A5084674340- Developmental Biology and Gene Regulation
- Epigenetics and DNA Methylation
- Genomics and Chromatin Dynamics
- Salivary Gland Tumors Diagnosis and Treatment
- RNA modifications and cancer
- Cancer-related gene regulation
- Lung Cancer Treatments and Mutations
- Genetic factors in colorectal cancer
- Neuroblastoma Research and Treatments
- Cancer-related molecular mechanisms research
- Ubiquitin and proteasome pathways
- Cancer-related Molecular Pathways
- RNA Research and Splicing
- Histone Deacetylase Inhibitors Research
- Ear and Head Tumors
- Hippo pathway signaling and YAP/TAZ
- Reproductive System and Pregnancy
- Inflammatory mediators and NSAID effects
- MicroRNA in disease regulation
- Acute Myeloid Leukemia Research
- Muscle Physiology and Disorders
- Chromatin Remodeling and Cancer
- Kruppel-like factors research
- Neonatal Respiratory Health Research
- Nuclear Structure and Function
University of Florida
2014-2025
University of Florida Health
2012-2024
Florida College
2015-2024
Laboratory of Molecular Genetics
2011-2021
Institute of Genetics
2018-2021
UF Health Cancer Center
2013-2021
Scripps Research Institute
2014
Moffitt Cancer Center
2014
University of South Florida
2014
University of North Carolina at Chapel Hill
2014
The LKB1 tumor suppressor gene is frequently mutated and inactivated in non-small cell lung cancer (NSCLC). Loss of promotes progression influences therapeutic responses preclinical studies; however, specific targeted therapies for with inactivation are currently unavailable. Here, we have identified a long noncoding RNA (lncRNA) signature that associated the loss function. We discovered LINC00473 consistently most highly induced LKB1-inactivated human primary NSCLC samples derived lines....
Abstract Faithful genome integrity maintenance plays an essential role in cell survival. Here, we identify the RNA demethylase ALKBH5 as a key regulator that protects cells from DNA damage and apoptosis during reactive oxygen species (ROS)-induced stress. We find ROS significantly induces global mRNA N6-methyladenosine (m6A) levels by modulating post-translational modifications (PTMs), leading to rapid efficient induction of thousands genes involved variety biological processes including...
ABSTRACT Cell-cell interactions mediated by Notch and its ligands are known to effect many cell fate decisions in both invertebrates vertebrates. However, the mechanisms involved ligand induced activation unknown. Recently it was shown that, at least some cases, endocytosis of extracellular domain signaling is required for signal induction receptive cell. These results imply that soluble (ligand domains) although capable binding would be unlikely activate it. To test potential activity...
The molecular mechanisms by which Notch receptors induce diverse biological responses are not fully understood. We recently cloned a mammalian homologue of the Mastermind gene Drosophila melanogaster, MAML1 (Mastermind-like-1 molecule) and determined that it functions as transcriptional coactivator for receptors. In this report, we characterize two additional genes in Mastermind-like family: MAML2 MAML3. three MAML widely expressed adult tissues but exhibit distinct expression patterns mouse...
The receptor tyrosine kinase/PI3K/AKT/mammalian target of rapamycin (RTK/PI3K/AKT/mTOR) pathway is frequently altered in cancer, but the underlying mechanism leading to tumorigenesis by activated mTOR remains less clear. Here we show that a positive regulator Notch signaling mouse and human cells, acting through induction STAT3/p63/Jagged cascade. Furthermore, response differential cues from mTOR, found served as molecular switch shift balance between cell proliferation differentiation. We...
The MAML (mastermind-like) proteins are a family of three co-transcriptional regulators that essential for Notch signaling, pathway critical cell fate determination. Though the functions in normal development remain unresolved, their distinct tissue distributions and differential activities cooperating with various receptors suggest they have unique roles. Here we show mice targeted disruption Maml1 gene severe muscular dystrophy. In vitro, Maml1-null embryonic fibroblasts failed to undergo...
Glioblastoma (GBM) is the most common malignant brain tumor that characterized by high proliferative rate and invasiveness. Since dysregulation of Notch signaling implicated in pathogenesis many human cancers, here we investigated role GBM. We found there aberrant activation GBM cell lines GBM-derived neurospheres. Inhibition via expression a dominant negative form coactivator, mastermind-like 1 (DN-MAML1), or treatment γ-secretase inhibitor, (GSI) MRK-003, resulted significant reduction...
The histone demethylase LSD1 facilitates epithelial-to-mesenchymal transition (EMT) and tumor progression by repressing epithelial marker expression. However, little is known about how its function may be modulated. Here, we report that acetylated in but not mesenchymal cells. Acetylation of reduces association with nucleosomes, thus increasing H3K4 methylation at target genes activating transcription. MOF acetyltransferase interacts responsible for acetylation. preferentially expressed...
Carcinoma cells can acquire increased motility and invasiveness through epithelial-to-mesenchymal transition (EMT). However, the significance of EMT in cancer metastasis has been controversial, exact fates functions vivo remain inadequately understood. Here, we tracked epithelial that underwent inducible or spontaneous various tumor transplantation models. Unlike cells, majority were specifically located perivascular space closely associated with blood vessels. markedly activated multiple...
No effective systemic treatment is available for patients with unresectable, recurrent, or metastatic mucoepidermoid carcinoma (MEC), the most common salivary gland malignancy. MEC frequently associated a t(11;19)(q14-21;p12-13) translocation that creates CRTC1-MAML2 fusion gene. The exhibited transforming activity in vitro; however, whether it serves as an oncogenic driver establishment and maintenance vivo remains unknown. Here, we show doxycycline-induced knockdown blocked growth of...
Intracellular inclusions are a unifying feature of polyglutamine (polyQ) neurodegenerative diseases, yet each polyQ disease displays unique pattern neuronal degeneration. This implies that the protein context expanded plays an important role in establishing selective neurotoxicity. Here, studies spinocerebellar ataxia type 3 ataxin-3, we demonstrate sequence surrounding specifies constituents nuclear (NI) formed by protein. The proteins cAMP response element-binding protein-binding (CBP) and...
Members of the evolutionarily conserved Mastermind (MAM) protein family, including three related mammalian Mastermind-like (MAML) proteins MAML1-3, function as crucial coactivators Notch-mediated transcriptional activation. Given recent evidence cross-talk between p53 and Notch signal transduction pathways, we have investigated whether MAML1 may also be a coactivator p53. Indeed, show here that is able to interact with We MAML1-p53 interaction involves N-terminal region DNA-binding domain...