(3bk) Biomolecular Recognition of Receptor Proteins and Their Roles in Tumor Cell Adhesion in the Vasculature

Cell-cell adhesive interactions play a pivotal role in major pathophysiological vascular processes, such as
inflammation, thrombosis, and cancer metastasis, and are regulated by
hemodynamic forces generated by blood flow. Elucidating molecular and biophysical
properties of membrane receptor-ligand interactions
may provide guidelines for developing promising therapeutic strategies to
combat these fatal diseases. Membrane receptor-ligand
interaction is not a simple lock-and-key problem in which only the right key
can operate the lock. The protein-protein interface is constructed by a series
of amino acid residues; therefore, the binding free energy may not be uniformly
distributed among these interfacial residues. The goal of my research career is
to elucidate the biomolecular recognition of receptor
proteins and their roles in tumor cell adhesion in the vasculature.

My research expertise is in the area of microfluidics
and protein-ligand interactions. I received Ph.D. at
the University of Arizona, where my dissertation focuses on the effect of shear
flow on the attachment, deformation and detachment of tumor cells in microchannels. In addition to research training, I also had
a precious opportunity to participate in the development of a new laboratory. At
the Johns Hopkins University, I continue my research with Prof. Konstantinos Konstantopoulos to investigate
the complex interplay and structure-activity relationship of receptor-ligand interactions pertinent to inflammation and cancer
metastasis. In 2011, I received a postdoctoral fellowship award from the
American Heart Association.

There are three core topics in my research as follows: (1)
Lab-on-a-chip devices: Design and fabricate microfluidic
devices for studying the cell adhesion in pathophysiological
vascular processes, such as inflammation and cancer metastasis. (2)
Bio-molecular recognition: Quantify the kinetic and micromechanical properties
(such as dissociation rate, reactive compliance and tensile strength) of
membrane protein-ligand interactions under dynamic
loading. (3) Tumor cell mechanics: Develop models and experimental techniques
to study the effect of shear flow on the cell deformation and migration during
intra- and extra-vasation processes. Cumulatively,
these studies will provide scientific insights on how the tumor cell receptors interact
with their target molecules in the vasculature.

Selected peer-reviewed publications:

1.  Z. Tong*, L.S.L. Cheung*, K.J. Stebe and K. Konstantopoulos,
"Selectin-mediated Adhesion in Shear Flow Using Micropatterned Substrates: Multiple-Bond Interactions
Govern the Critical Length for Cell Binding", Integr Biol, 2012 (accepted). *Equally
contribution authors

2.  L.S.L. Cheung, M. Kanwar, M. Ostermeier and K. Konstantopoulos,
"A Hot-Spot Motif Characterizes the Interface Between a Designed Ankyrin-Repeat Protein and Its Target ligand".
Biophys J, 102(3), 407-416, 2012.

3.  X.J. Zheng,
L.S.L. Cheung, J.A.
Schroeder, L. Jiang and Y. Zohar, "Cell Receptor
and Surface Ligand Density Effects on Dynamic States
of Adhering Circulating Tumor Cells", Lab
Chip, 11(20), 3431-3439, 2011.

4.  X. Zheng,
L.S.L. Cheung, J.A.
Schroeder, L. Jiang and Y. Zohar, "A
High-Performance Microsystem for Isolating
Circulating Tumor Cells", Lab Chip,
11(19), 3269-3276, 2011.

5.  L.S.L. Cheung, X. Zheng, L. Wang,
J.C. Baygents, R. Guzman, J.A. Schroeder, R.L. Heimark and Y. Zohar,
"Adhesion Dynamics of Circulating Tumor Cells under Shear Flow in a
Bio-Functionalized Microchannel", J Micromech Microeng, 21(5), 054033, 2011.

6.  P. Sundd,
M.K. Pospieszalska, L.S.L. Cheung, K. Konstantopoulos
and K. Ley, "Biomechanics of Leukocyte
Rolling", Biorheology,
48, 1-35, 2011.

7.  L.S.L. Cheung, K. Konstantopoulos,
"An Analytical Model for Determining Two-Dimensional Receptor-Ligand Kinetics", Biophys J, 100(10), 2338-2346, 2011.

8.  L.S.L. Cheung, P.S. Raman, E.M. Balzer,
D. Wirtz and K. Konstantopoulos,
"Biophysics of Selectin?Ligand Interactions in
Inflammation and Cancer", Phys Biol, 8(1), 015013, 2011.

9.  T. Gudipaty,
M. T. Stamm, L.S.L.
Cheung, L. Jiang and Y. Zohar, "Cluster
Formation and Growth in Microchannel Flow of Dilute
Particle Suspension", Microfluid Nanofluid, 10(3), 661-669, 2010.

10.  L.S.L. Cheung, X. Zheng, L. Wang,
R. Guzman, J.A. Schroeder, R.L. Heimark, J.C. Baygents and Y. Zohar, ?Kinematics
of Specifically Captured Circulating Tumor Cells in Bio-Functionalized Microchannels?, J Microelectromech S, 19(4), 752-763, 2010.

11.  L.S.L. Cheung, X. Zheng, A. Stopa, J.C. Baygents, R. Guzman,
J.A. Schroeder, R.L. Heimark and Y. Zohar, ?Detachment of Captured Cancer Cells under Flow
Acceleration in a Bio-functionalized Microchannel?, Lab Chip, 9, 1721-1731, 2009.

12.  M. Lee, L.S.L.
Cheung, Y.K. Lee and Y. Zohar, ?Height Effect
on Nucleation-Site Activity and Size-Dependent Bubble Dynamics in Microchannel Convective Boiling", J Micromech Microeng,
15, 2121-2129, 2005.

Book chapters:

13.  L.S.L. Cheung, P.S. Raman, D. Wirtz
and K. Konstantopoulos, "Biophysics of Selectin-Mediated Cell Adhesion", Comprehensive Biophysics: Cell Biophysics, Elsevier, 7, 2012 (in
press May 31st).

14.  L.M. Lee, L.S.L. Cheung and Y. Zohar, ?Microfluidics: Device
Science and Technology?, CISM Courses and
Lectures, International Centre for Mechanical Sciences, Springer, 428,
157-211, 2006.