4764
Email: mlemmon@mail.med.upenn.edu

  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
664 Clinical Research Building
Tel: 215-573-7711
Fax: 215-573-1940
Email: zhelu@mail.med.upenn.edu

  1. The laboratory of Dr. Zhe Lu focuses on examining the molecular and biophysical mechanisms of ion channels, and developing inhibitors of specific channels
  2. Using a combined approach of molecular biology, biochemistry and biophysics to study the structure and function relationship of ion channels
  3. Developing novel channel inhibitors both through passive screening various natural sources and peptide libraries, and through active designing

Kristen W. Lynch, Ph.D.
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

  1. Identification of sequences that regulate alternative splicing in T cells
  2. Identification of novel targets of signal-induced splicing in T cells
  3. Mutational analysis of proteins that control alternative splicing.

Michael S. Marks, Ph.D.
Professor of Pathology and Laboratory Medicine
Children's Hospital of Philadelphia and University of Pennsylvania
1107B Abramson Research Center
Tel: 215-590-3664
Email: marksm@mail.med.upenn.edu

  1. Regulation of melanosome amyloid fibril formation induced by resident melanosomal proteins using recombinant proteins
  2. Test effects of endosome-like acidification and altered redox conditions on copper binding by tyrosinase
  3. Development of an assay to reconstitute ESCRT-independent multivesicular body formation in vitro

Ronen Marmorstein, Ph.D.
Professor of Biochemistry and Biophysics
454 Biomedical Research Buildling
Tel: 215-898-7740
Email: marmor@mail.med.upenn.edu

  1. Structure-based design of organometallic kinase inhibitors
  2. Structure and biochemistry on proteins that regulate chromatin and epigenetics
  3. Structure and biochemistry on oncoproteins and tumor suppressors

John I. Murray, Ph.D.
Assistant Professor of Genetics
437A Clinical Research Building
Tel: 215-746-4387
Fax: 215-746-6258
Email: jmurr@mail.med.upenn.edu

1. Use quantitative microscopy to test predicted regulatory networks
2. Develop computational tools to quantitatively measure localization to subcellular compartments
3. Define combinatorial transcription factor targets by combining gain and loss of function genetics with genomic expression analysis
4. Characterize sequences required for temporally correct expression patterns
5. Determine how and why expression patterns are different in normal and stressful growth conditions

E. Michael Ostap, Ph.D.
Professor of Physiology
700 Clinical Research Building
Tel: 215-898-3685
Fax: 215-573-1171
Email: ostap@mail.med.upenn.edu

  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, and Biochemistry & Biophysics
1315 Biomedical Research Building II/III
Tel: 215-898-9445
Fax: 215-573-2236
Email: penning@pharm.med.upenn.edu

  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.

E. James Petersson, Ph.D.
Assistant Professor of Chemistry
350N Chemistry Building
Tel: 215-746-2221
Email: ejpetersson@sas.upenn.edu

All projects involve the synthesis of unnatural amino acids and their incorporation into proteins by unnatural amino acid mutagenesis and/or native chemical ligation.
1. Use of fluorescent probes and thioamide quenchers to detect conformational changes and proteolysis
2. Development of novel protein labeling and synthesis strategies
3. Use of bioorthogonal chemistry to detect and control protein activity in living cells

Benjamin L. Prosser, Ph.D.
Assistant Professor of Physiology
726 Clinical Research Building
Tel: 215-746-1488
Email: bpros@mail.med.upenn.edu

We utilize super-resolution and high-speed live cell imaging, manipulation of cell mechanics, electrophysiology, and molecular biology to gain insight into:
1. Transmission of mechanical stress through the microtubule cytoskeleton.
2. Stress-dependent production of reactive oxygen species and regulation of calcium signaling.
3. Mechano-signaling as a therapeutic target for muscular dystrophy in heart and skeletal muscle.

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

  1. Molecular dynamics simulations, free Energy calculations, and computational structural biology
  2. Modeling cell membranes, signal transduction in trafficking, cancer signaling
  3. Modeling targeted drug delivery: binding, trafficking, hydrodynamics

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

  1. Discovery and characterization of non-coding RNAs during C. elegans development.
  2. Making single molecule maps of gene expression in tumors.

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

  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
Email: bmsalzbe@mail.med.upenn.edu

  1. Light scattering changes during neuropeptide release from mammalian nerve terminals
  2. Calcium dynamics in mammalian nerve terminals
  3. High bandwidth atomic force microscopy of nerve terminals and pancreatic Islets

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

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

 
Kim A. Sharp, Ph.D.
Associate Professor of Biochemistry and Biophysics
805A Stellar-Chance Labs
Tel: 215-573-3506
Fax: 215-898-4217
Email: sharpk@mail.med.upenn.edu

  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.
Associate Professor of Biochemistry and Biophysics
805B Stellar-Chance Labs
Tel: 215-573-4256
Email: jshorter@mail.med.upenn.edu

  1. Defining the structural and mechanistic basis for Hsp104 function
  2. Applying Hsp104 to disease-associated amyloidogenesis
  3. Defining how small molecules disrupt amyloid structure
  4. Defining the misfolding trajectories of RNA-binding proteins
     

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

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

David W. Speicher, Ph.D.
Wistar Institute Professor of Biochemistry and Biophysics
272A Wistar Institute
Tel: 215-898-3972
Fax: 215-898-0664
Email: speicher@wistar.org

  1. Probing macromolecular interactions and structure using homology modeling, chemical crosslinking and mass spectrometry
  2. Structure-function analysis of membrane skeletons
  3. Systems biology analysis of tumor progression and therapeutic responses using proteomics
  4. Developing cancer biomarkers for personalized medicine

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

Phong T. Tran, Ph.D.
Associate Professor of Cell and Developmental Biology
1009 BRB II/III
Tel: 215-746-2755
Fax: 215-898-9871
Email: tranp@mail.med.upenn.edu

  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

 
Andrew Tsourkas, Ph.D.
Associate Professor of Engineering
110 Hayden Hall
Tel: 215-898-8167
Email: atsourk@seas.upenn.edu

1. Antibody engineering for biotherapeutic and molecular imaging applications

2. Nanotechnology development for molecular imaging and targeted drug delivery

3. Imaging of RNA in living cells using oligonucleotide-based probes

 

Gregory D. Van Duyne, Ph.D.
Jacob Gershon-Cohen Professor of Medical Science
Department of Biochemistry & Biophysics
809B Stellar-Chance Labs
Tel: 215-573-9730
Fax: 215-573-4764
Email: vanduyne@mail.med.upenn.edu

  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

Sergei Vinogradov, Ph.D.
Associate Professor of Biochemistry and Biophysics
1013B Stellar-Chance Labs
Tel: 215-573-7524
Email: vinograd@mail.med.upenn.edu

  1. Synthetic development of advanced optical imaging probes
  2. Photophysical studies of porphyrin-based nanosensors
  3. Construction of two-photon oxygen imaging microscope

A. Joshua Wand, Ph.D.
Benjamin Rush Professor of Biochemistry and Biophysics
905 Stellar-Chance Labs
Tel: 215-573-7288
Fax: 215-573-7289
Email: wand@mail.med.upenn.edu

  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
1154 BRB II/III
Tel: 215-898-3573
Email: weisel@mail.med.upenn.edu

  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.

Aalim Weljie, Ph.D.
Research Assistant Profesor of Pharmacology
10-113 Translational Research Center
Tel: 215-573-8085 (office); 215-898-2220 (lab)
Email: aalim@upenn.edu

1. Understanding the relationship between lipid processing, metabolism, sleep, and the circadian clock
2. Biomolecular profiling of metabolites in human serum from cancer, circadian and sleep studies
3. Development of analytical and statistical methods related to mass spectrometry and nuclear magnetic resonance spectroscopy.

Kathryn E. Wellen, Ph.D.
Assistant Professor of Cancer Biology
611 BRB II/III
Tel: 215-746-8599 (office); 215-746-4956 (lab)
Fax: 215-573-6725
Email: wellenk@exchange.upenn.edu

Please see Dr. Wellen for potential rotation projects.

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

    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

John H. Wolfe, V.M.D., Ph.D.
Professor of Pathology and Medical Genetics, School of Veterinary Medicine
503 Abramson Research Center
Tel: 215-590-7028
Fax: 215-590-3779
Email: jhwolfe@vet.upenn.edu

  1. Investigation of discrepancies between gene expression vs proteome changes in diseased brain
  2. Genetic modification of chimeric proteins to facilitate neuronal transport
  3. Modifications of viral vector (AAV cap or HIV glycoprotein) to enhance distribution within the CNS
  4. Collaborative studies using MRI or PET to study neural stem cells in vivo
  5. Role of GAGs in activating inflammatory molecules in brain disease

Kenneth S. Zaret, Ph.D.
Joseph Leidy Professor, Department of Cell and Developmental Biology
9-131 Smilow Center for Translational Research
502G Abramson Building (CHOP)
Tel: 215-573-5813 (office) / 215-573-5844 (lab) / Fax: 215-898-9871
Email: zaret@upenn.edu

1. Reconstitution of different types of chromatin in vitro as substrates for transcription factor binding
2. Assessing changes in chromatin structure elicited by transcription factor binding.
3. Understanding the mechanistic roles of cofactors that bind to transcription factors during the regulation of gene expression.


X. Long Zheng, M.D., Ph.D.

Associate 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

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

    1. Structure and function analysis of ADAMTS13 metalloprotease
    2. Biosynthesis and regulation of ADAMTS13 in endothelial cells
    3. Cofactor dependent regulation of ADAMTS13 function
    4. Characterization of autoantibodies against ADAMTS13
    5. Viral and stem cell mediated gene transfer for ADAMTS13 deficiency

Zhaolan (Joe) Zhou, Ph.D.
Assistant Professor of Genetics
452A Clinical Research Building
415 Curie Boulevard
Tel: 215-746-5025 / Fax: 215-573-7760
Email: zhaolan@mail.med.upenn.edu

Please see Dr. Zhou for potential rotation projects.