Constance E. Brinckerhoff, PhD
Professor of Medicine
Smith College, BA
SUNY - Buffalo, PHD
SUNY - Buffalo, MA
Molecular and Cellular Biology Graduate Programs
Dartmouth Medical School
Lebanon NH 03756
Research focuses on the molecular and cellular mechanisms by which the Matrix Metalloproteinases (MMPs), enzymes that degrade the extracellular matrix at neutral pH, facilitate the invasive and metastatic behavior of tumor cells. In most normal cells, constitutive expression of MMPs is low, but increases in response to cytokines and growth factors. In some tumors (e.g., breast cancer and melanoma), however, MMP expression is constutively high, and the high expression enhances their invasiveness. This lab is using a novel invasion assay to monitor the invasion of tumor cells through the extracellular matrix and to document the efficacy of novel agents that suppress MMPs to also suppress invasion and metastasis.
AR-26599-28. Regulation of Collagenase Gene Expression
CA-77267-07. Invasive Behavior of Tumor cells Producing Collagenase-1
The mitogen-activated protein kinase pathway plays a critical role in regulating immunological properties of BRAF mutant cutaneous melanoma cells.
The BRAF(V600E) inhibitor, PLX4032, increases type I collagen synthesis in melanoma cells.
CXCR3 signaling in BRAFWT melanoma increases IL-8 expression and tumorigenicity.
BRAF inhibition alleviates immune suppression in murine autochthonous melanoma.
Multiple murine BRaf(V600E) melanoma cell lines with sensitivity to PLX4032.
Differential mechanisms of tumor progression in clones from a single heterogeneous human melanoma.
Distal interleukin-1β (IL-1β) response element of human matrix metalloproteinase-13 (MMP-13) binds activator protein 1 (AP-1) transcription factors and regulates gene expression.
Matrix metalloproteinase and G protein coupled receptors: co-conspirators in the pathogenesis of autoimmune disease and cancer.
CXCR4 and matrix metalloproteinase-1 are elevated in breast carcinoma-associated fibroblasts and in normal mammary fibroblasts exposed to factors secreted by breast cancer cells.
Site controlled transgenic mice validating increased expression from human matrix metalloproteinase (MMP-1) promoter due to a naturally occurring SNP.