A B C D E F G H J K L M N O P R S T V W X Y Z

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Jesse Mager

Associate Professor

My interests lie in understanding epigenetic regulation of mammalian genomes during the earliest stages of mammalian development. Although brief in time, preimplantation development is an extremely dynamic period during which major epigenetic remodeling occurs and the very first cell fate decisions are made. These key biological processes require global, yet exquisitely precise chromatin remodeling and differential treatment of identical DNA sequence. We utilize various RNAi and knock-out approaches towards identification of genes that regulate these early epigenetic decisions that occur during oogenesis and preimplantation development.

Current Research

The Knockout Mouse Project 

The goal of this project is to characterize mutant mice generated by the Knock-out Mouse Consortium (KOMP2) that have lethal phenotypes occurring before to E9.5. Thus far we have nearly 100 distinct KOMP2 knockout lines successfully pass through our phenotyping pipeline. We will provide date to the IMPC to be incorporated into the international effort to functionally annotate the mammalian genome. This data set will drastically increase the number of documented early phenotypes and we believe it is the largest consistent characterization of early phenotypes on record. 

 

This primary screen will provide baseline phenotypic data for many novel knockouts. To our knowledge this is the first systematic study of early lethal knockouts conducted using similar mutation strategies on the same genetic background (C57Bl/6JN). This large-scale analysis allows us to draw conclusions regarding developmental constraints during mammalian development and will provide a road map to early phenotypic characterization. 

 

Thus far we have found approximately equal distribution of phenotypes – approximately half gastrulation/perigastrulation phenotypes and the other half with preimplantation/implantation phenotypes. This is not unexpected as one of our original goals was to determine if there are specific milestones during development at which embryos would arrest or present phenotypic abnormalities (as opposed to a gradient of phenotypes across all time points).

 

Genomic

Genomic imprinting is an epigenetic mechanism resulting in differential transcriptional activity between the two parental alleles. It is well established that differential chromatin structure accompanies this parent of origin gene expression. More specifically, DNA hypo/hyper-methylation, and core histone modifications (acetylation/methylation) differ between the active and silent alleles. Disruption of any one of these chromatin modifications may result in loss of imprinting at particular loci, making imprinted genes sensitive “reporters” of epigenetic regulatory mechanisms. Our group is engaged in an RNAi based screen to identify novel epigenetic regulatory genes. We screen for loss of imprinting, defects in trophoblast/ICM differentiation, as well as developmental arrest and morphological abnormalities all within the same preimplantation embryos.

Learn more at www.vasci.umass.edu/research-faculty/jesse-mager

https://blogs.umass.edu/magerlab/research/

Academic Background

  • PhD University of North Carolina
  • Postdoctoral Training: University of Pennsylvania
Cui W, Cheong A, Wang Y, et al. MCRS1 is essential for epiblast development during early mouse embryogenesis. Reproduction. 2020;159(1):1-13. doi:10.1530/REP-19-0334
Cheong A, Archambault D, Degani R, Iverson E, Tremblay KD, Mager J. Nuclear-encoded mitochondrial ribosomal proteins are required to initiate gastrulation. Development. 2020;147(10):dev188714. Published 2020 May 26. doi:10.1242/dev.188714
Archambault D, Cheong A, Iverson E, Tremblay KD, Mager J. Protein phosphatase 1 regulatory subunit 35 is required for ciliogenesis, notochord morphogenesis, and cell-cycle progression during murine development [published online ahead of print, 2020 Jul 3]. Dev Biol. 2020;S0012-1606(20)30186-X. doi:10.1016/j.ydbio.2020.06.011
Tellier AP, Archambault D, Tremblay KD, Mager J. The elongation factor Elof1 is required for mammalian gastrulation. PLoS One. 2019 Jul 5;14(7):e0219410. doi: 10.1371/journal.pone.0219410. eCollection 2019. PMID: 31276560
Dutta K, Bochicchio D, Ribbe AE, Alfandari D, Mager J, Pavan GM, Thayumanavan S. Symbiotic Self-Assembly Strategy toward Lipid-Encased Cross-Linked Polymer Nanoparticles for Efficient Gene Silencing. ACS Appl Mater Interfaces. 2019 Jul 17;11(28):24971-24983. doi: 10.1021/acsami.9b04731. Epub 2019 Jul 2.PMID: 31264399
Jiang Z, Cui W, Prasad P, Touve MA, Gianneschi NC, Mager J, Thayumanavan S.Bait-and-Switch Supramolecular Strategy To Generate Noncationic RNA-Polymer Complexes for RNA Delivery. Biomacromolecules. 2019 Jan 14;20(1):435-442. doi: 10.1021/acs.biomac.8b01321. Epub 2018 Dec 21. PMID: 30525500
Cheong A, Degani R, Tremblay KD, Mager J. A null allele of Dnaaf2 displays embryonic lethality and mimics human ciliary dyskinesia. Hum Mol Genet. 2019 May 20. pii: ddz106. doi: 10.1093/hmg/ddz106. [Epub ahead of print] PMID: 31107948
Paudel B, Gervasi MG, Porambo J, Caraballo DA, Tourzani DA, Mager J, Platt MD, Salicioni AM, Visconti PE. Sperm capacitation is associated with phosphorylation of the testis-specific radial spoke protein Rsph6a†. Biol Reprod. 2019 Feb 1;100(2):440-454. doi: 10.1093/biolre/ioy202. PMID: 30239614
El Sebae GK, Malatos JM, Cone ME, Rhee S, Angelo JR, Mager J, Tremblay KD. Single-cell murine genetic fate mapping reveals bipotential hepatoblasts and novel multi-organ endoderm progenitors. Development. 2018 Oct 11;145(19). pii: dev168658. doi: 10.1242/dev.168658. PMID: 30232173
Palaria A, Angelo JR, Guertin TM, Mager J, Tremblay KD. Patterning of the hepato-pancreatobiliary boundary by BMP reveals heterogeneity within the murine liver bud. Hepatology. 2018 Jul;68(1):274-288. doi: 10.1002/hep.29769. Epub 2018 May 9. PMID: 29315687
Cui W, Marcho C, Wang Y, Degani R, Golan M, Tremblay KD, Rivera-Pérez J, Mager J.Med20 is essential for early embryogenesis and regulates Nanog expression. Reproduction. 2018 Dec 1. pii: REP-18-0508.R1. doi: 10.1530/REP-18-0508. [Epub ahead of print] PMID: 30571656
Cui W, Mager J. Transcriptional Regulation and Genes Involved in First Lineage Specification During Preimplantation Development. Adv Anat Embryol Cell Biol. 2018;229:31-46. doi: 10.1007/978-3-319-63187-5_4. PMID: 29177763
 
Contact Info

Department of Veterinary and Animal Sciences
427M Integrated Science Building
661 North Pleasant Street
Amherst, MA 01003-9292

(413) 545-7368
jmager@vasci.umass.edu

www.vasci.umass.edu/research-faculty/jesse-mager