A5005213120- RNA modifications and cancer
- Epigenetics and DNA Methylation
- MicroRNA in disease regulation
- Estrogen and related hormone effects
- Cancer-related gene regulation
- Advanced Breast Cancer Therapies
- Ubiquitin and proteasome pathways
- Mitochondrial Function and Pathology
- PARP inhibition in cancer therapy
- Computational Drug Discovery Methods
- RNA Research and Splicing
- GDF15 and Related Biomarkers
- HER2/EGFR in Cancer Research
- Prostate Cancer Treatment and Research
- Bioinformatics and Genomic Networks
- Chemical Synthesis and Analysis
- Cancer Genomics and Diagnostics
- Endometriosis Research and Treatment
- Folate and B Vitamins Research
- Beetle Biology and Toxicology Studies
- Lipid metabolism and biosynthesis
- Kruppel-like factors research
- Histone Deacetylase Inhibitors Research
- Protein Degradation and Inhibitors
- Biotin and Related Studies
Georgetown University
2020-2025
Georgetown University Medical Center
2020-2025
University of Houston
2016-2021
The University of Texas MD Anderson Cancer Center
2017
University of Graz
2013
Alexandria University
2012
PURPOSE Current precision medicine (CPM) matches patients to therapies using traditional biomarkers, but inevitably resistance develops. Dynamic (DPM) is a new evolutionary guided (EGPM) approach undergoing translational development. It tracks intratumoral genetic heterogeneity and dynamics, adapts as frequently every 6 weeks, plans proactively for future development, incorporates multiple therapeutic agents. Simulations indicated DPM can significantly improve long-term survival cure rates...
Abstract Background Resistance to endocrine therapy in estrogen receptor–positive (ER+) breast cancer remains a significant clinical problem. Riluzole is FDA-approved for the treatment of amyotrophic lateral sclerosis. A benzothiazole-based glutamate release inhibitor with several context-dependent mechanism(s) action, riluzole has shown antitumor activity multiple malignancies, including melanoma, glioblastoma, and cancer. We previously reported that acquisition tamoxifen resistance...
Wnt ligand WNT4 is critical in female reproductive tissue development, with dysregulation linked to related pathologies including breast cancer (invasive lobular carcinoma, ILC) and gynecologic cancers. signaling these contexts distinct from canonical yet inadequately understood. We previously identified atypical intracellular activity of (independent secretion) regulating mitochondrial function, herein examine functions WNT4. further how convergent mechanisms impact metabolism. In ILC,...
SUMO post-translational modification of proteins or SUMOylation ensures normal cell function. Disruption dynamics prompts various pathophysiological conditions, including cancer. The burden deSUMOylating the large SUMO-proteome rests on 6 full-length mammalian SUMO-proteases SENP. While multiple SENP isoforms exist, function these remains undefined. We now delineate biological role a novel SENP7 isoform SENP7S in mammary epithelial cells. is predominant transcript human epithelia but...
// Feng-Ming Lin 1 , Santosh Kumar 2 Jing Ren Samaneh Karami Shaymaa Bahnassy Yue Li 3 Xiaofeng Zheng 4 Wang and Tasneem Bawa-Khalfe Department of Cardiology, The University Texas MD Anderson Cancer Center, Houston, TX, USA Center for Nuclear Receptors Cell Signaling, Biology Biochemistry, Integrative Pharmacology, Health Science at Bioinformatics Computational Biology, Correspondence to: Bawa-Khalfe, email: Keywords : SUMO, SENP7, HP1α, ncRNA, Rad51C Received March 31, 2016 Accepted April...
Abstract Background Hormone receptor positive (HR+) breast cancer (BCa) is the most frequently diagnosed subtype. Acquired and intrinsic resistance to conventional endocrine therapy (ET) commonly occurs prompts incurable metastatic disease. Hence, ET-resistant (ET-R) HR+ BCa presents a therapeutic challenge. Previous studies show elevated androgen (AR) that supports ET tamoxifen correlates with metastasis. Yet surprisingly, AR-blocker enzalutamide (Enz) in ET-R present conflicting results....
Breast tumors overexpressing human epidermal growth factor receptor (HER2) confer intrinsic resistance to endocrine therapy (ET), and patients with HER2/estrogen receptor-positive (HER2+/ER+) breast cancer (BCa) are less responsive ET than HER2-/ER+. However, real-world evidence reveals that a large subset of HER2+/ER+ receive as monotherapy, positioning this treatment pattern clinical challenge. In the present study, we developed characterized 2 in vitro models ET-resistant (ETR) BCa...
Abstract Preclinical model systems are essential research tools that help us understand the biology of invasive lobular carcinoma breast (ILC). The number well-established ILC models is increasing but remain limited. Lower incidence ILC, underrepresentation patients with in clinical trials, and intrinsic tumor characteristics all contribute to this challenge. Hence, there significant need continually develop better recapitulate biology, genetics, histology, empower preclinical therapeutic...
<div>Abstract<p>Wnt ligand WNT4 is critical in female reproductive tissue development, with <i>WNT4</i> dysregulation linked to related pathologies including breast cancer (invasive lobular carcinoma, ILC) and gynecologic cancers. signaling these contexts distinct from canonical Wnt yet inadequately understood. We previously identified atypical intracellular activity of (independent secretion) regulating mitochondrial function, herein examine functions WNT4. further...
<p>WNT4 overexpression rescues some metabolic effects of ER:WNT4 pathway inhibition. <b>A,</b> Small-molecule inhibitor targets in current model signaling pathway. <b>B,</b> Meta-analysis parental MM134 cells versus WNT4-OE across drug treatment series (i.e., WNT4 effect controlled for effect) identifies <i>n</i> = 71 metabolite levels altered by overexpression. Green overlap with siWNT4 dysregulated metabolites. <b>C,</b> Overall changes...
<p>RPPA networks in full cohort dataset</p>
<p>RPPA dataset clustering</p>
<p>WNT4 variant genotype is associated with active WNT4 signaling and metabolic remodeling in ovarian cancer cells. <b>A,</b> Left, Proliferation assessed by dsDNA quantification 6 days post-transfection siRNA (siNT = non-targeting control pool). Bars represent mean of biological replicates ± SD; *, <i>P</i> < 0.05, siWNT4 versus siNT, <i>t</i> test Welch correction. WT Var model comparison fold changes for siNT. Right, <i>WNT4</i>...
<p>Metabolic effects of WNT4 knockdown mirror ER but have expanded impact on fatty acid and amino metabolic pathways. <b>A,</b> Metabolite levels altered by (<i>n</i> = 77); pink text indicates a shared affected metabolite with knockdown. <b>B,</b> Metabolites dysregulated versus are strongly enriched for overlap. <b>C,</b> directly correlated, suggesting an overall parallel effect ILC cell metabolism. <b>D,</b> Pathway...
<p>ILC tumor metabolic gene expression</p>
<p>Cell line rs3820282 genotyping</p>
<p>Mass spectrometry methods supplement</p>
<p>Full RPPA dataset and analyses</p>
<p>BioID supports WNT4 localization to the mitochondria. <b>A,</b> Proteins enriched in HT1080 Wnt-BirA versus parental cells lacking BirA construct expression. <b>B,</b> Overlap of proteins identified (A) HT1080-PKO and MM134 identifies <i>n</i> = 72 “high-confidence” WNT4-associated proteins. <b>C,</b> Gene ontology analysis for cellular compartment WNT3A- Dashed line 1.3 (<i>P</i> 0.05). <b>D,</b> Network via...
<p>ER regulates glycolysis, oxidative phosphorylation, and fatty acid metabolism in ILC cells. <b>A,</b> Overall metabolomics study design MDA MB 134VI cells; all samples biological triplicate. <b>B,</b> Joint analysis of transcriptome + metabolome data identifies dysregulated pathways after ER knockdown. Transcriptome from GSE171364. <b>C,</b> Metabolites levels altered by knockdown (left, <i>n</i> = 63), with gene expression changes...
<p>WNT4 knockdown impairs respiration but not glycolysis. <b>A,</b> Seahorse MitoStress test in MM134. Points represent mean of 6 biological replicates ± SD. <b>B,</b> Basal is reduced by ER or WNT4 knockdown, respiratory capacity. <b>C,</b> suppresses OCR, that is, (from B), has a minimal effect on ECAR, <b>D,</b> From metabolomics data, cellular lactic acid levels are knockdown. B–D, comparisons ANOVA with Dunnett correction. *,...
<p>WNT4 knockdown impairs respiration but not glycolysis. <b>A,</b> Seahorse MitoStress test in MM134. Points represent mean of 6 biological replicates ± SD. <b>B,</b> Basal is reduced by ER or WNT4 knockdown, respiratory capacity. <b>C,</b> suppresses OCR, that is, (from B), has a minimal effect on ECAR, <b>D,</b> From metabolomics data, cellular lactic acid levels are knockdown. B–D, comparisons ANOVA with Dunnett correction. *,...
<p>Metabolomics datasets and siRNA analyses</p>
<p>Metabolic effects of WNT4 knockdown mirror ER but have expanded impact on fatty acid and amino metabolic pathways. <b>A,</b> Metabolite levels altered by (<i>n</i> = 77); pink text indicates a shared affected metabolite with knockdown. <b>B,</b> Metabolites dysregulated versus are strongly enriched for overlap. <b>C,</b> directly correlated, suggesting an overall parallel effect ILC cell metabolism. <b>D,</b> Pathway...