A5051006005- melanin and skin pigmentation
- Cellular Mechanics and Interactions
- Melanoma and MAPK Pathways
- Retinal Development and Disorders
- Cell Image Analysis Techniques
- CAR-T cell therapy research
- Biochemical Analysis and Sensing Techniques
- Mesenchymal stem cell research
- Immunotherapy and Immune Responses
- Calcium signaling and nucleotide metabolism
- Developmental Biology and Gene Regulation
- Cancer Immunotherapy and Biomarkers
- Cell Adhesion Molecules Research
- Hair Growth and Disorders
- Genomics and Chromatin Dynamics
- RNA regulation and disease
University of California, Irvine
2012-2023
Niche signals maintain stem cells in a prolonged quiescence or transiently activate them for proper regeneration1. Altering balanced niche signalling can lead to regenerative disorders. Melanocytic skin nevi human often display excessive hair growth, suggesting cell hyperactivity. Here, using genetic mouse models of nevi2,3, we show that dermal clusters senescent melanocytes drive epithelial exit and change their transcriptome composition, potently enhancing renewal. Nevus distinct...
Mutational activation of the
Highlights•Loss-of-function mutations in ATR are present human melanoma tumors•ATR mutant nevi and melanomas grow larger than tumors that have functional ATR•ATR recruit pro-tumorigenic macrophages block T cell recruitment•ATR accelerate tumor growth by modulating the microenvironmentSummaryMelanomas accumulate a high burden of could potentially generate neoantigens, yet somehow suppress immune response to facilitate continued growth. In this study, we identify subset loss-of-function ATR,...
Rho family GTPases regulate diverse processes in human melanoma ranging from tumor formation to metastasis and chemoresistance. In this study, a combination of vitro vivo approaches was utilized determine whether RHOJ, CDC42 homologue that regulates chemoresistance, also controls migration. Depletion or overexpression RHOJ altered cellular morphology, implicating role for modulating actin cytoskeletal dynamics. depletion inhibited cell migration invasion growth lymphatic spread mice....
Abstract MITF , a gene that is mutated in familial melanoma and Waardenburg syndrome, encodes multiple isoforms expressed from alternative promoters share common coding exons but have unique amino termini. It not completely understood how these influence pigmentation different tissues the expression of independent regulated. Here, we show melanocytes express two MITF‐A MITF‐M . The partially regulated by newly identified retinoid enhancer element located upstream promoter. Mitf‐A knockout...
Genes and pathways that allow cells to cope with oncogene-induced stress represent selective cancer therapeutic targets remain largely undiscovered. In this study, we identify a RhoJ signaling pathway is target for BRAF mutant cells. deletion in melanocytes modulates the expression of pro-apoptotic protein BAD as well genes involved cellular metabolism, impairing nevus formation, transformation, metastasis. Short-term treatment nascent melanoma tumors PAK inhibitors block halts growth vivo...
PIKfyve, VAC14, and FIG4 form a complex that catalyzes the production of PI(3,5)P2, signaling lipid implicated in process ranging from lysosome maturation to neurodegeneration. While previous studies have identified VAC14 mutations lead both neurodegeneration coat color defects, how PIKfyve regulates melanogenesis is unknown. In this study, we sought better understand role melanosome biogenesis. Melanocyte-specific knockout mice exhibit greying mouse accumulation single membrane vesicle...
Abstract Mutational activation of the BRAF proto-oncogene in melanocytes reliably produces benign nevi (pigmented “moles”), yet same change is most common driver mutation melanoma. The reason stop growing, and do not progress to melanoma, widely attributed a cell-autonomous process “oncogene-induced senescence”. Using mouse model Braf-driven nevus formation, analyzing both proliferative dynamics single-cell gene expression, we found no evidence that cells are senescent, either compared with...