A5089281522- Cancer Cells and Metastasis
- Cancer Genomics and Diagnostics
- Pancreatic and Hepatic Oncology Research
- Epigenetics and DNA Methylation
- Signaling Pathways in Disease
- Peptidase Inhibition and Analysis
- 3D Printing in Biomedical Research
- Mathematical Biology Tumor Growth
- PI3K/AKT/mTOR signaling in cancer
- Cancer-related gene regulation
- Ferroptosis and cancer prognosis
- Congenital heart defects research
- Gene Regulatory Network Analysis
- Genomics and Chromatin Dynamics
- Tissue Engineering and Regenerative Medicine
- Single-cell and spatial transcriptomics
- Ubiquitin and proteasome pathways
- Receptor Mechanisms and Signaling
- Cell death mechanisms and regulation
- MicroRNA in disease regulation
- Cancer-related Molecular Pathways
- Toxin Mechanisms and Immunotoxins
- Cancer Immunotherapy and Biomarkers
- Biochemical and Molecular Research
- Melanoma and MAPK Pathways
Oregon Health & Science University
2016-2025
OHSU Knight Cancer Institute
2022-2025
University of Portland
2023
Laboratory of Molecular Genetics
2019
University of Utah
2016
Washington University in St. Louis
2002-2011
The tumor microenvironment plays a critical role in growth, progression, and therapeutic resistance, but interrogating the of specific tumor-stromal interactions on tumorigenic phenotypes is challenging within vivo tissues. Here, we tested whether three-dimensional (3D) bioprinting could improve vitro models by incorporating multiple cell types into scaffold-free tissues with defined architecture. We generated from distinct subtypes breast or pancreatic cancer relevant microenvironments...
The SNAIL transcription factor contains C-terminal tandem zinc finger motifs and an N-terminal SNAG repression domain.The members of the family have recently emerged as major contributors to processes development metastasis via regulation epithelial-mesenchymal transition events during embryonic tumor progression.However, mechanisms by which represses gene expression are largely undefined.Previously we demonstrated that AJUBA LIM proteins function corepressors for and, such, may serve a...
Significance Increased kinase activity and suppressed phosphatase are hallmarks of oncogenic signaling. The transcription factor c-MYC, a master driver human cancer, is stabilized activated by persistent serine 62 phosphorylation. tumor suppressor protein 2A (PP2A) targets this site negatively regulates c-MYC. Here, we show that two cellular inhibitors PP2A, the SET oncoprotein cancerous inhibitor PP2A (CIP2A), overexpressed in breast depletion or inhibition CIP2A reduces c-MYC expression...
Abstract Intratumoral heterogeneity in cancers arises from genomic instability and epigenomic plasticity is associated with resistance to cytotoxic targeted therapies. We show here that cell-state heterogeneity, defined by differentiation-state marker expression, high triple-negative basal-like breast cancer subtypes, drug tolerant persister (DTP) cell populations altered expression emerge during treatment a wide range of pathway-targeted therapeutic compounds. MEK PI3K/mTOR inhibitor-driven...
Abstract The reprogramming of somatic cells to inducible pluripotent stem requires a mesenchymal-to-epithelial transition. While differentiating ESCs can undergo the reverse process or epithelial-to-mesenchymal transition (EMT), little is known about role EMT in ESC differentiation and fate commitment. Here, we show that Snail homolog 1 (Snail) expressed during capable inducing on day 2 differentiation. Induction by promotes mesoderm commitment while repressing markers primitive ectoderm...
During normal tumor growth and in response to some therapies, cells experience acute or chronic deprivation of nutrients oxygen induce vascularization. While this occurs predominately through sprouting angiogenesis, have also been shown directly contribute vessel formation vascular mimicry (VM) and/or endothelial transdifferentiation. The extrinsic intrinsic mechanisms underlying cell adoption phenotypes, however, are not well understood. Here we show that serum withdrawal induces...
The c-MYC (MYC) oncoprotein is often overexpressed in human breast cancer; however, its role driving disease phenotypes poorly understood. Here, we investigate the of MYC HER2+ disease, examining relationship between HER2 expression and phosphorylation patient tumors characterizing functional effects deregulating murine NeuNT model amplified-HER2 cancer. Deregulated alone was not tumorigenic, but coexpression with resulted increased Ser62 accelerated tumorigenesis. resulting were metastatic...
Abstract The SNAG repression domain is comprised of a highly conserved 21–amino acid sequence, named for its presence in the Snail/growth factor independence-1 class zinc finger transcription factors, and present variety proto-oncogenic factors developmental regulators. prototype containing oncogene, growth independence-1, responsible development T cell thymomas. SNAIL proteins also encode play key roles epithelial mesenchymal differentiation events during metastasis. Significantly, these...
Triple-negative breast cancer (TNBC) patients have a poor prognosis and few treatment options. Mouse models of TNBC are important for development new therapies, however, mouse represent the complexity TNBC. Here, we develop female murine model by mimicking two common mutations with high co-occurrence: amplification oncogene MYC deletion tumor suppressor PTEN. This Myc;Ptenfl develops heterogeneous triple-negative mammary tumors that display histological molecular features commonly found in...
Expression of the transcription factor Snail is required for normal vasculogenesis in developing mouse embryo. In addition, tumors expressing have been associated with a more malignant phenotype, both increased invasive properties and angiogenesis. Although relationship between has noted, no mechanistic analysis elucidated. Here, we show that addition to inducing an epithelial mesenchymal transition, promotes cell-autonomous induction Flk1(+) endothelial cells early subset differentiating...
Drug resistance in breast cancer cell populations has been shown to arise through phenotypic transition of cells a drug-tolerant state, for example epithelial-to-mesenchymal or stem state. However, many tumors are heterogeneous mixture types with numerous epigenetic states addition stem-like and mesenchymal phenotypes, the dynamic behavior this response drug treatment is not well-understood. Recently, we showed that plasticity between differentiation states, as identified intracellular...
cMYC (MYC) is a potent oncoprotein that subject to post-translational modifications affect its stability and activity. Here, we show Serine 62 phosphorylation, which increases MYC oncogenic activity, elevated while Threonine 58 targets for degradation, decreased in squamous cell carcinoma (SCC). The role of the development SCC unclear since studies have shown normal skin wild-type overexpression can drive loss stem cells epidermal differentiation. To investigate whether how altered...
Protein phosphatase 2A (PP2A) is a ubiquitously expressed Serine-Threonine mediating 30–50% of protein activity. PP2A functions as heterotrimeric complex, with the B subunits directing target specificity to regulate activity many key pathways that control cellular phenotypes. PP2A-B56α has been shown play tumor suppressor role and negatively c-MYC stability Loss B56α promotes transformation, likely at least in part through its regulation c-MYC. Here we report generation hypomorph mouse very...
PIN1 is a phosphorylation-directed member of the peptidyl-prolyl cis/trans isomerase family that facilitates conformational changes in phosphorylated targets such as c-MYC (MYC). Following signaling events mediate phosphorylation MYC at Serine 62, establishes structurally distinct pools through its trans-cis and cis-trans isomerization activity Proline 63. Through these steps, functionally regulates MYC's stability, molecular timing DNA binding transcriptional activity, subnuclear...
Pancreatic cancer remains a formidable challenge due to limited treatment options and its aggressive nature. In recent years, the naturally occurring anticancer compound juglone has emerged as potential therapeutic candidate, showing promising results in inhibiting tumor growth inducing cell apoptosis. However, concerns over toxicity have hampered juglone’s clinical application. To address this issue, we explored use of polymeric micelles delivery system for pancreatic treatment. These...