A5036802615- Melanoma and MAPK Pathways
- Hippo pathway signaling and YAP/TAZ
- Microtubule and mitosis dynamics
- Cellular Mechanics and Interactions
- Cutaneous Melanoma Detection and Management
- Epigenetics and DNA Methylation
- Bioinformatics and Genomic Networks
- PI3K/AKT/mTOR signaling in cancer
- Virus-based gene therapy research
- melanin and skin pigmentation
- Histone Deacetylase Inhibitors Research
- Chromatin Remodeling and Cancer
University of Massachusetts Chan Medical School
2020-2022
Massachusetts General Hospital
2011-2015
Center for Cancer Research
2011
Harvard University Press
2011
Human tumors often contain slowly proliferating cancer cells that resist treatment, but we do not know precisely how these arise. We show rapidly can divide asymmetrically to produce “G0-like” progeny are enriched following chemotherapy in breast patients. Asymmetric cell division results from asymmetric suppression of AKT/PKB kinase signaling one daughter during telophase mitosis. Moreover, inhibition AKT with small-molecule drugs induce and the production slow proliferators. Cancer...
All cancers contain an admixture of rapidly and slowly proliferating cancer cells. This proliferative heterogeneity complicates the diagnosis treatment patients with because slow proliferators are hard to eradicate, can be difficult detect, may cause disease relapse sometimes years after apparently curative treatment. While clonal selection theory explains presence evolution rapid within cell populations, circumstances molecular details how produced is not well understood. Here, a...
Abstract Melanoma is commonly driven by activating mutations in the MAP kinase BRAF; however, oncogenic BRAF alone insufficient to promote melanomagenesis. Instead, its expression induces a transient proliferative burst that ultimately ceases with development of benign nevi comprised growth-arrested melanocytes. The tumor suppressive mechanisms restrain nevus melanocyte proliferation remain poorly understood. Here we utilize cell and murine models demonstrate leads activation Hippo...
Abstract Melanomas and other solid tumors commonly have increased ploidy, with near-tetraploid karyotypes being most frequently observed. Such been shown to arise through whole-genome doubling events that occur during early stages of tumor progression. The generation tetraploid cells via is proposed allow nascent the ability sample various pro-tumorigenic genomic configurations while avoiding negative consequences chromosomal gains or losses in diploid cells. Whereas a high prevalence has...
Abstract Melanomas and other solid tumors commonly have increased ploidy, with near-tetraploid karyotypes being most frequently observed. Such been shown to arise through whole-genome doubling events that occur during early stages of tumor progression. The generation tetraploid cells via is proposed allow nascent the ability sample various pro-tumorigenic genomic configurations while avoiding negative consequences chromosomal gains or losses in diploid cells. Whereas a high prevalence has...
Abstract Human melanomas are commonly driven by activating mutations in BRAF , which promote melanocyte proliferation through constitutive stimulation of the MAPK pathway. However, oncogenic alone is insufficient to melanoma; instead, its expression merely induces a transient burst that ultimately ceases with development benign nevi ( i . e moles) comprised growth-arrested melanocytes. The tumor suppressive mechanisms induce this melanocytic growth arrest remain poorly understood. Recent...
Abstract Melanomas and other solid tumors commonly have increased ploidy, with near-tetraploid karyotypes being most frequently observed. Such been shown to arise through whole-genome doubling events that occur during early stages of tumor progression. The generation tetraploid cells via is proposed allow nascent the ability sample various protumorigenic genomic configurations while avoiding negative consequences chromosomal gains or losses in diploid cells. Whereas a high prevalence has...