Matrix viscoelasticity and cancer

Abstract: 

Changes in matrix stiffness is increasingly appreciated as a key variable in cancer research, but most current work ignores that tissues are viscoelastic, with time-dependent mechanical behavior. Using biomaterials that allow independent control over key variables, we find that the rate of matrix stress relaxation has dramatic effects on stem cell fate, and impacts multiple cell types in the tumor microenvironment, including cancer cells, monocytes, and T cells. Elucidation of the mechanical checkpoints underlying these relations is leading to new strategies to overcome the immunosuppressive tumor microenvironment.

Short biography:

Dave is studying the mechanisms that enable cells to receive and react to chemical and mechanical signals, such as cell adhesion molecules and cyclic strains. These signals carry information that tells cells to alter their behavior by changing their level of proliferation or area of specialization. Sometimes the message being sent is to promote tissue growth: sometimes it’s to attack diseased cells. Dave is working to understand the conditions under which these signals develop: how much of a particular mechanical or chemical factor is needed, at what location, and at what time. The results of these studies will help him design new materials and devices that mimic the conditions needed to send specific orders to the body’s cells. His current projects focus on therapeutic angiogenesis, regeneration of musculoskeletal tissues, and cancer therapies. In 2009, Dave’s team developed the first vaccine ever to eliminate melanoma tumors in mice. It is a tiny bioengineered disc filled with tumor-specific antigens that can be inserted under the skin where it activates the immune system to destroy tumor cells. While typical tissue engineering involves growing cells outside the body, his novel approach reprograms cells that are already in the body.

Dave is the Robert Pinkas Family Professor of Bioengineering in the Harvard School of Engineering and Applied Sciences, and a Core Faculty Member of the Wyss Institute at Harvard University.