A5018036894- Hippo pathway signaling and YAP/TAZ
- Cancer, Lipids, and Metabolism
- Epigenetics and DNA Methylation
- Pancreatic and Hepatic Oncology Research
- Cancer, Hypoxia, and Metabolism
- Sarcoma Diagnosis and Treatment
- Genetic and rare skin diseases.
- Cell death mechanisms and regulation
- NF-κB Signaling Pathways
- Dermatologic Treatments and Research
- Ferroptosis and cancer prognosis
- Cutaneous Melanoma Detection and Management
- Cancer-related gene regulation
- Ubiquitin and proteasome pathways
- melanin and skin pigmentation
- Polyamine Metabolism and Applications
- Immunotherapy and Immune Responses
- Cell Adhesion Molecules Research
- T-cell and Retrovirus Studies
- Genital Health and Disease
- Genomics and Chromatin Dynamics
- Infectious Diseases and Mycology
- Nonmelanoma Skin Cancer Studies
- CAR-T cell therapy research
- Animal Disease Management and Epidemiology
University of Pennsylvania
2017-2024
Cancer Research Institute
2018-2019
Pancreatic ductal adenocarcinoma (PDA) has a poor prognosis, and new strategies for prevention treatment are urgently needed. We previously reported that histone H4 acetylation is elevated in pancreatic acinar cells harboring
This study reveals how epigenetic errors drive skin cancer initiation via altered cell fate and impaired ferroptosis.
Self-renewing somatic tissues depend upon the proper balance of chromatin-modifying enzymes to coordinate progenitor cell maintenance and differentiation, disruption which can promote carcinogenesis. As a result, drugs targeting epigenome hold significant therapeutic potential. The histone demethylase, LSD1 (KDM1A), is overexpressed in numerous cancers, including epithelial cancers; however, its role skin virtually unknown. Here we show that directly represses master transcription factors...
Abstract To date, no consistent oncogenic driver mutations have been identified in most adult soft tissue sarcomas; these tumors are thus generally insensitive to existing targeted therapies. Here we investigated alternate mechanisms underlying sarcomagenesis identify potential therapeutic interventions. Undifferentiated pleomorphic sarcoma (UPS) is an aggressive tumor frequently found skeletal muscle where deregulation of the Hippo pathway and aberrant stabilization its transcriptional...
Abstract Terminal differentiation opposes proliferation in the vast majority of tissue types. As a result, loss lineage is hallmark aggressive cancers, including soft sarcomas (STS). Consistent with these observations, undifferentiated pleomorphic sarcoma (UPS), an STS subtype devoid markers, among most lethal adults. Though tissue-specific features are lost mesenchymal tumors they commonly diagnosed skeletal muscle, and thought to develop from transformed muscle progenitor cells. We have...
Mutation of the ATP2A2 gene encoding sarco-endoplasmic reticulum calcium ATPase 2 (SERCA2) was linked to Darier disease more than two decades ago; however, there remain no targeted therapies for this disorder causing recurrent skin blistering and infections. Since Atp2a2 knockout mice do not phenocopy its pathology, we established a human tissue model elucidate pathogenesis identify potential therapies. Leveraging CRISPR/Cas9, generated keratinocytes lacking SERCA2, which replicated features...
ABSTRACT Mutation of the ATP2A2 gene encoding sarco-endoplasmic reticulum calcium ATPase 2 (SERCA2) was linked to Darier disease more than two decades ago; however, there remain no targeted therapies for this disorder causing recurrent skin blistering and infections. Since Atp2a2 knockout mice do not phenocopy its pathology, we established a human tissue model elucidate pathogenesis identify potential therapies. Leveraging CRISPR/Cas9, generated keratinocytes lacking SERCA2, which replicated...
ABSTRACT The epigenetic regulator, MLL4 ( KMT2D ), has been described as an essential gene in both humans and mice 1,2 . In addition, it is one of the most commonly mutated genes all cancer biology 3–7 Here, we identify a critical role for Mll4 promotion epidermal differentiation ferroptosis, key mechanism tumor suppression 8,9 Mice lacking , but not related enzyme Mll3 Kmt2c display features impaired human pre-cancerous neoplasms, including hyperplasia, atypical keratinocytes, loss...
<div>Abstract<p>To date, no consistent oncogenic driver mutations have been identified in most adult soft tissue sarcomas; these tumors are thus generally insensitive to existing targeted therapies. Here we investigated alternate mechanisms underlying sarcomagenesis identify potential therapeutic interventions. Undifferentiated pleomorphic sarcoma (UPS) is an aggressive tumor frequently found skeletal muscle where deregulation of the Hippo pathway and aberrant stabilization its...
<p>Supplementary methods, references, and legends</p>
<p>Supplemental Ingenuity Pathway Analysis and cleaved caspase 3 findings</p>
<p>Supplemental patient information from tissue microarray and additional quantitations.</p>
<p>The role of myc in UPS and the effects SAHA/JQ1 on YAP1 levels sarcoma cell lines</p>
<p>The role of AMOT in sarcomagenesis</p>
<p>Supplemental in vitro rescue assays and qRT-PCR of SAHA/JQ1 treated cells</p>
<p>Supplemental ChIP-Seq and RNA-seq information</p>
<p>The effects of SAHA/JQ1 on phospho-YAP1</p>
<p>The effects of SAHA/JQ1 on phospho-YAP1</p>
<p>Supplemental patient information from tissue microarray and additional quantitations.</p>
<p>Supplemental ChIP-Seq and RNA-seq information</p>
<p>Supplementary methods, references, and legends</p>