Maragkakis Lab

Emmanouil "Manolis" Maragkakis, PhD

Mon, 01 Jan 0001 00:00:00 +0000

Stadtman Tenure-Track Investigator, Laboratory of Genetics and Genomics, NIA/NIH.

Stress Response in Senescence and Aging

Mon, 01 Jan 0001 00:00:00 +0000

Understand the molecular mechanisms of stress response and cellular senescence using machine learning, long-read nanopore sequencing and ribosome profiling.

RNA Metabolism and Translation in Aging

Mon, 01 Jan 0001 00:00:00 +0000

Discover the dynamics of post-transcriptional modulators of aging using long-read single-cell sequencing, spatial transcriptomics, and statistical modeling

RNA Processing in Aging-Associated Disease

Mon, 01 Jan 0001 00:00:00 +0000

Discover the role of RNA-binding proteins (RBPs) in mRNA processing and alternative splicing in neurodegeneration, and provide high-quality long-read transcriptomic resources through large collaborative initiatives.

Abid Rehman

Mon, 01 Jan 0001 00:00:00 +0000

Bio

Abid Rehman is a PhD student in an individual graduate partnership program (GPP) between the National Instituite on Aging and the University of California, San Diego.

His research interests are in RNA isoform remodeling and epitranscriptomic changes during aging, utilizing recent technologies such as single-cell long-read sequencing and direct RNA sequencing.

Education

Ph.D. in Bioinformatics & Systems Biology - University of California, San Diego, present
B.S. in Bioengineering - University of Illinois, Urbana-Champaign, 2022

Showkat A. Dar, PhD

Mon, 01 Jan 0001 00:00:00 +0000

Studies RNA decay and stress granule biology using direct RNA sequencing.

Sulochan Malla, PhD

Mon, 01 Jan 0001 00:00:00 +0000

Working on long-read sequencing and brain aging.

Jessica Martin

Mon, 01 Jan 0001 00:00:00 +0000

Machine learning approaches for RNA sequencing analysis.

Srila Palanikumar

Mon, 01 Jan 0001 00:00:00 +0000

Studying isoform remodeling in the aging brain.

Ani Nangunoori

Mon, 01 Jan 0001 00:00:00 +0000

MD Student at University of Pittsburgh

Matthew J. Payea, PhD

Mon, 01 Jan 0001 00:00:00 +0000

Studies cellular stress responses and senescence.

Cedric Belair, PhD

Mon, 01 Jan 0001 00:00:00 +0000

Working on RNA metabolism and transcriptome dynamics using long-read RNA sequencing.

Christopher T Lee, PhD

Mon, 01 Jan 0001 00:00:00 +0000

Studies RNA modifications and decay using direct RNA sequencing

Circulating cell type senescence signatures track distinct dimensions of health status and trajectories in human longitudinal cohorts

Thu, 11 Jun 2026 00:00:00 +0000

Summary

This study profiles cell-type-specific senescence signatures in circulating blood cells from human longitudinal cohorts and shows that these signatures track distinct dimensions of health status and aging trajectories. The findings establish circulating senescence signatures as high-resolution biomarkers of biological aging with potential utility for monitoring healthspan in humans.

SenCat: Redefining human cell senescence through multiomic profiling of multiple senescent primary cell types

Mon, 01 Jun 2026 00:00:00 +0000

Summary

SenCat is a comprehensive multiomic atlas of human cell senescence generated by profiling multiple primary cell types induced to senescence through distinct triggers. Integrated analysis of transcriptome, epigenome, and proteome data across cell types and senescence inducers redefines the core features of the senescent state and identifies cell-type-specific and universal senescence signatures.

Transcript-guided targeted cell enrichment for scalable single-nucleus RNA sequencing

Wed, 11 Mar 2026 00:00:00 +0000

Summary

This study introduces a method for transcript-guided targeted enrichment of specific cell populations prior to single-nucleus RNA sequencing. By selecting nuclei based on expression of specific transcripts, the approach achieves deep profiling of rare cell types at scale, enabling discovery of cell-type-specific transcriptional programs that would be missed by unbiased approaches.

Senescence: An overlooked VSMC phenotype and therapeutic opportunity?

Thu, 13 Nov 2025 00:00:00 +0000

Summary

This review examines the evidence for senescence in vascular smooth muscle cells (VSMCs) and its contribution to vascular aging and disease. The authors discuss the mechanisms driving VSMC senescence, its downstream consequences for vascular function, and the potential for senolytic and senomorphic interventions.

Viral Infection Induces Alzheimer's Disease-Related Pathways and Senescence in iPSC-Derived Neuronal Models

Wed, 11 Jun 2025 00:00:00 +0000

Summary

Using iPSC-derived neurons and cerebral organoids, this study demonstrates that viral infections — including HSV-1 and tick-borne encephalitis virus — activate Alzheimer’s disease-related pathways and induce cellular senescence. The findings support a causal link between viral infection and neurodegeneration, suggesting that vaccination-based prevention of viral infections may reduce Alzheimer’s disease risk.

Cell-specific RNA isoform remodeling in the aging mouse brain

Sun, 08 Jun 2025 00:00:00 +0000

Summary

This study combines single-cell analysis with long-read nanopore sequencing to capture full-length RNA isoforms and uncover temporal changes in RNA transcription, processing, and alternative splicing in the aging mouse cortex and hippocampus.

Spatial transcriptomics of the aging mouse brain reveals origins of inflammation in the white matter

Fri, 04 Apr 2025 00:00:00 +0000

Summary

Spatial transcriptomics profiling of the aging mouse brain reveals that inflammatory gene expression changes during aging are not uniformly distributed but originate preferentially in white matter regions. The findings provide a spatially resolved map of the aging brain transcriptome and identify candidate cellular drivers of neuroinflammation.

Topoisomerase 3b facilitates piRNA biogenesis to promote transposon silencing and germ cell development

Thu, 03 Apr 2025 00:00:00 +0000

Summary

This study identifies Topoisomerase 3β as a factor that facilitates piRNA biogenesis, with loss of TOP3B leading to reduced piRNA production, derepression of transposable elements, and impaired germ cell development. The findings reveal a novel role for a DNA/RNA topoisomerase in small RNA biology.

Full-length direct RNA sequencing uncovers stress granule-dependent RNA decay upon cellular stress

Thu, 19 Dec 2024 00:00:00 +0000

Summary

Using full-length direct RNA sequencing, this study uncovers a previously unrecognized role for stress granules in promoting selective mRNA decay during cellular stress. The findings show that mRNAs recruited to stress granules undergo preferential degradation, linking stress granule biology to RNA homeostasis.

Senescence suppresses the integrated stress response and activates a stress-remodeled secretory phenotype

Thu, 21 Nov 2024 00:00:00 +0000

Summary

This study reveals that senescent cells suppress the canonical integrated stress response (ISR) while activating a remodeled secretory program. The suppression of ISR in senescence is mechanistically linked to altered eIF2α phosphorylation dynamics, and the resulting secretory phenotype differs from the classical SASP, with implications for age-related tissue dysfunction.

Deep learning and direct sequencing of labeled RNA captures transcriptome dynamics

Sun, 29 Sep 2024 00:00:00 +0000

Summary

We developed RNAkinet, a neural network that identifies newly synthesized RNA molecules labeled with 5-ethynyl uridine (5EU) using nanopore direct RNA sequencing, processing raw electrical signals without requiring basecalling or sequence alignment. RNAkinet enables simultaneous analysis of RNA metabolism alongside poly(A) tail length and RNA modifications at single-molecule resolution.

Gene body DNA hydroxymethylation restricts the magnitude of transcriptional changes during aging

Sun, 28 Jul 2024 00:00:00 +0000

Summary

This study reveals that 5-hydroxymethylcytosine (5hmC) enrichment in gene bodies acts as an epigenetic mechanism that constrains the amplitude of transcriptional changes occurring during aging. Genes with high 5hmC show attenuated age-related expression changes, identifying DNA hydroxymethylation as a regulator of transcriptional stability in aging tissues.

Mis-spliced transcripts generate de novo proteins in TDP-43-related ALS/FTD

Fri, 26 Jan 2024 00:00:00 +0000

Summary

This study demonstrates that loss of TDP-43 function leads to widespread cryptic splicing events that produce novel protein isoforms not normally expressed in healthy cells. These de novo proteins may contribute to the pathogenesis of ALS and FTD by triggering immune responses or impairing cellular functions.

Differential Poly(A) Tail Length Analysis Using Nanopore Sequencing

Fri, 13 Oct 2023 00:00:00 +0000

Summary

This methods chapter describes a protocol for transcriptome-wide measurement of differential poly(A) tail lengths using nanopore direct RNA sequencing, combined with linear mixed models for statistical analysis. The approach enables quantitative comparison of poly(A) tail dynamics across conditions and provides a framework for studying the role of deadenylation in post-transcriptional gene regulation.

RNA-mediated control of protein translation under stress

Thu, 20 Jul 2023 00:00:00 +0000

Summary

This review covers the post-transcriptional mechanisms by which cells regulate protein synthesis in response to stress, focusing on the roles of RNA-binding proteins, non-coding RNAs, and mRNA modifications in controlling translation. The connections between stress-responsive translational control and aging are discussed.

Biology of Stress Responses in Aging

Tue, 27 Jun 2023 00:00:00 +0000

Summary

This review covers the major cellular stress response pathways and how they are altered during aging. Topics include the integrated stress response, heat shock response, oxidative stress, proteostasis, and their connections to age-associated physiological decline and disease.

The MOV10 RNA helicase is a dosage-dependent host restriction factor for LINE1 retrotransposition in mice

Mon, 01 May 2023 00:00:00 +0000

Summary

This study shows that MOV10, an RNA helicase with roles in the piRNA pathway, acts as a dosage-dependent restriction factor for LINE1 retrotransposons in mice. Reduction of MOV10 levels leads to increased LINE1 retrotransposition, implicating MOV10 in genome defense against mobile elements.

SamQL: A Structured Query Language and filtering tool for the SAM/BAM file format

Sat, 02 Oct 2021 00:00:00 +0000

Summary

SamQL implements a SQL-like query language for filtering and extracting reads from SAM/BAM alignment files based on arbitrary combinations of alignment attributes. The tool enables complex queries that are not possible with existing SAM/BAM filtering utilities, facilitating flexible downstream analysis of sequencing data.

TERA-Seq: True end-to-end sequencing of native RNA molecules for transcriptome characterization

Tue, 24 Aug 2021 00:00:00 +0000

Summary

TERA-Seq is a method that combines chemical ligation of adapters to both RNA ends with nanopore direct RNA sequencing to capture complete native RNA molecules from the 5’ cap to the 3’ poly(A) tail. This enables simultaneous characterization of RNA modifications, poly(A) tail length, and transcript boundaries at single-molecule resolution.

Modulation of Aub-TDRD interactions elucidates piRNA amplification and germplasm formation

Mon, 01 Mar 2021 00:00:00 +0000

Summary

This study dissects the molecular interactions between Aubergine and Tudor-domain proteins and their roles in piRNA amplification through the ping-pong cycle and in the formation of the germ plasm. The findings provide mechanistic insight into how piRNA pathway components are organized in germ granules.

Retention of CD19 intron 2 contributes to CART-19 resistance in leukemias with subclonal frameshift mutations in CD19

Wed, 01 Apr 2020 00:00:00 +0000

Summary

This study identifies intron 2 retention in CD19 transcripts as a mechanism contributing to CAR-T19 therapy resistance in leukemias harboring subclonal frameshift mutations in CD19. The findings reveal how alternative splicing can undermine antigen-targeted cancer immunotherapy.

Amyotrophic Lateral Sclerosis associated FUS mutation shortens mitochondria and induces neurotoxicity

Mon, 22 Oct 2018 00:00:00 +0000

Summary

This study shows that disease-associated FUS mutations cause mitochondrial shortening and fragmentation in neurons, leading to neurotoxicity. The findings connect FUS dysfunction to mitochondrial dynamics, providing a potential mechanism for neurodegeneration in ALS patients carrying FUS mutations.

Ribothrypsis, a novel process of canonical mRNA decay, mediates ribosome-phased mRNA endonucleolysis

Sun, 01 Apr 2018 00:00:00 +0000

Summary

This study discovers ribothrypsis, a previously unknown mRNA decay process in which ribosomes trigger endonucleolytic cleavage of mRNAs in a ribosome-phased pattern. Ribothrypsis operates during active translation and represents a major pathway of canonical mRNA decay in human cells.

cCLIP-Seq: Retrieval of Chimeric Reads from HITS-CLIP (CLIP-Seq) Libraries

Mon, 01 Jan 2018 00:00:00 +0000

Summary

This methods chapter describes cCLIP-seq, a computational approach for identifying and retrieving chimeric reads from HITS-CLIP libraries, where a small RNA and its target RNA are co-ligated and sequenced as a single molecule. By resolving these chimeric tags, cCLIP-seq enables direct identification of small RNA binding sites and precise base-pairing profiles at single-nucleotide resolution.

bíogo: a simple high-performance bioinformatics toolkit for the Go language

Sat, 18 Feb 2017 00:00:00 +0000

Summary

bíogo is a bioinformatics library written in the Go programming language, providing high-performance tools for common genomic data processing tasks. The toolkit offers a clean API for sequence manipulation, alignment, and genomic data parsing with the performance characteristics of a compiled language.

Kc167, a widely used Drosophila cell line, contains an active primary piRNA pathway

Sun, 01 Jan 2017 00:00:00 +0000

Summary

This study characterizes the small RNA content of the Drosophila Kc167 cell line and demonstrates that it contains an active primary piRNA pathway. The findings establish Kc167 cells as a useful model system for studying piRNA biogenesis and function in vitro.

Sequence-dependent but not sequence-specific piRNA adhesion traps mRNAs to the germ plasm

Thu, 17 Mar 2016 00:00:00 +0000

Summary

This study shows that piRNAs promote germ plasm localization of mRNAs through a sequence-dependent but not sequence-specific adhesion mechanism. The findings reveal that the overall sequence composition, rather than specific complementarity, determines which mRNAs are retained in the germ plasm.

CLIPSeqTools — a novel bioinformatics CLIP-seq analysis suite

Fri, 01 Jan 2016 00:00:00 +0000

Summary

CLIPSeqTools is a modular bioinformatics pipeline for the analysis of CLIP-seq data, providing tools for read processing, peak calling, motif analysis, and visualization. The suite enables comprehensive characterization of RNA-binding protein interaction sites across the transcriptome.

The RNA helicase MOV10L1 binds piRNA precursors to initiate piRNA processing

Sun, 15 Mar 2015 00:00:00 +0000

Summary

This study demonstrates that MOV10L1, a germline-specific RNA helicase, directly binds to piRNA precursors and is required for their processing into mature piRNAs. MOV10L1 acts upstream of Piwi proteins in the piRNA biogenesis pathway, providing mechanistic insight into piRNA production.

A MicroRNA precursor surveillance system in quality control of MicroRNA synthesis

Thu, 18 Sep 2014 00:00:00 +0000

Summary

This study identifies a surveillance mechanism that monitors microRNA precursors and selectively degrades aberrant pre-miRNAs, ensuring the quality of miRNA biogenesis. The findings reveal a previously unknown layer of post-transcriptional regulation in the miRNA processing pathway.

Mitochondrial protein BmPAPI modulates the length of mature piRNAs

Tue, 01 Oct 2013 00:00:00 +0000

Summary

This study identifies BmPAPI, a mitochondrial protein in the silkworm Bombyx mori, as a factor that modulates the length of mature piRNAs. The findings provide mechanistic insight into the piRNA 3’ end processing pathway and link mitochondria to piRNA biogenesis.

FUS regulates genes coding for RNA-binding proteins in neurons by binding to their highly conserved introns

Mon, 01 Apr 2013 00:00:00 +0000

Summary

CLIP-seq analysis reveals that FUS, an ALS-associated RNA-binding protein, preferentially binds to highly conserved intronic sequences of genes encoding other RNA-binding proteins in neurons. This autoregulatory network suggests a mechanism by which FUS dysfunction could broadly disrupt neuronal RNA metabolism.

Identification of in vivo, conserved, TAF15 RNA binding sites reveals the impact of TAF15 on the neuronal transcriptome

Thu, 21 Feb 2013 00:00:00 +0000

Summary

Using CLIP-seq, this study identifies the in vivo binding sites of TAF15, an ALS-associated RNA-binding protein, across the neuronal transcriptome. The findings reveal evolutionarily conserved binding sites and provide insight into the role of TAF15 in neuronal RNA metabolism.

DIANA-LncBase: experimentally verified and computationally predicted microRNA targets on long non-coding RNAs

Tue, 01 Jan 2013 00:00:00 +0000

Summary

DIANA-LncBase is the first database dedicated to microRNA interactions with long non-coding RNAs, combining experimentally validated interactions with high-confidence computational predictions. The resource enables systematic study of miRNA-lncRNA regulatory networks.

Mili and Miwi target RNA repertoire reveals piRNA biogenesis and function of Miwi in spermiogenesis

Wed, 01 Aug 2012 00:00:00 +0000

Summary

Using CLIP-seq, this study maps the RNA targets of mouse PIWI proteins Mili and Miwi, providing insights into the mechanisms of piRNA biogenesis and the specific role of Miwi in regulating spermiogenesis through piRNA-mediated gene silencing.

DIANA miRPath v.2.0: investigating the combinatorial effect of microRNAs in pathways

Sun, 01 Jul 2012 00:00:00 +0000

Summary

DIANA miRPath v.2.0 enables researchers to study how multiple microRNAs cooperatively regulate biological pathways. The updated tool incorporates improved statistical methods and expanded databases for pathway enrichment analysis based on miRNA target predictions.

Functional microRNA targets in protein coding sequences

Thu, 15 Mar 2012 00:00:00 +0000

Summary

This study demonstrates that microRNAs can regulate gene expression through binding sites located within protein-coding sequences, not only the canonical 3’ UTR sites. Functional coding sequence targets are identified and validated, broadening the scope of miRNA-mediated gene regulation.

TarBase 6.0: capturing the exponential growth of miRNA targets with experimental support

Sun, 01 Jan 2012 00:00:00 +0000

Summary

TarBase 6.0 is a manually curated database of experimentally validated microRNA targets, significantly expanding the collection of miRNA-target interactions with experimental support from the literature. The database provides a gold standard for benchmarking computational prediction methods.

DIANA-microT Web server upgrade supports Fly and Worm miRNA target prediction and bibliographic miRNA to disease association

Fri, 01 Jul 2011 00:00:00 +0000

Summary

This update to the DIANA-microT web server extends its target prediction capabilities to Drosophila melanogaster and Caenorhabditis elegans microRNAs, and introduces a bibliographic module linking microRNAs to diseases based on the scientific literature.

Online resources for microRNA analysis

Mon, 17 Jan 2011 00:00:00 +0000

Summary

This article provides a curated overview of the online tools, databases, and web servers available for microRNA research, covering target prediction, expression analysis, and pathway analysis resources.

Accurate microRNA Target Prediction Using Detailed Binding Site Accessibility and Machine Learning on Proteomics Data

Sat, 01 Jan 2011 00:00:00 +0000

Summary

This study improves the accuracy of microRNA target prediction by modeling the accessibility of miRNA binding sites using detailed RNA secondary structure calculations and training machine learning models on proteomic measurements of miRNA-mediated repression.

Editing of Epstein-Barr virus-encoded BART6 microRNAs controls their dicer targeting and consequently affects viral latency

Fri, 22 Oct 2010 00:00:00 +0000

Summary

This study shows that adenosine-to-inosine editing of Epstein-Barr virus BART6 miRNAs alters their recognition by Dicer, leading to changes in miRNA processing and abundance. The editing events modulate viral latency, linking RNA editing to EBV biology.

The DIANA-mirExTra web server: from gene expression data to microRNA function

Thu, 11 Feb 2010 00:00:00 +0000

Summary

DIANA-mirExTra identifies microRNAs driving observed gene expression changes by combining miRNA target predictions with gene expression data. Users provide a list of differentially expressed genes and receive ranked microRNAs predicted to regulate that expression signature.

Lost in translation: an assessment and perspective for computational microRNA target identification

Tue, 01 Dec 2009 00:00:00 +0000

Summary

This work provides a systematic assessment of the state of computational microRNA target identification, examining the performance of existing tools and discussing the challenges in translating predictions into biological insight. Guidelines are provided for researchers interpreting computational miRNA target predictions.

Accurate microRNA target prediction correlates with protein repression levels

Fri, 18 Sep 2009 00:00:00 +0000

Summary

This study benchmarks microRNA target prediction methods against protein repression data, showing that the DIANA-microT algorithm achieves high correlation with experimentally measured protein repression. The work provides a framework for evaluating and improving computational miRNA target prediction.

DIANA-mirPath: Integrating human and mouse microRNAs in pathways

Sat, 01 Aug 2009 00:00:00 +0000

Summary

DIANA-mirPath is a web-based tool that integrates microRNA target predictions with KEGG pathway data to identify biological pathways regulated by user-specified microRNAs. The tool supports both human and mouse miRNAs and provides statistical analysis of pathway enrichment.

DIANA-microT web server: elucidating microRNA functions through target prediction

Wed, 01 Jul 2009 00:00:00 +0000

Summary

The DIANA-microT web server provides access to the DIANA-microT algorithm for microRNA target prediction. The server enables researchers to identify genes regulated by specific microRNAs, query microRNAs targeting specific genes, and perform pathway-level analysis of miRNA regulatory networks.