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Tanmay Lele
Assistant Professor
Ph.D., 2002, Purdue University
Molecular imaging in live cells
Cellular engineering
Cell-cell and cell-substrate adhesion
Cell motility
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Brief Description of Current Research
 Our
laboratory uses cellular engineering approaches to understand how cells
that comprise our tissues attach to substrates and to each other, how
they move and divide, and how these processes are deregulated in tumor
formation. Our work has direct applications in a broad range of areas,
from systems biology models of cell regulation and pharmaceutical drug
development to identifying the molecular origins of cancer.
In order to study in-situ protein biochemistry inside living cells, we employ
tools like high resolution molecular imaging, specialized techniques like
fluorescence photo-bleaching, fluorescence correlation spectroscopy, femto-second
laser ablation, molecular biology techniques like cloning and siRNA gene
sliencing, and traditional chemical engineering principles based on chemical
kinetics and reaction engineering. We have recently measured protein-protein
binding interactions in focal adhesions of live cells and related these dynamic
interactions to intracellular contractile forces for the first time.
We are currently developing new methods to study transcriptional regulation
inside the nucleus by borrowing ideas from catalysis and reaction engineering.
Emerging data over the last five years suggest that transcription factors that
bind to DNA and regulate gene expression are transiently bound in large protein
complexes that assemble on DNA. We are currently developing methods to 1)
measure the rate limiting steps in transcription, 2) quantify rate laws that
describe protein binding to DNA, and 3) measure protein diffusion inside a
tortuous, live nucleus. Since a number of nuclear proteins are known to strongly
correlate with tumor progression, we are identifying which of these processes
are abnormal in tumors.
Figure Caption: Image of a single capillary endothelial cell
immunolabelled for proteins. Actin (red) terminates into adhesions (green for
vinculin). Nucleus is stained blue.
Selected Publications
- Lele TP, Wagner S,
Nickerson J and Ingber DE: Methods for measuring rates of protein
binding to insoluble scaffolds in living cells: Histone H1-chromatin
interactions. Journal of Cellular Biochemistry,
in press, 2006
- Lele TP, Pendse J, Kumar S, Salanga M, Karavitis
J, Ingber DE. Mechanical forces alter zyxin unbinding
kinetics within focal adhesions of living cells. J Cell Physiol.
2006; 207(1):187-194. (Cover article)
- Lele TP, Thodeti CK, Ingber DE. Force meets chemistry: Analysis
of mechanochemical conversion in focal adhesions using fluorescence
recovery after photobleaching. J Cell Biochem.
2006 Apr 15; 97(6):1175-83. (Cover article)
- Lele TP and Ingber D: A
mathematical model to determine molecular kinetic rate constants
under non-steady conditions using FRAP. Biophysical Chemistry,
120:32-35, 2005.
- Lele TP, Oh P, Nickerson JA, Ingber DE.
An improved mathematical model for determination of molecular
kinetics in living cells with FRAP. Mechanics & Chemistry of
Biosystems Vol. 1, No. 3, pp.181-190 (2004).
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