Elizabeth Rhoades

Photo: 
First Name: 
Elizabeth
Last Name: 
Rhoades
Official Title: 
Associate Professor of Chemistry
Contact Information
Office Location: 
258 Chemistry Building
Email: 
elizabeth.rhoades@sas.upenn.edu
Phone: 
215-573-6477
Fax: 
215-573-2112
Admin Support: 
Education: 
  • postdoctoral associate with Professor Watt Webb at Cornell University (2003-2006)
  • postdoctoral associate with Professor Gilad Haran at the Weizmann Institute of Science (2001-2003)
  • PhD in Biophysics from the University of Michigan, Ann Arbor (2001)
  • B.S. in Physics from Duke University (1994)
Research Interests: 

Research in the Rhoades lab aims to elucidate the principles that link protein conformational change with structure-function relationships, focusing on understanding structural plasticity in intrinsically disordered proteins (IDPs). IDPs do not form stable structures under physiological conditions; for many, function is dependent upon disorder. This is in striking contrast to the structure-function paradigm that dominates our understanding of globular proteins. Given the large fraction of the eukaryotic proteome predicted to be disordered, the scope of the problem and the need for new insights are enormous.

 

Much of our effort is directed towards IDPs whose aggregation is central to the pathology of several degenerative diseases: α-synuclein (Parkinson’s disease), tau (Alzheimer’s disease), and IAPP (Type II Diabetes). These three proteins have diverse native functions and binding partners, but share intriguing commonalities of toxic mechanism and the importance of templated selfassembly. Studying systems in parallel allows us to generate protein and disease-specific insights as well as determine principles relevant to general functional and dysfunctional mechanisms of IDPs.

 

Our primary approaches center on single molecule optical techniques. These approaches enable quantitative and structural assessments of our systems in isolation and in the context of biologically relevant interactions. Single molecule approaches are unique in their ability to characterize systems which exist and function as a dynamic ensemble of states.

Selected Publications: 

1.      X.-H. Li, J. A. Culver, and E. Rhoades (2015) “Tau binds to multiple tubulin dimers with helical structure” Journal of the American Chemical Society, 137: 9218-921


2.     A. Nath, D. E. Schlamadinger, E. Rhoades, and A.D. Miranker (2015) “Structure-based small molecule modulation of a pre-amyloid state: pharmacological enhancement of IAPP membrane-binding and toxicity” Biochemistry, 349: 54-58

3.     D. Jülich, G. Cobb,  A.M. Melo, P. McMillen, A. Lawton,  S.G.J. Mochrie, E. Rhoades, and S.A. Holley (2015) “Cross-scale Integrin regulation organizes ECM and tissue topology” Developmental Cell, 34: 33-44

4.     J. LaRochelle, G. Cobb, A. Steinauer, E. Rhoades, and A. Schepartz (2015) “Fluorescence correlation spectroscopy revealsy highly efficient endosomal escape by certain penta-arg proteins and stapled peptides” Journal of the American Chemical Society. 127: 2536-2541 January 2015

5.     S.Kumar, D.E. Schlamadinger, M.A. Brown, J.M. Dunn, B. Mercado, J.A. Hebda, I Saraogi, E. Rhoades, A.D. Hamilton, and A.D. Miranker (2014) “IAPP and the shared molecular origins of leakage and toxicity” Chemistry and Biology, 19: 369-378

6.     A.R. Braun, M.M. Lacy, V.C. Ducas, E. Rhoades, and J.N. Sachs (2014) “α-Synuclein-induced membrane remodeling is driven by binding affinity, partition depth, and interleaflet order asymmetry” Journal of the American Chemical Society, 136: 9962-9972

7.  S. Elbaum-Garfinkle, G. Cobb, J. T. Compton, X. Li and E. Rhoades (2014)“Tau mutants bind tubulin heterodimers with enhanced affinity” Proceedings of the National Academy of Sciences U.S.A., 111: 6311-6316

8.  D. C. DeWitt and E. Rhoades (2013) “α-Synuclein Inhibits SNARE-mediated Vesicle Fusion Through Direct Interactions with Lipid Bilayer” Biochemistry, 52: 2385-2387

9.  B. R. Capraro, Z. Shi, J.M. Dunn, T. Wu, E. Rhoades, and T. Baumgart (2013) “Kinetics of endophilin N-BAR domain dimerization and membrane interactions” Journal of Biological Chemistry, 288: 12533-12543

10.  S. Elbaum-Garfinkle and E. Rhoades (2012) “Long-Range Interactions Modulate Aggregation of Tau by Altering the Conformational Ensemble” Journal of the American Chemical Society, 134: 16607-16613

11.     A. Nath, M. Sammalkorpi, D. DeWitt, A.J. Trexler, S. Elbaum-Garfinkle, C.S. O’Hern and  E. Rhoades (2012) “The Conformational Ensembles of  α-Synuclein and Tau:  Combining Single-Molecule FRET and Simulations”  Biophysical Journal, 103: 1940-1949

12.     V. Ducas and E. Rhoades (2012) “Quantifying β-Synuclein and g-Synuclein Membrane Interactions”  Journal of Molecular Biology, 423:528-539

13.     A.J. Trexler and E. Rhoades  (2012) “N-terminal acetylation is critical for forming α-helical oligomer of α-Synuclein” Protein Science, 21:601-605  

14.     A.R. Braun, E. Sevcsik, P. Chin, E. Rhoades, S. Tristram-Nagle, and J.N. Sachs (2012) “α-Synuclein Induces Both Positive Mean Curvature and Negative Gaussian Curvature in Membranes” Journal of the American Chemical Society,  134: 2613-2620  

15.     A. Nath, A. D. Miranker, and E. Rhoades (2011) “A Membrane-bound Dimer of Islet Amyloid  Polypeptide Studied by Single-Particle FRET”  Angewandte Chemie, 50: 10859-10862   
   
16.     N.B. Last, E. Rhoades, and A.D. Miranker (2011) “Islet Amyloid Polypeptide Demonstrates A Persistent Capacity to Disrupt Membrane Integrity” Proceedings of the National Academy of Sciences, U.S.A., 108: 9460-9465   

17.     E. Sevcsik, A.J. Trexler, J.M. Dunn, and E. Rhoades (2011) “Allostery in a disordered protein: Oxidative modifications to α-Synuclein act distally to regulate membrane binding” Journal of the American Chemical Society, 133: 7152-7158  

18.  A.J. Trexler and E. Rhoades (2010) “Single molecule characterization of α-Synuclein in aggregation-prone states” Biophysical Journal, 99: 3048-3055    

19.  E. R. Middleton and E. Rhoades (2010) “Effects of vesicle curvature and composition on α-Synuclein binding to lipid vesicles” Biophysical Journal, 99: 2279-2288  

20.  A . J. Trexler and E. Rhoades (2009) “α-Synuclein binds large unilamellar vesicles as an extended helix”Biochemistry, 48: 2304-2306  

Junrong Zheng, Rice University , Physical Chemistry Seminar

Thu, 2014-04-24 13:00 - 14:00
Speaker: 

Junrong Zheng

Location: 

Lynch Lecture Hall

Chemistry Department

Inquiries Please contact Rosa Vargas rvargas@sas.upenn.edu

Edgar Fahs Smith Lecture (Benjamin Widom, Cornell)

Thu, 2015-03-19 18:00 - 19:00
Speaker: 

Prof. Benjamin Widom

Cornell University

 

A Tale of Three Equations: Thermodynamics and Molecular Correlations

Location: 
Lynch Lecture Hall
Attached Document: 

The equations of the title relate thermodynamic functions to correlation-function integrals. They are central to much of statistical mechanics. Their meaning and origin are reviewed here.

BMS Lecture (Phil Baran, Scripps)

Tue, 2015-05-12 14:00 - 17:00
Speaker: 

Prof. Phil Baran, Scripps

 

Dr. Albert DelMonte, BMS

Location: 
Lynch Lecture Hall

Axalta Lecture (Omar Yaghi, Berkeley)

Wed, 2014-10-22 16:00 - 17:00
Speaker: 
Prof. Omar M. Yaghi University of California, Berkeley
Location: 
Room 102 Chemistry Building
Attached Document: 

Reticular Chemistry and the Design of New Materials

Trost Lecture (Larry Overman, UC Irvine)

Wed, 2014-09-10 16:00 - 17:00
Speaker: 

Prof. Larry Overman

University of California, Irvine

 

Rearranged Spongian Diterpenes: Linking Chiral Rings at Stereocenters

Location: 
Lynch Lecture Hall
Attached Document: 

Tom Markland, Stanford University , Physical Chem Seminar

Thu, 2014-03-27 13:00 - 14:00
Speaker: 

Tom Markland

Location: 

Lynch Lecture Hall, Chem Dept

Inquiries Please contact Rosa Vargas rvargas@sas.upenn.edu

Laura Anderson, UIC, Special Org. Sem.

Tue, 2014-05-06 12:00 - 17:30
Location: 

Lynch Rm.

Special Biological Seminar: Joshua Rabinowitz, Princeton University

Thu, 2014-03-13 10:30 - 11:30
Speaker: 

Prof. Joshua D. Rabinowitz

Princeton University

Location: 

Lynch Lecture Hall

Attached Document: 

Towards a Comprehensive Understanding of Cellular Metabolism

 

For more information on Prof. Rabinowitz, please visit here.

Department of Chemistry

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

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

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