Cell Signaling and Protein Dynamics
Cell signaling and protein dynamics focus on intercellular and intracellular communications between proteins and cells at both cellular and molecular levels. Researchers integrate both in vitro and in vivo biological experiments with cell, protein and fluid transport dynamics in the areas of cancer metastasis, tumor microenvironment and extravasation, leukocyte adhesion, mechanobiology, energy metabolism, and system network biology. At the cellular level, investigators develop cell mechanics and biofluid transport models within the microcirculation. At the molecular level, we construct models in reaction kinetics, protein diffusion and convection, and signaling pathway network. Interdisciplinary collaborations extend bioengineering research within the College of Engineering to College of Medicine, College of Science, Huck Institutes for Life Sciences, and the Penn State Cancer Institute.
Research Topics
Cancer Metastasis
One of the principal requirements for cancer metastasis (cancer spread) is tumor cell adhesion and motility. Metastases from a primary tumor to secondary locations throughout the body are a major cause of cancer related deaths. In order to metastasize, tumor cells must undergo a series of steps. First they are shed into the blood stream (intravasation), survive while traveling through the blood vessels, and finally migrate again out of the vessels (extravasation) into a new location in the body. Finally they must proliferate. The interactions between cancer cells and the host immune system are of particular interest to our group. Innate immune system processes can potentially promote tumor progression through inflammation dependent mechanisms. White blood cells, neutrophils (PMN) in particular, are being studied to better understand how the host immune system affects cancer cell adhesion and subsequent migration in metastasis.
Faculty: Cheng Dong, Erwin Vogler, Andrea Mastro, Hank Donahue | Collaborators: Gavin Robertson
Tumor Microenvironment and Signaling
There has been compelling evidence showing the role of MAP Kinase in cancer metastasis and survival. However, the molecular mechanisms by which melanoma cells signal surrounding endothelial cells to undergo transendothelial migration and subsequent metastasis has yet to be elucidated. The objective of researchers in this area is to characterize the signaling mechanism between melanoma cells and endothelial cells when the two cell types are in direct contact. Specifically, researchers investigate potential involvement of calcium and p38 MAP Kinase in melanoma cell-induced endothelial junction disassembly.
Faculty: Cheng Dong, Andrea Mastro | Collaborators: Avery August, Gavin Robertson
Cell Adhesion and Migration
Cell adhesion and migration is an important area in cancer metastasis, wound healing, and in the covering of biomaterials with cells. Because many of these processes occur under the influence of flowing blood, researchers will often conduct experiments on migration and adhesion using flow chambers. In the picture to the left, an example of a dual flow/migration chamber is illustrated. This chemotactic-flow chamber models a capillary. Under flow conditions, circulating cell adhesion to the endothelial cell substrate represents binding to the vessel wall. Tumor cell extravasation from the top to the bottom compartment models entry into the tissue space. The extent of cell migration to the bottom-side filter was quantified by staining and counting. Using such techniques, researchers at Penn State have found tumor cell extravasation to be a complex multi-step process that is regulated by both microfluid-mechanics, protein transport and signaling.
Faculty: Cheng Dong, Christopher Siedlecki, Erwin Vogler, Alan Snyder, Hank Donahue
Cellular Biomechanics
Researchers at Penn State Bioengineering are interested in the interface of mechanics and cellular chemical signaling: termed mechanotransduction or mechanobiology. More information on these efforts can be found on the mechanobiology site. In addition, molecular models of receptor-ligand binding has been used in simulations of cell-cell adhesion under flow conditions. These interactions of force and adhesion are important in inflammatory diseases and in cancer metastasis.
Faculty: William Hancock, Peter Butler, Cheng Dong, Herbert Lipowsky | Collaborators: Robert Kunz, Qiang Du, Costas Maranas, Tom Jackson
List of Courses
ME 461 Finite Elements in Engineering
BIOE 503 (CH E 503) Fluid Mechanics of Bioengineering Systems
BIOE 505 Bioengineering Mechanics
BIOE 512 Cell and Molecular Bioengineering
Feature Story
Cheng Dong Lab
The major research focus of the Cellular Biomechanics Lab is to develop novel approaches to study micro-hemodynamics, cell adhesion, cell migration, intercellular and intracellular signaling, systems biology and kinetic network modeling. In particular, we are investigating how tumor microenvironment changes leukocyte and/or endothelial immune functions which subsequently affect cancer cell extravasation and metastasis. Dr. Dong’s graduate and undergraduate students also collaborate with other laboratories from Immunology, Pharmacology and Penn State Cancer Institute in drug discoveries for therapeutic intervention.
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Margaret Slattery, Hsin-Hsin Peng and Shile Liang are all recent PhD graduates with Dr. Dong, who have published several novel papers recently in Cancer Research, Experimental Cell Research, American Journal of Physiology, and Annals of Biomedical Engineering in developing bioengineering approaches for cancer research. Dr. Slattery is currently an assistant professor at Penn State Bioengineering; Dr. Hsin-Hsin Peng is a research associate at the National Cheng-Kung University in Taiwan; and Dr. Shile Liang is a research associate at Pfizer Pharmaceuticals in San Diego. The computational fluid dynamics (CFD) simulation work conducted by Meghan Hoskins from Dr. Dong’s Lab in collaboration with the Penn State Applied Research Laboratory was recently published as a Feature Article in the HPC Wire under “CFD Simulations Take Cancer Research to a New Dimension”(6/4/2008) link; a website publishes the Leading Source for Global News and Information Covering the Ecosystem of High Productivity Computing. Details can be found at link .