A5025408937- Sarcoma Diagnosis and Treatment
- Musculoskeletal synovial abnormalities and treatments
- Soft tissue tumors and treatment
- Protein Degradation and Inhibitors
- Ear and Head Tumors
- Peptidase Inhibition and Analysis
- Ubiquitin and proteasome pathways
- Tumors and Oncological Cases
- Bone Tumor Diagnosis and Treatments
- Neuroendocrine Tumor Research Advances
- Cancer-related molecular mechanisms research
- Lung Cancer Research Studies
- Photonic and Optical Devices
- Multiple Myeloma Research and Treatments
- Histiocytic Disorders and Treatments
- Neuroblastoma Research and Treatments
- Power Systems Fault Detection
- Cancer, Hypoxia, and Metabolism
- Virus-based gene therapy research
- Cardiac tumors and thrombi
- FOXO transcription factor regulation
- Chemokine receptors and signaling
- Urologic and reproductive health conditions
- Metabolism, Diabetes, and Cancer
- Neurofibromatosis and Schwannoma Cases
Tulane University
2018-2024
University of California, Los Angeles
2023-2024
APLA Health
2024
Neuroendocrine carcinomas, such as neuroendocrine prostate cancer and small-cell lung cancer, commonly have a poor prognosis limited therapeutic options. We report that ubiquitin carboxy-terminal hydrolase L1 (UCHL1), deubiquitinating enzyme, is elevated in tissues plasma from patients with carcinomas. Loss of UCHL1 decreases tumor growth inhibits metastasis these malignancies. maintains differentiation promotes progression by regulating nucleoporin, POM121, p53. binds, deubiquitinates,...
Abstract Desmoplastic small round cell tumors (DSRCT) are a type of aggressive, pediatric sarcoma characterized by the EWSR1::WT1 fusion oncogene. Targeted therapies for DSRCT have not been developed, and standard multimodal therapy is insufficient, leading to 5-year survival rate only 15% 25%. Here, we depleted in established its essentiality vivo. Transcriptomic analysis revealed that induces unique transcriptional alterations compared with WT1 other oncoproteins binding directly mediates...
Abstract Purpose: Desmoplastic small round cell tumor (DSRCT) is a highly lethal intra-abdominal sarcoma of adolescents and young adults. DSRCT harbors t(11;22)(p13:q12) that generates the EWSR1-WT1 chimeric transcription factor, key oncogenic driver DSRCT. rewires global gene expression networks activates aberrant targets together mediate oncogenesis. also neural program. Experimental Design: Among these markers, we found prominent neurotrophic tyrosine kinase receptor 3 (NTRK3), druggable...
Desmoplastic Small Round Cell Tumor (DSRCT) is a rare and aggressive malignant cancer caused by chromosomal translocation t(11;22)(p13;q12) that produces an oncogenic transcription factor, EWSR1-WT1. EWSR1-WT1 essential for the initiation progression of DSRCT. However, precise mechanism which drives DSRCT oncogenesis remains unresolved. Through our integrative gene expression analysis, we identified Salt Inducible Kinase 1 (SIK1) as direct target SIK1 member AMPK related kinase involved in...
Abstract Desmoplastic Small Round Cell Tumor (DSRCT) is a rare, pediatric cancer caused by the EWSR1::WT1 fusion protein. DSRCT predominantly occurs in males, which comprise 80-90% of patient population. While reason for this male predominance remains unknown, one hypothesis that androgen receptor (AR) plays critical role and elevated testosterone levels males help drive tumor growth. Here, we demonstrate AR highly expressed relative to other fusion-driven sarcomas antagonists enzalutamide...
Background & AimsDiminished forkhead box O3 (FOXO3) function drives inflammation and cancer growth; however, mechanisms fostering these pathobiologies are unclear. Here, we aimed to identify in colon loss of FOXO3-dependent cellular molecular changes that facilitate inflammation-mediated tumor growth.MethodsFOXO3 knockout (KO) wild-type (WT) mice were used the AOM/DSS model cancer. Bioinformatics for profiling mRNA sequencing data from human mouse tumors; specific targets validated cells...
Obesity is associated with poorer responses to chemo- and radiation therapy for breast cancer, which leads higher mortality rates obese women who develop cancer. Adipose stem cells (ASCs) are an integral stromal component of the tumor microenvironment (TME). In this study, effects obesity-altered ASCs (obASCs) on estrogen receptor positive cancer cell’s (ER+BCCs) response radiotherapy (RT) were evaluated. We determined that BCCs had a decreased apoptotic index increased surviving fraction...
Abstract Obesity is a worldwide epidemic associated with increased risk and progression of colon cancer. Here, we aimed to determine the role adipose triglyceride lipase (ATGL), responsible for intracellular lipid droplet (LD) utilization, in obesity-driven colonic tumorigenesis. In local cancer patients, significantly ATGL levels tumor tissue, compared controls, were augmented obese individuals. Elevated human cells (CCC) relative non-transformed by an obesity mediator, oleic acid (OA). CCC...
Desmoplastic small round cell tumor (DSRCT) is characterized by the t(11;22)(p13;q12) translocation, which fuses transcriptional regulatory domain of EWSR1 with DNA-binding WT1, resulting in oncogenic EWSR1-WT1 fusion protein. The paucity DSRCT disease models has hampered preclinical therapeutic studies on this aggressive cancer. Here, we developed and mined expression profiles to identify genetic vulnerabilities that could be leveraged for new therapies. We describe four lines one...
Desmoplastic small round cell tumor (DSRCT) is a rare pediatric cancer caused by the EWSR1-WT1 fusion oncogene. Despite initial response to chemotherapy, DSRCT has recurrence rate of over 80% leading poor patient prognosis with 5-year survival only 15–25%. Owing rarity DSRCT, sample scarcity barrier in understanding biology and developing effective therapies. Utilizing novel pair primary recurrent DSRCTs, we present first map genomic breakpoints comparison gene expression alterations between...
Desmoplastic Small Round Cell Tumor (DSRCT) is a rare and aggressive pediatric cancer driven by the EWSR1-WT1 fusion oncogene. Combinations of chemotherapy, radiation surgery are not curative, 5-years survival rate less than 25%. One potential explanation for refractoriness existence stem cell (CSC) subpopulation able escape current treatment modalities. However, no study to-date has examined role CSCs in DSRCT or established vitro culture conditions to model this subpopulation. In study, we...
Abstract Desmoplastic small round cell tumor (DSRCT) is an aggressive pediatric cancer caused by the EWSR1-WT1 fusion oncoprotein. The refractory to treatment with a 5-year survival rate of only 15–25%, necessitating development novel therapeutics, especially those able target chemoresistant subpopulations. Novel in vitro stem cell-like (CSC-like) culture conditions increase expression stemness markers (SOX2, NANOG) and reduce DSRCT line susceptibility chemotherapy while maintaining ability...
Abstract Background Neuroendocrine phenotype is commonly associated with therapy resistance and poor prognoses in small-cell neuroendocrine cancers (SCNCs), such as prostate cancer (NEPC) lung (SCLC). Expression levels of current markers exhibit high case-by-case variability, so multiple are used combination to identify SCNCs. Here, we report that ACAA2 elevated SCNCs a potential molecular indicator for Methods expressions tumour xenografts, tissue microarrays (TMAs), patient tissues from...
Abstract Desmoplastic small round cell tumor (DSRCT) is characterized by the t(11;22)(p13;q12) chromosomal translocation, which fuses transcriptional regulatory domain of EWSR1 with zinc finger DNA-binding WT1 , resulting in oncogenic transcription factor EWS-WT1. DSRCT primarily affects young males and has a 5-year overall survival about 15%. Typical treatment approaches for patients involve multi-modal combination surgery, chemotherapy radiation. The paucity disease models hampered...
Abstract Neuroendocrine carcinomas, such as neuroendocrine prostate cancer (NEPC), small cell lung (SCLC), and neuroblastoma, share common histological features, including expression of markers, rapid relapse after treatment, poor prognosis. Due to the clinical outcome patients with there is a critical need identify new drivers, therapeutic targets, effective strategies for these malignancies. Ubiquitin carboxy-terminal hydrolase L1 (UCHL1) protease that has dual function in regulating...
Abstract The G-protein-coupled chemokine receptor (GPCR), CXCR4, is ubiquitously expressed in malignant tumor tissues, and controls migration other survival mechanisms upon interaction with its agonist, stromal cell-derived 1α (SDF1α). CXCR4/SDF1α axis relevant to shaping the microenvironment mainly metastatic spread of primary tumors distal organs immune response; thus, expression CXCR4 vital aggressiveness, probability, metastasis-associated mortality. signals through a homodimer, but also...
Abstract Desmoplastic small round cell tumor (DSRCT) is an aggressive, pediatric cancer caused by the EWSR1-WT1 fusion oncoprotein. Targeted therapies are lacking and current standard of care, multimodal therapy, insufficient, leading to a 5-year survival rate less than 25%. While oncoprotein critical growth in vitro, its importance has yet be examined vivo. Further, set downstream targets oncogenesis mechanism which two isoforms regulate them remain underinvestigated. Here we generate...
Abstract Prostate cancer is estimated to contribute over 34,000 deaths in men residing the United States, with majority fatality due metastatic disease. CDC7 a kinase that regulates DNA replication and an emerging biomarker for poor prognosis carcinomas such as Wilms tumor hepatocellular carcinomas. In this study, we demonstrated high level of associated prostate when compared benign tissues or localized cancer. Furthermore, found expression highest patient-derived xenografts (PDX) models...
<div>Abstract<p>Desmoplastic small round cell tumors (DSRCT) are a type of aggressive, pediatric sarcoma characterized by the EWSR1::WT1 fusion oncogene. Targeted therapies for DSRCT have not been developed, and standard multimodal therapy is insufficient, leading to 5-year survival rate only 15% 25%. Here, we depleted in established its essentiality <i>in vivo</i>. Transcriptomic analysis revealed that induces unique transcriptional alterations compared with WT1...
<p>EWSR1::WT1 Upregulated Pathways</p>
<p>Supplementary Figures and Tables</p>
<p>EWSR1::WT1 Downregulated Pathways</p>
<div>Abstract<p>Desmoplastic small round cell tumors (DSRCT) are a type of aggressive, pediatric sarcoma characterized by the EWSR1::WT1 fusion oncogene. Targeted therapies for DSRCT have not been developed, and standard multimodal therapy is insufficient, leading to 5-year survival rate only 15% 25%. Here, we depleted in established its essentiality <i>in vivo</i>. Transcriptomic analysis revealed that induces unique transcriptional alterations compared with WT1...
<p>Supplementary Figures and Tables</p>
<p>EWSR1::WT1 Downregulated Pathways</p>