A5065614954- melanin and skin pigmentation
- RNA regulation and disease
- Hair Growth and Disorders
- Cancer Genomics and Diagnostics
- Single-cell and spatial transcriptomics
- Heat shock proteins research
- Cancer-related molecular mechanisms research
- Skin Protection and Aging
- Molecular Biology Techniques and Applications
- Cutaneous Melanoma Detection and Management
- RNA Research and Splicing
- Nonmelanoma Skin Cancer Studies
- Gene expression and cancer classification
- Epigenetics and DNA Methylation
- Endoplasmic Reticulum Stress and Disease
- Viral gastroenteritis research and epidemiology
University of California, San Francisco
2022-2025
UCSF Helen Diller Family Comprehensive Cancer Center
2024
University of Maryland, Baltimore
2012-2023
University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center
2017
The AU-rich elements (AREs) encoded within many mRNA 3' untranslated regions (3'UTRs) are targets for factors that control transcript longevity and translational efficiency. Hsp70, best known as a protein chaperone with well-defined peptide-refolding properties, is to interact ARE-like RNA substrates in vitro. Here, we show cofactor-free preparations of Hsp70 form direct, high-affinity complexes ARE based on specific recognition U-rich sequences by both the ATP- peptide-binding domains....
Melanocyte stem cells (McSCs) are the undifferentiated melanocytic of mammalian hair follicle (HF) responsible for recurrent generation a large number differentiated melanocytes during each HF cycle. McSCs reside in both CD34+ bulge/lower permanent portion (LPP) and CD34- secondary germ (SHG) regions telogen. Using Dct-H2BGFP mice, we separate bulge/LPP SHG using FACS with GFP anti-CD34 to show that these two subsets functionally distinct. Genome-wide expression profiling results support...
Abstract To better understand the homeostatic mechanisms governing melanocytes, we performed deep phenotyping of clonal expansions single melanocytes from human skin. In total, interrogated mutational landscapes, gene expression profiles, and morphological features 297 31 donors. our surprise, a population with low mutation burden was maintained in sun damaged These were more stem-like, smaller, less dendritic displayed distinct profiles compared to their counterparts high burdens. We used...
Objectives/Goals: Despite the documented link between ultraviolet (UV) exposure and skin cancer, potential protective role of pigmentation in preventing carcinogenesis is not fully understood. This project will test hypothesis that individuals with light tones are more susceptible to cancer due a higher accumulation somatic mutations from UV exposure. Methods/Study Population: Skin biopsies were collected various anatomical sites seven donors aged 70 80 years dark used generate clones normal...
Abstract Objectives/Goals: Despite the documented link between UV exposure and skin cancer, role of pigmentation in preventing carcinogenesis is not fully understood. This project aims to investigate how influences earliest stages cancer development by examining genomic landscape cells across individuals diverse tones, which will uncover potential differences susceptibility mutation patterns. Methods/Study Population: We collected biopsies from various body sites exposed different levels...
Spatial transcriptomic technologies, such as the Visium platform, measure gene expression in different regions of tissues. Here, we describe new software, STmut, to visualize somatic point mutations, allelic imbalance, and copy number alterations data. STmut is tested on fresh-frozen data, formalin-fixed paraffin-embedded (FFPE) tumors with without matching DNA sequencing Copy inferred all conditions, but chemistry FFPE platform does not permit analyses single nucleotide variants. Taken...
Hsp70 is a protein chaperone that prevents aggregation and aids folding by binding to hydrophobic peptide domains through reversible mechanism directed an ATPase cycle. However, also binds U-rich RNA including some AU-rich elements (AREs) regulate the decay kinetics of select mRNAs has recently been shown bind stabilize ARE-containing transcripts in cells. Previous studies indicated both ATP- peptide-binding contributed stability Hsp70-RNA complexes ATP might inhibit recruitment. This...
Abstract We performed multi-omic profiling of epidermal keratinocytes, precancerous actinic keratoses, and squamous cell carcinomas to understand the molecular transitions during skin carcinogenesis. Single-cell mutational analyses showed that most keratinocytes in normal had lower mutation burdens than melanocytes fibroblasts, however with TP53 or NOTCH1 mutations substantially higher burdens, suggesting these prime for transformation by increasing their rate. Mutational spatial...
Abstract Tools to visualize genetic alterations within tissues remain underdeveloped despite the growth of spatial transcriptomic technologies, which measure gene expression in different regions tissues. Since can be detected RNA-sequencing data, we explored feasibility observing somatic transcriptomics data. Extracting information from data would illuminate distribution clones and allow for correlations with regional changes support genotype-phenotype studies. Recent work demonstrates that...
Abstract Background Tanning bed users have a significantly increased risk of melanoma, but it remains unclear how indoor tanning drives melanomagenesis. radiation is often thought as substitute for natural UV despite differences in the maximum doses, content, body sites exposed, and patterns melanoma that arise. Methods To better understand epidemiologic trends etiology associated with use, we described patients quantifiable usage performed exome sequencing 182 melanocytes from normal skin...
Abstract Melanocyte stem cells (McSCs) are key components of the hair follicle (HF) cell system that regenerate differentiated melanocytes during successive HF cycles. To facilitate continued research on melanocyte development and differentiation McSCs, we backcrossed inducible Dct ‐H2BGFP mice into C57BL/6J background (B6‐ ‐H2BGFP). We compared expression pattern B6‐ to a mixed genetic reported previously. characterize mice, confirmed not only GFP in all lineage cells, but also doxycycline...
ABSTRACT Melanocyte stem cells (McSCs) are key components of the hair follicle (HF) cell system that derived from neural crest during embryogenesis and responsible for regeneration differentiated melanocytes successive HF cycles. Our previous research has shown presence two subsets phenotypically functionally distinct McSCs exist in murine telogen HFs, CD34+ bulge/lower permanent portion (LPP) CD34− secondary germ (SHG). Whether these maintained independently or a developmental hierarchy is...