A5088947754- Diabetes and associated disorders
- Pancreatic function and diabetes
- Microtubule and mitosis dynamics
- Cell Adhesion Molecules Research
- Diabetes Management and Research
- Cellular Mechanics and Interactions
- Protist diversity and phylogeny
- Renal and related cancers
- RNA regulation and disease
- Cellular transport and secretion
- Zebrafish Biomedical Research Applications
- Genetic and Kidney Cyst Diseases
- Genomics and Chromatin Dynamics
- Force Microscopy Techniques and Applications
- Platelet Disorders and Treatments
- Protease and Inhibitor Mechanisms
- Monoclonal and Polyclonal Antibodies Research
- Angiogenesis and VEGF in Cancer
- Photosynthetic Processes and Mechanisms
- Glycosylation and Glycoproteins Research
- Endoplasmic Reticulum Stress and Disease
- Nuclear Structure and Function
- Chromosomal and Genetic Variations
- Occupational and environmental lung diseases
- Micro and Nano Robotics
University of Massachusetts Chan Medical School
2009-2024
Duke University
2000-2005
University of Iowa
2005
Duke University Hospital
2000-2001
Duke Medical Center
2000-2001
University of North Carolina at Chapel Hill
1998-2000
KU Leuven
2000
Princeton University
1995
University of Georgia
1989
Primary cilia are nonmotile microtubule structures that assemble from basal bodies by a process called intraflagellar transport (IFT) and associated with several human diseases. Here, we show the centrosome protein pericentrin (Pcnt) colocalizes IFT proteins to base of primary motile cilia. Immunogold electron microscopy demonstrates Pcnt is on or near at depletion RNA interference disrupts body localization cation channel polycystin-2 (PC2), inhibits assembly in epithelial cells....
Type 1 diabetes studies consistently generate data showing islet β-cell dysfunction and T cell–mediated anti-β-cell–specific autoimmunity. To explore the pathogenesis, we interrogated transcriptomes from donors with without type using both bulk-sorted single β-cells. Consistent immunohistological studies, β-cells displayed increased Class I transcripts associated mRNA species. These also expressed for II antigen presentation pathway components, but lacked macrophage marker CD68....
Fibronectin's RGD-mediated binding to the α5β1 integrin is dramatically enhanced by a synergy site within fibronectin III domain 9 (FN9). Guided crystal structure of cell-binding domain, we selected amino acids in FN9 that project same direction as RGD, presumably toward integrin, and mutated them alanine. R1379 peptide PHSRN, nearby R1374 have been shown previously be important for α5β1-mediated adhesion (Aota, S., M. Nomizu, K.M. Yamada. 1994. J. Biol. Chem. 269:24756–24761). Our more...
An important component of muscle elasticity is the PEVK region titin, so named because preponderance these amino acids. However, region, similar to other elastomeric proteins, thought form a random coil and therefore its structure cannot be determined by standard techniques. Here we combine single-molecule electron microscopy atomic force examine conformations human cardiac titin region. In contrast simple coil, have found that shows wide range elastic with end-to-end distances ranging from...
Using an integrated approach to characterize the pancreatic tissue and isolated islets from a 33-year-old with 17 years of type 1 diabetes (T1D), we found that donor contained β cells without insulitis lacked glucose-stimulated insulin secretion despite normal response cAMP-evoked stimulation. With these unexpected findings for T1D, sequenced DNA pathogenic heterozygous variant in gene encoding hepatocyte nuclear factor-1α (HNF1A). In one first studies human disease-causing HNF1A associated...
RNA-seq protocols that focus on transcript termini are well suited for applications in which template quantity is limiting. Here we show that, when applied to end-sequencing data, analytical methods designed global produce computational artifacts. To remedy this, created the End Sequence Analysis Toolkit (ESAT). As a test, first compared and bulk using RNA from dendritic cells stimulated with lipopolysaccharide (LPS). predicted by telescripting model transcriptional bursts, ESAT detected an...
The bacterial cell division protein FtsZ assembles into straight protofilaments, one subunit thick, in which subunits appear to be connected by identical bonds or interfaces. These involve the top surface of making extensive contact with bottom above it. We have investigated this interface site-directed mutagenesis. found nine and eight mutants that were unable function for division. had expected some might poison substoichiometrically, but was not any mutant. Eight exhibited dominant...
We described previously the cell cycle- and microtubule-related functions of two splice isoforms centrosome spindle pole-associated protein (CSPP CSPP-L). Here, we show that endogenous CSPP not only localize to centrosomes midbody in cycling cells but also extend cilia axoneme postmitotic resting cells. They are required for ciliogenesis hTERT-RPE1 vitro expressed ciliated renal, retinal, respiratory vivo. report require their common C-terminal domain interact with Nephrocystin 8...
Previous studies have demonstrated dimerization of intercellular adhesion molecule-1 (ICAM-1) on the cell surface and suggested a role for immunoglobulin superfamily domain 5 and/or transmembrane in mediating such dimerization. Crystallization suggest that 1 may also mediate ICAM-1 binds through to I integrin α<sub>L</sub>β<sub>2</sub> (lymphocyte function-associated antigen 1). Soluble C-terminally dimerized was made by replacing cytoplasmic domains with an α-helical coiled coil. Electron...
Abstract RUNX/AML transcription factors are critical regulators of cell growth and differentiation in multiple lineages have been linked to human cancers including acute myelogenous leukemia (RUNX1), as well breast (RUNX2) gastric (RUNX3). RUNX proteins targeted gene regulatory micro‐environments within the nucleus via a specific subnuclear targeting signal. However, dynamics distribution compartmentalization between cytoplasm is minimally understood. Here we show by immunofluorescence...
Pericentrin is an integral centrosomal component that anchors regulatory and structural molecules to centrosomes. In a yeast two-hybrid screen with pericentrin we identified chromodomain helicase DNA-binding protein 4 (CHD4/Mi2beta). CHD4 part of the multiprotein nucleosome remodeling deacetylase (NuRD) complex. We show many NuRD components interacted by coimmunoprecipitation they localized centrosomes midbodies. Overexpression pericentrin-binding domain or another family member (CHD3)...
// Beatriz Araujo Cortez 1,2 , Paula Rezende Teixeira 1 Sambra Redick 3 Stephen Doxsey and Glaucia Maria Machado-Santelli Depto Biologia Celular e do Desenvolvimento, Instituto de Ciências Biomédicas, Universidade São Paulo, Brasil 2 Genética Evolutiva, Biociências, Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, USA Correspondence to: Cortez, email: Keywords : chrysotile, cytokinesis regression, multipolar mitosis, aneuploidy Received August 31,...
Enteroviral infections are implicated in islet autoimmunity and type 1 diabetes (T1D) pathogenesis. Significant β-cell stress damage occur with viral infection, leading to cells that dysfunctional vulnerable destruction. Human stem cell-derived β (SC-β) insulin-producing cell clusters closely resemble native cells. To better understand the events precipitated by enteroviral infection of cells, we investigated transcriptional proteomic changes SC-β challenged coxsackie B virus (CVB). We...
Viral infections leading to inflammation have been implicated in several common diseases such as Alzheimer&rsquo;s disease (AD) and type 1 diabetes (T1D). Of note, herpes simplex virus (HSV-1) has reported be associated with AD. We sought identify the transcriptomic changes due HSV-1 infection anti-viral drug (acyclovir, ACV) treatment of dissoci-ated cells from human cerebral organoids (dcOrgs) versus stem cell-derived pancreatic islets (sc-islets) gain potential biological insights...
Viral infections leading to inflammation have been implicated in several common diseases, such as Alzheimer’s disease (AD) and type 1 diabetes (T1D). Of note, herpes simplex virus (HSV-1) has reported be associated with AD. We sought identify the transcriptomic changes due HSV-1 infection anti-viral drug (acyclovir, ACV) treatment of dissociated cells from human cerebral organoids (dcOrgs) versus stem cell-derived pancreatic islets (sc-islets) gain potential biological insights into...
ABSTRACT Tenascin, an extracellular matrix protein that modulates cell adhesion, exists as a unique six-armed structure called hexabrachion. The human hexabrachion is composed of six identical 320 kDa subunits and the stabilized by inter-subunit disulfide bonds between amino-terminal segments. We have examined biosynthesis tenascin its assembly into hexabrachions using pulsechase labeling U-138 MG glioma cells. Newly synthesized hexamers are secreted within 60 minutes translation initiation....