Ka Yee Lee
Professor, Department of Chemistry, James Franck Institute, Materials Research Science and Engineering Center
Affiliation: Professor, Department of Chemistry, James Franck Institute, Materials Research Science and Engineering Center, Institute for Biophysical Dynamics
Membrane, Lipid-protein interactions, Lung surfactant, Alzheimer’s amyloid-beta peptide, Antimicrobial peptides
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-.
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.
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.
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 Alzheimerâ€™s DiseaseAmyloid-ï�¢Peptide. Eva Y. Chi, CanayEge, Amy Winans, JaroslawMajewski, KristianKjaer, and Ka Yee C. Lee, Proteins 72 (2008) 1â€“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)