Recommended Readings: Elaine Fuchs PhD October 24, 2016

Monday Lecture Series

Monday October 24, 2016   3:45 p.m.

Caspary Auditorium

Elaine Fuchs, Ph.D.

Rebecca Lancefield Professor

Laboratory of Mammalian Cell Biology and Development

Skin Stem Cells in Silence, Action and Cancer

Recommended Readings:

Quist, S. R.; Eckardt, M.; Kriesche, A.; et al.  Expression of epidermal stem cell markers in skin and adnexal malignancies. BRITISH JOURNAL OF DERMATOLOGY   175(3):520-530     SEP 2016

 Holland, Jane D.; Klaus, Alexandra; Garratt, Alistair N.; et al.  Wnt signaling in stem and cancer stem cells.  CURRENT OPINION IN CELL BIOLOGY    25(2):254-264  APR 2013

Arwert, Esther N.; Hoste, Esther; Watt, Fiona M.    Epithelial stem cells, wound healing and cancer.  NATURE REVIEWS CANCER   12(3):170-180   MAR 2012

Blanpain, Cedric; Fuchs, Elaine  STEM CELL PLASTICITY Plasticity of epithelial stem cells in tissue regeneration.  SCIENCE   344(6189):1243-+  ( Article Number: 1242281)  JUN 13 2014

Hsu, Ya-Chieh; Li, Lishi; Fuchs, Elaine  Transit-Amplifying Cells Orchestrate Stem Cell Activity and Tissue Regeneration. CELL   157(4):935-949     MAY 8 2014

Fuchs, Elaine; Chen, Ting  A matter of life and death: self-renewal in stem cells.  EMBO REPORTS   14 (1): 39-48   JAN 2013 

Oshimori, Naoki; Fuchs, Elaine   The Harmonies Played by TGF-beta in Stem Cell Biology.    CELL STEM CELL   11(6):751-764    DEC 7 2012

Recommended Readings: Frank Grosveld, Ph.D., June 5th

Friday Lecture Series
Friday, June 5, 2015
3:45 p.m., Caspary Auditorium

Frank Grosveld, Ph.D.
Professor and Head,
Department of Cell Biology
Chair, Research School MGC,
Erasmus MC

Transcription Factors and Genomic Architecture

Recommended Readings

Empirical Articles

Ghamari, A., van de Corput, M. P., Thongjuea, S., van Cappellen, W. A., van IJcken, W., van Haren, J., … & Grosveld, F. G. (2013). In vivo live imaging of RNA polymerase II transcription factories in primary cells. Genes & Development, 27(7), 767-777. doi:10.1101/gad.216200.113

Mylona, A., Andrieu-Soler, C., Thongjuea, S., Martella, A., Soler, E., Jorna, R., … & Grosveld, F. (2013). Genome-wide analysis shows that Ldb1 controls essential hematopoietic genes/pathways in mouse early development and reveals novel players in hematopoiesis. Blood, 121(15), 2902-2913. doi:10.1182/blood-2012-11-467654

Nuez, B., Michalovich, D., Bygrave, A., Ploemacher, R., & Grosveld, F. (1995). Defective haematopoiesis in fetal liver resulting from inactivation of the EKLF gene. Nature, 375(6529), 316-318.

Soler, E., Andrieu-Soler, C., de Boer, E., Bryne, J. C., Thongjuea, S., Stadhouders, R., … & Grosveld, F. (2010). The genome-wide dynamics of the binding of Ldb1 complexes during erythroid differentiation. Genes & Development, 24(3), 277-289. doi:10.1101/gad.551810

Stadhouders, R., Thongjuea, S., Andrieu‐Soler, C., Palstra, R. J., Bryne, J. C., van den Heuvel, A., … & Soler, E. (2012). Dynamic long‐range chromatin interactions control Myb proto‐oncogene transcription during erythroid development. The EMBO Journal, 31(4), 986-999. doi:10.1038/emboj.2011.450

Review Papers

Kolovos, P., Knoch, T. A., Grosveld, F. G., Cook, P. R., & Papantonis, A. (2012). Enhancers and silencers: an integrated and simple model for their function. Epigenetics Chromatin, 5(1). doi:10.1186/1756-8935-5-1

Recommended Readings: Kivanc Birsoy, Ph.D., January 14

Special Lecture
Friday, January 14, 2015
4:00 p.m., Carson Family Auditorium (CRC)

Kivanc Birsoy, Ph.D.
Jane Coffin Childs Medical Fund Fellow,
Whitehead Institute for Biomedical Research
Broad Institute of Harvard and MIT

Systematic Approaches to Study Metabolic Plasticity of Cancer Cells

Recommended Readings

Empirical Articles

Birsoy, K., Possemato, R., Lorbeer, F. K., Bayraktar, E. C., Thiru, P., Yucel, B., … Sabatini, D. M. (2014). Metabolic determinants of cancer cell sensitivity to glucose limitation and biguanides. Nature, 508(7494), 108–112. doi:10.1038/nature13110

Birsoy, K., Wang, T., Possemato, R., Yilmaz, O. H., Koch, C. E., Chen, W. W., … Sabatini, D. M. (2013). MCT1-mediated transport of a toxic molecule is an effective strategy for targeting glycolytic tumors. Nature Genetics, 45(1), 104–108. doi:10.1038/ng.2471

Grabiner, B. C., Nardi, V., Birsoy, K., Possemato, R., Shen, K., Sinha, S., … Sabatini, D. M. (2014). A diverse array of cancer-associated MTOR mutations are hyperactivating and can predict rapamycin sensitivity. Cancer Discovery, 4(5), 554–563. doi:10.1158/2159-8290.CD-13-0929

Review Papers

Birsoy, K., Sabatini, D. M., & Possemato, R. (2012). Untuning the tumor metabolic machine: Targeting cancer metabolism: a bedside lesson. Nature Medicine, 18(7), 1022–1023. doi:10.1038/nm.2870

Recommended Readings: Louis M. Staudt, M.D., Ph.D. January 9

Friday Lecture Series
Friday, January 9, 2015
3:45 p.m., Caspary Auditorium

Louis M. Staudt, M.D., Ph.D.
Director, Center for Cancer Genomics
Co-chief, Lymphoid Malignancies Branch
Head, Molecular Biology of Lymphoid Malignancies Section,
Center for Cancer Research,
National Cancer Institute at the National Institutes of Health

Therapy of Lymphoma Inspired by Functional and Structural Genomics

Recommended Readings

Empirical Articles

Alizadeh, A., Eisen, M., Davis, R., & Ma, C. (2000). Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature, 403(6769), 503-511.

Ngo, V. N., Davis, R. E., Lamy, L., Yu, X., Zhao, H., Lenz, G., … Staudt, L. M. (2006). A loss-of-function RNA interference screen for molecular targets in cancer. Nature, 441(7089), 106–110. doi:10.1038/nature04687

Rosenwald, A., Wright, G., Chan, W. C., Connors, J. M., Campo, E., Fisher, R. I., … Staudt, L. M. (2002). The use of molecular profiling to predict survival after chemotherapy for diffuse large-B-cell lymphoma. The New England Journal of Medicine, 346(25), 1937–1947. doi:10.1056/NEJMoa012914

Yang, Y., III, A. S., Emre, N., & Ceribelli, M. (2012). Exploiting synthetic lethality for the therapy of ABC diffuse large B cell lymphoma. Cancer Cell, 21(6), 723–737. doi:10.1016/j.ccr.2012.05.024.Exploiting

Review Papers

Lenz, G., & Staudt, L. M. (2010). Aggressive lymphomas. The New England Journal of Medicine, 362(15), 1417–1429. doi:10.1056/NEJMra0807082

Shaffer, A. L., Young, R. M., & Staudt, L. M. (2012). Pathogenesis of human B cell lymphomas. Annual Review of Immunology, 30, 565–610. doi:10.1146/annurev-immunol-020711-075027

Recommended Readings: Sohail Tavazoie, Ph.D. October 6

Monday Lecture Series
Monday, October 6, 2014
3:45 p.m., Caspary Auditorium

Sohail Tavazoie, Ph.D.
Leon Hess Assistant Professor and Head,
Elizabeth and Vincent Meyer Laboratory of Systems Cancer Biology,
The Rockefeller University
Senior Attending Physician,
The Rockefeller University Hospital

Molecular Control of Cancer Metastasis

Recommended Readings

Empirical Articles

Pencheva, N., Tran, H., Buss, C., Huh, D., Drobnjak, M., Busam, K., & Tavazoie, S. F. (2012). Convergent multi-miRNA targeting of ApoE drives LRP1/LRP8-dependent melanoma metastasis and angiogenesis. Cell, 151(5), 1068–1082. doi:10.1016/j.cell.2012.10.028

Png, K. J., Halberg, N., Yoshida, M., & Tavazoie, S. F. (2012). A microRNA regulon that mediates endothelial recruitment and metastasis by cancer cells. Nature, 481(7380), 190–194. doi:10.1038/nature10661

Png, K. J., Yoshida, M., Zhang, X. H.-F., Shu, W., Lee, H., Rimner, A., … Tavazoie, S. F. (2011). MicroRNA-335 inhibits tumor reinitiation and is silenced through genetic and epigenetic mechanisms in human breast cancer. Genes & Development, 25(3), 226–231. doi:10.1101/gad.1974211

Tavazoie, S. F., Alarcón, C., Oskarsson, T., Padua, D., Wang, Q., Bos, P. D., … Massagué, J. (2008). Endogenous human microRNAs that suppress breast cancer metastasis. Nature, 451(7175), 147–52. doi:10.1038/nature06487

Review Papers

Pencheva, N., & Tavazoie, S. F. (2013). Control of metastatic progression by microRNA regulatory networks. Nature Cell Biology, 15(6), 546–54. doi:10.1038/ncb2769

Recommended Readings: Wei Yang, Ph.D. March 10

Monday, March 10, 2014
4:00 p.m., Carson Family Auditorium

Wei Yang, Ph.D.
Senior Investigator and Section Chief
Department of Molecular Biology
National Institute of Diabetes and Digestive and Kidney Diseases
National Institutes of Health

Human DNA polymerase η: from Chemistry to Cancer Biology

Recommended Readings:

Empirical Articles

Biertümpfel, C., Zhao, Y., Kondo, Y., Ramón-Maiques, S., Gregory, M., Lee, J. Y., … Yang, W. (2010). Structure and mechanism of human DNA polymerase η. Nature, 465(7301), 1044–1048. doi:10.1038/nature09196

Nakamura, T., Zhao, Y., Yamagata, Y., Hua, Y., & Yang, W. (2012). Watching DNA polymerase η make a phosphodiester bond. Nature, 487(7406), 196–201. doi:10.1038/nature11181

Zhao, Y., Biertümpfel, C., Gregory, M. T., Hua, Y.-J., Hanaoka, F., & Yang, W. (2012). Structural basis of human DNA polymerase η-mediated chemoresistance to cisplatin. Proceedings of the National Academy of Sciences of the United States of America, 109(19), 7269–7274. doi:10.1073/pnas.1202681109

Zhao, Y., Gregory, M. T., Biertümpfel, C., Hua, Y., Hanaoka, F., & Yang, W. (2013). Mechanism of somatic hypermutation at the WA motif by human DNA polymerase η. Proceedings of the National Academy of Sciences of the United States of America, 110(20), 8146–8151. doi:10.1073/pnas.1303126110

Review Papers

Lange, S. S., Takata, K., & Wood, R. D. (2011). DNA polymerases and cancer. Nature Reviews Cancer, 11(2), 96–110. doi:10.1038/nrc2998

Sale, J. E., Lehmann, A. R., & Woodgate, R. (2012). Y-family DNA polymerases and their role in tolerance of cellular DNA damage. Nature Reviews Molecular Cell Biology, 13(3), 141–152. doi:10.1038/nrm3289

Yang, W. (2003). Damage repair DNA polymerases Y. Current Opinion in Structural Biology, 13(1), 23–30. doi:10.1016/S0959-440X(02)00003-9

Recommended Readings: Leonard Zon, M.D.

Monday, November 4, 2013
4:00 p.m., Carson Family Auditorium

Leonard Zon, M.D.
Director of the Stem Cell Program at Children’s Hospital Boston
Grousbeck Professor of Pediatric Medicine, Harvard Medical School
Investigator, Howard Hughes Medical Institute

Pathways that Stimulate Stem Cell Development and Self-Renewal

Recommended Readings:

Review Papers

De Jong, J. L. O., & Zon, L. I. (2005). Use of the zebrafish system to study primitive and definitive hematopoiesis. Annual Review of Genetics, 39, 481–501. doi:10.1146/annurev.genet.39.073003.095931

Orkin, S. H., & Zon, L. I. (2008). Hematopoiesis: an evolving paradigm for stem cell biologyCell132(4), 631–644. doi:10.1016/j.cell.2008.01.025

White, R., Rose, K., & Zon, L. (2013). Zebrafish cancer: the state of the art and the path forward. Nature Reviews Cancer, 13(9), 624–636. doi:10.1038/nrc3589

Zon, L. I. (2008). Intrinsic and extrinsic control of haematopoietic stem-cell self-renewal. Nature, 453(7193), 306–313. doi:10.1038/nature07038

Empirical Articles

Goessling, W., North, T. E., Loewer, S., Lord, A. M., Lee, S., Stoick-Cooper, C. L., … Zon, L. I. (2009). Genetic interaction of PGE2 and Wnt signaling regulates developmental specification of stem cells and regeneration. Cell, 136(6), 1136–1147. doi:10.1016/j.cell.2009.01.015

Lengerke, C., Schmitt, S., Bowman, T. V, Jang, I. H., Maouche-Chretien, L., McKinney-Freeman, S., … Daley, G. Q. (2008). BMP and Wnt specify hematopoietic fate by activation of the Cdx-Hox pathway. Cell Stem Cell, 2(1), 72–82. doi:10.1016/j.stem.2007.10.022

North, T. E., Goessling, W., Peeters, M., Li, P., Ceol, C., Lord, A. M., … Zon, L. I. (2009). Hematopoietic stem cell development is dependent on blood flow. Cell, 137(4), 736–748. doi:10.1016/j.cell.2009.04.023

North, T. E., Goessling, W., Walkley, C. R., Lengerke, C., Kopani, K. R., Lord, A. M., … Zon, L. I. (2007). Prostaglandin E2 regulates vertebrate haematopoietic stem cell homeostasis. Nature, 447(7147), 1007–1011. doi:10.1038/nature05883

Breakthrough Science: Cancer Immunotherapy – a new “One-Two” Punch SIRPalpha

 Engineered SIRPα Variants as Immunotherapeutic Adjuvants to Anticancer

K. Weiskoff et al.    ScienceExpress  May 31, 2013

AntibodiesCD47 is an antiphagocytic signal that cancer cells employ to inhibit macrophage-mediated destruction. Here, we modified the binding domain of human SIRPα, the receptor for CD47, for use as a CD47 antagonist. We engineered high-affinity SIRPα variants with approximately 50,000-fold increased affinity for human CD47 relative to wild-type SIRPα. As high-affinity SIRPα monomers, they potently antagonized CD47 on cancer cells but did not induce macrophage phagocytosis on their own. Instead, they exhibited remarkable synergy with all tumor-specific monoclonal antibodies tested by increasing phagocytosis in vitro and enhancing antitumor responses in vivo. This “one-two punch” directs immune responses against tumor cells while lowering the threshold for macrophage activation, thereby providing a universal method for augmenting the efficacy of therapeutic anticancer antibodies.


Recommended Readings: Titia de Lange, Ph.D.

Friday Lecture Series

Cancer Biology Lecture

How Telomeres Solved the End-protection Problem

Titia de Lange, Ph.D., Leon Hess Professor and head,

Laboratory of Cell Biology and Genetics,

The Rockefeller University

March 23, 2012

3:45 p.m.-5:00 p.m. (Refreshments, 3:15 p.m., Abby Lounge)

Caspary Auditorium


Recommended Readings:

Davoli, T., E. L. Denchi, and T. de Lange. 2010. “Persistent Telomere Damage Induces Bypass of Mitosis and Tetraploidy.” Cell 141 (1): 81-93

Davoli, T. and T. De Lange. 2011. The Causes and Consequences of Polyploidy in Normal Development and Cancer. Annual Review of Cell and Developmental Biology. Vol. 27: 585-610

De Lange, T. 2009. “How Telomeres Solve the End-Protection Problem.” Science 326 (5955): 948-952

Gong, Y. and T. de Lange. 2010. “A Shld1-Controlled POT1a Provides Support for Repression of ATR Signaling at Telomeres through RPA Exclusion.” Molecular Cell 40 (3): 377-387

Kabir, S., A. Sfeir, and T. De Lange. 2010. “Taking Apart Rap1: An Adaptor Protein with Telomeric and Non-Telomeric Functions.” Cell Cycle 9 (20): 4061-4067

Palm, W. and T. De Lange. 2008. How Shelterin Protects Mammalian Telomeres. Annual Review of Genetics. Vol. 42.

Sfeir, A., S. Kabir, M. Van Overbeek, G. B. Celli, and T. De Lange. 2010. “Loss of Rap1 Induces Telomere Recombination in the Absence of NHEJ Or a DNA Damage Signal.” Science 327 (5973): 1657-1661

Sfeir, A., S. T. Kosiyatrakul, D. Hockemeyer, S. L. MacRae, J. Karlseder, C. L. Schildkraut, and T. de Lange. 2009. “Mammalian Telomeres Resemble Fragile Sites and Require TRF1 for Efficient Replication.” Cell 138 (1): 90-103

Scherthan, H., A. Sfeir, and T. De Lange. 2011. “Rap1-Independent Telomere Attachment and Bouquet Formation in Mammalian Meiosis.” Chromosoma 120 (2): 151-157