A5056918379- Pancreatic and Hepatic Oncology Research
- Hippo pathway signaling and YAP/TAZ
- Cancer Cells and Metastasis
- Amino Acid Enzymes and Metabolism
- Polyamine Metabolism and Applications
- Microtubule and mitosis dynamics
- Advanced Breast Cancer Therapies
- TGF-β signaling in diseases
- Neuroblastoma Research and Treatments
- Cancer Genomics and Diagnostics
- Cell Adhesion Molecules Research
- Cellular Mechanics and Interactions
- 3D Printing in Biomedical Research
- Mast cells and histamine
- Cancer Research and Treatments
- Mesenchymal stem cell research
- Endoplasmic Reticulum Stress and Disease
- Cancer, Hypoxia, and Metabolism
- HER2/EGFR in Cancer Research
- Ubiquitin and proteasome pathways
- Epigenetics and DNA Methylation
- Kruppel-like factors research
- Cancer-related gene regulation
- Pancreatic function and diabetes
- Molecular Biology Techniques and Applications
Baylor University
2023-2025
California State University, Northridge
2016-2025
University of California, San Diego
2007-2024
Vassar College
2024
University of California, Berkeley
2023
Integra (United States)
2023
Wellcome Centre for Cell-Matrix Research
2020
University of Manchester
2020
Harvard University
2020
California State University System
2014
Little is known about how metastatic cancer cells arrest in small capillaries and traverse the vascular wall during extravasation vivo. Using real-time intravital imaging of human tumor transplanted into transparent zebrafish, we show here that a highly dynamic process involves modulation cell adhesion to endothelium intravascular migration along luminal surface wall. Tumor do not damage or induce leak at site extravasation, but rather local vessel remodeling characterized by clustering...
Cripto is a multifunctional cell surface protein with important roles in vertebrate embryogenesis and the progression of human tumors. While has been shown to modulate multiple signaling pathways, its binding partners do not appear fully explain molecular actions. Therefore, we conducted screen aimed at identifying novel Cripto-interacting proteins. This led our identification glucose-regulated 78 (GRP78), an endoplasmic reticulum (ER) chaperone that also expressed surfaces tumor cells. Here...
Breast cancer and melanoma cells commonly metastasize to the brain using homing mechanisms that are poorly understood. Cancer patients with metastases display poor prognosis survival due lack of effective therapeutics treatment strategies. Recent work intravital microscopy preclinical animal models indicates metastatic colonize specifically in close contact existing vasculature. However, it is not known how vascular niche promotes microtumor formation. Here, we investigate role connexins...
Regulation of the actin-myosin cytoskeleton plays a central role in cell migration and cancer progression. Here, we report discovery cytoskeleton-associated kinase, pseudopodium-enriched atypical kinase 1 (PEAK1). PEAK1 is 190-kDa nonreceptor tyrosine that localizes to actin filaments focal adhesions. undergoes Src-induced phosphorylation, regulates p130Cas-Crk-paxillin Erk signaling pathways, operates downstream integrin epidermal growth factor receptors (EGFR) control spreading, migration,...
Early biomarkers and effective therapeutic strategies are desperately needed to treat pancreatic ductal adenocarcinoma (PDAC), which has a dismal 5-year patient survival rate. Here, we report that the novel tyrosine kinase PEAK1 is upregulated in human malignancies, including PDACs intraepithelial neoplasia (PanIN). Oncogenic KRas induced PEAK1-dependent amplification loop between Src, PEAK1, ErbB2 drive PDAC tumor growth metastasis vivo. Surprisingly, blockade of expression increased...
Deregulation of protein synthesis is a hallmark cancer cell proliferation, survival, and metastatic progression. eIF5A1 its highly related isoform eIF5A2 are translation initiation factors that have been implicated in range human malignancies, but how they control development disease progression still poorly understood. Here, we investigated eIF5A proteins regulate pancreatic ductal adenocarcinoma (PDAC) pathogenesis. the only known regulated by distinct posttranslational modification termed...
In pancreatic ductal adenocarcinoma (PDAC), mutant KRAS stimulates the translation initiation factor eIF5A and upregulates focal adhesion kinase PEAK1, which transmits integrin growth signals mediated by tumor microenvironment. Although eIF5A-PEAK1 signaling contributes to multiple aggressive cancer cell phenotypes, downstream processes that mediate these responses are uncharacterized. Through proteomics informatic analyses of PEAK1-depleted PDAC cells, we defined protein translation,...
Pancreatic ductal adenocarcinoma (PDAC) has single-digit 5-year survival rates at <7%. There is a dire need to improve pre-malignant detection methods and identify new therapeutic targets for abrogating PDAC progression. To this end, we mined our previously published pseudopodium-enriched (PDE) protein/phosphoprotein datasets novel PDAC-specific biomarkers and/or targets. We discovered that integrin alpha 1 (ITGA1) frequently upregulated in pancreatic cancers associated precursor lesions....
Abstract Three-dimensional (3D) in vitro tumor models that can capture the pathophysiology of human tumors are essential for cancer biology and drug development. However, simulating microenvironment is still challenging because it consists a heterogeneous mixture various cellular components biological factors. In this regard, current extracellular matrix (ECM)-mimicking hydrogels used tissue engineering lack physical interactions keep factors released by encapsulated cells within hydrogel...
Cripto is a developmental oncoprotein and member of the epidermal growth factor-Cripto, FRL-1, Cryptic family extracellular signaling molecules. In addition to having essential functions during embryogenesis, highly expressed in tumors promotes tumorigenesis. During development, acts as an obligate coreceptor for transforming factor beta (TGF-beta) ligands, including nodals, differentiation 1 (GDF1), GDF3. As oncogene, thought promote tumor via mechanisms activation mitogenic pathways...
Little is known about the extracellular signaling factors that govern mammary stem cell behavior. Here, we identify CRIPTO and its cell-surface receptor GRP78 as regulators of behavior in isolated fetal adult epithelial cells. We develop a antagonist promotes differentiation reduces self-renewal cell-enriched populations cultured ex vivo. By contrast, treatment maintains phenotype these cultures yields colonies with enhanced gland reconstitution capacity. Surface expression marks...
Transforming Growth Factor β (TGFβ) has dual functions as both a tumor suppressor and promoter of cancer progression within the microenvironment, but molecular mechanisms by which TGFβ signaling switches between these outcomes contexts in this switch occurs remain to be fully elucidated. We previously identified PEAK1 new non-receptor tyrosine kinase that associates with cytoskeleton, facilitates HER2/Src complexes. also showed downstream KRas promote growth, metastasis therapy resistance...
Reliable approaches to identify stem cell mechanisms that mediate aggressive cancer could have great therapeutic value, based on the growing evidence of embryonic signatures in metastatic cancers. However, how best and target stem-like aberrantly acquired by cells has been challenging. We harnessed power reprogramming examine GRP78, a chaperone protein generally restricted endoplasmic reticulum normal tissues, but which is expressed surface human many types. discovered (1) GRP78 (sGRP78)...
This article refers to:Cripto Binds Transforming Growth Factor β (TGF-β) and Inhibits TGF-β Signaling
SMADs are the canonical intracellular effector proteins of TGF-β (transforming growth factor-β). translocate from plasma membrane receptors to nucleus regulated by many SMAD-interacting through phosphorylation and other post-translational modifications that govern their nucleocytoplasmic shuttling subsequent transcriptional activity. The signaling pathway TGF-β/SMAD exhibits both tumor-suppressing tumor-promoting phenotypes in epithelial-derived solid tumors. Collectively, pleiotropic nature...
CRIPTO (CR-1, TDGF1) is a cell surface/secreted oncoprotein actively involved in development and cancer. Here, we report that high expression of correlates with poor survival stratified risk groups prostate cancer (PCa) patients. its signaling partner glucose-regulated protein 78 (GRP78) are highly expressed PCa metastases display higher levels the metastatic ALDHhigh sub-population PC-3M-Pro4Luc2 cells compared non-metastatic ALDHlow. Coculture osteotropic differentiated primary human...
Breast cancer (BC) is the second leading cause of cancer-related death among women in U.S. Organoid models solid tumors have been shown to faithfully recapitulate aspects progression such as proliferation and invasion. Although patient-derived organoids (PDOs) xenograft (PDXOs) are pathophysiologically relevant, they costly propagate, difficult manipulate comprised primarily most proliferative cell types within tumor microenvironment (TME). These limitations prevent their use for elucidating...