Mechanisms of Carcinoma Progression: From Bench to Bedside
Arthur M. Mercurio
We are interested in the mechanisms that underlie the genesis of high-grade, aggressive carcinomas of the breast and prostate. Our reserach is rooted in the hypothesis that high-grade carcinomas are characterized by specific autocrine signaling pathways involving growth factor (VEGF) receptors and integrins, and that autocrine signaling promotes a de-differentiated, EMT phenotype and increases the frequecy and self-renewal of tumor-initiating/stem cells. Components of this autocrine singaling pathway are prime targets for therapeutic intervention.
Cell Death and Autophagy
Our laboratory studies the mechanisms that regulate autophagy, cell survival and programmed cell death in the context of normal and abnormal development. Altered autophagy, cell survival and cell death are associated with a variety of human disorders including cancer.
Genetic Control of Programmed Cell Death (Apoptosis) in Drosophila
The long-term objective of our research is to gain a comprehensive understanding of the genetic control of apoptosis and cell proliferation, and their connection to human cancer. Apoptosis and cell proliferation are critical for normal development, homeostasis and aging.
Hereditary Breast Cancer
Breast cancer is the most common hereditary cancer syndrome in the United States. Two genes are associated with hereditary cancer, BRCA1 and BRCA2. Mutations in these genes predispose women to early onset breast and ovarian cancer
Cancer Epidemiology; Prenatal Origin of Cancer
Our laboratory area of interest is cancer epidemiology with research focusing on (1) prenatal origin of cancer risk, with special interest in the association of stem cells and perinatal factors with breast cancer risk, (2) gestational characteristics and maternal risk for breast and ovarian cancer, and (3) breast cancer risk factors for women of different ethnic backgrounds.
Mouse models of leukemia
Michelle A. Kelliher
Aberrant expression of developmentally important regulatory genes has been increasingly implicated among hematopoietic malignancies. Abnormalities in either abundance or activity of these gene products can result in inappropriate expression of genes critical to the processes of cell growth and differentiation.
Adult Epithelial Stem Cells
We are interested in key molecular and cell biologic properties of cancer stem cells, which are responsible for tumor growth, recurrence and metastasis. We are applying techniques and knowledge developed in earlier studies of normal epithelial stem cells to characterize cellular subsets of human tumors that display stem cell properties. The ultimate goal is to more efficiently target chemoresistant cancer stem cells for destruction, leading to better patient outcomes.
The Hedgehog (Hh) Signaling Pathway in Development and Cancer
My lab is interested in the molecular mechanisms that underlie organogenesis and tumorigenesis of the gastrointestinal tract. Our work is focused on the regulation of several key signaling pathways such as The Hedgehog (Hh), Wnt and BMP. We use a combination of transgenic mouse models and cellular approaches to identify their roles in stem cell/progenitor function, epithelial-mesenchymal interactions, and their contribution to gastrointestinal tumor intiation and progression.
Insulin Receptor Substrate Signaling in Breast Cancer
The research interests of the Shaw Lab are aimed at understanding the mechanisms involved in the progression of cancer from carcinoma in situ to metastatic disease. Progression requires that these cells acquire the abilities to invade, survive in non-breast tissues and stimulate angiogenesis. One of the major interests of the lab is the contribution of Insulin Receptor Substrate (IRS)-dependent signaling pathways to breast cancer progression. The IRS proteins are adaptor proteins that are recruited to surface receptors in response to ligand binding where they organize complexes that initiate intracellular signaling cascades.
Epithelial Mesenchymal Transition and Cancer Progression
Our current research is focused on the role of tight junction complexes in regulating epithelial to mesenchymal transition (EMT) and invasive cell behavior. EMT describes processes that cause epithelial cells, which normally form sheets of interconnected cells, to dissemble their intercellular junctions, lose apical-basal polarity, and acquire mesenchymal characteristics, such as increased motility.