Postdoctoral Positions Available in the Yi Zhang Lab the Zhang Lab

Total Page：16

File Type：pdf, Size：1020Kb

Postdoctoral Positions Available in the Yi Zhang Lab the Zhang Lab

RED OSEN ROFESSOR OF EDIATRICS OSTON PROFESSOR OF GENETICS INVESTIGATOR F R P P B HARVARD MEDICAL SCHOOL HOWARD HUGHES MEDICAL INSTITUTE CHILDREN’S HOSPITAL PROGRAM IN CELLULAR & MOLECULAR MEDICINE Postdoctoral Positions Available in the Yi Zhang lab The Zhang lab is interested in how epigenetic and chromatin modification-mediated transcriptional regulation affects various biological processes, including preimplantation development, somatic cell nuclear transfer-mediated reprogramming, pancreatic cancer, and reward-mediated learning and memory. The lab is using a comprehensive approach, including embryo manipulation, somatic cell nuclear transfer, functional genomics, CRISPR-based genetic screen, single cell transcriptomics and epigenomics, MERFISH imaging, organoids, chemogenetics, optogenomics, neuronal tracing, IVSA, and other behavior assays to address the questions. For more information, please visit the lab web site (https://www.zhanglab.tch.harvard.edu/) and the Google Scholar (https://scholar.google.com/citations?user=7UjSqHEAAAAJ&hl=en&oi=ao). We are interested in recruiting ambitious and outstanding postdocs to push the technical and conceptual boundaries to reveal the unknowns. Applicants with excellent track record and/or the following background are preferred: • Bioinformatics (with math or computer science BS major) • Epigenetics and genomics • Mouse early embryonic development & SCNT • Innate immunity and biochemistry • Neurobiology (addiction or pain) • Stem cells and aging Applicants please send CV and an explanation as to the specific scientific question he/she would like to address and why the questions can be addressed in the Zhang lab better to Dr. Yi Zhang ([email protected]). Yi Zhang, Ph.D. Harvard Medical School 200 Longwood Avenue, WAB-149G Boston, MA 02115 [email protected] https://zhanglab.tch.harvard.edu/ .

Copy Link

Recommended publications

Acetyltransferase 10 Protein in DNA Methylation and Genomic Imprinting
Article The Role of N-a-acetyltransferase 10 Protein in DNA Methylation and Genomic Imprinting Graphical Abstract Authors Chen-Cheng Lee, Shih-Huan Peng, Genomic imprinting Li Shen, ..., Yu-Ting Yan, Yi Zhang, Paternally imprinted gene Maternally imprinted gene Li-Jung Juan ICR ICR Correspondence ICR ICR [email protected] (Y.Z.), Naa10-KO or WT Naa10p clinical mutation: [email protected] (L.-J.J.) S37P, V107F or R116W Dnmt1 Naa10p Naa10p Dnmt1 X In Brief X Mut X X Lee et al. reveal an unexpected function G H19 G H19 for Naa10p, which is primarily known to ICR of imprinted allele (ex: H19) ICR of imprinted allele (ex: H19) acetylate nascent peptides from ribosomes, in maintaining global DNA Methylated CpG H3K9me3/H4K20me3 methylation and marking the imprinted Unmethylated CpG H3K9Ac allele for genomic imprinting Imprinting maintenance Imprinting dysregulation maintenance. Their results suggest that Successful development Developmental defect Embryonic lethality defects in DNA methylation and genomic Growth retardation imprinting may contribute to Naa10p- Brain disorder associated Ogden syndrome. Maternal-effect lethality Highlights d Naa10p KO causes defects in genomic imprinting and embryonic development d Naa10p maintains Dnmt1 activity by facilitating Dnmt1 binding to DNA substrate d Naa10p selectively binds to ICRs of the imprinted allele via non-methylated GCXGXG d Ogden syndrome-causing Naa10p mutation disrupts ICR binding of Naa10p and Dnmt1 Lee et al., 2017, Molecular Cell 68, 1–15 October 5, 2017 ª 2017 Elsevier Inc. http://dx.doi.org/10.1016/j.molcel.2017.08.025 Please cite this article in press as: Lee et al., The Role of N-a-acetyltransferase 10 Protein in DNA Methylation and Genomic Imprinting, Molecular Cell (2017), http://dx.doi.org/10.1016/j.molcel.2017.08.025 Molecular Cell Article The Role of N-a-acetyltransferase 10 Protein in DNA Methylation and Genomic Imprinting Chen-Cheng Lee,1,9 Shih-Huan Peng,1,2,9 Li Shen,3,8,9 Chung-Fan Lee,1 Ting-Huei Du,1 Ming-Lun Kang,1 Guo-Liang Xu,4 Anup K.
[Show full text]
Study Identifies a Protein Complex Possibly Crucial for Triggering Embryo Development 6 January 2010
Study identifies a protein complex possibly crucial for triggering embryo development 6 January 2010 modifications that often prevent them from curbing the proliferation of cancer cells. The discovery may also have implications for stem cell research by providing a tool to quickly reprogram adult cells to possess the same attributes as embryonic stem cells, but without the ethical or safety issues of cells currently used for such studies. The results of the study appear on- line in the Jan. 6, 2010 issue of the journal Nature. "The implications of such research have always been clear, and that is why for years researchers have tried to identify a factor responsible for erasing these epigenetic markers," said senior This is a fertilized human egg, prior to division. Two nuclei (one from the egg and one from the sperm) can author Yi Zhang, Ph.D., Howard Hughes Medical be seen in the center. Credit: Photo courtesy of Stan Institute Investigator and Kenan Distinguished Beyler, Ph.D. UNC A.R.T. laboratory. Professor of biochemistry and biophysics at UNC. He is also a member of the UNC Lineberger Comprehensive Cancer Center. The DNA contained within each of our cells is Epigenetic markers are essentially chemical tags exactly the same, yet different types of cells - skin attached to the genomes of each cell, determining cells, heart cells, brain cells - perform very different which genes will be turned on or off and, ultimately, functions. The ultimate fate of these cells is what role that cell type will have in the body. One encoded not just in the DNA, but in a specific way this comes about is through DNA methylation, pattern of chemical modifications that overlay the a process by which methyl groups are stamped DNA structure.
[Show full text]
Jimmunol.1302943.Full.Pdf
Published April 23, 2014, doi:10.4049/jimmunol.1302943 The Journal of Immunology Ezh2 Regulates Transcriptional and Posttranslational Expression of T-bet and Promotes Th1 Cell Responses Mediating Aplastic Anemia in Mice Qing Tong,*,† Shan He,†,‡ Fang Xie,† Kazuhiro Mochizuki,† Yongnian Liu,†,‡ Izumi Mochizuki,† Lijun Meng,‡,x Hongxing Sun,x Yanyun Zhang,x Yajun Guo,* Elizabeth Hexner,{ and Yi Zhang†,‡ Acquired aplastic anemia (AA) is a potentially fatal bone marrow (BM) failure syndrome. IFN-g–producing Th1 CD4+ T cells mediate the immune destruction of hematopoietic cells, and they are central to the pathogenesis. However, the molecular events that control the development of BM-destructive Th1 cells remain largely unknown. Ezh2 is a chromatin-modifying enzyme that regulates multiple cellular processes primarily by silencing gene expression. We recently reported that Ezh2 is crucial for inflammatory T cell responses after allogeneic BM transplantation. To elucidate whether Ezh2 mediates pathogenic Th1 responses in AA and the mechanism of Ezh2 action in regulating Th1 cells, we studied the effects of Ezh2 inhibition in CD4+ T cells using a mouse model of human AA. Conditionally deleting Ezh2 in mature T cells dramatically reduced the production of BM- destructive Th1 cells in vivo, decreased BM-infiltrating Th1 cells, and rescued mice from BM failure. Ezh2 inhibition resulted in significant decrease in the expression of Tbx21 and Stat4, which encode transcription factors T-bet and STAT4, respectively. Introduction of T-bet but not STAT4 into Ezh2-deficient T cells fully rescued their differentiation into Th1 cells mediating AA. Ezh2 bound to the Tbx21 promoter in Th1 cells and directly activated Tbx21 transcription.
[Show full text]
Dedifferentiation, Transdifferentiation, and Reprogramming: Future Directions in Regenerative Medicine
82 Dedifferentiation, Transdifferentiation, and Reprogramming: Future Directions in Regenerative Medicine Cristina Eguizabal, PhD1 Nuria Montserrat, PhD1 Anna Veiga, PhD1,2 Juan Carlos Izpisua Belmonte, PhD1,3 1 Center for Regenerative Medicine in Barcelona Address for correspondence and reprint requests Juan Carlos Izpisua 2 Reproductive Medicine Service, Institut Universitari Dexeus, Belmonte, PhD, Gene Expression Laboratory, The Salk Institute for Barcelona, Spain Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 93027 3 Gene Expression Laboratory, The Salk Institute for Biological Studies, (e-mail: [email protected]). La Jolla, California Semin Reprod Med 2013;31:82–94 Abstract The main goal of regenerative medicine is to replace damaged tissue. To do this it is Keywords necessary to understand in detail the whole regeneration process including differenti- ► regenerative ated cells that can be converted into progenitor cells (dedifferentiation), cells that can medicine switch into another cell type (transdifferentiation), and somatic cells that can be ► stem cells induced to become pluripotent cells (reprogramming). By studying the regenerative ► dedifferentiation processes in both nonmammal and mammal models, natural or artificial processes ► transdifferentiation could underscore the molecular and cellular mechanisms behind these phenomena and ► reprogramming be used to create future regenerative strategies for humans. To understand any regenerative system, it is crucial to find the potency and differentiate and how they can revert to pluri- cellular origins of renewed tissues. Using techniques like potency (reprogramming) or switch lineages (dedifferentia- genetic lineage tracing and single-cell transplantation helps tion and transdifferentiation). to identify the route of regenerative sources. These tools were We synthesize the studies of different model systems to developed first in nonmammal models (flies, amphibians, and highlight recent insights that are integrating the field.
[Show full text]
Cell Reprogramming: Expectations and Challenges for Chemistry in Stem Cell Biology and Regenerative Medicine
Cell Death and Differentiation (2010) 17, 1230–1237 & 2010 Macmillan Publishers Limited All rights reserved 1350-9047/10 $32.00 www.nature.com/cdd Review Cell reprogramming: expectations and challenges for chemistry in stem cell biology and regenerative medicine L Anastasia*,1,2, G Pelissero2, B Venerando1,2 and G Tettamanti2 The possibility of reprogramming adult somatic cells into pluripotent stem cells (iPSCs) has generated a renewed interest into stem cell research and promises to overcome several key issues, including the ethical concerns of using human embryonic stem cells and the difficulty of obtaining large numbers of adult stem cells (Belmonte et al., Nat Rev Genet, 2009). This approach is also not free from challenges like the mechanism of the reprogramming process, which has yet to be elucidated, and the warranties for safety of generated pluripotent cells, especially in view of their possible therapeutic use. Very recently, several new reprogramming methods have surfaced, which seem to be more appropriate than genetic reprogramming. Particularly, chemically induced pluripotent cells (CiPSs), obtained with recombinant proteins or small synthetic molecules, may represent a valid approach, simpler and possibly safer than the other ones. Cell Death and Differentiation (2010) 17, 1230–1237; doi:10.1038/cdd.2010.14; published online 19 February 2010 Stem cells and cell reprogramming have generated an vitro to large numbers, in contrast to adult stem cells, that enormous interest in the past 2 years, since the generation normally possess very low self-renewal in vitro, and (3) iPSCs of induced pluripotent stem cells (iPSCs) from mouse can be patient customized, because they can be generated embryonic fibroblasts was first reported by Yamanaka and from an easily accessible source, that is fibroblasts, obtain- coworkers in 2006.1,2 In fact, it was shown that the forced able from any individual (Figure 1).
[Show full text]
Rational Optimization of Reprogramming Culture Conditions for the Generation of Induced Pluripotent Stem Cells with Ultra-High Efficiency and Fast Kinetics
npg Rational medium optimization for efficient reprogramming Cell Research (2011) 21: 884-894. 884 © 2011 IBCB, SIBS, CAS All rights reserved 1001-0602/11 $ 32.00 npg ORIGINAL ARTICLE www.nature.com/cr Rational optimization of reprogramming culture conditions for the generation of induced pluripotent stem cells with ultra-high efficiency and fast kinetics Jiekai Chen1, *, Jing Liu1, *, You Chen1, Jiaqi Yang1, Jing Chen1, He Liu1, Xiangjie Zhao1, Kunlun Mo1, Hong Song1, Lin Guo1, Shilong Chu1, Deping Wang1, Ke Ding1, Duanqing Pei1 1Key Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine at Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China The ectopic expression of several transcription factors can restore embryonic cell fate to cultured somatic cells and generate induced pluripotent stem cells (iPSCs), revealing a previously unknown pathway to pluripotency. However, this technology is currently limited by low efficiency, slow kinetics and multi-factorial requirement. Here we show that reprogramming can be improved and dramatically accelerated by optimizing culture conditions. First, we developed an optimized defined medium, iCD1, which allows Oct4/Sox2/Klf4 (OSK)-mediated reprogramming to achieve ultra-high efficiency (~10% at day 8). We also found that this optimized condition renders both Sox2 and Klf4 dispensable, although the elimination of these two factors leads to lower efficiency and slower kinetics. Our studies define a shortened route, both in timing and factor requirement, toward pluripotency. This new paradigm not only provides a rationale to further improve iPSC generation but also simplifies the conceptual understanding of reprogramming by defined factors.
[Show full text]
Experimental and Computational Approaches to Direct Cell Reprogramming: Recent Advancement and Future Challenges
cells Review Experimental and Computational Approaches to Direct Cell Reprogramming: Recent Advancement and Future Challenges Rihab Gam *, Minkyung Sung and Arun Prasad Pandurangan MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK; [email protected] (M.S.); [email protected] (A.P.P.) * Correspondence: [email protected]; Tel.: +44-1223-267820 Received: 6 September 2019; Accepted: 1 October 2019; Published: 2 October 2019 Abstract: The process of direct cell reprogramming, also named transdifferentiation, permits for the conversion of one mature cell type directly into another, without returning to a dedifferentiated state. This makes direct reprogramming a promising approach for the development of several cellular and tissue engineering therapies. To achieve the change in the cell identity, direct reprogramming requires an arsenal of tools that combine experimental and computational techniques. In the recent years, several methods of transdifferentiation have been developed. In this review, we will introduce the concept of direct cell reprogramming and its background, and cover the recent developments in the experimental and computational prediction techniques with their applications. We also discuss the challenges of translating this technology to clinical setting, accompanied with potential solutions. Keywords: transdifferentiation; direct reprogramming; computational biology; regenerative medicine; cell therapy 1. Introduction The epigenetic landscape model proposed by Conrad Waddington in 1957 provided a framework to explain cellular differentiation through epigenetic changes rather than genetic inheritance [1]. In this model, a pluripotent cell takes a complex path defined by ridges and valleys on the developmental landscape to reach a final fully-differentiated and specialized cell (Figure1).
[Show full text]
A New Model for Human Blastocyst Development
Signal Transduction and Targeted Therapy www.nature.com/sigtrans RESEARCH HIGHLIGHT OPEN Blastoids: a new model for human blastocyst development Heiner Niemann1 and Bob Seamark2 Signal Transduction and Targeted Therapy (2021) 6:239; https://doi.org/10.1038/s41392-021-00663-8 Recently, two research groups report in Nature1,2 the ex-vivo and neither has yet been sufficiently disclosed for full assesment of production of blastocyst-like structures, called blastoids, that the blastoids. Given the specific embyo culture procedures required, exhibit many of the landmarks in human early development found the epigenetic status of the blastoids is of particular interest. in viable blastocysts (Fig. 1). Numerous studies have shown that in vitro culture of early embryos The formation of a blastocyst is a critical step in early embryo can profoundly affect normal patterns of DNA methylation, resulting development denoting a key change from the early cleavage stages in deviations from the physiological gene expression patterns.4 to gastrulation. Typically, the blastocyst, differentiated from the early Following fertilisation, the parental genomes undergo a wave of de- cleavage stages, is a fluid filled vesicular structure comprised of cells and re-methylation, during early embryogenesis, creating the of now, three distinct cell lineages, namely those of the trophoblast, methylation patterns, needed for normal development, through the outer enclosing cell layer, and those of the inner cell mass (ICM) the activation and silencing of specific genes. Typically, global with the hypoblast and epiblast, found in the central fluid filled methylation of the mammalian genome declines to a nadir at the cavity (the blastocoel).
[Show full text]
Improve Induced Pluripotent Stem Cell Generation by Manipulating Epigenetic Statuses
IMPROVE INDUCED PLURIPOTENT STEM CELL GENERATION BY MANIPULATING EPIGENETIC STATUSES Gaoyang Liang A dissertation submitted to the faculty of the University of North Carolina at Chapel Hill in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Department of Biochemistry and Biophysics. Chapel Hill 2012 Approved by Yi Zhang, Ph.D. William Marzluff, Ph.D. Larysa Pevny, Ph.D. Lishan Su, Ph.D. Yue Xiong, Ph.D. ©2012 Gaoyang Liang ALL RIGHTS RESERVED ii ABSTRACT GAOYANG LIANG: Improve induced pluripotent stem cell generation by manipulating epigenetic statuses (Under the direction of Dr. Yi Zhang) Reprogramming of somatic cells to a pluripotent state can be achieved by introduction of defined transcription factors. The derived induced pluripotent stem (iPS) cells have molecular profiles and developmental potentials similar to embryonic stem (ES) cells. However, this reprogramming process is inefficient and its underlying mechanisms are poorly understood. To improve the efficiency of iPS cell generation and shed light on its mechanisms, I aimed to identify epigenetic modulations that can enhance iPS cell generation. By studying chemicals modulating epigenetic status and ES-cell enriched epigenetic factors, I demonstrate that butyrate, a histone deacetylase (HDAC) inhibitor, and Kdm2b, a histone demethylase specific for H3 lysine 36 dimethylation (H3K36me2) are capable of facilitating iPS cell generation. Butyrate not only enhances the efficiency of iPS cell generation, but also suppresses the formation of partially reprogrammed cells and transformed cells. The enhancing effect of butyrate on reprogramming appears to depend on c-Myc and occurs early in reprogramming. Genome-wide microarray analysis shows that a set of ES cell-enriched genes are upregulated upon butyrate treatment.
[Show full text]
Epigenetic Reprogramming by TET Enzymes Impacts Co-Transcriptional R-Loops 2 3 João C
bioRxiv preprint doi: https://doi.org/10.1101/2021.04.26.441414; this version posted April 27, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY 4.0 International license. 1 Epigenetic reprogramming by TET enzymes impacts co-transcriptional R-loops 2 3 João C. Sabino1, Madalena R. de Almeida1, Patricia L. Abreu1, Ana M. Ferreira1, Marco M. 4 Domingues1, Nuno C. Santos1, Claus M. Azzalin1, Ana R. Grosso1†, Sérgio F. de Almeida1* 5 6 Affiliations: 1Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina da 7 Universidade de Lisboa, Lisboa, Portugal. 8 *Correspondence to: [email protected] 9 †Current address: UCIBIO-REQUIMTE, Departamento de Ciências da Vida, Faculdade de 10 Ciências e Tecnologia, Universidade NOVA de Lisboa, 2829-516 Caparica, Portugal 11 12 13 Abstract 14 DNA oxidation by ten-eleven translocation (TET) family enzymes is essential for epigenetic 15 reprogramming. The conversion of 5-methylcytosine (5mC) into 5-hydroxymethylcytosine 16 (5hmC) initiates developmental and cell-type-specific transcriptional programs through 17 mechanisms that include changes in the chromatin structure. Here, we show that the 18 presence of 5hmC in the transcribed DNA promotes the annealing of the nascent RNA to its 19 template DNA strand, leading to the formation of an R-loop. The genome-wide distribution 20 of 5hmC and R-loops show a positive correlation in mouse and human embryonic stem cells 21 and overlap in half of all active genes.
[Show full text]
Working Party of National Coordinators of the Test Guidelines Programme
Organisation for Economic Co-operation and Development ENV/CBC/TG(2021)31 For Official Use English - Or. English 7 May 2021 ENVIRONMENT DIRECTORATE CHEMICALS AND BIOTECHNOLOGY COMMITTEE Working Party of National Coordinators of the Test Guidelines Programme Adverse Outcome Pathway 220 on Cyp2E1 Activation Leading to Liver Cancer Nathalie Delrue, Administrator [email protected] JT03476102 OFDE This document, as well as any data and map included herein, are without prejudice to the status of or sovereignty over any territory, to the delimitation of international frontiers and boundaries and to the name of any territory, city or area. 2 ENV/CBC/TG(2021)31 Foreword This Adverse Outcome Pathway (AOP) on Cyp2E1 Activation Leading to Liver Cancer, has been developed under the auspices of the OECD AOP Development Programme, overseen by the Extended Advisory Group on Molecular Screening and Toxicogenomics (EAGMST), which is an advisory group under the Working Party of the National Coordinators of the Test Guidelines Programme (WNT). The AOP has been reviewed internally by the EAGMST, externally by experts nominated by the WNT, and has been endorsed by the WNT and the Working Party on Hazard Assessment (WPHA) on XXX. Through endorsement of this AOP, the WNT and the WPHA express confidence in the scientific review process that the AOP has undergone and accept the recommendation of the EAGMST that the AOP be disseminated publicly. Endorsement does not necessarily indicate that the AOP is now considered a tool for direct regulatory application. The OECD's Chemicals and Biotechnology Committee agreed to declassification of this AOP on XXX.
[Show full text]
Reprogramming of Chromatin Accessibility in Somatic Cell Nuclear Transfer Is DNA Replication Independent
Report Reprogramming of Chromatin Accessibility in Somatic Cell Nuclear Transfer Is DNA Replication Independent Graphical Abstract Authors Mohamed Nadhir Djekidel, Azusa Inoue, SCNT reprogrammed 1cell donor cumulus cell Shogo Matoba, ..., Falong Lu, Lan Jiang, 12 hours Yi Zhang with or without Aphidicolin Correspondence [email protected] Replication-independent reprogramming of DHSs No. of DHS In Brief open closed 14924 Djekidel et al. used low-input DNase-seq to map the chromatin accessibility dynamics of donor cells and SCNT one- closed open cell embryos. They revealed a drastic and 179 fast global DHS reprogramming of donor cells in a DNA replication-independent manner. resemble paternal pronucelus successful reprogramiming open open 524 closed closed resistant 262 somatic memory Highlights Data and Software Availability d Genome-wide DHS maps for donor cumulus cells, one-cell GSE110851 SCNT, and IVF embryos d Rapid and DNA replication-independent DHS reprogramming in SCNT embryos d Transcription factor network switch accompanies DHS reprogramming in SCNT embryos d Loss of donor cell DHSs correlates with suppression of somatic transcription program Djekidel et al., 2018, Cell Reports 23, 1939–1947 May 15, 2018 ª 2018 The Authors. https://doi.org/10.1016/j.celrep.2018.04.036 Cell Reports Report Reprogramming of Chromatin Accessibility in Somatic Cell Nuclear Transfer Is DNA Replication Independent Mohamed Nadhir Djekidel,1,2,3,9 Azusa Inoue,1,2,3,6,9 Shogo Matoba,1,2,3,7 Tsukasa Suzuki,1,2,3 Chunxia Zhang,1,2,3 Falong
[Show full text]