Read by QxMD icon Read

Xaralabos Varelas

Paul B Dieffenbach, Christina Mallarino Haeger, Anna Maria F Coronata, Kyoung Moo Choi, Xaralabos Varelas, Daniel J Tschumperlin, Laura E Fredenburgh
Pulmonary arterial stiffness is an independent risk factor for mortality in pulmonary hypertension (PH), and plays a critical role in PH pathophysiology. We have recently demonstrated arterial stiffening early in experimental PH, along with evidence for a mechanobiologic feedback loop by which arterial stiffening promotes further cellular remodeling behaviors. Cyclooxygenase-2 (COX-2) and prostaglandin signaling have been implicated in stiffness-mediated regulation, with prostaglandin activity inversely correlated to matrix stiffness and remodeling behaviors in vitro, as well as to disease progression in rodent PH models...
June 22, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
Aleksander D Szymaniak, Rongjuan Mi, Shannon E McCarthy, Adam C Gower, Taylor L Reynolds, Michael Mingueneau, Maria Kukuruzinska, Xaralabos Varelas
Salivary glands, such as submandibular glands (SMGs), are composed of branched epithelial ductal networks that terminate in acini that together produce, transport and secrete saliva. Here, we show that the transcriptional regulator Yap, a key effector of the Hippo pathway, is required for the proper patterning and morphogenesis of SMG epithelium. Epithelial deletion of Yap in developing SMGs results in the loss of ductal structures, arising from reduced expression of the EGF family member Epiregulin, which we show is required for the expansion of Krt5/Krt14-positive ductal progenitors...
May 11, 2017: ELife
Mohammad Hossein Rohban, Shantanu Singh, Xiaoyun Wu, Julia B Berthet, Mark-Anthony Bray, Yashaswi Shrestha, Xaralabos Varelas, Jesse S Boehm, Anne E Carpenter
We hypothesized that human genes and disease-associated alleles might be systematically functionally annotated using morphological profiling of cDNA constructs, via a microscopy-based Cell Painting assay. Indeed, 50% of the 220 tested genes yielded detectable morphological profiles, which grouped into biologically meaningful gene clusters consistent with known functional annotation (e.g., the RAS-RAF-MEK-ERK cascade). We used novel subpopulation-based visualization methods to interpret the morphological changes for specific clusters...
March 18, 2017: ELife
Amy J Jorgenson, Kyoung Moo Choi, Delphine Sicard, Karry M J Smith, Samantha E Hiemer, Xaralabos Varelas, Daniel J Tschumperlin
Recent studies have implicated the Hippo pathway and its transcriptional effectors YAP and TAZ as necessary for fibroblast activation and tissue fibrosis. To test the specific and sufficient roles for TAZ in driving autonomous fibroblast activation, we cultured NIH3T3 fibroblasts expressing a doxycycline-inducible nuclear-localized mutant of TAZ (TAZ4SA) in scaffold-free 3D hanging drop spheroids, or on matrices of specified mechanical rigidity. Control NIH3T3 fibroblasts formed spheroids in hanging drop culture that remained stable and neither increased nor decreased in size significantly over 15 days...
March 1, 2017: American Journal of Physiology. Cell Physiology
Liye Zhang, Chih-Sheng Yang, Xaralabos Varelas, Stefano Monti
RNA editing is a molecular event that alters specific nucleotides in RNA post-transcriptionally. RNA editing has the potential to impact a variety of cellular processes and is implicated in diseases such as cancer. Yet, the precise mechanisms by which RNA editing controls cellular processes are poorly understood. Here, we characterize sequences altered by RNA editing in patient samples from lymphoma, neuroblastoma and head and neck cancers. We show that A-to-I RNA editing sites are highly conserved across samples of the same tissue type and that most editing sites identified in tumors are also detectable in normal tissues...
March 16, 2016: Scientific Reports
Aleksander D Szymaniak, John E Mahoney, Wellington V Cardoso, Xaralabos Varelas
Epithelial cells undergo dynamic polarity changes as organs pattern, but the relationship between epithelial polarity and cell fate is poorly understood. Using the developing lung as a model, we found that distinct alterations in apical-basal polarity dictate airway epithelial differentiation. We demonstrate that Crb3, a Crumbs isoform that determines epithelial apical domain identity, is required for airway differentiation by controlling the localization of the transcriptional regulator Yap. We show that Crb3 promotes the interaction between Yap and the Hippo pathway kinases Lats1/2 at apical cell junctions to induce Yap phosphorylation and cytoplasmic retention, which drive cell differentiation...
August 10, 2015: Developmental Cell
Samantha E Hiemer, Liye Zhang, Vinay K Kartha, Trevor S Packer, Munirah Almershed, Vikki Noonan, Maria Kukuruzinska, Manish V Bais, Stefano Monti, Xaralabos Varelas
UNLABELLED: Oral squamous cell carcinoma (OSCC) is a prevalent form of cancer that develops from the epithelium of the oral cavity. OSCC is on the rise worldwide, and death rates associated with the disease are particularly high. Despite progress in understanding the mutational and expression landscape associated with OSCC, advances in deciphering these alterations for the development of therapeutic strategies have been limited. Further insight into the molecular cues that contribute to OSCC is therefore required...
June 2015: Molecular Cancer Research: MCR
Masahiro Narimatsu, Payman Samavarchi-Tehrani, Xaralabos Varelas, Jeffrey L Wrana
We and others have shown that the Hippo pathway effectors TAZ and YAP direct Smad activity to regulate TGFβ family-induced cellular responses in stem cell and cancer biology. In polarized epithelial cells we showed that the Crumbs complex promotes Hippo-dependent cytoplasmic TAZ/YAP localization that restricts TGFβ-induced Smad nuclear accumulation and activity. In this Developmental Cell issue, basal-lateral restriction of TGFβ receptors is proposed as the sole mechanism suppressing Smad signaling in epithelial cells...
March 9, 2015: Developmental Cell
Munemasa Mori, John E Mahoney, Maria R Stupnikov, Jesus R Paez-Cortez, Aleksander D Szymaniak, Xaralabos Varelas, Dan B Herrick, James Schwob, Hong Zhang, Wellington V Cardoso
Basal cells are multipotent airway progenitors that generate distinct epithelial cell phenotypes crucial for homeostasis and repair of the conducting airways. Little is known about how these progenitor cells expand and transition to differentiation to form the pseudostratified airway epithelium in the developing and adult lung. Here, we show by genetic and pharmacological approaches that endogenous activation of Notch3 signaling selectively controls the pool of undifferentiated progenitors of upper airways available for differentiation...
January 15, 2015: Development
Xaralabos Varelas, Maria A Kukuruzinska
Cumulative findings from many research groups have identified new signaling mechanisms associated with head and neck cancers. We summarize these findings, including discussion of aberrant NOTCH, PI3K, STAT3, immune recognition, oxidative pathway, and regulation of cell cycle and cell death. The genomic landscape of head and neck cancers has been shown to differ depending on human papillomavirus (HPV) status. We discuss studies examining the integration of HPV into genomic regions, as well as the epigenetic alterations that occur in response to HPV infection, and how these may help reveal new biomarker and treatment predictors...
December 2014: Annals of the New York Academy of Sciences
Fei Liu, David Lagares, Kyoung Moo Choi, Lauren Stopfer, Aleksandar Marinković, Vladimir Vrbanac, Clemens K Probst, Samantha E Hiemer, Thomas H Sisson, Jeffrey C Horowitz, Ivan O Rosas, Laura E Fredenburgh, Carol Feghali-Bostwick, Xaralabos Varelas, Andrew M Tager, Daniel J Tschumperlin
Pathological fibrosis is driven by a feedback loop in which the fibrotic extracellular matrix is both a cause and consequence of fibroblast activation. However, the molecular mechanisms underlying this process remain poorly understood. Here we identify yes-associated protein (YAP) (homolog of drosophila Yki) and transcriptional coactivator with PDZ-binding motif (TAZ) (also known as Wwtr1), transcriptional effectors of the Hippo pathway, as key matrix stiffness-regulated coordinators of fibroblast activation and matrix synthesis...
February 15, 2015: American Journal of Physiology. Lung Cellular and Molecular Physiology
John E Mahoney, Munemasa Mori, Aleksander D Szymaniak, Xaralabos Varelas, Wellington V Cardoso
How epithelial progenitor cells integrate local signals to balance expansion with differentiation during organogenesis is still little understood. Here, we provide evidence that the Hippo pathway effector Yap is a key regulator of this process in the developing lung. We show that when epithelial tubules are forming and branching, a nucleocytoplasmic shift in Yap localization marks the boundary between the airway and the distal lung compartments. At this transition zone, Yap specifies a transcriptional program that controls Sox2 expression and ultimately generates the airway epithelium...
July 28, 2014: Developmental Cell
Xaralabos Varelas, Meghan P Bouchie, Maria A Kukuruzinska
N-Linked glycosylation (N-glycosylation) of proteins has long been associated with oncogenesis, but not until recently have the molecular mechanisms underlying this relationship begun to be unraveled. Here, we review studies describing how dysregulation of the N-glycosylation-regulating gene, DPAGT1, drives oral cancer. DPAGT1 encodes the first and rate-limiting enzyme in the assembly of the lipid-linked oligosaccharide precursor in the endoplasmic reticulum and thus mediates N-glycosylation of many cancer-related proteins...
July 2014: Glycobiology
Xaralabos Varelas
Studies over the past 20 years have defined the Hippo signaling pathway as a major regulator of tissue growth and organ size. Diverse roles for the Hippo pathway have emerged, the majority of which in vertebrates are determined by the transcriptional regulators TAZ and YAP (TAZ/YAP). Key processes regulated by TAZ/YAP include the control of cell proliferation, apoptosis, movement and fate. Accurate control of the levels and localization of these factors is thus essential for early developmental events, as well as for tissue homeostasis, repair and regeneration...
April 2014: Development
Samantha E Hiemer, Aleksander D Szymaniak, Xaralabos Varelas
Uncontrolled transforming growth factor-β (TGFβ) signaling promotes aggressive metastatic properties in late-stage breast cancers. However, how TGFβ-mediated cues are directed to induce tumorigenic events is poorly understood, particularly given that TGFβ has clear tumor suppressing activity in other contexts. Here, we demonstrate that the transcriptional regulators TAZ and YAP (TAZ/YAP), key effectors of the Hippo pathway, are necessary to promote and maintain TGFβ-induced tumorigenic phenotypes in breast cancer cells...
May 9, 2014: Journal of Biological Chemistry
Tobias A Beyer, Alexander Weiss, Yuliya Khomchuk, Kui Huang, Abiodun A Ogunjimi, Xaralabos Varelas, Jeffrey L Wrana
A small toolkit of morphogens is used repeatedly to direct development, raising the question of how context dictates interpretation of the same cue. One example is the transforming growth factor β (TGF-β) pathway that in human embryonic stem cells fulfills two opposite functions: pluripotency maintenance and mesendoderm (ME) specification. Using proteomics coupled to analysis of genome occupancy, we uncover a regulatory complex composed of transcriptional effectors of the Hippo pathway (TAZ/YAP/TEAD), the TGF-β pathway (SMAD2/3), and the pluripotency regulator OCT4 (TSO)...
December 26, 2013: Cell Reports
Steven G Chaulk, Victoria J Lattanzi, Samantha E Hiemer, Richard P Fahlman, Xaralabos Varelas
MicroRNAs (miRNAs) are genome-encoded small double-stranded RNAs that have emerged as key regulators of gene expression and are implicated in most aspects of human development and disease. Canonical miRNA biogenesis involves processing of ∼70-nucleotide pre-miRNA hairpins by Dicer to generate mature ∼22-nucleotide miRNAs, which target complementary RNA sequences. Despite the importance of miRNA biogenesis, signaling mechanisms controlling this process are poorly defined. Here we demonstrate that the post-transcriptional regulation of Dicer is controlled by the cell density-mediated localization of the Hippo pathway effectors TAZ (transcriptional co-activator with PDZ-binding motif) and YAP (Yes-associated protein) (TAZ/YAP)...
January 24, 2014: Journal of Biological Chemistry
Tone B Enger, Arman Samad-Zadeh, Meghan P Bouchie, Kathrine Skarstein, Hilde K Galtung, Toshiyuki Mera, Janice Walker, A Sue Menko, Xaralabos Varelas, Denise L Faustman, Janicke L Jensen, Maria A Kukuruzinska
Sjogren's syndrome (SS) is a complex autoimmune disease that primarily affects salivary and lacrimal glands and is associated with high morbidity. Although the prevailing dogma is that immune system pathology drives SS, increasing evidence points to structural defects, including defective E-cadherin adhesion, to be involved in its etiology. We have shown that E-cadherin has pivotal roles in the development of the mouse salivary submandibular gland (SMG) by organizing apical-basal polarity in acinar and ductal progenitors and by signaling survival for differentiating duct cells...
November 2013: Laboratory Investigation; a Journal of Technical Methods and Pathology
Gangli Liu, Pritam K Sengupta, Basem Jamal, Hsiao-Ying Yang, Meghan P Bouchie, Volkhard Lindner, Xaralabos Varelas, Maria A Kukuruzinska
Oral squamous cell carcinoma (OSCC) is one of the most pernicious malignancies, but the mechanisms underlying its development and progression are poorly understood. One of the key pathways implicated in OSCC is the canonical Wnt/β-catenin signaling pathway. Previously, we reported that canonical Wnt signaling functions in a positive feedback loop with the DPAGT1 gene, a principal regulator of the metabolic pathway of protein N-glycosylation, to hyperglycosylate E-cadherin and reduce intercellular adhesion...
July 12, 2013: Journal of Biological Chemistry
Samantha E Hiemer, Xaralabos Varelas
BACKGROUND: The Hippo pathway coordinates cell proliferation, apoptosis, and differentiation, and has emerged as a major regulator of organ development and regeneration. Central to the mammalian Hippo pathway is the action of the transcriptional regulators TAZ (also known as WWTR1) and YAP, which are controlled by a kinase cascade that is sensitive to mechanosensory and cell polarity cues. SCOPE OF REVIEW: We review recent studies focused on the Hippo pathway in embryonic and somatic stem cell renewal and differentiation...
February 2013: Biochimica et Biophysica Acta
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"