Protein Conformation and Dynamics

The Laboratory of Protein Conformation and Dynamics integrates complementary biophysical and biochemical techniques to understand the molecular mechanisms of amyloid formation.

Jennifer Lee

Graphical Abstracts

Biomedical Society cover
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Ramos, S. & Lee, J.C. (2024) Raman spectroscopy in the study of amyloid formation and phase separation, Biochem. Soc. Trans. 52 1121-1130. DOI: 10.1042/BST2023055

Genetically encoded lysine photocage for spatiotemporal control of TDP-43 nuclear import
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Shadish, J.R. & Lee, J.C. (2024) Genetically encoded lysine photocage for spatiotemporal control of TDP-43 nuclear import, Biophys. Chem. 307, 107191. DOI: 10.1016/j.bpc.2024.107191

Water bend‒libration as a cellular Raman imaging probe of hydration
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Ramos, S. & Lee, J.C. (2023) Water bend‒libration as a cellular Raman imaging probe of hydration, Proc. Natl. Acad. Sci. U.S.A., 120, e2313133120. DOI: 10.1073/pnas.2313133120

Genetically encoded aryl alkyne for Raman imaging of intracellular α-synuclein fibrils
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Watson, M.D. & Lee, J.C. (2023) Genetically encoded aryl alkyne for Raman imaging of intracellular α-synuclein fibrils, J. Mol. Biol. 435, 167716. DOI: 10.1016/j.jmb.2022.167716

Tryptophan probes of TDP-43 C-terminal domain amyloid formation
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Shuster, S.O. & Lee, J.C. (2021) Tryptophan probes of TDP-43 C-terminal domain amyloid formation, J. Phys. Chem. B., 125, 3781-3789. DOI: 10.1021/acs.jpcb.1c00767

Membrane interactions of α-synuclein probed by neutrons and photons
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Kaur U. & Lee, J.C. (2021) Membrane interactions of α-synuclein probed by neutrons and photons, Acc. Chem. Res. 54, 302-310. DOI: 10.1021/acs.accounts.0c00453

Raman spectral imaging of 13C2H15N-labeled α-synuclein amyloid fibrils in cells
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Watson, M.D., Flynn, J.D., Lee, J.C. (2021) Raman spectral imaging of 13C2H15N-labeled α-synuclein amyloid fibrils in cells, Biophys. Chem. 269, 106528. DOI: 10.1016/j.bpc.2020.106528

Terminal alkynes as Raman probes of α-synuclein in solution and in cells
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Flynn, J.D., Gimmen, M., Dean, D.N., Lacy, S.M., Lee, J.C. (2020) Terminal alkynes as Raman probes of α-synuclein in solution and in cells, ChemBioChem, 21, 1582-1586. DOI: 10.1002/cbic.202000026

N-terminal acetylation affects α-synuclein fibril polymorphism
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Watson, M.D. & Lee, J.C. (2019) N-terminal acetylation affects α-synuclein fibril polymorphism, Biochemistry, 58, 3630-3633. DOI: 10.1021/acs.biochem.9b00629

J. Mol. Biol cover
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Ni, X., McGlinchey, R.P., Jiang, J., Lee, J.C. (2019) Structural insights into α-synuclein fibril polymorphism: Effects of Parkinson’s disease-related C-terminal truncations, J. Mol. Biol. 431, 3913-3919. DOI: 10.1016/j.jmb.2019.07.001

Segmental 13C-labeling and Raman microspectroscopy of α-synuclein amyloid formation
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Flynn, J.D., Jiang, Z., Lee, J.C. (2018) Segmental 13C-labeling and Raman microspectroscopy of α-synuclein amyloid formation, Angew. Chem. Int. Ed. Engl. 57, 17069-17072. DOI: 10.1002/anie.201809865

Raman fingerprints of amyloid structures
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Flynn, J.D. & Lee, J.C. (2018) Raman fingerprints of amyloid structures, Chem. Commun. 54, 6983-6986. DOI: 10.1039/c8cc03217c

Stimulation of α-synuclein amyloid formation by phosphatidyglycerol micellar tubules,
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Jiang, Z., Flynn, J.D., Teague, W.E., Gawrisch, K., Lee, J.C. (2018) Stimulation of α-synuclein amyloid formation by phosphatidyglycerol micellar tubules, Biochim. Biophys. Acta Biomembr.1860, 1840-1847. DOI:10.1016/j.bbamem.2018.02.025

J. Biol. Chem. Cover
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Flynn, J.D., McGlinchey, R.P., Walker III, R.L., Lee, J.C. (2018) Structural features of α-synuclein amyloid fibrils revealed by Raman spectroscopy, J. Biol. Chem. 293, 767-776. DOI:10.1074/jbc.M117.812388

Journal Cover - Biochemistry
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McGlinchey, R.P., Dominah, G., Lee, J.C. (2017) Taking a bite out of amyloid: Mechanistic insights into α-synuclein degradation by cathepsin L, Biochemistry, 56, 3881-3884. DOI: 10.1021/acs.biochem.7b00360

 

 

Segmental deuteration of α-synuclein for neutron reflectometry on tethered bilayers
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Jiang, Z., Heinrich, F., McGlinchey, R.P., Gruschus, J.M., Lee, J.C. (2017) Segmental deuteration of α-synuclein for neutron reflectometry on tethered bilayers, J. Phys. Chem. Lett. 8, 29-34. DOI: 10.1021/acs.jpclett.6b02304

Apolipoprotein C-III nanodiscs studied by site-specific tryptophan fluorescence
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Brisbois, C.A. & Lee, J.C. (2016) Apolipoprotein C-III nanodiscs studied by site-specific tryptophan fluorescence, Biochemistry, 55, 4939-4948. DOI: 10.1021/acs.biochem.6b00599

Single particle-tracking of human lipoproteins
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de Messieres M., Ng A., Duarte, C.J., Remaley, A.T., Lee, J.C. (2016) Single particle-tracking of human lipoproteins, Anal. Chem. 88, 596-599. DOI: 10.1021/acs.analchem.5b03749

Tryptophan probes reveal residue-specific phospholipid interactions of apolipoprotein C-III
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Pfefferkorn, C.M., Walker III, R.L., He, Y., Lee, J.C. (2015) Tryptophan probes reveal residue-specific phospholipid interactions of apolipoprotein C-III, Biochim. Biophys. Acta Biomembr.,1848, 2821-2828. DOI: 10.1016/j.bbamem.2015.08.018

Molecular details of α-synuclein membrane association probed by neutrons and photons
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Jiang, Z., Hess, S.K., Heinrich, F., Lee, J.C. (2015) Molecular details of α-synuclein membrane association probed by neutrons and photons, J. Phys. Chem. B 119, 4812-4823. DOI: 10.1021/jp512499r

Structural features of membrane-bound glucocerebrosidase and α-synuclein probed by neutron reflectometry and fluorescence spectroscopy
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Yap, T.L., Jiang, Z., Heinrich, F., Gruschus, J.M., Pfefferkorn, C.M., Barros M., Curtis, J.E., Sidransky, E., Lee, J.C. (2015) Structural features of membrane-bound glucocerebrosidase and α-synuclein probed by neutron reflectometry and fluorescence spectroscopy, J. Biol. Chem. 290, 744-754. DOI: 10.1074/jbc.M114.610584

Lysophospholipid-containing membranes modulate the fibril formation of the repeat domain of a human functional amyloid
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Jiang, Z. & Lee, J.C. (2014) Lysophospholipid-containing membranes modulate the fibril formation of the repeat domain of a human functional amyloid, Pmel17, J. Mol. Biol. 426, 4074-4086. DOI: 10.1016/j.jmb.2014.10.009

Journal Cover - Chem Bio Chem
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McGlinchey, R.P., Jiang, Z., Lee, J.C. (2014) Molecular origin of the pH dependent fibril formation of a functional amyloid, ChemBioChem, 15, 1569-1572. DOI: 10.1002/cbic.201402074

Membrane remodeling by α-synuclein and effects on amyloid formation
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Jiang, Z., de Messieres, M., Lee, J.C. (2013) Membrane remodeling by α-synuclein and effects on amyloid formation, J. Am. Chem. Soc. 135, 15970-15973. DOI: 10.1021/ja405993r

Saposin C protects glucocerebrosidase against α-synuclein inhibition
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Yap, T.L., Gruschus, J.M., Velayati, A., Sidransky, E., Lee, J.C. (2013) Saposin C protects glucocerebrosidase against α-synuclein inhibition, Biochemistry 52, 7161-7163. DOI: 10.1021/bi401191v

NMR structure of calmodulin complexed to an N-terminally acetylated α-synuclein peptide
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Gruschus, J.M., Yap, T.L., Pistolesi, S., Maltsev, A.S., Lee, J.C. (2013) NMR structure of calmodulin complexed to an N-terminally acetylated α-synuclein peptide, Biochemistry 52, 3436-3445.

Probing fibril dissolution of the repeat domain of a functional amyloid, Pmel17, on the microscopic and residue level
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McGlinchey, R.P., Gruschus, J.M., Nagy, A., Lee, J.C. (2011) Probing fibril dissolution of the repeat domain of a functional amyloid, Pmel17, on the microscopic and residue level, Biochemistry 50, 10567-10569. DOI: 10.1021/bi201578h

Residue-specific fluorescent probes of α-synuclein: Detection of early events at the N- and C-termini during fibril assembly
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Yap, T.L., Pfefferkorn, C.M., Lee, J.C. (2011) Residue-specific fluorescent probes of α-synuclein: Detection of early events at the N- and C-termini during fibril assembly, Biochemistry 50, 1963-1965. DOI: 10.1021/bi2000824

 

Evidence for copper-dioxygen reactivity during α-synuclein fibril formation
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Lucas, H.R., DeBeer, S., Hong, M.-S., Lee, J.C. (2010) Evidence for copper-dioxygen reactivity during α-synuclein fibril formation, J. Am. Chem. Soc. 132, 6636-6637.DOI: 10.1021/ja101756m

Tryptophan probes at the α-synuclein and membrane interface
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Pfefferkorn, C.M. & Lee, J.C. (2010) Tryptophan probes at the α-synuclein and membrane interface, J. Phys. Chem. B. 114, 4615-4622. DOI: 10.1021/jp908092e

Meet the Team

Jennifer Lee

Jennifer Lee, Ph.D.

Senior Investigator

Jennifer C. Lee graduated with a B.S. in chemistry and a B.A. in economics from the University of California, Berkeley, in 1997, and earned her Ph.D. in chemistry from the California Institute of Technology in 2002. Following a one-year postdoctoral stint at the University of Southern California, she became a Beckman Senior Research Fellow at the Beckman Institute Laser Resource Center at the California Institute of Technology where she investigated the structures and dynamics of an intrinsically disordered and amyloid forming protein using time-resolved spectroscopic measurements. In 2006, Dr. Lee joined the NHLBI as a tenure-track Investigtor. She was awarded an NIH Graduate Partnerships Program Outstanding Mentor Award in 2009. Dr. Lee is a member of the American Chemical Society and the Protein Society.

Contact the lab

Group photo of the Protein Conformation and Dynamics lab team.

Join Our Lab

Current Vacancy

Postdoctoral Fellowship

In expanding the scope of our research, a candidate with strong backgrounds in cell biology and fluorescence microscopy, including…

Alumni

Jared Shadish, Ph.D.

Postdoctoral Fellow
2020 - 2024
Jared Shadish, Ph.D. is currently a Senior Scientist at AstraZeneca.

Genevieve A. Verville

Postbaccalaureate Fellow
2020 - 2021

Sydney O. Shuster

Postbaccalaureate Fellow
2019 - 2021
Sydney O. Shuster is currently a Ph.D. Student at Chemistry Department, Yale University.

Dexter N. Dean, Ph.D.

Postdoctoral Fellow
2018 - 2021
Dexter N. Dean, Ph.D. is currently a Instructional Laboratory Instrumentation Manager at College of Sciences, Georgia Institute of Technology.

Upneet Kaur

Postbaccalaureate Fellow
2019 - 2020
Upneet Kaur is currently a M.D./Ph.D. Student at University of California, San Francisco.

Jessica D. Flynn, Ph.D.

Postdoctoral Fellow
2015 - 2020
Jessica D. Flynn, Ph.D. is currently a Staff Fellow at U.S. Food and Drug Administration.

Shannon M. Lacy

Postbaccalaureate Fellow
2016 - 2018
Shannon M. Lacy is currently a Ph.D. Student at Cellular and Molecular Biology Program, University of Michigan.

Emma I. O'Leary

Postbaccalaureate Fellow
2016 - 2018
Emma I. O'Leary is currently a M.D./Ph.D. Student at University of Pittsburgh.

Zhiping Jiang, Ph.D.

Visiting Fellow and Research Fellow
2011 - 2017
Zhiping Jiang, Ph.D. is currently a Senior Scientist at Pfizer.

Gifty Dominah

Postbaccalaureate Fellow
2015 - 2016
Gifty Dominah is currently a MD Student at George Washington University.

Chase A. Brisbois

Postbaccalaureate Fellow
2014 - 2016
Chase A. Brisbois is currently a Ph.D. Student at Department of Materials Science and Engineering, Northwestern University.

Michel de Messieres, Ph.D.

Postdoctoral IRTA Fellow
2012 - 2015
Michel de Messieres, Ph.D. is currently a Associate Research Scientist at Tech-X Corp..

Sara K. Hess

Postbaccalaureate Fellow
2013 - 2015
Sara K. Hess is currently a Ph.D. Student at Department of Chemistry, University of Chicago.

Stephanie A. Hill

Ox-Cam Graduate Student
2009 - 2013
Stephanie A. Hill is currently a Visiting Assistant Professor of Biology at Rose-Hulman Institute of Technology.

Thai Leong Yap, Ph.D.

Visiting Fellow
2008 - 2013
Thai Leong Yap, Ph.D. is currently a Research Scientist at Institute of Bioengineering and Nanotechnology, Singapore.

Candace M. Pfefferkorn

GPP-Maryland Chemical Physics Graduate Student
2007 - 2012
Candace M. Pfefferkorn is currently a Project Manager at U.S. Nuclear Regulatory Commission.

Robert L. Walker III

Postbaccalaureate Fellow
2010 - 2011
Robert L. Walker III is currently a M.D. Student at Howard University.

Heather R. Lucas, Ph.D.

Postdoctoral Fellow
2008 - 2011
Heather R. Lucas, Ph.D. is currently a Assistant Professor of Chemistry at Virginia Commonwealth University.

Amy F. Petrik, Ph.D.

Postdoctoral Fellow
2007 - 2009
Amy F. Petrik, Ph.D. is currently a Technology Development Associate at Technology Transfer and Intellectual Property Office, NIAID, NIH.

Mark S. Jackson

Postbaccalaureate Fellow
2008 - 2009
Mark S. Jackson is currently a Research Assistant at University of Wisconsin.