Kristian Pietras Group
Kristian Pietras' profile page.
It is increasingly appreciated that cancer results from the concerted performance of genetically altered tumor cells interacting with ostensibly normal cells in the microenvironment. In addition to the now well-accepted tumor endothelial cells in the angiogenic vasculature, mounting attention is focused on other elements of the stromal compartment, i.e. carcinoma-associated fibroblasts, vascular pericytes, and infiltrating inflammatory cells, as being functionally important for tumor progression. Our current work is part of ongoing efforts to map the support functions that are being performed by the various cell types comprising the tumor stroma. We believe that decisive treatment benefit can only be achieved by targeting multiple, but distinct, cell types and pathways that collectively sustain the growth of tumors.
A common theme for our work is blood vessel formation (angiogenesis) within tumors. Specifically, molecular interactions and paracrine signaling involving cancer-associated fibroblasts, endothelial cells, and pericytes, and their dependence on signaling through members of the Platelet-Derived Growth Factor (PDGF), Transforming Growth Factor-beta (TGF-beta) and Notch families, are explored in vivo through the use of genetically engineered mouse models of cancer.
Genetically engineered mouse models of carcinogenesis have become a cornerstone of research into mechanisms by which cancers develop. The reproducibility of the system allows for very precise mapping of tumor progression and for the possibility to accurately study the effects of any given perturbation, such as pharmacological treatments or incorporation of additional genetic alterations. When combined with mice expressing markers or inducible/knocked-down genes of interest in a cell-type specific manner, the resulting mice create a powerful arrangement to identify, biologically probe and validate drug targets for anti-cancer therapies. Therefore, our work focuses on such models because of the prospect to uncover important, but perhaps subtle, contributions by the stroma to the tumor phenotype.
We currently pursue three main avenues of research:
- Molecular studies of the endothelial cell-pericyte interplay
To elucidate the molecular signaling events involved in cell-to-cell crosstalk between endothelial cells and pericytes in tumor blood vessels.
- Carcinoma-associated fibroblasts: Recruitment into tumors, phenotype and therapeutic opportunities
To elucidate the origin and unique phenotype of CAFs, as well as explore the therapeutic potential of CAF-targeting treatments.
- TGF-beta signaling in the tumor microenvironment
To elucidate the function of TGF-beta family members during vascular homeostasis, as well as in the angiogenic tumor vasculature.
Taken together, the overall aim of our work is to generate basic knowledge about the interdependent way cells within a tumor relate to each other, as well as produce information that will be immediately useful for the design and modification of clinical practice.