The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases

Pamela L. Wenzel, Ph.D.

Research

Mechanobiology of blood development

One arm of our research is designed to address how biomechanical force promotes the hematopoietic program in the embryo and how we might use this information to expand improved sources of hematopoietic cells for the clinic. A number of genetic and biochemical pathways are currently under investigation as key players mediating this signaling cascade, and we employ various approaches to evaluate their role in blood development, including microfluidics, pharmacology, mouse genetics, and transplantation assays.

Biomechanical modulation of anti-inflammatory genetic programs in mesenchymal stem cells

Shear stress, or frictional force, also modulates the behavior of mesenchymal stem cells, and impacts proliferation, cell survival, and fate decisions. A growing body of literature suggests that these types of cells can suppress unchecked inflammatory signaling and innate immune response in patients. Consequently, our second area of interest is to determine how mechanical force alters the biology of mesenchymal stem cells, including their ability to modulate anti-inflammatory programs and vascular permeability. We utilize culture-based assays, cellular phenotyping, and mesenchymal stem cell-based therapy models of traumatic brain injury as readouts of response to mechanical stimuli.

Role of force in initiation of metastatic programs

Finally, fluid flow and hydrostatic pressure have been implicated in tumor biology, but it remains unclear what role lymphatic or vascular shear stresses may play in modulating the gene expression programs or metastatic potential of cancer cells. Using custom microfluidics, we are modulating the shear stress present in the cancer cell environment and evaluating its impact on metalloprotease activity, invasive potential, and activation of oncogenic pathways.