Publications by authors named "Joshua V Pondick"

9 Publications

  • Page 1 of 1

Heterointerface Effects on Lithium-Induced Phase Transitions in Intercalated MoS.

ACS Appl Mater Interfaces 2021 Mar 17;13(8):10603-10611. Epub 2021 Feb 17.

Department of Mechanical Engineering and Materials Science, Yale University, New Haven, Connecticut 06511, United States.

The intercalation-induced phase transition of MoS from the semiconducting 2H to the semimetallic 1T' phase has been studied in detail for nearly a decade; however, the effects of a heterointerface between MoS and other two-dimensional (2D) crystals on the phase transition have largely been overlooked. Here, calculations show that intercalating Li at a MoS-hexagonal boron nitride (BN) interface stabilizes the 1T phase over the 2H phase of MoS by ∼100 mJ m , suggesting that encapsulating MoS with BN may lower the electrochemical energy needed for the intercalation-induced phase transition. However, Raman spectroscopy of BN-MoS-BN heterostructures during the electrochemical intercalation of Li shows that the phase transition occurs at the same applied voltage for the heterostructure as for bare MoS. We hypothesize that the predicted thermodynamic stabilization of the 1T'-MoS-BN interface is counteracted by an energy barrier to the phase transition imposed by the steric hindrance of the heterointerface. The phase transition occurs at lower applied voltages upon heating the heterostructure, which supports our hypothesis. Our study highlights that interfacial effects of 2D heterostructures can go beyond modulating electrical properties and can modify electrochemical and phase transition behaviors.
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http://dx.doi.org/10.1021/acsami.0c21495DOI Listing
March 2021

cm-Scale Synthesis of MoTe Thin Films with Large Grains and Layer Control.

ACS Nano 2021 Jan 19;15(1):410-418. Epub 2020 Nov 19.

Energy Sciences Institute, Department of Mechanical Engineering and Materials Science, Yale University, West Haven, Connecticut 06516, United States.

Owing to the small energy differences between its polymorphs, MoTe can access a full spectrum of electronic states from the 2H semiconducting state to the 1T' semimetallic state and from the T Weyl semimetallic state to the superconducting state in the 1T' and T phase at low temperature. Thus, it is a model system for phase transformation studies as well as quantum phenomena such as the quantum spin Hall effect and topological superconductivity. Careful studies of MoTe and its potential applications require large-area MoTe thin films with high crystallinity and thickness control. Here, we present cm-scale synthesis of 2H-MoTe thin films with layer control and large grains that span several microns. Layer control is achieved by controlling the initial thickness of the precursor MoO thin films, which are deposited on sapphire substrates by atomic layer deposition and subsequently tellurized. Despite the van der Waals epitaxy, the precursor-substrate interface is found to critically determine the uniformity in thickness and grain size of the resulting MoTe films: MoTe grown on sapphire show uniform films while MoTe grown on amorphous SiO substrates form islands. This synthesis strategy decouples the layer control from the variabilities of growth conditions for robust growth results and is applicable to growing other transition-metal dichalcogenides with layer control.
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http://dx.doi.org/10.1021/acsnano.0c08069DOI Listing
January 2021

lncRNA DIGIT and BRD3 protein form phase-separated condensates to regulate endoderm differentiation.

Nat Cell Biol 2020 10 7;22(10):1211-1222. Epub 2020 Sep 7.

Gastrointestinal Unit, Massachusetts General Hospital, Boston, MA, USA.

Cooperation between DNA, RNA and protein regulates gene expression and controls differentiation through interactions that connect regions of nucleic acids and protein domains and through the assembly of biomolecular condensates. Here, we report that endoderm differentiation is regulated by the interaction between the long non-coding RNA (lncRNA) DIGIT and the bromodomain and extraterminal domain protein BRD3. BRD3 forms phase-separated condensates of which the formation is promoted by DIGIT, occupies enhancers of endoderm transcription factors and is required for endoderm differentiation. BRD3 binds to histone H3 acetylated at lysine 18 (H3K18ac) in vitro and co-occupies the genome with H3K18ac. DIGIT is also enriched in regions of H3K18ac, and the depletion of DIGIT results in decreased recruitment of BRD3 to these regions. Our findings show that cooperation between DIGIT and BRD3 at regions of H3K18ac regulates the transcription factors that drive endoderm differentiation and suggest that protein-lncRNA phase-separated condensates have a broader role as regulators of transcription.
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http://dx.doi.org/10.1038/s41556-020-0572-2DOI Listing
October 2020

Unveiling the Interfacial Effects for Enhanced Hydrogen Evolution Reaction on MoS /WTe Hybrid Structures.

Small 2019 May 8;15(19):e1900078. Epub 2019 Apr 8.

Department of Mechanical Engineering and Materials Science, Yale University, New Haven, CT, 06511, USA.

Using the MoS -WTe heterostructure as a model system combined with electrochemical microreactors and density function theory calculations, it is shown that heterostructured contacts enhance the hydrogen evolution reaction (HER) activity of monolayer MoS . Two possible mechanisms are suggested to explain this enhancement: efficient charge injection through large-area heterojunctions between MoS and WTe and effective screening of mirror charges due to the semimetallic nature of WTe . The dielectric screening effect is proven minor, probed by measuring the HER activity of monolayer MoS on various support substrates with dielectric constants ranging from 4 to 300. Thus, the enhanced HER is attributed to the increased charge injection into MoS through large-area heterojunctions. Based on this understanding, a MoS /WTe hybrid catalyst is fabricated with an HER overpotential of -140 mV at 10 mA cm , a Tafel slope of 40 mV dec , and long stability. These results demonstrate the importance of interfacial design in transition metal dichalcogenide HER catalysts. The microreactor platform presents an unambiguous approach to probe interfacial effects in various electrocatalytic reactions.
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http://dx.doi.org/10.1002/smll.201900078DOI Listing
May 2019

Revealing the Contribution of Individual Factors to Hydrogen Evolution Reaction Catalytic Activity.

Adv Mater 2018 May 24;30(18):e1706076. Epub 2018 Mar 24.

Department of Mechanical Engineering and Materials Science, Yale University, New Haven, CT, 06511, USA.

For the electrochemical hydrogen evolution reaction (HER), the electrical properties of catalysts can play an important role in influencing the overall catalytic activity. This is particularly important for semiconducting HER catalysts such as MoS , which has been extensively studied over the last decade. Herein, on-chip microreactors on two model catalysts, semiconducting MoS and semimetallic WTe , are employed to extract the effects of individual factors and study their relations with the HER catalytic activity. It is shown that electron injection at the catalyst/current collector interface and intralayer and interlayer charge transport within the catalyst can be more important than thermodynamic energy considerations. For WTe , the site-dependent activities and the relations of the pure thermodynamics to the overall activity are measured and established, as the microreactors allow precise measurements of the type and area of the catalytic sites. The approach presents opportunities to study electrochemical reactions systematically to help establish rational design principles for future electrocatalysts.
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http://dx.doi.org/10.1002/adma.201706076DOI Listing
May 2018

Genome-Wide Maps of m6A circRNAs Identify Widespread and Cell-Type-Specific Methylation Patterns that Are Distinct from mRNAs.

Cell Rep 2017 Aug;20(9):2262-2276

Gastrointestinal Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA. Electronic address:

N-methyladenosine (mA) is the most abundant internal modification of mRNAs and is implicated in all aspects of post-transcriptional RNA metabolism. However, little is known about mA modifications to circular (circ) RNAs. We developed a computational pipeline (AutoCirc) that, together with depletion of ribosomal RNA and mA immunoprecipitation, defined thousands of mA circRNAs with cell-type-specific expression. The presence of mA circRNAs is corroborated by interaction between circRNAs and YTHDF1/YTHDF2, proteins that read mA sites in mRNAs, and by reduced mA levels upon depletion of METTL3, the mA writer. Despite sharing mA readers and writers, mA circRNAs are frequently derived from exons that are not methylated in mRNAs, whereas mRNAs that are methylated on the same exons that compose mA circRNAs exhibit less stability in a process regulated by YTHDF2. These results expand our understanding of the breadth of mA modifications and uncover regulation of circRNAs through mA modification.
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http://dx.doi.org/10.1016/j.celrep.2017.08.027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5705222PMC
August 2017

Tricyclic Antidepressants Promote Ceramide Accumulation to Regulate Collagen Production in Human Hepatic Stellate Cells.

Sci Rep 2017 03 21;7:44867. Epub 2017 Mar 21.

Gastrointestinal Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA USA.

Activation of hepatic stellate cells (HSCs) in response to injury is a key step in hepatic fibrosis, and is characterized by trans-differentiation of quiescent HSCs to HSC myofibroblasts, which secrete extracellular matrix proteins responsible for the fibrotic scar. There are currently no therapies to directly inhibit hepatic fibrosis. We developed a small molecule screen to identify compounds that inactivate human HSC myofibroblasts through the quantification of lipid droplets. We screened 1600 compounds and identified 21 small molecules that induce HSC inactivation. Four hits were tricyclic antidepressants (TCAs), and they repressed expression of pro-fibrotic factors Alpha-Actin-2 (ACTA2) and Alpha-1 Type I Collagen (COL1A1) in HSCs. RNA sequencing implicated the sphingolipid pathway as a target of the TCAs. Indeed, TCA treatment of HSCs promoted accumulation of ceramide through inhibition of acid ceramidase (aCDase). Depletion of aCDase also promoted accumulation of ceramide and was associated with reduced COL1A1 expression. Treatment with B13, an inhibitor of aCDase, reproduced the antifibrotic phenotype as did the addition of exogenous ceramide. Our results show that detection of lipid droplets provides a robust readout to screen for regulators of hepatic fibrosis and have identified a novel antifibrotic role for ceramide.
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http://dx.doi.org/10.1038/srep44867DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5359599PMC
March 2017

DIGIT Is a Conserved Long Noncoding RNA that Regulates GSC Expression to Control Definitive Endoderm Differentiation of Embryonic Stem Cells.

Cell Rep 2016 10;17(2):353-365

Gastrointestinal Unit, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA. Electronic address:

Long noncoding RNAs (lncRNAs) exhibit diverse functions, including regulation of development. Here, we combine genome-wide mapping of SMAD3 occupancy with expression analysis to identify lncRNAs induced by activin signaling during endoderm differentiation of human embryonic stem cells (hESCs). We find that DIGIT is divergent to Goosecoid (GSC) and expressed during endoderm differentiation. Deletion of the SMAD3-occupied enhancer proximal to DIGIT inhibits DIGIT and GSC expression and definitive endoderm differentiation. Disruption of the gene encoding DIGIT and depletion of the DIGIT transcript reveal that DIGIT is required for definitive endoderm differentiation. In addition, we identify the mouse ortholog of DIGIT and show that it is expressed during development and promotes definitive endoderm differentiation of mouse ESCs. DIGIT regulates GSC in trans, and activation of endogenous GSC expression is sufficient to rescue definitive endoderm differentiation in DIGIT-deficient hESCs. Our study defines DIGIT as a conserved noncoding developmental regulator of definitive endoderm.
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http://dx.doi.org/10.1016/j.celrep.2016.09.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5120872PMC
October 2016

Long noncoding RNAs expressed in human hepatic stellate cells form networks with extracellular matrix proteins.

Genome Med 2016 Mar 23;8(1):31. Epub 2016 Mar 23.

Gastrointestinal Unit, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, Boston, MA, 02114, USA.

Background: Hepatic fibrosis is the underlying cause of cirrhosis and liver failure in nearly every form of chronic liver disease, and hepatic stellate cells (HSCs) are the primary cell type responsible for fibrosis. Long noncoding RNAs (lncRNAs) are increasingly recognized as regulators of development and disease; however, little is known about their expression in human HSCs and their function in hepatic fibrosis.

Methods: We performed RNA sequencing and ab initio assembly of RNA transcripts to define the lncRNAs expressed in human HSC myofibroblasts. We analyzed chromatin immunoprecipitation data and expression data to identify lncRNAs that were regulated by transforming growth factor beta (TGF-β) signaling, associated with super-enhancers and restricted in expression to HSCs compared with 43 human tissues and cell types. Co-expression network analyses were performed to discover functional modules of lncRNAs, and principle component analysis and K-mean clustering were used to compare lncRNA expression in HSCs with other myofibroblast cell types.

Results: We identified over 3600 lncRNAs that are expressed in human HSC myofibroblasts. Many are regulated by TGF-β, a major fibrotic signal, and form networks with genes encoding key components of the extracellular matrix (ECM), which is the substrate of the fibrotic scar. The lncRNAs directly regulated by TGF-β signaling are also enriched at super-enhancers. More than 400 of the lncRNAs identified in HSCs are uniquely expressed in HSCs compared with 43 other human tissues and cell types and HSC myofibroblasts demonstrate different patterns of lncRNA expression compared with myofibroblasts originating from other tissues. Co-expression analyses identified a subset of lncRNAs that are tightly linked to collagen genes and numerous proteins that regulate the ECM during formation of the fibrotic scar. Finally, we identified lncRNAs that are induced during progression of human liver disease.

Conclusions: lncRNAs are likely key contributors to the formation and progression of fibrosis in human liver disease.
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http://dx.doi.org/10.1186/s13073-016-0285-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4804564PMC
March 2016