A5070618651- Pancreatic and Hepatic Oncology Research
- Cancer Genomics and Diagnostics
- Cancer-related Molecular Pathways
- Protein Tyrosine Phosphatases
- Epigenetics and DNA Methylation
- Melanoma and MAPK Pathways
- NF-κB Signaling Pathways
- Cancer Research and Treatments
- Histone Deacetylase Inhibitors Research
- Pancreatic function and diabetes
- Protein Kinase Regulation and GTPase Signaling
- Microtubule and mitosis dynamics
- Cellular Mechanics and Interactions
- Retinoids in leukemia and cellular processes
- Pancreatitis Pathology and Treatment
- PI3K/AKT/mTOR signaling in cancer
- Psoriasis: Treatment and Pathogenesis
- Cancer therapeutics and mechanisms
- Hippo pathway signaling and YAP/TAZ
- Skin Protection and Aging
- Cancer, Hypoxia, and Metabolism
- Dermatology and Skin Diseases
- Estrogen and related hormone effects
- Immune Response and Inflammation
- HER2/EGFR in Cancer Research
Loyola University Chicago
2025
Stanford University
2017-2024
Stratford University
2024
National Cancer Institute
2016-2021
Center for Cancer Research
2019-2021
William & Mary
2014-2018
Williams (United States)
2017-2018
National Institutes of Health
2017
Abstract Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease with 5-year survival rate of approximately 9%. An improved understanding PDAC initiation and progression paramount for discovering strategies to better detect combat this disease. Although transcriptomic analyses have uncovered distinct molecular subtypes human PDAC, the factors that influence subtype development remain unclear. Here, we interrogate impact cell origin different Trp53 alleles on tumor evolution, using panel...
The vast majority of human pancreatic ductal adenocarcinomas (PDACs) harbor TP53 mutations, underscoring p53’s critical role in PDAC suppression. can arise when acinar cells undergo acinar-to-ductal metaplasia (ADM), giving rise to premalignant intraepithelial neoplasias (PanINs), which finally progress PDAC. occurrence mutations late-stage PanINs has led the idea that p53 acts suppress malignant transformation However, cellular basis for action during development not been explored detail....
Abstract Development of systems that reconstitute hallmark features human pancreatic intraepithelial neoplasia (PanINs), the precursor to ductal adenocarcinoma, could generate new strategies for early diagnosis and intervention. However, cell-based PanIN models with defined mutations are unavailable. Here, we report genetic modification primary cells leads development lesions resembling native PanINs. Primary pancreas duct harbouring oncogenic KRAS induced in CDKN2A , SMAD4 TP53 expand vitro...
As a highly heterogeneous tumor, pancreatic ductal adenocarcinoma (PDAC) exhibits non-uniform responses to therapies across subtypes. Overcoming therapeutic resistance stemming from this heterogeneity remains significant challenge. Here, we report that Vitamin D-resistant PDAC cells hijacked D signaling promote tumor progression, whereas epigenetic priming with glyceryl triacetate (GTA) and 5-Aza-2'-deoxycytidine (5-Aza) overcame shifted the transcriptomic phenotype of toward D-susceptible...
Resistance to endocrine therapies remains a major clinical hurdle in breast cancer. Mutations estrogen receptor alpha (ERα) arise after continued therapeutic pressure. Next generation selective modulators and degraders/downregulators (SERMs SERDs) show efficacy, but responses are often non-durable. A tyrosine serine point mutation at position 537 the ERα ligand binding domain (LBD) is among most common pathogenic alteration this setting. It enables therapy resistance by superceding intrinsic...
We previously reported that the pseudophosphatase MK-STYX (mitogen activated kinase phosphoserine/threonine/tyrosine binding protein) dramatically increases number of what appeared to be primary neurites in rat pheochromocytoma (PC-12) cells; however, question remained whether these MK-STYX-induced outgrowths were bona fide neurites, and formed synapses. Here, we report microtubules microfilaments, components cytoskeleton are involved formation present outgrowths. In addition, response nerve...
The rat pheochromocytoma PC12 cell line is a widely used system to study neuronal differentiation for which sustained activation of the extracellular signaling related kinase (ERK) pathway required. Here, we investigate function MK-STYX [MAPK (mitogen-activated protein kinase) phosphoserine/threonine/tyrosine-binding protein] in differentiation. member MAPK phosphatase (MKP) family, generally responsible dephosphorylating ERKs. However, lacks catalytic activity due absence nucleophilic...
Abstract Cellular senescence is a well‐documented response to oncogene activation in many tissues. Multiple pathways are invoked achieve indicating its importance counteract the transforming activities of oncogenic stimulation. We now report that Rho‐associated protein kinase (ROCK) signaling pathway critical regulator oncogene‐induced skin carcinogenesis. Transformation mouse keratinocytes with RAS upregulates ROCK activity and initiates characterized by cell enlargement, growth inhibition,...
Abstract Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with 5-year survival rate of only 11%. Slated to be the 2nd most deadly cancer by 2026, pancreatic rates have not improved substantially over years. With lack early detection methods and highly immunosuppressive tumor microenvironment (TME), PDAC tumors are resistant treatment. Oncogenic mutations in KRAS present >90% cases suppressor gene TP53 ~72% cases. However, why p53 so prevalent how they enhance...
Abstract As a highly heterogeneous tumor, pancreatic ductal adenocarcinoma (PDAC) exhibits non-uniform responses to therapies across subtypes. Overcoming therapeutic resistance due tumor heterogeneity in PDAC remains challenge. Here, we report that Vitamin D-resistant cells hijacked D signaling promote progression, whereas epigenetic priming with glyceryl triacetate (GTA) and 5-Aza-2′-deoxycytidine (5-Aza) overcame shifted the transcriptomic phenotype of toward D-susceptible state....
<div>Abstract<p>Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease with 5-year survival rate of approximately 9%. An improved understanding PDAC initiation and progression paramount for discovering strategies to better detect combat this disease. Although transcriptomic analyses have uncovered distinct molecular subtypes human PDAC, the factors that influence subtype development remain unclear. Here, we interrogate impact cell origin different <i>Trp53</i>...
<p>Analysis of pancreatic cancer development from adult mouse acinar cells</p>
<p>Analysis of pancreatic cancer development from adult mouse ductal cells</p>
<p>Analysis of p53 missense mutants in acinar cell-derived pancreatic cancer development</p>
<p>Acinar and ductal cell-derived tumor signature enrichment in TCGA cohort</p>
<p>Transcriptome and histological analysis of mouse acinar ductal cell-derived tumors</p>
<p>Phenotypes in acinar cell-of-origin Trp53 wild-type, heterozygous, and knockout mouse cohorts</p>
<p>Cox proportional hazard analysis of the Canadian ICGC and TCGA cohorts</p>
<p>Phenotypes in acinar cell-of-origin Trp53 missense mutation mouse cohorts</p>
<p>Acinar and ductal cell-derived tumor gene expression analysis</p>
<p>Phenotypes in ductal cell-of-origin mouse cohorts</p>