University of California-Berkeley Physical Sciences-Oncology Center
University of California-Berkeley, Berkeley, CA
Center Summary:
University of California-Berkeley Physical Sciences-Oncology Center (UCB PS-OC) will determine how mechanobiology influences tumorigenesis in breast cancer. This center’s primary focus will be on the triple negative subtype of basal breast cancer, which lacks the estrogen, progesterone, and Her2/neu receptors. Patients with this more aggressive, triple negative subtype have fewer treatment options and an overall poor prognosis. These investigators hypothesize that the malignant phenotype is maintained by exchanges with its microenvironment and that reversion can occur if these pressures are normalized. This center will also examine how mechanical signals trigger genetic changes that induce tumorigenesis. Groundbreaking force probes and imaging techniques will gauge the forces within breast cancer model systems. The integration of these state-of-the-art tools in the physical, theoretical and biological sciences will cultivate models of various interactions of the model systems with their microenvironment. Furthermore, cellular plasticity and reversion research will be executed and could lead to potential therapeutics targeted to the cellular microenvironment.
Project 1 – Fundamental Mechano-Chemical Mechanisms of Signaling in Cancer
Project Leader: Jay Groves (University of California- Berkeley)
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Project 1 seeks a fundamental understanding of how the mechanical environment of a cell influences its intracellular signaling. Specifically, we will investigate the interplay of chemistry and mechanics in the EphA2 receptor signaling pathway as well as Ras signaling. By controlling the mechanical forces that drive receptor spatial organization, we may be able to elicit structural and functional phenotypes characteristic of defined phases of tumor progression.
Project 2 – Mechanobiology of Acinar Stability
Project Leader: Valerie Weaver (University of California- San Francisco)
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Project 2 explores how force regulates subcellular organization of adhesion molecules to promote acini morphogenesis. While a reductionist approach is typically used to clarify the molecular mechanisms that drive development and maintain homeostasis, we take the view that cell and tissue behavior are phenotypically plastic, mediated by adhesion and modified by mechanical force. We will test the idea that (1) force regulates the organization of proteins at the subcellular level to alter cellular organization at the tissue level and (2) that emergent properties of multi-cellular tissues and feedback mechanisms alter the responsiveness of cells to mechanical cues within a growing tumor.
Project 3 – Dynamics in the Tissue State Space: From Normal to Tumor and Back
Project Leader: Jan Liphardt (University of California- Berkeley)
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Cancer is both a disease of uncontrolled growth and loss of organ architecture. Remarkably, as shown by animal studies and 3D cell culture models, enforcing a ‘normal’ context or architecture on malignant cells can cause them to behave like non-malignant cells, despite retaining a host of genetic mutations. This ‘reversion’ of malignant cells to a non-malignant phenotype is an example of the plasticity (malleability) of cells, which can change their organization and function in response to external signals in their microenvironment. This projects seeks to uncover fundamentals of tissue plasticity and outline new strategies to understand both how tumors lose structure and how to restore tumors to a non-malignant state.
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Jan Liphardt, Ph.D.
Jan Liphardt, PhD, is an Associate Prof. of Physics at UC Berkeley and the Deputy Director of the LBNL Physical Biosciences Division. His scientific training is in single-molecule biophysics and thermodynamics of small systems. The main focus of his research is to determine how biological systems function. Systems under investigation range from the self-organisation of receptors in membranes, the transport of cargos through biological pores, and the control of the DNA loopscape in the nucleus. Typically, research in his lab involves super-resolution light microscopy, optical tweezers, or optical control strategies. More information can be found on his website:
http://www.physics.berkeley.edu/research/liphardt/
Valerie M. Weaver, Ph.D.
Valerie M. Weaver, PhD, is the Director of the Center for Bioengineering and Tissue Regeneration in the Department of Surgery and Associate Professor in the Department of Surgery and Anatomy and Bioengineering and Therapeutic Sciences at UCSF. Her group studies the molecular mechanisms whereby extracellular matrix receptors and mechanical force and matrix topology modulate normal and transformed cell behavior and alter embryonic cell fate. The research involves bioengineered matrices, microscopy techniques (traction force microscopy, atomic force microscopy, second harmonic generation microscopy), cell biology and animal work.
