Department of Cell Biology

New Publications

From the Schildkraut Lab - Pan X, Drosopoulos WC, Sethi L, Madireddy A, Schildkraut CL, Zhang D. FANCM, BRCA1, and BLM cooperatively resolve the replication stress at the ALT telomeres. (2017) Proc Natl Acad Sci U S A.:E5940-E5949. PMID: 28673972.
"Inhibition of telomere length is an important goal in tumor therapy. Some cancer cells use a repair-based human alternative lengthening telomere (ALT) pathway to maintain telomeres. We describe new opportunities to target cancers involving ALT."

From the Fyodorov and Skoultchi Labs - Evgeniya N. Andreyeva, Travis J. Bernardo, Tatyana D. Kolesnikova, Xingwu Lu, Lyubov A. Yarinich, Boris A. Bartholdy, Xiaohan Guo, Olga V. Posukh, Sean Healton, Michael A. Willcockson, Alexey V. Pindyurin, Igor F. Zhimulev, Arthur I. Skoultchi, and Dmitry V. Fyodorov. Regulatory functions and chromatin loading dynamics of linker histone H1 during endoreplication in Drosophila. Genes Dev. 2017; 31: 603-616. PMID: 28404631.
"This study uncovers a direct role for the H1 linker histone in DNA replication, specifically during endoreplication of polytene chromosomes in Drosophila where H1 is critical for formation of under replicated domains. We also discovered that the distribution of H1 changes dramatically during the endocycle S phase. Early in S phase, H1 is heavily deposited in late replicating chromatin and then redistributed as endoreplication proceeds. The results suggest that H1 may play a key role in regulating the locus-specific timing of DNA replication during S phase."

From the Skoultchi Lab - Kokavec J, Zikmund T, Savvulidi F, Kulvait V, Edelmann W, Skoultchi AI, Stopka T. Smarca5 (Snf2h) is required for Proliferation of Hematopoietic Stem Cells Differentiating into Erythroid and Myeloid lineages. Stem Cells. 2017 Mar 9. doi: 10.1002/stem.2604. [Epub ahead of print]. PMID: 28276606
“This study utilizes a new conditional knock-out mouse model for the essential chromatin remodeling ATPase Smarca5 (Snf2h) to explore its role in hematopoiesis. The results show that Smarca5 is required for the proliferation and differentiation of hematopoietic stem and multipotent progenitor cells as well as fully committed erythroid progenitors.”

From the Guo Lab - Wang C., Christin JR., Oktay MH., Guo W.. Lineage-Biased Stem Cells Maintain Estrogen-Receptor-Positive and -Negative Mouse Mammary Luminal Lineages. Cell Reports. 2017 Mar 21;18(12):2825-2835. doi: 10.1016/j.celrep.2017.02.071.
“This study uncovers that estrogen-receptor-positive and -negative luminal cells are two separate lineages that are maintained by distinct lineage-biased stem cells. This finding provides a new framework for studying mammary differentiation and breast cancer etiology.”

From the Stanley Lab - Shogo Sawaguchi, Shweta Varshney, Mitsutaka Ogawa, Yuta Sakaidani, Hirokazu Yagi, Kyosuke Takeshita, Toyoaki Murohara, Koichi Kato, Subha Sundaram, Pamela Stanley, Tetsuya Okajima. O-GlcNAc on NOTCH1 EGF repeats regulates ligand-induced Notch signaling and vascular development in mammals. eLife 2017;6:e24419. DOI: http://dx.doi.org/10.7554/eLife.24419.
"It is known that Notch receptors are regulated by O-fucose and O-glucose glycans attached to Ser and Thre in the EGF repeats of their extracellular domain. Our paper shows for the first time that modification by N-acetylglucosamine (O-GlcNAc) also regulates ligand-induced Notch signaling. Importantly, O-GlcNAc regulates signaling by Delta Notch ligands but not by Jagged Notch ligands. Loss of EOGT, the enzyme that transferase O-GlcNAc to Notch, leads to Adams-Oliver Syndrome in humans.”

From the Frenette Lab - Pierce H, Zhang D, Magnon C, Lucas D, Christin JR, Huggins M, Schwartz GJ, Frenette PS. Cholinergic Signals from the CNS Regulate G-CSF-Mediated HSC Mobilization from Bone Marrow via a Glucocorticoid Signaling Relay. Cell Stem Cell. 2017 Feb 4. pii: S1934-5909(17)30002-4. doi: 10.1016/j.stem.2017.01.002. [Epub ahead of print].
“This work uncovers a new link between brain and bone marrow where muscarinic receptors expressed in the hypothalamus regulate the HPA axis and alter hematopoietic stem cell migration via hormonal influence.”

From the Frenette Lab - Asada N, Kunisaki Y, Pierce H, Wang Z, Fernandez NF, Birbrair A, Ma'ayan A, Frenette PS. Differential cytokine contributions of perivascular haematopoietic stem cell niches. Nat Cell Biol. 2017 Feb 20. doi: 10.1038/ncb3475. [Epub ahead of print]
“This work shows that perivascular stromal cells are heterogeneous in their supply of cytokines (CXCL12 and SCF) that regulate hematopoietic stem cell maintenance.”

From the Query Lab - Qing Tang, Susana Rodriguez-Santiago, Jing Wang, Jia Pu, Andrea Yuste, Varun Gupta, Alberto Moldón, Yong-Zhen Xu, and Charles C. Query. SF3B1/Hsh155 HEAT motif mutations affect interaction with the spliceosomal ATPase Prp5, resulting in altered branch site selectivity in pre-mRNA splicing. Genes Dev. 2017; 30: 2710-2723.
“In this study, Tang et al. investigated the mechanisms underlying alternate splicing. They show that hsh155 mutant alleles in S. cerevisiae, counterparts of SF3B1 mutations frequently found in cancers, specifically change splicing of suboptimal branch site pre-mRNA substrates, thus providing a mechanistic framework to explain the consequences of intron recognition and splicing of SF3B1 mutations found in disease.”

From the Ye Lab - Alvarez M.J., Shen Y., Giorgi F.M., Lachmann A., Ding B.B., Ye B.H., Califano A. Functional characterization of somatic mutations in cancer using network-based inference of protein activity. Nat Genet. 2016 Aug;48(8):838-47. doi: 10.1038/ng.3593. Epub 2016 Jun 20.
“In this study, a computational algorithm, virtual inference of protein activity by enriched regulon analysis (VIPER), was developed and experimentally validated. We show that VIPER can accurate measure protein activity based on gene expression data, thus accurately predicting aberrant protein functions independent of cancer-associated mutations.”

From the Ye Lab - Mai Y., Yu J.J., Bartholdy B., Xu-Monette Z.Y., Knapp E.E., Yuan F., Chen H., Ding B.B., Yao Z., Das B., Zou Y., Young K.H., Parekh S., Ye B.H. An oxidative stress-based mechanism of doxorubicin cytotoxicity suggests new therapeutic strategies in ABC-DLBCL. Blood. 2016 Oct 13. pii: blood-2016-03-705814. [Epub ahead of print].
“In this study, we discovered that a key ingredient in the first-line therapy for diffuse large B-cell lymphomas, doxorubicin, has subtype-specific mechanism of cytotoxicity due to differences in subcellular localization. We also demonstrated that STAT3 promotes resistance to ROS-mediated Dox cytotoxicity by upregulating the expression of SOD2.”

From the Ye Lab - Alvarez M.J., Shen Y., Giorgi F.M., Lachmann A., Ding B.B., Ye B.H., Califano A. Functional characterization of somatic mutations in cancer using network-based inference of protein activity. Nat Genet. 2016 Aug;48(8):838-47. doi: 10.1038/ng.3593. Epub 2016 Jun 20.
“In this study, a computational algorithm, virtual inference of protein activity by enriched regulon analysis (VIPER), was developed and experimentally validated. We show that VIPER can accurate measure protein activity based on gene expression data, thus accurately predicting aberrant protein functions independent of cancer-associated mutations.”

From the Guo Lab - Zhang Z., Christin J.R,, Wang C., Ge K., Oktay M.H., Guo W.. Mammary-Stem-Cell-Based Somatic Mouse Models Reveal Breast Cancer Drivers Causing Cell Fate Dysregulation. Cell Rep. 2016 Sep 20;16(12):3146-56. doi: 10.1016/j.celrep.2016.08.048.
“We have developed an efficient method for generating somatic GEMMs for breast cancer through ex vivo expansion and genome editing of mammary stem cells. Using this platform, We have uncovered the functional roles of several human cancer-associated genes in tumorigenesis and mammary cell fate dysregulation.”.

From the Kielian Lab - Dubé M, Etienne L, Fels M, Kielian M.. Calcium-Dependent Rubella Virus Fusion Occurs in Early Endosomes. J Virol. 2016 Jun 24;90(14):6303-13. doi: 10.1128/JVI.00634-16. Print 2016 Jul 15..
Here we addressed the mechanism of the unusual calcium requirement and the required location of calcium during Rubella virus entry.

From the Fyodorov and Skoultchi Labs - Kavi, H., A. V. Emelyanov, D. V. Fyodorov and A. I. Skoultchi. Independent biological and biochemical functions for individual structural domains of Drosophila linker histone H1. J Biol Chem. 2016 May 18. pii: jbc.M116.730705.
This study reports the first in-depth structure-function analysis of the contributions of individual domains and sub-domains of the H1 linker histone to its multiple functions in chromatin structure and activity in vivo.

From the Skoultchi Lab - Geeven, G., Y. Zhu, B. J. Kim, B. A. Bartholdy, S. M. Yang, T. S. Macfarlan, W. D. Gifford, S. L. Pfaff, M. J. Verstegen, H. Pinto, M. W. Vermunt, M. P. Creyghton, P. J. Wijchers, J. A. Stamatoyannopoulos, A. I. Skoultchi and W. de Laat. Local compartment changes and regulatory landscape alterations in histone H1-depleted cells. Genome Biol 16: 289
• This study uses a combination of genome-wide approaches, including chromosome capture (Hi-C), DNA methylation, histone modification and DNase I hypersensitivity profiling to investigate the impact of reducing cellular levels of H1 linker histone in embryonic stem cells on chromatin folding and function. The results show that H1 plays a major role in the maintenance of topologically associated domains (TADs) and the epigenetic landscape within TADs..

From the Kielian lab - Stiles, KM., Kielian, M. Role of TSPAN9 in Alphavirus Entry and Early Endosomes. 2016. J Virol 90:4289–4297. doi:10.1128/JVI.00018-16.
• TSPAN9 Modulates Early Endosomes To Enhance Fusion of Early-Penetrating Viruses.

From the Steidl lab - Okoye-Okafor UC, Bartholdy B, Cartier J, Gao EN, Pietrak B, Rendina AR, Rominger C, Quinn C, Smallwood A, Wiggall KJ, Reif AJ, Schmidt SJ, Qi H, Zhao H, Joberty G, Faelth-Savitski M, Bantscheff M, Drewes G, Duraiswami C, Brady P, Groy A, Narayanagari SR, Antony-Debre I, Mitchell K, Wang HR, Kao YR, Christopeit M, Carvajal L, Barreyro L, Paietta E, Makishima H, Will B, Concha N, Adams ND, Schwartz B, McCabe MT, Maciejewski J, Verma A, Steidl U. New IDH1 mutant inhibitors for treatment of acute myeloid leukemia. Nature Chemical Biology (2015); doi:10.1038/nchembio.1930
• Neomorphic mutations in isocitrate dehydrogenase 1 (IDH1) are common in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). A novel class of allosteric IDH1 inhibitors is effective against multiple clinically relevant mutants, promoting differentiation of AML blasts and stem-like cells and restoring DNA cytosine methylation patterns.

From the Kielian Lab - Fields, W. Kielian, M. Interactions Involved in pH Protection of the Alphavirus Fusion Protein. Virology 486:173-179. (2015).
• Using site-directed mutagenesis and revertant analysis, we define residues that promote pH protection of the alphavirus fusion protein during its transit through the exocytic pathway.

From the Stanley Lab - Huang HH, Hassinen A, Sundaram S, Spiess AN, Kellokumpu S, Stanley P. GnT1IP-L specifically inhibits MGAT1 in the Golgi via its luminal domain. Elife. 2015 Sep 15;4. doi: 10.7554/eLife.08916.
• We previously identified a testis-specific inhibitor of complex N-glycan synthesis, GnT1IP-L, and now show that it forms heteromers specifically with the glycosyltransferase MGAT1 in the Golgi but not the ER, is expressed in spermatocytes and spermatids, and is absent in men with Sertoli Only Syndrome.

 

Departmental Office

Albert Einstein College of Medicine
1300 Morris Park Avenue
Chanin Building, Room 405
New York, NY 10461

Telephone : 718.430.2815
Fax :            718.430.8574
Email :        cellbio@einstein.yu.edu 

Laboratory Directory 

 

Upcoming Events

Work-in-Progress
Friday, 11/10/2017
Cell Biology Library
Dr. Guojun Yu
Mentor: Dr. Scharff

Friday, 11/17/2017
Cell Biology Library
Dr. Fumio Nakahara
Mentor: Dr. Frenette

Friday, 12/01/2017
Cell Biology Library
Dr. Chunhui Wang
Mentor: Dr. Guo

 

Journal Club
Wednesday, 11/15/2017
4:30PM
Jennifer Kimble/Rich Piszczatowski
Mentor: Dr. Kielian/ Dr. Steidl

Wednesday, 01/10/2018
4:30PM
Michael Willcockson/Geoge Georgiev
Mentor: Dr. Skoultchi/ Dr. Will
 

Outside Speaker
Wednesday,11/08/2017
12:00 noon
Third Floor Lecture Hall
Forchheimer Building
Dr. Donna Zhang
Host: Dr. Ye

Wednesday,12/06/2017
12:00 noon
Third Floor Lecture Hall
Forchheimer Building
Dr. Paul Cohen
Host: Dr. Kitsis
 

Friday Get Together
Friday, 11/17/2017
Host: the Will Lab

Complete Event Listing 

 
Click here to log in