A5067389678- Protease and Inhibitor Mechanisms
- Peptidase Inhibition and Analysis
- RNA modifications and cancer
- Cancer, Hypoxia, and Metabolism
- Prostate Cancer Treatment and Research
- Cancer Cells and Metastasis
- Ion Transport and Channel Regulation
- Metabolomics and Mass Spectrometry Studies
- ATP Synthase and ATPases Research
- Gene expression and cancer classification
- Nutrition, Genetics, and Disease
- Molecular Biology Techniques and Applications
- Microtubule and mitosis dynamics
- Genomics and Chromatin Dynamics
- Epigenetics and DNA Methylation
- Cancer Immunotherapy and Biomarkers
- Immunotherapy and Immune Responses
- Cancer-related Molecular Pathways
- Ferroptosis and cancer prognosis
- Ubiquitin and proteasome pathways
- Cancer-related gene regulation
- Cancer-related molecular mechanisms research
- Cell Adhesion Molecules Research
- S100 Proteins and Annexins
- Cancer Genomics and Diagnostics
University of Notre Dame
2014-2024
Cancer Research Institute
2016-2024
Mike and Josie Harper Cancer Research Institute
2016-2024
Indiana University Health
2019
University of California, San Francisco
2005-2018
Indiana University – Purdue University Indianapolis
2016
Indiana University School of Medicine
2016
Lawrence Berkeley National Laboratory
2012
Stanford University
2012
Howard Hughes Medical Institute
2012
The mitotic kinase Aurora A (Aur-A) is required for formation of a bipolar spindle and accurate chromosome segregation. In somatic cells, Aur-A protein activity levels peak during mitosis, degraded exit. Here, we investigated how are regulated, taking advantage the rapid synchronous cell division cycles Xenopus eggs cell-free systems derived from them. oscillates in early embryonic cycles, just as but constant, indicating that regulated activation inactivation, instead periodic proteolysis,...
The activity of the kinase Aurora-A (Aur-A) peaks during mitosis and depends on phosphorylation by one or more unknown kinases. Mitotic sites were mapped mass spec sequencing recombinant Aur-A protein that had been activated incubation in extracts metaphase-arrested Xenopus eggs. Three identified: serine 53 (Ser-53), threonine 295 (Thr-295), 349 (Ser-349), which are equivalent to Ser-51, Thr-288, Ser-342, respectively, human Aur-A. To ask how these residues might affect activity, each was...
Abstract Prostate cancer is the leading form of in men. tumors often contain neuroendocrine differentiation, which correlates with androgen-independent progression and poor prognosis. Matrix metalloproteinases (MMP), a family enzymes that remodel microenvironment, are associated tumorigenesis metastasis. To evaluate MMPs during metastatic prostatic development, we used transgenic mice expressing SV40 large T antigen their cells, under control transcriptional regulatory elements from mouse...
Abstract Bone is one of the most common sites for metastasis across cancers. Cancer cells that travel through vasculature and invade new tissues can remain in a non-proliferative dormant state years before colonizing metastatic site. Switching from dormancy to colonization rate-limiting step bone metastasis. Here we develop an ex vivo co-culture method grow cancer mouse bones assess cell proliferation using healthy or cancer-primed bones. Profiling soluble factors conditioned media...
Women with dense breasts have an increased lifetime risk of malignancy that has been attributed to a higher epithelial density. Quantitative proteomics, collagen analysis, and mechanical measurements in normal tissue revealed stroma the high-density breast contains more oriented, fibrillar is stiffer correlates cell microRNA (miR) profiling identified miR-203 as matrix stiffness-repressed transcript downregulated by density reduced epithelium women high mammographic Culture studies...
Potassium ion channels are critical in the regulation of cell motility. The acquisition motility is an essential parameter cancer metastasis. However, role K+ metastasis has been poorly studied. High expression hG1 gene, which encodes for Kv11.1 channel associates with good prognosis estrogen receptor-negative breast (BC). We evaluated efficacy activator NS1643 arresting a triple negative (TNBC) mouse model. significantly reduces metastatic spread tumors vivo by inhibiting motility,...
The discoidin domain receptor 1 (DDR1) is overexpressed in breast carcinoma cells. Low DDR1 expression associated with worse relapse-free survival, reflecting its controversial role cancer progression. We detected on luminal cells but not myoepithelial of DDR1+/+ mice. found that loss compromises cell adhesion, consistent data older DDR1-/- mammary glands had more basal/myoepithelial Basal isolated from mice exerted higher traction forces than the cells, agreement increased branches observed...
Cell cycle progression is driven by waves of cyclin expression coupled with regulated protein degradation. An essential step for initiating mitosis the inactivation proteolysis mediated anaphase-promoting complex/cyclosome (APC/C) bound to its regulator Cdh1p/Hct1p. Yeast APCCdh1 was proposed previously be inactivated at Start G1 cyclin/cyclin-dependent kinase (CDK). Here, we demonstrate that in a normal cell graded manner and not extinguished until S phase. Complete requires phase cyclins....
The transcription factor ZNF217 is a candidate oncogene in the amplicon on chromosome 20q13 that occurs 20% to 30% of primary human breast cancers and correlates with poor prognosis. We show Znf217 overexpression drives aberrant differentiation signaling events, promotes increased self-renewal capacity, mesenchymal marker expression, motility, metastasis, represses an adult tissue stem cell gene signature downregulated cancers. By silico screening, we identified therapeutics at low...
Abstract CSN5 has been implicated as a candidate oncogene in human breast cancers by genetic linkage with activation of the poor-prognosis, wound response gene expression signature. is subunit eight-protein COP9 signalosome, signaling complex multiple biochemical activities; mechanism action cancer development remains poorly understood. Here, we show that isopeptidase activity essential for epithelial transformation and progression. Amplification required primary cells defined oncogenes. The...
Breast cancer incidence and mortality vary significantly among different nations racial groups. African have the highest breast rates in world, even though are below those of many nations. Differences disease progression suggest that aggressive tumors may harbor a unique molecular signature to promote progression. However, few studies investigated pathology clinical markers expressed tissue from regional patient populations. We collected 68 malignant 89 non-cancerous samples Kenyan tissue....
The complex yet interrelated connections between cancer metabolism and oncogenic driver genes are relatively unexplored but have the potential to identify novel biomarkers drug targets with prognostic therapeutic value. goal of this study was global metabolic profiles breast tumors isolated from multiple transgenic mouse models unique signatures driven by these oncogenes. Using mass spectrometry (GC-MS, LC-MS/MS, capillary zone electrophoresis (CZE)-MS platforms), we quantified compared...
The ZNF217 gene, encoding a C2H2 zinc finger protein, is located at 20q13 and found amplified overexpressed in greater than 20% of breast tumors. Current studies indicate drives tumorigenesis, yet the regulatory mechanisms are largely unknown. Because associates with chromatin modifying enzymes, we postulate that functions to regulate specific gene signaling networks. Here, present large-scale functional genomic analysis ZNF217, which provides insights into role MCF7 cancer cells. ChIP-seq...
Metabolomics is a powerful systems biology approach that monitors changes in biomolecule concentrations to diagnose and monitor health disease. However, leading metabolomics technologies, such as NMR mass spectrometry (MS), access only small portion of the metabolome. Now an presented uses high sensitivity chemical specificity surface-enhanced Raman scattering (SERS) for online detection metabolites from tumor lysates following liquid chromatography (LC). The results demonstrate this LC-SERS...