A5081155388- Dermatology and Skin Diseases
- Advancements in Transdermal Drug Delivery
- Skin and Cellular Biology Research
- Contact Dermatitis and Allergies
- Cancer Genomics and Diagnostics
- Ion channel regulation and function
- Psoriasis: Treatment and Pathogenesis
- Skin Protection and Aging
- Wound Healing and Treatments
- Ion Channels and Receptors
- Genetic and rare skin diseases.
- Connexins and lens biology
- Cancer and Skin Lesions
- Hedgehog Signaling Pathway Studies
- melanin and skin pigmentation
- Neonatal skin health care
- Allergic Rhinitis and Sensitization
- BRCA gene mutations in cancer
- Transgenic Plants and Applications
- Polysaccharides and Plant Cell Walls
- Wnt/β-catenin signaling in development and cancer
- Breast Cancer Treatment Studies
- Neuroscience and Neuropharmacology Research
- Plant Reproductive Biology
- Sphingolipid Metabolism and Signaling
University of California, San Francisco
2015-2024
San Francisco VA Medical Center
2015-2024
San Francisco VA Health Care System
2020-2024
Northern California Institute for Research and Education
2011-2024
University of California San Francisco Medical Center
2021
University of Colorado Denver
2018
United States Department of Veterans Affairs
1998-2013
University of San Francisco
2003-2012
Brigham and Women's Hospital
2011
University of California, Berkeley
2011
Squamous cell carcinomas (SCCs) are one of the most frequent forms human malignancy, but, other than TP53 mutations, few causative somatic aberrations have been identified. We identified NOTCH1 or NOTCH2 mutations in ∼75% cutaneous SCCs and a lesser fraction lung SCCs, defining spectrum for prevalent tumor suppressor specific to these epithelial malignancies. Notch receptors normally transduce signals response ligands on neighboring cells, regulating metazoan lineage selection developmental...
Timely intervention for cancer requires knowledge of its earliest genetic aberrations. Sequencing tumors and their metastases reveals numerous abnormalities occurring late in progression. A means to temporally order aberrations a single cancer, rather than inferring them from serially acquired samples, would define changes preceding even clinically evident disease. We integrate DNA sequence copy number information reconstruct the as individual evolve 2 separate types. detect vast, unreported...
Inflammatory conditions represent the largest class of chronic skin disease, but molecular dysregulation underlying many individual cases remains unclear. Single-cell RNA sequencing (scRNA-seq) has increased precision in dissecting complex mixture immune and stromal cell perturbations inflammatory disease states. We single-cell–profiled CD45 + transcriptomes from samples 31 patients (7 atopic dermatitis, 8 psoriasis vulgaris, 2 lichen planus (LP), 1 bullous pemphigoid (BP), 6...
We report the phenotype of mice with targeted disruption Trpv6 (Trpv6 KO) epithelial calcium channel. The exhibit disordered Ca(2+) homeostasis, including defective intestinal absorption, increased urinary excretion, decreased BMD, deficient weight gain, and reduced fertility. Although our KO affects closely adjacent EphB6 gene, reported here is not related to dysfunction.
The skin is the first line of defense against microbial infection, and psychological stress (PS) has been shown to have adverse effects on cutaneous barrier function. Here we show that PS increased severity group A Streptococcus pyogenes (GAS) infection in mice; this was accompanied by production endogenous glucocorticoids (GCs), which inhibited epidermal lipid synthesis decreased lamellar body (LB) secretion. LBs encapsulate antimicrobial peptides (AMPs), or systemic topical GC...
The outermost epidermal layer, the stratum corneum (SC), exhibits an acidic surface pH, whereas pH at its base approaches neutrality. NHE1 is only Na(+)/H(+) antiporter isoform in keratinocytes and epidermis, has been shown to regulate intracellular pH. We now demonstrate a novel function for NHE1, as we find that it also controls acidification of extracellular "microdomains" SC are essential activation pH-sensitive enzymes formation permeability barrier. expression epidermis most pronounced...
Extracellular calcium concentrations (Cao) > 0.1 mM are required for the differentiation of normal human keratinocytes in culture. Increments Cao result acute and sustained increases intracellular level (Cai), postulated to involve both a release from stores subsequent increase influx through nonspecific cation channels. The rise Cai appears be necessary keratinocyte differentiation. To understand mechanism by which respond Cao, we measured effects on at various stages We then demonstrated...
Vitamin D receptor (VDR)-dependent mechanisms regulate human cathelicidin antimicrobial peptide (CAMP)/LL-37 in various cell types, but CAMP expression also increases after external perturbations (such as infection, injuries, UV irradiation, and permeability barrier disruption) parallel with induction of endoplasmic reticulum (ER) stress. We demonstrate that mRNA protein increase epithelial cells (human primary keratinocytes, HaCaT HeLa cells), not myeloid (U937 HL-60) cells, following ER...
The term retinoid includes both natural and synthetic derivatives of vitamin A. Retinoid-containing treatments have been used since ∼1550BC by the early Egyptians. Treatment ichthyosiform disorders with retinoids dates back at least to 1930s. Early use high-dose A demonstrated efficacy, but because is stored in liver, toxicity limited usefulness. Interest turned an effort enhance efficacy limit toxicity. Acetretin, isotretinoin and, past etretinate, provided most effective therapy for...
Cornification and epidermal barrier defects are associated with a number of clinically diverse skin disorders. However, suitable in vitro model for studying normal function is still lacking. Here, we demonstrate the generation human equivalents (HEEs) from embryonic stem cells (hESCs) induced pluripotent (iPSCs). HEEs structurally similar to native epidermis, functional permeability barrier. We exposed pure population hESC/iPSC-derived keratinocytes, whose transcriptome corresponds gene...