A5072848206- Sarcoma Diagnosis and Treatment
- Cancer-related gene regulation
- Genomics and Chromatin Dynamics
- Cancer-related molecular mechanisms research
- RNA Interference and Gene Delivery
- RNA modifications and cancer
- Virus-based gene therapy research
- Cancer Cells and Metastasis
- Genetics and Neurodevelopmental Disorders
- NF-κB Signaling Pathways
- Diet, Metabolism, and Disease
- Protein Degradation and Inhibitors
- CAR-T cell therapy research
- Cancer-related Molecular Pathways
- Muscle Physiology and Disorders
- Diet and metabolism studies
- Cancer Genomics and Diagnostics
- Ubiquitin and proteasome pathways
- Liver Disease Diagnosis and Treatment
- Pluripotent Stem Cells Research
- Peptidase Inhibition and Analysis
- Metabolism, Diabetes, and Cancer
- Natural product bioactivities and synthesis
- Adipokines, Inflammation, and Metabolic Diseases
- Tumors and Oncological Cases
The University of Texas Health Science Center at Houston
2017-2024
The University of Texas Health Science Center at San Antonio
2019-2024
Mays Cancer Center at UT Health San Antonio
2024
Longevity Biotech (United States)
2024
Children's Cancer Center
2017-2023
Centre for Cellular and Molecular Biology
2009-2015
Institute for Stem Cell Biology and Regenerative Medicine
2013-2015
Council of Scientific and Industrial Research
2015
National Centre for Biological Sciences
2010
A ketogenic diet (KD) is a high-fat, low-carbohydrate that leads to the generation of ketones. While KDs improve certain health conditions and are popular for weight loss, detrimental effects have also been reported. Here, we show mice on two different and, at ages, induce cellular senescence in multiple organs, including heart kidney. This effect mediated through adenosine monophosphate–activated protein kinase (AMPK) inactivation mouse double minute 2 (MDM2) by caspase-2, leading p53...
Most cells in adult tissues are nondividing. In skeletal muscle, differentiated myofibers have exited the cell cycle permanently, whereas satellite stem withdraw transiently, returning to active proliferation repair damaged myofibers. We examined epigenetic mechanisms operating conditional quiescence by analyzing function of a predicted chromatin regulator mixed lineage leukemia 5 (MLL5) culture model reversible arrest. MLL5 is induced quiescent myoblasts and regulates both differentiation...
Tumor-propagating cells (TPCs) share self-renewal properties with normal stem and drive continued tumor growth. However, mechanisms regulating TPC are largely unknown, especially in embryonal rhabdomyosarcoma (ERMS)-a common pediatric cancer of muscle. Here, we used a zebrafish transgenic model ERMS to identify role for intracellular NOTCH1 (ICN1) increasing TPCs by 23-fold. ICN1 expanded enabling the de-differentiation into self-renewing myf5+ TPCs, breaking rigid differentiation...
Rhabdomyosarcoma (RMS) is an aggressive pediatric malignancy of the muscle, that includes Fusion Positive (FP)-RMS harboring PAX3/7-FOXO1 and Negative (FN)-RMS commonly with RAS pathway mutations. RMS express myogenic master transcription factors MYOD MYOG yet are unable to terminally differentiate. Here, we report SNAI2 highly expressed in FN-RMS, oncogenic, blocks differentiation, promotes growth. activates via super enhancers striped 3D contact architecture. Genome wide chromatin binding...
Acetyl-CoA synthetase short-chain family member 1 (ACSS1) uses acetate to generate mitochondrial acetyl-CoA and is regulated by deacetylation sirtuin 3. We generated an ACSS1-acetylation (Ac) mimic mouse, where lysine-635 was mutated glutamine (K635Q). Male Acss1 K635Q/K635Q mice were smaller with higher metabolic rate blood decreased liver/serum ATP lactate levels. After a 48-hour fast, presented hypothermia liver aberrations, including enlargement, discoloration, lipid droplet...
Most cells in adult mammals are non-dividing: differentiated exit the cell cycle permanently, but stem exist a state of reversible arrest called quiescence. In damaged skeletal muscle, quiescent satellite re-enter cycle, proliferate and subsequently execute divergent programs to regenerate both post-mitotic myofibers cells. The molecular basis for these alternative is poorly understood. this study, we used an established myogenic culture model (C2C12 myoblasts) generate states investigate...
Adult stem cell quiescence is critical to ensure regeneration while minimizing tumorigenesis. Epigenetic regulation contributes cycle control and differentiation, but few regulators of the chromatin state in quiescent cells are known. Here we report that tumor suppressor PRDM2/RIZ, an H3K9 methyltransferase, enriched muscle invivo controls reversible cultured myoblasts. We find PRDM2 associates with >4400 promoters G0 myoblasts, 55% which also marked H3K9me2 for myogenic, developmental...
In embryonal rhabdomyosarcoma (ERMS) and generally in sarcomas, the role of wild-type loss- or gain-of-function TP53 mutations remains largely undefined. Eliminating mutant restoring p53 is challenging; nevertheless, understanding variant effects on tumorigenesis central to realizing better treatment outcomes. ERMS, >70% patients retain TP53, yet when present are associated with worse prognosis. Employing a kRASG12D-driven ERMS tumor model tp53 null (tp53-/-) zebrafish, we define...
Rhabdomyosarcoma (RMS) is a pediatric soft tissue cancer with lack of precision therapy options for patients. We hypothesized that general paucity known mutations in RMS, chromatin structural driving mechanisms are essential tumor proliferation. Thus, we carried out high-depth
Abstract Rhabdomyosarcomas (RMS) are pediatric mesenchymal-derived malignancies encompassing PAX3/7-FOXO1 Fusion Positive (FP)-RMS, and Negative (FN)-RMS with frequent RAS pathway mutations. RMS express the master myogenic transcription factor MYOD that, whilst essential for survival, cannot support differentiation. Here we discover SKP2, an oncogenic E3-ubiquitin ligase, as a critical pro-tumorigenic driver in FN-RMS. We show that SKP2 is overexpressed through binding of to intronic...
Abstract Ionizing radiation (IR) and chemotherapy are mainstays of treatment for patients with rhabdomyosarcoma, yet the molecular mechanisms that underlie success or failure radiotherapy remain unclear. The transcriptional repressor SNAI2 was previously identified as a key regulator IR sensitivity in normal malignant stem cells through its repression proapoptotic BH3-only gene PUMA/BBC3. Here, we demonstrate clear correlation between expression levels radiosensitivity across multiple...
Abstract Rhabdomyosarcoma (RMS) is a tumor of the muscle and most common soft tissue cancer in children teens, with approximately 400 to 500 new cases every year United States. While we have good understanding interplay between pro- anti-apoptotic regulators, much remains be learned about how decision trigger apoptosis or not controlled at transcriptional level RMS tumors. We strive elucidate pathways that drive avoidance are epi-genetically pre-programmed cells. discovered SNAI2, repressor,...
Rhabdomyosarcoma (RMS) is a pediatric malignancy of the muscle with characteristics cells blocked in differentiation. NOTCH1 an oncogene that promotes self-renewal and blocks differentiation fusion negative-RMS sub-type. However, how expression transcriptionally maintained tumors unknown. Analyses SNAI2 CTCF chromatin binding HiC analyses revealed conserved SNAI2/CTCF overlapping peak downstream locus marking sub-topologically associating domain (TAD) boundary. Deletion SNAI2-CTCF showed it...
<div>Abstract<p>Ionizing radiation (IR) and chemotherapy are mainstays of treatment for patients with rhabdomyosarcoma, yet the molecular mechanisms that underlie success or failure radiotherapy remain unclear. The transcriptional repressor SNAI2 was previously identified as a key regulator IR sensitivity in normal malignant stem cells through its repression proapoptotic BH3-only gene <i>PUMA/BBC3</i>. Here, we demonstrate clear correlation between expression levels...
<p>Materials and Methods used for experiments in Supplemental Figures References</p>
<p>Supplementary Figures S1-S9</p>
<p>Supplementary Figures S1-S9</p>
<p>Materials and Methods used for experiments in Supplemental Figures References</p>
<p>Supplementary Materials, Methods, and References</p>
Abstract Rhabdomyosarcoma (RMS) is tumor of the muscle and most common soft tissue cancer in children teens, with approximately 400 to 500 new cases every year United States. There are two main subtypes rhabdomyosarcoma: 1) Alveolar rhabdomyosarcoma (fusion-positive RMS FP-RMS), classified primarily by presence fusion between PAX3/PAX7 FOXO1 proteins. 2) Embryonal (fusion-negative FN-RMS) more subtype. The survival rate for patients 70%, but at relapse it less than 30%. standard care this...