 |
| Born
Hong Kong, 1964. |
| Brown
University, Sc.B., 1986. |
| Harvard
University, M.S., 1987; Ph.D., 1992. |
| Stanford
University, Postdoctoral Fellow, 1992-1994. National Research Service
Award Postdoctoral Fellow, 1994-95. |
| University
of California, Santa Barbara, University of California President's
Postdoctoral Fellow, 1995-97. National Research Service Award
Postdoctoral Fellow, 1997-98. |
| The
University of Chicago, Professor, 1998-. |
| |
| Accolades |
| 2007
Llewellyn John and Harriet Manchester Quantrell Award for Excellence in
Undergraduate Teaching. |
| 2002
J & J Neubauer Faculty Development Fellowship. |
| 2001
Alfred P. Sloan Fellow. |
| 2001
Margaret Oakley Dayhoff Award. |
| 1999
Ruth Salta Junior Investigator Achievement Award in Alzheimer's Disease
Research. |
| 1999
David and Lucile Packard Fellow, 1999-2004. |
| 1999
Crain´s Chicago Business "40 Under 40" Award. |
| 1999
Searle Scholar. |
| 1999
Basil O'Connor Starter Scholar Research Award. |
| 1998
Camille and Henry Dreyfus New Faculty Award, 1998-2003. |
|
|
| Ka Yee
C. Lee |
| Professor |
|
|
| |
| Research
Interests: |
| A wide
variety of diseases are results of deficient or abnormal protein-lipid
interactions. The elucidation of the interactions between specific
proteins and lipids, and the ability to examine and manipulate
biomembranes that mimic real life systems hold the key to a better
understanding of these diseases. Our research interests lie in the
interdisciplinary area which can be termed as "interfacial medicine".
Using two-dimensional monolayers, either at the air-water interface or
transferred onto solid substrates, and supported bilayers as model
systems, along with various microscopy and scattering techniques, we
plan to carry out fundamental studies on the interactions between
lipids and proteins to gain insights into the biophysical aspects of
these diseases. Two diseases of particular interest are listed below. |
| |
| Lung
Surfactant System and Respiratory Distress Syndrome (RDS) |
| A complex
mixture of lipids and proteins, known as lung surfactant, forms
monolayers at the alveolar air-water interface. The surfactant lowers
the surface tension to near zero, and is responsible for reducing the
work of breathing. A lack of surfactant, either due to immaturity in
premature infants or disease or trauma in adults, can result in RDS. In
spite of the serious morbidity and mortality of the disease, a firm
understanding of the role of surfactant in both normal and diseased
lungs is still lacking. My group is interested in developing a detailed
structure-function relationship for the various components of lung
surfactant. In particular, we will examine the phase behavior of
various mixtures of lung surfactant components, as well as the
interactions between lung surfactant specific proteins and the
surrounding lipid matrix. We will explore the effect of lung surfactant
proteins on monolayer collapse dynamics, and the effect of serum
proteins on the normal functioning of the lung surfactant. The
knowledge gained from this should lead to an understanding of the
morphological consequences of monolayer phase separation and collapse,
which is necessary for the continued development of positive
interventions for patients suffering from RDS. |
| |
| Amyloid-Beta
(Ab) Peptides and Alzheimer's Disease |
| A-beta, a
self-assembling 39-43 residue peptide generated by the proteolytic
processing of the amyloid precursor protein, comprises the major
proteinaceous component of neuritic plaques and vascular deposits that
appear in Alzheimer's disease, and is implicated as one of the causal
factors in the pathology of the disease. Since the Ab peptide fragment
includes 28 residues just outside the membrane plus the first 11-15
residues of the transmembrane domain, it has been shown to display
properties commonly
d with surfactants. My group is interested
in understanding the aggregation of the Ab peptides, and in using
two-dimensional thin films (either free-standing monolayers or
supported bilayers) as "templates" to explore the possibility of
surface-induced aggregation. We plan to study various isoforms of Ab
and examine their surface activities and their association with model
membrane systems in both their monomeric and aggregated states. This
can elucidate the residue length dependence of the aggregation process,
and help explain why the longer Ab isoforms may be more intimately
associated with Alzheimer's disease pathology than their shorter
counterparts. Ab is also known to aggregate and form fibrils, though
the mechanism involved is still not well understood. Since the rate of
this process can be adjusted by various experimental parameters, we
plan to monitor the formation process, and characterize the structure
of the fibrils formed. Our goal is to provide a model for Ab
aggregation. |
| |
| Other
research projects in the group include the insertion of antimicrobial
peptide protegrin-1 into model membrane systems, structures and
dynamics of monolayer and bilayer domains, membrane sealing using
poloxamers, and two-dimensional ordering of rod-coil copolymers.
Experimental techniques employed in these studies include optical and
scanning probe microscopy as well as x-ray and neutron scattering. |
| |
| Selected
References |
| 1. Ordered Nanoclusters in Lipid/Cholesterol Membranes. Maria K Ratajczak, Shelli L. Frey, Eva Y. Chi, JaroslawMajewski, KristianKjaer, and Ka Yee C. Lee, Phys. Rev.
Lett., in press (2009). |
| 2. Stress and Fold Localization in Thin Elastic Membranes. Luka Pocivavsek, Robert Dellsy, Andy Kern, Sebastian Johnson, Binhua Lin, Ka Yee C. Lee and Enrique Cerda, Science 320 (2008) 912-916 |
| 3. Collapse Mechanisms of Langmuir Monolayers. Ka Yee C. Lee, Annual Review of Physical Chemistry 59 (2008) 771-791 |
| 4. Lipid Membrane Templates the Ordering and Induces the Fibrillogenesis of Alzheimer’s DiseaseAmyloid-Peptide. Eva Y. Chi, CanayEge, Amy Winans, JaroslawMajewski, KristianKjaer, and Ka Yee C. Lee, Proteins 72 (2008) 1–24. |
| 5. Cholesterol Displacement from Membrane Phospholipids by Hexadecanol. Maria K. Ratajczak, Y.T. Chris Ko, Yvonne Lange, Theodore L. Steck and Ka Yee C. Lee, Biophysical Journal, 93 (2007) 2038-2047. |
| 6. Ganglioside GM1 Mediated Amyloid-beta Fibrillogenesis and MembraneDisruption.
Eva Y. Chi, Shelli L. Frey and Ka Yee C. Lee, Biochemistry, 46 (2007) 1913-1924. |
| 7. Mechanism of Membrane Disruption by Antimicrobial Peptide Protegrin-1.
Kin Lok Lam, Yuji Ishitsuka, Yishan Cheng,Karen Chien, Alan J. Waring, Robert I. Lehrer, and Ka Yee C. Lee, Journal of Physical Chemistry B, 110 (2006) 21282-21286 |
| 8. Interaction between Lipid Monolayers and Poloxamer 188: An X-ray Reflectivity and Diffraction Study. Guohui Wu, JaroslawMajewski, CanayEge, KristianKjaer, Markus Weygand, and Ka Yee C. Lee, Biophysical Journal 89 (2005) 3159-3173. |
| 9. Lipid Corralling and Poloxamer Squeeze-out in Membranes. Guohui Wu, JaroslawMajewski, CanayEge, KristianKjaer, Markus Weygand, and Ka Yee C. Lee, Physical Review Letters 93 (2004) 02810. |
| 10. Interaction of Antimicrobial Peptide Protegrin with Biomembranes. David Gidalevitz, Adrian S. Muresan, Alan J. Waring, Robert I. Lehrer, and Ka Yee C. Lee, Proc. Nat. Acad. Sci. 100, 6302-6305 (2003) |
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Physical Chemistry 