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Eric Lander

Marios Giannakis, Xinmeng Jasmine Mu, Sachet A Shukla, Zhi Rong Qian, Ofir Cohen, Reiko Nishihara, Samira Bahl, Yin Cao, Ali Amin-Mansour, Mai Yamauchi, Yasutaka Sukawa, Chip Stewart, Mara Rosenberg, Kosuke Mima, Kentaro Inamura, Katsuhiko Nosho, Jonathan A Nowak, Michael S Lawrence, Edward L Giovannucci, Andrew T Chan, Kimmie Ng, Jeffrey A Meyerhardt, Eliezer M Van Allen, Gad Getz, Stacey B Gabriel, Eric S Lander, Catherine J Wu, Charles S Fuchs, Shuji Ogino, Levi A Garraway
No abstract text is available yet for this article.
October 18, 2016: Cell Reports
David A Barrington, Sarah E Dilley, Emily E Landers, Eric D Thomas, Jonathon D Boone, J Michael Straughn, Gerald McGwin, Charles A Leath
OBJECTIVE: To evaluate the potential relationship between outcomes in cervical cancer patients based on distance from our Comprehensive Cancer Center (CCC). METHODS: A retrospective cohort study of cervical cancer patients was performed. Abstracted data included: demographics, clinicopathologic variables, treatment, and survival. Analyses both by quartiles and distance <100 and ≥100miles from our institution were performed. Data were analyzed using SAS version 9...
October 6, 2016: Gynecologic Oncology
Charles P Fulco, Mathias Munschauer, Rockwell Anyoha, Glen Munson, Sharon R Grossman, Elizabeth M Perez, Michael Kane, Brian Cleary, Eric S Lander, Jesse M Engreitz
Gene expression in mammals is regulated by noncoding elements that can impact physiology and disease, yet the functions and target genes of most noncoding elements remain unknown. We present a high-throughput approach that uses CRISPR interference (CRISPRi) to discover regulatory elements and identify their target genes. We assess >1 megabase (Mb) of sequence in the vicinity of 2 essential transcription factors, MYC and GATA1, and identify 9 distal enhancers that control gene expression and cellular proliferation...
September 29, 2016: Science
Chunxing Yang, Eric W Danielson, Tao Qiao, Jake Metterville, Robert H Brown, John E Landers, Zuoshang Xu
Mutations in the profilin 1 (PFN1) gene cause amyotrophic lateral sclerosis (ALS), a neurodegenerative disease caused by the loss of motor neurons leading to paralysis and eventually death. PFN1 is a small actin-binding protein that promotes formin-based actin polymerization and regulates numerous cellular functions, but how the mutations in PFN1 cause ALS is unclear. To investigate this problem, we have generated transgenic mice expressing either the ALS-associated mutant (C71G) or wild-type protein. Here, we report that mice expressing the mutant, but not the wild-type, protein had relentless progression of motor neuron loss with concomitant progressive muscle weakness ending in paralysis and death...
October 11, 2016: Proceedings of the National Academy of Sciences of the United States of America
Neva C Durand, James T Robinson, Muhammad S Shamim, Ido Machol, Jill P Mesirov, Eric S Lander, Erez Lieberman Aiden
Hi-C experiments study how genomes fold in 3D, generating contact maps containing features as small as 20 bp and as large as 200 Mb. Here we introduce Juicebox, a tool for exploring Hi-C and other contact map data. Juicebox allows users to zoom in and out of Hi-C maps interactively, just as a user of Google Earth might zoom in and out of a geographic map. Maps can be compared to one another, or to 1D tracks or 2D feature sets.
July 2016: Cell Systems
Neva C Durand, Muhammad S Shamim, Ido Machol, Suhas S P Rao, Miriam H Huntley, Eric S Lander, Erez Lieberman Aiden
Hi-C experiments explore the 3D structure of the genome, generating terabases of data to create high-resolution contact maps. Here, we introduce Juicer, an open-source tool for analyzing terabase-scale Hi-C datasets. Juicer allows users without a computational background to transform raw sequence data into normalized contact maps with one click. Juicer produces a hic file containing compressed contact matrices at many resolutions, facilitating visualization and analysis at multiple scales. Structural features, such as loops and domains, are automatically annotated...
July 2016: Cell Systems
Lori Robbins, Karen Zaghiyan, Gil Melmed, Eric Vasiliauskas, Shahzad Ahmed, Dermot McGovern, Shervin Rabizadeh, Namita Singh, Carol Landers, Andrew Ippoliti, David Shih, Stephan Targan, Phillip Fleshner
BACKGROUND AND AIMS: A subset of patients who undergo ileal pouch-anal anastomosis [IPAA] for ulcerative colitis [UC] will later be diagnosed with denovo Crohn's disease [CD]. These patients have a higher risk of pouch failure. In this study we evaluated inflammatory bowel disease [IBD] serology in patients with denovo CD and examined the success of anti-tumour necrosis factor-alpha [anti-TNFα] therapy in preventing ileostomy in denovo CD patients who failed anti-TNFα therapy before IPAA...
July 27, 2016: Journal of Crohn's & Colitis
Emily M Darrow, Miriam H Huntley, Olga Dudchenko, Elena K Stamenova, Neva C Durand, Zhuo Sun, Su-Chen Huang, Adrian L Sanborn, Ido Machol, Muhammad Shamim, Andrew P Seberg, Eric S Lander, Brian P Chadwick, Erez Lieberman Aiden
During interphase, the inactive X chromosome (Xi) is largely transcriptionally silent and adopts an unusual 3D configuration known as the "Barr body." Despite the importance of X chromosome inactivation, little is known about this 3D conformation. We recently showed that in humans the Xi chromosome exhibits three structural features, two of which are not shared by other chromosomes. First, like the chromosomes of many species, Xi forms compartments. Second, Xi is partitioned into two huge intervals, called "superdomains," such that pairs of loci in the same superdomain tend to colocalize...
August 2, 2016: Proceedings of the National Academy of Sciences of the United States of America
Christian Fuchsberger, Jason Flannick, Tanya M Teslovich, Anubha Mahajan, Vineeta Agarwala, Kyle J Gaulton, Clement Ma, Pierre Fontanillas, Loukas Moutsianas, Davis J McCarthy, Manuel A Rivas, John R B Perry, Xueling Sim, Thomas W Blackwell, Neil R Robertson, N William Rayner, Pablo Cingolani, Adam E Locke, Juan Fernandez Tajes, Heather M Highland, Josee Dupuis, Peter S Chines, Cecilia M Lindgren, Christopher Hartl, Anne U Jackson, Han Chen, Jeroen R Huyghe, Martijn van de Bunt, Richard D Pearson, Ashish Kumar, Martina Müller-Nurasyid, Niels Grarup, Heather M Stringham, Eric R Gamazon, Jaehoon Lee, Yuhui Chen, Robert A Scott, Jennifer E Below, Peng Chen, Jinyan Huang, Min Jin Go, Michael L Stitzel, Dorota Pasko, Stephen C J Parker, Tibor V Varga, Todd Green, Nicola L Beer, Aaron G Day-Williams, Teresa Ferreira, Tasha Fingerlin, Momoko Horikoshi, Cheng Hu, Iksoo Huh, Mohammad Kamran Ikram, Bong-Jo Kim, Yongkang Kim, Young Jin Kim, Min-Seok Kwon, Juyoung Lee, Selyeong Lee, Keng-Han Lin, Taylor J Maxwell, Yoshihiko Nagai, Xu Wang, Ryan P Welch, Joon Yoon, Weihua Zhang, Nir Barzilai, Benjamin F Voight, Bok-Ghee Han, Christopher P Jenkinson, Teemu Kuulasmaa, Johanna Kuusisto, Alisa Manning, Maggie C Y Ng, Nicholette D Palmer, Beverley Balkau, Alena Stancáková, Hanna E Abboud, Heiner Boeing, Vilmantas Giedraitis, Dorairaj Prabhakaran, Omri Gottesman, James Scott, Jason Carey, Phoenix Kwan, George Grant, Joshua D Smith, Benjamin M Neale, Shaun Purcell, Adam S Butterworth, Joanna M M Howson, Heung Man Lee, Yingchang Lu, Soo-Heon Kwak, Wei Zhao, John Danesh, Vincent K L Lam, Kyong Soo Park, Danish Saleheen, Wing Yee So, Claudia H T Tam, Uzma Afzal, David Aguilar, Rector Arya, Tin Aung, Edmund Chan, Carmen Navarro, Ching-Yu Cheng, Domenico Palli, Adolfo Correa, Joanne E Curran, Denis Rybin, Vidya S Farook, Sharon P Fowler, Barry I Freedman, Michael Griswold, Daniel Esten Hale, Pamela J Hicks, Chiea-Chuen Khor, Satish Kumar, Benjamin Lehne, Dorothée Thuillier, Wei Yen Lim, Jianjun Liu, Yvonne T van der Schouw, Marie Loh, Solomon K Musani, Sobha Puppala, William R Scott, Loïc Yengo, Sian-Tsung Tan, Herman A Taylor, Farook Thameem, Gregory Wilson, Tien Yin Wong, Pål Rasmus Njølstad, Jonathan C Levy, Massimo Mangino, Lori L Bonnycastle, Thomas Schwarzmayr, João Fadista, Gabriela L Surdulescu, Christian Herder, Christopher J Groves, Thomas Wieland, Jette Bork-Jensen, Ivan Brandslund, Cramer Christensen, Heikki A Koistinen, Alex S F Doney, Leena Kinnunen, Tõnu Esko, Andrew J Farmer, Liisa Hakaste, Dylan Hodgkiss, Jasmina Kravic, Valeriya Lyssenko, Mette Hollensted, Marit E Jørgensen, Torben Jørgensen, Claes Ladenvall, Johanne Marie Justesen, Annemari Käräjämäki, Jennifer Kriebel, Wolfgang Rathmann, Lars Lannfelt, Torsten Lauritzen, Narisu Narisu, Allan Linneberg, Olle Melander, Lili Milani, Matt Neville, Marju Orho-Melander, Lu Qi, Qibin Qi, Michael Roden, Olov Rolandsson, Amy Swift, Anders H Rosengren, Kathleen Stirrups, Andrew R Wood, Evelin Mihailov, Christine Blancher, Mauricio O Carneiro, Jared Maguire, Ryan Poplin, Khalid Shakir, Timothy Fennell, Mark DePristo, Martin Hrabé de Angelis, Panos Deloukas, Anette P Gjesing, Goo Jun, Peter Nilsson, Jacquelyn Murphy, Robert Onofrio, Barbara Thorand, Torben Hansen, Christa Meisinger, Frank B Hu, Bo Isomaa, Fredrik Karpe, Liming Liang, Annette Peters, Cornelia Huth, Stephen P O'Rahilly, Colin N A Palmer, Oluf Pedersen, Rainer Rauramaa, Jaakko Tuomilehto, Veikko Salomaa, Richard M Watanabe, Ann-Christine Syvänen, Richard N Bergman, Dwaipayan Bharadwaj, Erwin P Bottinger, Yoon Shin Cho, Giriraj R Chandak, Juliana C N Chan, Kee Seng Chia, Mark J Daly, Shah B Ebrahim, Claudia Langenberg, Paul Elliott, Kathleen A Jablonski, Donna M Lehman, Weiping Jia, Ronald C W Ma, Toni I Pollin, Manjinder Sandhu, Nikhil Tandon, Philippe Froguel, Inês Barroso, Yik Ying Teo, Eleftheria Zeggini, Ruth J F Loos, Kerrin S Small, Janina S Ried, Ralph A DeFronzo, Harald Grallert, Benjamin Glaser, Andres Metspalu, Nicholas J Wareham, Mark Walker, Eric Banks, Christian Gieger, Erik Ingelsson, Hae Kyung Im, Thomas Illig, Paul W Franks, Gemma Buck, Joseph Trakalo, David Buck, Inga Prokopenko, Reedik Mägi, Lars Lind, Yossi Farjoun, Katharine R Owen, Anna L Gloyn, Konstantin Strauch, Tiinamaija Tuomi, Jaspal Singh Kooner, Jong-Young Lee, Taesung Park, Peter Donnelly, Andrew D Morris, Andrew T Hattersley, Donald W Bowden, Francis S Collins, Gil Atzmon, John C Chambers, Timothy D Spector, Markku Laakso, Tim M Strom, Graeme I Bell, John Blangero, Ravindranath Duggirala, E Shyong Tai, Gilean McVean, Craig L Hanis, James G Wilson, Mark Seielstad, Timothy M Frayling, James B Meigs, Nancy J Cox, Rob Sladek, Eric S Lander, Stacey Gabriel, Noël P Burtt, Karen L Mohlke, Thomas Meitinger, Leif Groop, Goncalo Abecasis, Jose C Florez, Laura J Scott, Andrew P Morris, Hyun Min Kang, Michael Boehnke, David Altshuler, Mark I McCarthy
The genetic architecture of common traits, including the number, frequency, and effect sizes of inherited variants that contribute to individual risk, has been long debated. Genome-wide association studies have identified scores of common variants associated with type 2 diabetes, but in aggregate, these explain only a fraction of the heritability of this disease. Here, to test the hypothesis that lower-frequency variants explain much of the remainder, the GoT2D and T2D-GENES consortia performed whole-genome sequencing in 2,657 European individuals with and without diabetes, and exome sequencing in 12,940 individuals from five ancestry groups...
August 4, 2016: Nature
David O Garcia, Eric M Lander, Betsy C Wertheim, JoAnn E Manson, Stella L Volpe, Rowan T Chlebowski, Marcia L Stefanick, Lawrence S Lessin, Lewis H Kuller, Cynthia A Thomson
BACKGROUND: Pet ownership and cancer are both highly prevalent in the United States. Evidence suggests that associations may exist between this potentially modifiable factor and cancer prevention, though studies are sparse. The present report examined whether pet ownership (dog, cat, or bird) is associated with lower risk for total cancer and site-specific obesity-related cancers. METHODS: This was a prospective analysis of 123,560 participants (20,981 dog owners; 19,288 cat owners; 1,338 bird owners; and 81,953 non-pet owners) enrolled in the Women's Health Initiative observational study and clinical trials...
September 2016: Cancer Epidemiology, Biomarkers & Prevention
Moran Yassour, Tommi Vatanen, Heli Siljander, Anu-Maaria Hämäläinen, Taina Härkönen, Samppa J Ryhänen, Eric A Franzosa, Hera Vlamakis, Curtis Huttenhower, Dirk Gevers, Eric S Lander, Mikael Knip, Ramnik J Xavier
The gut microbial community is dynamic during the first 3 years of life, before stabilizing to an adult-like state. However, little is known about the impact of environmental factors on the developing human gut microbiome. We report a longitudinal study of the gut microbiome based on DNA sequence analysis of monthly stool samples and clinical information from 39 children, about half of whom received multiple courses of antibiotics during the first 3 years of life. Whereas the gut microbiome of most children born by vaginal delivery was dominated by Bacteroides species, the four children born by cesarean section and about 20% of vaginally born children lacked Bacteroides in the first 6 to 18 months of life...
June 15, 2016: Science Translational Medicine
Ryan Tewhey, Dylan Kotliar, Daniel S Park, Brandon Liu, Sarah Winnicki, Steven K Reilly, Kristian G Andersen, Tarjei S Mikkelsen, Eric S Lander, Stephen F Schaffner, Pardis C Sabeti
Although studies have identified hundreds of loci associated with human traits and diseases, pinpointing causal alleles remains difficult, particularly for non-coding variants. To address this challenge, we adapted the massively parallel reporter assay (MPRA) to identify variants that directly modulate gene expression. We applied it to 32,373 variants from 3,642 cis-expression quantitative trait loci and control regions. Detection by MPRA was strongly correlated with measures of regulatory function. We demonstrate MPRA's capabilities for pinpointing causal alleles, using it to identify 842 variants showing differential expression between alleles, including 53 well-annotated variants associated with diseases and traits...
June 2, 2016: Cell
Omar O Abudayyeh, Jonathan S Gootenberg, Silvana Konermann, Julia Joung, Ian M Slaymaker, David B T Cox, Sergey Shmakov, Kira S Makarova, Ekaterina Semenova, Leonid Minakhin, Konstantin Severinov, Aviv Regev, Eric S Lander, Eugene V Koonin, Feng Zhang
The clustered regularly interspaced short palindromic repeat (CRISPR)-CRISPR-associated genes (Cas) adaptive immune system defends microbes against foreign genetic elements via DNA or RNA-DNA interference. We characterize the class 2 type VI CRISPR-Cas effector C2c2 and demonstrate its RNA-guided ribonuclease function. C2c2 from the bacterium Leptotrichia shahii provides interference against RNA phage. In vitro biochemical analysis shows that C2c2 is guided by a single CRISPR RNA and can be programmed to cleave single-stranded RNA targets carrying complementary protospacers...
August 5, 2016: Science
Jan A Burger, Dan A Landau, Amaro Taylor-Weiner, Ivana Bozic, Huidan Zhang, Kristopher Sarosiek, Lili Wang, Chip Stewart, Jean Fan, Julia Hoellenriegel, Mariela Sivina, Adrian M Dubuc, Cameron Fraser, Yulong Han, Shuqiang Li, Kenneth J Livak, Lihua Zou, Youzhong Wan, Sergej Konoplev, Carrie Sougnez, Jennifer R Brown, Lynne V Abruzzo, Scott L Carter, Michael J Keating, Matthew S Davids, William G Wierda, Kristian Cibulskis, Thorsten Zenz, Lillian Werner, Paola Dal Cin, Peter Kharchencko, Donna Neuberg, Hagop Kantarjian, Eric Lander, Stacey Gabriel, Susan O'Brien, Anthony Letai, David A Weitz, Martin A Nowak, Gad Getz, Catherine J Wu
Resistance to the Bruton's tyrosine kinase (BTK) inhibitor ibrutinib has been attributed solely to mutations in BTK and related pathway molecules. Using whole-exome and deep-targeted sequencing, we dissect evolution of ibrutinib resistance in serial samples from five chronic lymphocytic leukaemia patients. In two patients, we detect BTK-C481S mutation or multiple PLCG2 mutations. The other three patients exhibit an expansion of clones harbouring del(8p) with additional driver mutations (EP300, MLL2 and EIF2A), with one patient developing trans-differentiation into CD19-negative histiocytic sarcoma...
2016: Nature Communications
Gary A Churchill
No abstract text is available yet for this article.
May 2016: Genetics
Brendan Blumenstiel, Matthew DeFelice, Ozge Birsoy, Anthony J Bleyer, Stanislav Kmoch, Todd A Carter, Andreas Gnirke, Kendrah Kidd, Heidi L Rehm, Lucienne Ronco, Eric S Lander, Stacey Gabriel, Niall J Lennon
Mucin-1 kidney disease, previously described as medullary cystic kidney disease type 1 (MCKD1, OMIM 174000), is an autosomal dominant tubulointerstitial kidney disease recently shown to be caused by a single-base insertion within the variable number tandem repeat region of the MUC1 gene. Because of variable age of disease onset and often subtle signs and symptoms, clinical diagnosis of mucin-1 kidney disease and differentiation from other forms of hereditary kidney disease have been difficult. The causal insertion resides in a variable number tandem repeat region with high GC content, which has made detection by standard next-generation sequencing impossible to date...
July 2016: Journal of Molecular Diagnostics: JMD
Marios Giannakis, Xinmeng Jasmine Mu, Sachet A Shukla, Zhi Rong Qian, Ofir Cohen, Reiko Nishihara, Samira Bahl, Yin Cao, Ali Amin-Mansour, Mai Yamauchi, Yasutaka Sukawa, Chip Stewart, Mara Rosenberg, Kosuke Mima, Kentaro Inamura, Katsuhiko Nosho, Jonathan A Nowak, Michael S Lawrence, Edward L Giovannucci, Andrew T Chan, Kimmie Ng, Jeffrey A Meyerhardt, Eliezer M Van Allen, Gad Getz, Stacey B Gabriel, Eric S Lander, Catherine J Wu, Charles S Fuchs, Shuji Ogino, Levi A Garraway
Large-scale genomic characterization of tumors from prospective cohort studies may yield new insights into cancer pathogenesis. We performed whole-exome sequencing of 619 incident colorectal cancers (CRCs) and integrated the results with tumor immunity, pathology, and survival data. We identified recurrently mutated genes in CRC, such as BCL9L, RBM10, CTCF, and KLF5, that were not previously appreciated in this disease. Furthermore, we investigated the genomic correlates of immune-cell infiltration and found that higher neoantigen load was positively associated with overall lymphocytic infiltration, tumor-infiltrating lymphocytes (TILs), memory T cells, and CRC-specific survival...
April 14, 2016: Cell Reports
Amit V Khera, Hong-Hee Won, Gina M Peloso, Kim S Lawson, Traci M Bartz, Xuan Deng, Elisabeth M van Leeuwen, Pradeep Natarajan, Connor A Emdin, Alexander G Bick, Alanna C Morrison, Jennifer A Brody, Namrata Gupta, Akihiro Nomura, Thorsten Kessler, Stefano Duga, Joshua C Bis, Cornelia M van Duijn, L Adrienne Cupples, Bruce Psaty, Daniel J Rader, John Danesh, Heribert Schunkert, Ruth McPherson, Martin Farrall, Hugh Watkins, Eric Lander, James G Wilson, Adolfo Correa, Eric Boerwinkle, Piera Angelica Merlini, Diego Ardissino, Danish Saleheen, Stacey Gabriel, Sekar Kathiresan
BACKGROUND: Approximately 7% of American adults have severe hypercholesterolemia (untreated low-density lipoprotein [LDL] cholesterol ≥190 mg/dl), which may be due to familial hypercholesterolemia (FH). Lifelong LDL cholesterol elevations in FH mutation carriers may confer coronary artery disease (CAD) risk beyond that captured by a single LDL cholesterol measurement. OBJECTIVES: This study assessed the prevalence of an FH mutation among those with severe hypercholesterolemia and determined whether CAD risk varies according to mutation status beyond the observed LDL cholesterol level...
June 7, 2016: Journal of the American College of Cardiology
Fons van der Plas, Peter Manning, Eric Allan, Michael Scherer-Lorenzen, Kris Verheyen, Christian Wirth, Miguel A Zavala, Andy Hector, Evy Ampoorter, Lander Baeten, Luc Barbaro, Jürgen Bauhus, Raquel Benavides, Adam Benneter, Felix Berthold, Damien Bonal, Olivier Bouriaud, Helge Bruelheide, Filippo Bussotti, Monique Carnol, Bastien Castagneyrol, Yohan Charbonnier, David Coomes, Andrea Coppi, Cristina C Bastias, Seid Muhie Dawud, Hans De Wandeler, Timo Domisch, Leena Finér, Arthur Gessler, André Granier, Charlotte Grossiord, Virginie Guyot, Stephan Hättenschwiler, Hervé Jactel, Bogdan Jaroszewicz, François-Xavier Joly, Tommaso Jucker, Julia Koricheva, Harriet Milligan, Sandra Müller, Bart Muys, Diem Nguyen, Martina Pollastrini, Karsten Raulund-Rasmussen, Federico Selvi, Jan Stenlid, Fernando Valladares, Lars Vesterdal, Dawid Zielínski, Markus Fischer
There is considerable evidence that biodiversity promotes multiple ecosystem functions (multifunctionality), thus ensuring the delivery of ecosystem services important for human well-being. However, the mechanisms underlying this relationship are poorly understood, especially in natural ecosystems. We develop a novel approach to partition biodiversity effects on multifunctionality into three mechanisms and apply this to European forest data. We show that throughout Europe, tree diversity is positively related with multifunctionality when moderate levels of functioning are required, but negatively when very high function levels are desired...
2016: Nature Communications
Eric M Lander, Betsy C Wertheim, Stephanie M Koch, Zhao Chen, Chiu-Hsieh Hsu, Cynthia A Thomson
OBJECTIVE: This study aimed to measure associations between gallbladder disease and protein intake patterns, separated by quantity and type (vegetable vs. animal), among postmenopausal women. METHODS: Analyses were based on 130,859 postmenopausal women enrolled from 1993 to 1998 at 40 U.S. clinical centers in the Women's Health Initiative clinical trials and observational study. Women were excluded if they reported a history of gallbladder disease prior to baseline...
July 2016: Preventive Medicine
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