A5066468370- Cutaneous Melanoma Detection and Management
- Melanoma and MAPK Pathways
- RNA regulation and disease
- melanin and skin pigmentation
- interferon and immune responses
- Protein Kinase Regulation and GTPase Signaling
- CRISPR and Genetic Engineering
- PARP inhibition in cancer therapy
- Endoplasmic Reticulum Stress and Disease
- DNA Repair Mechanisms
- Ocular Oncology and Treatments
- Hippo pathway signaling and YAP/TAZ
- Mitochondrial Function and Pathology
- Cancer Genomics and Diagnostics
- Microtubule and mitosis dynamics
- Cellular Mechanics and Interactions
- SARS-CoV-2 and COVID-19 Research
- Advanced Breast Cancer Therapies
- CAR-T cell therapy research
- Ubiquitin and proteasome pathways
- Cancer Research and Treatments
- Viral Infections and Vectors
- Fibroblast Growth Factor Research
- Historical Studies on Reproduction, Gender, Health, and Societal Changes
- Cancer, Hypoxia, and Metabolism
UCSF Helen Diller Family Comprehensive Cancer Center
2018-2023
University of California, San Francisco
2018-2023
Integral Molecular (United States)
2017
University of Pennsylvania
2014-2016
Philadelphia University
2014
In the absence of low-level ER-to-mitochondrial Ca2+ transfer, ATP levels fall, and AMPK-dependent, mTOR-independent autophagy is induced as an essential survival mechanism in many cell types. Here, we demonstrate that tumorigenic cancer lines, transformed primary human fibroblasts, tumors vivo respond similarly but insufficient for survival, cells die while their normal counterparts are spared. Cancer death due to compromised bioenergetics can be rescued with metabolic substrates or...
Deletion of the entire CDKN2B-CDKN2A gene cluster is among most common genetic events in cancer. The tumor-promoting effects are generally attributed to loss CDKN2A-encoded p16 and p14ARF tumor suppressors. degree which associated CDKN2B-encoded p15 contributes human tumorigenesis unclear. Here, we show that CDKN2B highly upregulated benign melanocytic nevi, maintaining nevus melanocytes a growth-arrested premalignant state, commonly lost melanoma. Using primary isolated directly from...
Drug combinations are synergistic when their combined efficacy exceeds the sum of individual actions, but they rarely include ineffective drugs that become effective only in combination. We identified several "enabling pairs" neutralizing and non-neutralizing anti-ebolavirus monoclonal antibodies, whose combination exhibited new functional profiles, including transforming a antibody to neutralizer. Sub-neutralizing concentrations antibodies 2G4 or m8C4 enabled FVM09 (IC50 >1 μM) exhibit...
Benign melanocytic nevi frequently emerge when an acquired BRAF V600E mutation triggers unchecked proliferation and subsequent arrest in melanocytes. Recent observations have challenged the role of oncogene-induced senescence nevus formation, necessitating investigations into alternative mechanisms for establishment maintenance nevi. We compared transcriptomes melanocytes from healthy human skin, nevi, melanomas arising identified a set microRNAs as highly expressed nevus-enriched...
Abstract Over one million cases of gastric cancer are diagnosed each year globally, and the metastatic disease continues to have a poor prognosis. A significant proportion tumors defects in DNA damage response pathway, creating therapeutic opportunities through synthetic lethal approaches. Several small-molecule inhibitors ATR, key regulator response, now clinical development as targeted agents for cancer. Here, we performed large-scale CRISPR interference screen discover genetic...
Fibroblast growth factor receptor 3 (FGFR3) activating mutations are drivers of malignancy in several human tissues, including bladder, lung, cervix, and blood. However, skin, these associated predominantly with benign, common epidermal growths called seborrheic keratoses (SKs). How epidermis resists FGFR3 mediated transformation is unclear, but previous studies have suggested that activation skin keratinocytes may serve a tumor-suppressive role by driving differentiation antagonizing Ras...
Abstract Every cell in the human body has a unique set of somatic mutations, yet it remains difficult to comprehensively genotype an individual cell. Here, we developed solutions overcome this obstacle context normal skin, thus offering first glimpse into genomic landscapes melanocytes from skin. We genotyped 133 19 sites across 6 donors. As expected, sun-shielded had fewer mutations than sun-exposed melanocytes. However, within sites, on chronically skin (e.g. face) displayed lower mutation...
Abstract The CDKN2A locus on chromosome 9p21 encodes two tumor suppressors: the cyclin dependent kinase inhibitor p16INK4a and MDM2 regulator p14ARF. Homozygous deletion of this is among most common genetic events in human cancer across tissues, with resultant selective advantage to cells generally attributed loss proteins, which help maintain functional Rb p53. However, greater than 90% tissues harboring deletion, adjacent CDKN2B gene encoding p15 inhibitor, also deleted. degree...
<div>Abstract<p>Over one million cases of gastric cancer are diagnosed each year globally, and the metastatic disease continues to have a poor prognosis. A significant proportion tumors defects in DNA damage response pathway, creating therapeutic opportunities through synthetic lethal approaches. Several small-molecule inhibitors ATR, key regulator response, now clinical development as targeted agents for cancer. Here, we performed large-scale CRISPR interference screen discover...
<div>Abstract<p>Over one million cases of gastric cancer are diagnosed each year globally, and the metastatic disease continues to have a poor prognosis. A significant proportion tumors defects in DNA damage response pathway, creating therapeutic opportunities through synthetic lethal approaches. Several small-molecule inhibitors ATR, key regulator response, now clinical development as targeted agents for cancer. Here, we performed large-scale CRISPR interference screen discover...
Supplementary Figure from Resistance to ATR Inhibitors Is Mediated by Loss of the Nonsense-Mediated Decay Factor UPF2
Supplementary Data from Resistance to ATR Inhibitors Is Mediated by Loss of the Nonsense-Mediated Decay Factor UPF2
Supplementary Data from Resistance to ATR Inhibitors Is Mediated by Loss of the Nonsense-Mediated Decay Factor UPF2
Supplementary Data from Resistance to ATR Inhibitors Is Mediated by Loss of the Nonsense-Mediated Decay Factor UPF2
Supplementary Data from Resistance to ATR Inhibitors Is Mediated by Loss of the Nonsense-Mediated Decay Factor UPF2
Supplementary Figure from Resistance to ATR Inhibitors Is Mediated by Loss of the Nonsense-Mediated Decay Factor UPF2
<p>Supplementary Figure S1. p15, p16, and Ki-67 expression in a benign BRAF(V600E) nevus. Supplementary S2. Active CDK4 reverses BRAF(V600E)-mediated melanocyte growth arrest. S3. BRAF(V600E), p16 normal nevus MCs. S4. Engineered p15 melanocytes. S5. Effects of shRNA rescue lentiCRISPRCAS9 mediated loss diBRAF(V600E) S6. Loss CDKN2A CDKN2B promotes proliferation Melanocytes. S7. Expression Benign Nevi Melanoma. S8. Nevus with Adjacent S9. Erk 1/2 Target EGR-1 is Upregulated BRAFV600E...
<div>Abstract<p>Deletion of the entire <i>CDKN2B–CDKN2A</i> gene cluster is among most common genetic events in cancer. The tumor-promoting effects are generally attributed to loss <i>CDKN2A</i>-encoded p16 and p14ARF tumor suppressors. degree which associated <i>CDKN2B</i>-encoded p15 contributes human tumorigenesis unclear. Here, we show that <i>CDKN2B</i> highly upregulated benign melanocytic nevi, maintaining nevus melanocytes a...
<div>Abstract<p>Deletion of the entire <i>CDKN2B–CDKN2A</i> gene cluster is among most common genetic events in cancer. The tumor-promoting effects are generally attributed to loss <i>CDKN2A</i>-encoded p16 and p14ARF tumor suppressors. degree which associated <i>CDKN2B</i>-encoded p15 contributes human tumorigenesis unclear. Here, we show that <i>CDKN2B</i> highly upregulated benign melanocytic nevi, maintaining nevus melanocytes a...