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Seminar:

Understanding Cell Matrix Interactions: From Fundamental Thermodynamics to Applications in Tumor Metastasis


Speaker: Dr. Muhammad Hamid Zaman, The University of Texas at Austin, USA.

Venue: Institute of Biochemistry and Biotechnology, University of the Punjab, Lahore.

Time and Date: 8/5/2008 (month/day/year)

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Introduction:


Cells reside and operate in a complex and dynamic extra-cellular matrix. The mechanical, structural and chemical properties of the matrix regulate a variety of cellular functions including signaling, adhesion, migration as well as invasion and metastasis in tumor systems. Unfortunately cell-matrix interactions have traditionally been studied in the context of artificial 2D environments, which are far from in vivo conditions. As a result, our understanding of the complex interactions at the cell-matrix interface have been quite limited. In particular, the mechano-chemical effects of the matrix, the proteolytic pathways and surface receptor dynamics on a 3D surface that are critical in invasion and tumor metastasis, and can not be fully studied in a 2D environment. In order to overcome the limited powers of observation in 2D, we utilize a combination of high resolution and high throughput confocal microscopy, bulk and micro-rheological measurements and multi-scale simulations rooted in statistical and continuum mechanics. Using an interdisciplinary approach allows us to understand and quantify the mechanical and chemical roles of the matrix in regulating signaling, adhesion and motility. Our results demonstrate that both cell structure and cell function are strikingly different in 3D than in 2D and that cellular response to minor mechanical changes in its extra-cellular environment is amplified in 3D than in 2D environments. Our experimental results are complemented by multi-scale simulations, that probe the physical foundations of cell-matrix interactions from the nano to the macro level. Our hybrid approach, combining high-resolution experimental and computational techniques demonstrates how a balance of cellular parameters (e.g. integrin expression and MMP activity) co-operate with matrix properties (e.g. composition, stiffness and porosity) to regulate adhesion, invasion and motility of tumor cells in native like environments.

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About the Speaker : Hamid Zaman is an Asst. Prof. in the Departments of Biomedical Engineering and Cell and Molecular Biology and member of Institute of Theoretical Chemistry as well as Institute for Computational Engineering and Sciences and of Center for Synthetic and Systems Biology at UT Austin. He obtained his PhD from the Chemistry Department at the University of Chicago, focusing on the protein folding, dynamics and interactions. His current research focuses on developing interdisciplinary tools to study interaction of cells with extra-cellular matrices, particularly in cancer progression and metastasis. He has developed new techniques, both theoretically and experimentally to study this problem. Hamid has and continues to publish extensively in highly prestigious international journals. His research has been recognized broadly through various international awards. In 2007, he was awarded the FEBS (Federation of European Biochemical Societies) Young Investigator Award in Matrix Biology, an award rarely given to anyone outside the European Union. Recently, he was also named International Visiting Fellow at the University of Sydney, Australia. His work on cell migration in 3D, published in the Proceedings of the National Academy of Sciences, was hailed world-wide as one of the major breakthroughs in cancer in 2006. Prior to his position at UT Austin, Hamid was Hermann and Margaret Sokol Foundation Post-Doctoral Fellow at MIT and was a Burroughs Wellcome Foundation Graduate Fellow at the University of Chicago during his Ph.D. During his undergraduate, Hamid was also the awarded Alfred Crabaugh Outstanding Senior Award, given to the best undergraduate student at the entire University. More information about Hamid’s work at UT Austin is available at zlabs.bme.utexas.edu.

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Dr. Muhammad H. Zaman, Assistant Professor of Biomedical Engineering, has been selected to participate in the 6th Annual National Academies Keck Futures Initiative Conference this year in November. This years topic of complexity will focus on complex biological, physical and social systems. The conference board, comprising of members of national academy of sciences, national academy of engineering and the Institute of medicine selected participants from over 350 applicants which included assistant, associate and full professors from institutions across that nation, leading researchers in industry and national labs.</p>Dr. Muhammad H. Zaman selected to participate in the 6th Annual NAFKI Conference.

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MIT Post doctoral Resercher,Muhammad Zaman brings revolution in the Cancer research , MIT News Office:Whitehead Institute July , 2006 :Whitehead brings new dimension to cancer research by Alyssa Kneller :New research at MIT may lead the pharmaceutical industry to take a whole new approach to battling the spread of cancer.Cancer spreads when a cell breaks away from a primary tumor, settles in a new location and once again divides -- a process known as metastasis. Pharmaceutical companies evaluating anti-cancer therapeutics typically use simplistic two-dimensional assays, or tests, to measure success in stopping metastasis. In these assays, cells crawl across the surface of a matrix, traveling in a single plane. A new MIT study indicates that this common approach for evaluating anti-cancer therapeutics misses some crucial phenomena.Working in the labs of Whitehead member and MIT Professor Paul Matsudaira and MIT Professor Douglas Lauffenburger, postdoctoral researcher Muhammad Zaman discovered that cells move quite differently in three dimensions. His study, which focused on human prostate tumor cells, appeared the week of July 10 in the online early edition of Proceedings of the National Academy of Sciences.Two-dimensional assays ignore the obstacles that cells face in their natural contexts, said Zaman, who recently became an assistant professor at the University of Texas at Austin. In 3-D, cells move through a thick jungle of fibers, or 'vines,' that hinder forward progress.Cells must either squeeze through or chop up these putative vines to get anywhere. As a result, they move more slowly in three dimensions.In an interesting twist, all cells need at least some vines to move, as they latch onto the branches with claw-like proteins called integrins and pull themselves forward. When Zaman disabled some of these claws, in a manner analogous to the workings of certain anti-cancer drugs, the cells moving across the top of the jungle canopy (in two dimensions) needed a greater number of vines to keep up their pace, while cells plowing through the jungle instead needed fewer vines to maintain the same speed.
Muhammad was successful for two reasons,&quot; said Matsudaira, an MIT professor of biology and biological engineering. &quot;His computational model predicted what would happen in virtual experiments and then he was able to go straight to test the predictions with these complicated 3-D experiments. As a result, the sophisticated models of cell movement enhance our understanding of key biological processes, including metastasis.&quot;The research was funded by the National Institutes of Health, the National Science Foundation and the Sokol Foundation for Cancer Research.
>>>>>>>>>>>>>>>>>>>>>>>>>Whitehead brings new dimension to cancer research - MIT News Office

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