Many diseases are the result of deficient or abnormal protein-lipid interactions. The elucidation of these interactions and the ability to examine and manipulate biomembranes that mimic real life systems hold the key to better understanding these diseases. Using microscopy and scattering techniques on two-dimensional monolayers and supported bilayers as model systems, we carry out fundamental studies on the interactions between lipids and proteins to gain a better understanding of respiratory distress syndrome and Alzheimer's disease.
The Lung Surfactant System and Respiratory Distress Syndrome (RDS)
Lung surfactant, a complex mixture of lipids and proteins, forms monolayers at the alveolar air-water interface. The surfactant lowers surface tension to almost zero and thus 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 does not yet exist. My group is interested in developing a detailed structure-function relationship for the various components of lung surfactant. In particular, we 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 specifically focus on the effects of lung surfactant proteins on monolayer collapse dynamics and the effects of serum proteins on the normal functioning of the lung surfactant. We hope to gain 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, in addition to the first 11-15 residues of the transmembrane domain, it has been shown to display properties common to 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 our 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.
Brown University
Sc.B.
1986Harvard University
M.S.
1987Harvard University
Ph.D.
1992Stanford University
Postdoctoral Fellow
1995University of California, Santa Barbara
Postdoctoral Fellow
1998University of Chicago
Assistant Professor
2002University of Chicago
Associate Professor
2008University of Chicago
Professor
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).
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
Collapse Mechanisms of Langmuir Monolayers. Ka Yee C. Lee, Annual Review of Physical Chemistry 59(2008) 771-791
Lipid Membrane Templates the Ordering and Induces the Fibrillogenesis of Alzheimer’s DiseaseAmyloid-ï¢Peptide. Eva Y. Chi, CanayEge, Amy Winans, JaroslawMajewski, KristianKjaer, and Ka Yee C. Lee, Proteins 72 (2008) 1–24.
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.
Ganglioside GM1 Mediated Amyloid-beta Fibrillogenesis and MembraneDisruption. Eva Y. Chi, Shelli L. Frey and Ka Yee C. Lee, Biochemistry, 46 (2007) 1913-1924.
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
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.
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.
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)Fellow, American Institute for Medical and Biological Engineering
2013Fellow, American Physical Society
2009Musselman Visiting Scientist, Gettysburg College
2016Phi Beta Kappa Scholar
2012 - 2013Robert A. Pritzker Visiting Scientist • Inventor • Engineer in Residence
2011 - 2012Astella USA Foundation Award, American Chemical Society
2009Academic Leadership Program Fellow, Committee on Institutional Cooperation
2009Llewellyn John and Harriet Manchester Quantrell Award for Excellence in Undergraduate Teaching
2007J & J Neubauer Faculty Development Fellowship
2002Alfred P. Sloan Fellow
2001Margaret Oakley Dayhoff Award
2001Ruth Salta Junior Investigator Achievement Award in Alzheimer's Disease Research
1999David and Lucile Packard Fellow
1999Crain´s Chicago Business "40 Under 40" Award
1999Searle Scholar
1999Basil O'Connor Starter Scholar Research Award
1999Camille and Henry Dreyfus New Faculty Award
1998