A5038692751- Cancer-related Molecular Pathways
- Hippo pathway signaling and YAP/TAZ
- Wnt/β-catenin signaling in development and cancer
- Microtubule and mitosis dynamics
- Cancer-related gene regulation
- Renal and related cancers
- Ubiquitin and proteasome pathways
- Tissue Engineering and Regenerative Medicine
- RNA Research and Splicing
- Epigenetics and DNA Methylation
- Axon Guidance and Neuronal Signaling
- Nuclear Structure and Function
- Peptidase Inhibition and Analysis
- Genetic and Kidney Cyst Diseases
- DNA Repair Mechanisms
- RNA modifications and cancer
- Lymphoma Diagnosis and Treatment
- Antimicrobial Peptides and Activities
- PI3K/AKT/mTOR signaling in cancer
- Invertebrate Immune Response Mechanisms
- RNA Interference and Gene Delivery
- Chromatin Remodeling and Cancer
- Neurofibromatosis and Schwannoma Cases
- Effects and risks of endocrine disrupting chemicals
- Cancer-related molecular mechanisms research
University of North Carolina at Chapel Hill
2020-2025
The University of Texas MD Anderson Cancer Center
2012-2021
The University of Texas Health Science Center at Houston
2017-2021
Massachusetts General Hospital
2010-2012
Harvard University
2010-2012
Center for Cancer Research
2012
University of Pennsylvania
2002-2007
UPMC Hillman Cancer Center
2002-2007
Cancer Research Institute
2002-2007
Pfizer (Canada)
2006
The molecular signals that control the maintenance and activation of liver stem/progenitor cells are poorly understood, role progenitor in hepatic tumorigenesis is unclear. We report here liver-specific deletion neurofibromatosis type 2 (Nf2) tumor suppressor gene developing or adult mouse specifically yields a dramatic, progressive expansion throughout without affecting differentiated hepatocytes. All surviving mice eventually developed both cholangiocellular hepatocellular carcinoma,...
There is increasing evidence that p21<sup>Cip1</sup> and p27<sup>Kip1</sup> are requisite positive regulators of cyclin D1·CDK4 assembly nuclear accumulation. Both Cip Kip proteins can promote accumulation D1, but the underlying mechanism has not been elucidated. We now provide promotes D1 complexes via inhibition export. <i>In vivo</i>, we demonstrate inhibit glycogen synthase kinase 3β-triggered export phosphorylation-dependent nucleocytoplasmic shuttling. Furthermore, find in p21/p27 null...
Significance The control of organ growth involves cell–cell communication that is mediated by signal transduction pathways. Hippo signaling pathway has emerged as an essential regulator size in Drosophila and mammals, defects drive cancer progression. An important unresolved question the field is, How regulated? Recent reports show adherens junctions cell polarity complexes regulate pathway, but controversy exists about mechanisms involved. Here we report mammalian cells, basolateral...
Deregulation of cyclin D1 occurs in numerous human cancers through mutations, alternative splicing, and gene amplification. Although cancer-derived mutants are potent oncogenes vitro vivo, the mechanisms whereby they contribute to neoplasia poorly understood. We now provide evidence derived from both mouse models cells revealing that nuclear accumulation catalytically active mutant D1/CDK4 complexes triggers DNA rereplication, resulting Cdt1 stabilization, which turn damage checkpoint...
The ability to generate asymmetry at the cell cortex underlies polarization and asymmetric division. Here we demonstrate a novel role for tumor suppressor Merlin closely related ERM proteins (Ezrin, Radixin, Moesin) in generating cortical absence of external cues. Our data reveal that functions restrict distribution actin regulator Ezrin, which turn positions interphase centrosome single epithelial cells three-dimensional organotypic cultures. In Merlin, ectopic Ezrin yields mispositioned...
The capacity of the cyclin D-dependent kinase to promote G1 progression through modulation RB·E2F is well documented. We now demonstrate that D1/CDK4 binds components MCM complex. MCM7 and MCM3 were identified as D1-binding proteins. Catalytically active complexes incorporated into chromatin-bound protein with same kinetics MCM3, where they associated specifically MCM7. Although D1-dependent did not phosphorylate MCM7, D1/CDK4, but E/CDK2, catalyze dissociation an RB·MCM7 Finally, expression...
Previously, we discovered a conserved interaction between RB proteins and the Condensin II protein CAP-D3 that is important for ensuring uniform chromatin condensation during mitotic prophase. The Drosophila melanogaster homologs RBF1 dCAP-D3 co-localize on non-dividing polytene chromatin, suggesting existence of shared, non-mitotic role these two proteins. Here, show absence alters expression many same genes in larvae adult flies. Strikingly, most affected by loss are not classic cell cycle...
Endometrial cancer (EC) is a growing public health concern. This secondary data study of case series leveraged existing samples and to explore the potential link between exposure heavy metals/essential elements stage EC. We analyzed urine from women with EC, measuring levels toxic metals (cadmium, mercury, lead) essential (zinc copper). Our findings revealed that higher cadmium, lead are associated more advanced EC stages. Conversely, zinc showed protective effect, potentially mitigating...
Cell adhesion and apicobasal polarity together maintain epithelial tissue organization homeostasis. Loss of has been described as a prerequisite for the to mesenchymal transition. However, what role misregulation promotes tumor initiation and/or early progression remains unclear. We find that human low-grade endometrial cancers are associated with disrupted localization apical protein Par3 Ezrin while, molecule E-cadherin unchanged, accompanied by decreased Notch signaling, altered receptor...
E-cadherin junctions facilitate assembly and disassembly of cell contacts that drive development homeostasis epithelial tissues. In this study, using Xenopus embryonic kidney Madin-Darby canine (MDCK) cells, we investigate the role Wnt/planar polarity (PCP) formin Daam1 (Dishevelled-associated activator morphogenesis 1) in regulating E-cadherin-based intercellular adhesion. Using live imaging, show localizes to newly formed developing nephron. Furthermore, analyses junctional filamentous...
Kidneys are composed of numerous ciliated epithelial tubules called nephrons. Each nephron functions to reabsorb nutrients and concentrate waste products into urine. Defects in primary cilia associated with abnormal formation nephrons cyst a wide range kidney disorders. Previous work Xenopus laevis zebrafish embryos established that loss components make up the Wnt/PCP pathway, Daam1 ArhGEF19 (wGEF) perturb tubulogenesis. Dishevelled, which activates both canonical non-canonical affect...
Abstract The purpose of this work is to test the hypothesis that loss ARID1A promotes endometrial cancer progression by destabilizing tumor cell adherens junctions proteins. ARID1A, an important structural subunit SWI/SNF chromatin remodeling complex, mutated in 26-39% endometrioid tumors. In has been classically linked expression and shown correlate with increasing grade. However, little known about functional impact on progression. A common hallmark aggressive decreased membranous junction...
Abstract The present study aims to understand the mechanisms of mutant β-catenin in endometrial cancer (EC) patients with exon 3 CTNNB1 mutations. Endometrial mutations tend be younger age and have low grades, but they exhibit worse recurrence-free survival than similar clinical characteristics. It is unknown why EC survival. encodes protein β-catenin, which functions primarily at cell membrane adherens junction complex Wnt signaling pathway, where it localizes cytoplasm or nucleus. Exon are...
Abstract The purpose of this study is to identify novel mechanisms immune evasion in mismatch repair deficient endometrial cancers. Despite having a hypermutated phenotype that proposed lead the accumulation many neoantigens for recognition, our group has found cancers characterized by MLH1 protein loss display large variations number tumors infiltrating CD8+ T cells (TILs) across different tumors. To better understand how TILs arise cancers, we utilized human cancer samples from UNCseq...