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Search Results to Manuel Garber PhD

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One or more keywords matched the following properties of Garber, Manuel

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Manuel Garber received his Ph.D. in Mathematics at Brandeis University in 1999. From 1999 to 2004 Dr. Garber worked on applications of incipient web technologies to telecommunications, financial services and distribution channels. In 2004 Dr. Garber joined the Broad Institute as a computational biologist. At the Broad Institute, he focused on analyzing the human genome sequence and led studies of the evolution of segmental duplications. He developed comparative sequence analysis methods to detect regions undergoing natural selection using the growing number of sequenced genomes of related mammalian species. Dr. Garber’s focus shifted to functional characterization of genomic elements using genome-wide functional assays such as RNA-Seq and ChIP-Seq. Dr. Garber’s methods have been critical to the discovery and characterization of a novel set of large intergenic non-coding RNAs (lincRNAs) and to our understanding of the immune transcriptional response to pathogens. In September 2012, Dr. Garber moved to the University of Massachusetts Medical School to establish his laboratory and direct the Bioinformatics core. He is an associated professor in the Program in Bioinformatics and Integrative Biology. Dr. Garber continues to study lincRNAs and in particular their evolutionary history, as well as the systematic dissection of the transcriptional regulation of the immune response.
  1. The Functional Genome
  2. Of the 3 billion bases of the human genome, only ~1.2% encodes genes that are translated into proteins. Yet, a much larger percentage encodes functional genetic elements. Many of these functional elements control how genes are regulated to produce specific patterns of expression in different tissues and cell types. Precisely how these elements work remains an open question in biology.We collaborate closely with experimental labs to develop algorithms and design experiments for analyzing and integrating genome-wide experiments with the goal of mapping and characterizing the functional genome and how it orchestrates gene expression across development and in response to environmental stimulus. Current advances in sequencing technologies have enabled systematic, genome-wide readouts of cell function. Bioinformatics approaches are critical to fully take advantage of these new approaches. Dr Garber’s group strives to develop the tools to analyze, integrate and fully leverage the advancements in genome wide experimental technologies. We have developed and continue to enhance the Scripture toolkit for short read analysis (ChIP-Seq and RNA-Seq) and the SiPhy suite for comparative sequence analysis. Both tools have been critical in our exploration of the functional landscape of the human genome.
  3. Evolution of non-coding genes
  4. Large intergenic non-coding RNAs are spliced, polyadenylated and capped transcripts that do not overlap annotated protein coding genes and have little to no protein coding potential. We recently identified about 1500 lincRNAs using both epigenetic signatures of expression and transcriptional profiling by RNA-Seq. LincRNAs are an integral part of the cell’s transcriptional network. Interestingly, while lincRNAs display clear signatures of selection, their conservation profiles are markedly different from those of protein coding genes. Our lab aims to integrate functional data such us protein-RNA, RNA-DNA and RNA-RNA interactions with comparative analysis to understand the evolution of these interactions and how they have changed the molecular circuitry of the cell.
  5. Gene regulation
  6. It is now clear that most phenotypic changes observed across vertebrates are not due to changes in protein coding genes, but are due to changes in gene regulation. However, how gene regulation is encoded in the genome is only now beginning to be understood. How the binding of a transcription factor to a promoter or enhancer affects target gene expression is still unclear. Only by studying the interplay between regulatory elements and their targets can we evaluate the functional role of cis-regulatory elements. Sequencing assays now allow us to monitor transcription factor binding (ChIP-Seq) and cellular output (RNA-Seq) at an unprecedented scale. We are currently studying this interplay by using the response of bone marrow derived dendritic cells (BMDCs) to pathogen stimuli as our biological system. Up to this point, our integrated analysis of temporal datasets of transcription binding and gene expression showed that binding of different factors is responsible for subtle expression patterns that control specific pathways. These pathways have very distinct forms of regulation: a minority of pathways are regulated by few transcription factors (e.g. Stat1 and Stat2) whose targets are very responsive to knock down of these factors and have very conserved binding sites. In contrast, most pathways are controlled by a larger set of redundant transcription factors, whose binding has an additive effect and expression where the number rather than the type of factors bound gives rise to different expression levels. Our group continues to work closely with experimental groups to further enhance and characterize these datasets in order to crack the regulatory code of mammalian immune cells.
Rotation Projects

If you are interesting in applying computational methods to biological problems please contact me. 

Potential projects in my lab are

  1. Modeling of transcription factor gene expression control in innate immune cells 
  2. Evolutionary analysis of gene transcription factor networks in mammals
  3. Epigenetics inheritance in mice: From male sperm to phenotypic effect in grandchildren
  4. Application of genome and exome sequencing to newborn screening
  5. Development of computational methods for analysis of RNA-protein interactions


One or more keywords matched the following items that are connected to Garber, Manuel

Item TypeName
Academic Article Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals.
Academic Article A large intergenic noncoding RNA induced by p53 mediates global gene repression in the p53 response.
Academic Article Large intergenic non-coding RNA-RoR modulates reprogramming of human induced pluripotent stem cells.
Academic Article Genome of the marsupial Monodelphis domestica reveals innovation in non-coding sequences.
Academic Article Many human large intergenic noncoding RNAs associate with chromatin-modifying complexes and affect gene expression.
Academic Article Unbiased reconstruction of a mammalian transcriptional network mediating pathogen responses.
Academic Article Ab initio reconstruction of cell type-specific transcriptomes in mouse reveals the conserved multi-exonic structure of lincRNAs.
Academic Article Metabolic labeling of RNA uncovers principles of RNA production and degradation dynamics in mammalian cells.
Academic Article Computational methods for transcriptome annotation and quantification using RNA-seq.
Academic Article lincRNAs act in the circuitry controlling pluripotency and differentiation.
Academic Article A high-resolution map of human evolutionary constraint using 29 mammals.
Academic Article Systematic identification of long noncoding RNAs expressed during zebrafish embryogenesis.
Academic Article Gene expression is circular: factors for mRNA degradation also foster mRNA synthesis.
Concept RNA
Concept RNA, Ribosomal
Concept Sequence Analysis, RNA
Concept RNA, Guide
Concept RNA, Fungal
Concept RNA, Untranslated
Concept RNA Stability
Concept RNA, Messenger
Concept RNA, Transfer, Gly
Concept RNA, Transfer
Concept RNA Polymerase II
Concept RNA-Binding Proteins
Academic Article Evolutionary dynamics and tissue specificity of human long noncoding RNAs in six mammals.
Academic Article Simultaneous generation of many RNA-seq libraries in a single reaction.
Academic Article Novel Observations From Next-Generation RNA Sequencing of Highly Purified Human Adult and Fetal Islet Cell Subsets.
Academic Article DNA-binding-domain fusions enhance the targeting range and precision of Cas9.
Academic Article Biogenesis and function of tRNA fragments during sperm maturation and fertilization in mammals.
Academic Article Evolutionary analysis across mammals reveals distinct classes of long non-coding RNAs.
Academic Article End Sequence Analysis Toolkit (ESAT) expands the extractable information from single-cell RNA-seq data.
Academic Article Transcriptome-wide Analysis of Roles for tRNA Modifications in Translational Regulation.

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