Search Our Scientific Publications & Authors

Cell 2018 Jun 9. Epub 2018 Jun 9.

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; The Eli and Edythe L. Broad Institute, Cambridge, MA 02142, USA; Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA 02215, USA. Electronic address:

Increased androgen receptor (AR) activity drives therapeutic resistance in advanced prostate cancer. The most common resistance mechanism is amplification of this locus presumably targeting the AR gene. Here, we identify and characterize a somatically acquired AR enhancer located 650 kb centromeric to the AR. Read More

Cell 2018 Jun 11. Epub 2018 Jun 11.

Institute for Tumor Biology and Experimental Therapy, Georg-Speyer-Haus, 60596 Frankfurt am, Germany; German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany. Electronic address:

In colorectal cancer patients, a high density of cytotoxic CD8 T cells in tumors is associated with better prognosis. Using a Stat3 loss-of-function approach in two wnt/β-catenin-dependent autochthonous models of sporadic intestinal tumorigenesis, we unravel a complex intracellular process in intestinal epithelial cells (IECs) that controls the induction of a CD8 T cell based adaptive immune response. Elevated mitophagy in IECs causes iron(II)-accumulation in epithelial lysosomes, in turn, triggering lysosomal membrane permeabilization. Read More

Cell 2018 Jun 11. Epub 2018 Jun 11.

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Cancer Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA; Harvard Medical School, Boston, MA, USA; Brigham and Women's Hospital, Boston, MA, USA. Electronic address:

Nearly all prostate cancer deaths are from metastatic castration-resistant prostate cancer (mCRPC), but there have been few whole-genome sequencing (WGS) studies of this disease state. We performed linked-read WGS on 23 mCRPC biopsy specimens and analyzed cell-free DNA sequencing data from 86 patients with mCRPC. In addition to frequent rearrangements affecting known prostate cancer genes, we observed complex rearrangements of the AR locus in most cases. Read More

Cell 2018 Jun 12. Epub 2018 Jun 12.

Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA 02115, USA; Harvard Medical School, Boston, MA 02115, USA. Electronic address:

Extracellular proTGF-β is covalently linked to "milieu" molecules in the matrix or on cell surfaces and is latent until TGF-β is released by integrins. Here, we show that LRRC33 on the surface of microglia functions as a milieu molecule and enables highly localized, integrin-αVβ8-dependent TGF-β activation. Lrrc33 mice lack CNS vascular abnormalities associated with deficiency in TGF-β-activating integrins but have microglia with a reactive phenotype and after 2 months develop ascending paraparesis with loss of myelinated axons and death by 5 months. Read More

Cell 2018 Jun 9. Epub 2018 Jun 9.

Department of Biology, New York University, New York, NY 10003, USA; New York University Abu Dhabi, Saadiyat Island, Abu Dhabi, United Arab Emirates. Electronic address:

Transcription factors regulate the molecular, morphological, and physiological characteristics of neurons and generate their impressive cell-type diversity. To gain insight into the general principles that govern how transcription factors regulate cell-type diversity, we used large-scale single-cell RNA sequencing to characterize the extensive cellular diversity in the Drosophila optic lobes. We sequenced 55,000 single cells and assigned them to 52 clusters. Read More

Cell 2018 Jun 9. Epub 2018 Jun 9.

VIB Center for Brain & Disease Research, KU Leuven, Leuven 3000, Belgium; Department of Human Genetics KU Leuven, Leuven 3000, Belgium. Electronic address:

The diversity of cell types and regulatory states in the brain, and how these change during aging, remains largely unknown. We present a single-cell transcriptome atlas of the entire adult Drosophila melanogaster brain sampled across its lifespan. Cell clustering identified 87 initial cell clusters that are further subclustered and validated by targeted cell-sorting. Read More

Cell 2018 Jun 6. Epub 2018 Jun 6.

Department of Microbiology and Immunology, Cornell University, Ithaca, NY 14853, USA. Electronic address:

Heterogeneity is a hallmark feature of the adaptive immune system in vertebrates. Following infection, naive T cells differentiate into various subsets of effector and memory T cells, which help to eliminate pathogens and maintain long-term immunity. The current model suggests there is a single lineage of naive T cells that give rise to different populations of effector and memory T cells depending on the type and amounts of stimulation they encounter during infection. Read More

Cell 2018 Jun;173(7):1823

Cell 2018 Jun;173(7):1823

Cell 2018 Jun;173(7):1770-1782.e14

Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Rogel Cancer Center, University of Michigan, Ann Arbor, MI 48109, USA; Department of Urology, University of Michigan, Ann Arbor, MI 48109, USA; Howard Hughes Medical Institute, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address:

Using integrative genomic analysis of 360 metastatic castration-resistant prostate cancer (mCRPC) samples, we identified a novel subtype of prostate cancer typified by biallelic loss of CDK12 that is mutually exclusive with tumors driven by DNA repair deficiency, ETS fusions, and SPOP mutations. CDK12 loss is enriched in mCRPC relative to clinically localized disease and characterized by focal tandem duplications (FTDs) that lead to increased gene fusions and marked differential gene expression. FTDs associated with CDK12 loss result in highly recurrent gains at loci of genes involved in the cell cycle and DNA replication. Read More

Cell 2018 Jun;173(7):1742-1754.e17

Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA; Chan Zuckerberg Biohub, San Francisco, CA 94158, USA. Electronic address:

Osmotic diarrhea is a prevalent condition in humans caused by food intolerance, malabsorption, and widespread laxative use. Here, we assess the resilience of the gut ecosystem to osmotic perturbation at multiple length and timescales using mice as model hosts. Osmotic stress caused reproducible extinction of highly abundant taxa and expansion of less prevalent members in human and mouse microbiotas. Read More

Cell 2018 Jun;173(7):1705-1715.e16

Schizophrenia and bipolar disorder are two distinct diagnoses that share symptomology. Understanding the genetic factors contributing to the shared and disorder-specific symptoms will be crucial for improving diagnosis and treatment. In genetic data consisting of 53,555 cases (20,129 bipolar disorder [BD], 33,426 schizophrenia [SCZ]) and 54,065 controls, we identified 114 genome-wide significant loci implicating synaptic and neuronal pathways shared between disorders. Read More

Cell 2018 Jun;173(7):1663-1677.e21

Structural Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Howard Hughes Medical Institute, 1275 York Avenue, New York, NY 10065, USA. Electronic address:

The ribonucleolytic RNA exosome interacts with RNA helicases to degrade RNA. To understand how the 3' to 5' Mtr4 helicase engages RNA and the nuclear exosome, we reconstituted 14-subunit Mtr4-containing RNA exosomes from Saccharomyces cerevisiae, Schizosaccharomyces pombe, and human and show that they unwind structured substrates to promote degradation. We loaded a human exosome with an optimized DNA-RNA chimera that stalls MTR4 during unwinding and determined its structure to an overall resolution of 3. Read More

Cell 2018 Jun;173(7):1593-1608.e20

Stowers Institute for Medical Research, Kansas City, MO 64110, USA; Howard Hughes Medical Institute, Kansas City, MO 64110, USA. Electronic address:

Proliferating cells known as neoblasts include pluripotent stem cells (PSCs) that sustain tissue homeostasis and regeneration of lost body parts in planarians. However, the lack of markers to prospectively identify and isolate these adult PSCs has significantly hampered their characterization. We used single-cell RNA sequencing (scRNA-seq) and single-cell transplantation to address this long-standing issue. Read More

Cell 2018 Jun;173(7):1573-1580

Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia; Queensland Brain Institute, The University of Queensland, Brisbane, Australia.

The evidence that most adult-onset common diseases have a polygenic genetic architecture fully consistent with robust biological systems supported by multiple back-up mechanisms is now overwhelming. In this context, we consider the recent "omnigenic" or "core genes" model. A key assumption of the model is that there is a relatively small number of core genes relevant to any disease. Read More

Cell 2018 Jun;173(7):1570-1572

Department of Neurobiology, Howard Hughes Medical Institute, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA. Electronic address:

Sunlight can alter mood, behavior, and cognition, but the cellular basis of this phenomenon remains to be fully elucidated. In this issue of Cell, Zhu et al. shed light on a UV-dependent metabolic pathway that leads to increased synaptic release of glutamate and enhanced motor learning and memory in mice. Read More

Cell 2018 Jun;173(7):1568-1570

Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN, USA; Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.

Heritability studies are essential for defining genetic influences on disease risk and trait variability. Polubriaginof et al. show how massive amounts of data contained in electronic health records can be used for heritability studies on hundreds of phenotypes. Read More

Cell 2018 Jun;173(7):1566-1567

Morgridge Institute for Research, Madison, WI, USA; Howard Hughes Medical Institute, Madison, WI, USA; Department of Integrative Biology, University of Wisconsin-Madison, Madison, WI, USA. Electronic address:

Planarians are renowned for extraordinary regenerative abilities that are driven by stem cells maintained throughout their lives. In this issue of Cell, Zeng et al. report the prospective isolation of planarian pluripotent stem cells. Read More

Cell 2018 Jun;173(7):1562-1565

Division of Genetics, Department of Medicine, University of California San Diego, La Jolla, CA, USA; Cancer Cell Map Initiative, University of California San Diego, La Jolla, CA, USA; UCSD Program in Bioinformatics and Systems Biology, University of California San Diego, La Jolla, CA, USA. Electronic address:

A major ambition of artificial intelligence lies in translating patient data to successful therapies. Machine learning models face particular challenges in biomedicine, however, including handling of extreme data heterogeneity and lack of mechanistic insight into predictions. Here, we argue for "visible" approaches that guide model structure with experimental biology. Read More

Cell 2018 Jun;173(7):1560-1561

Cell 2018 Jun;173(7):1557-1559

With the complexities of organelle communication and their dynamics under intense investigation, what are the new principles that are emerging, and where is the field headed? Cell's Robert Kruger recently discussed these questions with Erika Holzbaur, Jennifer Lippincott-Schwartz, and Ivan Dikic. Annotated excerpts from this conversation are presented below, and the full conversation is available with the article online. Read More

Cell 2018 Jun;173(7):1553-1555

Cell 2018 May 31. Epub 2018 May 31.

Division of Biology and Biological Engineering, Caltech, Pasadena, CA 91125, USA. Electronic address:

Visualization of the transcriptome and the nuclear organization in situ has been challenging for single-cell analysis. Here, we demonstrate a multiplexed single-molecule in situ method, intron seqFISH, that allows imaging of 10,421 genes at their nascent transcription active sites in single cells, followed by mRNA and lncRNA seqFISH and immunofluorescence. This nascent transcriptome-profiling method can identify different cell types and states with mouse embryonic stem cells and fibroblasts. Read More

Cell 2018 Jun 4. Epub 2018 Jun 4.

MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK. Electronic address:

Multiple proteins act co-operatively in mammalian clathrin-mediated endocytosis (CME) to generate endocytic vesicles from the plasma membrane. The principles controlling the activation and organization of the actin cytoskeleton during mammalian CME are, however, not fully understood. Here, we show that the protein FCHSD2 is a major activator of actin polymerization during CME. Read More

Cell 2018 Jun 4. Epub 2018 Jun 4.

Howard Hughes Medical Institute, Cambridge, MA 02142, USA; Whitehead Institute of Biomedical Research, Cambridge, MA 02142, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Electronic address:

Noncoding RNAs (ncRNAs) play increasingly appreciated gene-regulatory roles. Here, we describe a regulatory network centered on four ncRNAs-a long ncRNA, a circular RNA, and two microRNAs-using gene editing in mice to probe the molecular consequences of disrupting key components of this network. The long ncRNA Cyrano uses an extensively paired site to miR-7 to trigger destruction of this microRNA. Read More

Cell 2018 Jun 7;173(7):1581-1592. Epub 2018 Jun 7.

Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA; Department of Biological Engineering and Institute for Medical Engineering & Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Electronic address:

Machine learning, a collection of data-analytical techniques aimed at building predictive models from multi-dimensional datasets, is becoming integral to modern biological research. By enabling one to generate models that learn from large datasets and make predictions on likely outcomes, machine learning can be used to study complex cellular systems such as biological networks. Here, we provide a primer on machine learning for life scientists, including an introduction to deep learning. Read More

Cell 2018 Jun 4. Epub 2018 Jun 4.

Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA. Electronic address:

Eukaryotic genomes are packaged into a 3-dimensional structure in the nucleus. Current methods for studying genome-wide structure are based on proximity ligation. However, this approach can fail to detect known structures, such as interactions with nuclear bodies, because these DNA regions can be too far apart to directly ligate. Read More

Cell 2018 Jun 7;173(7):1650-1662.e14. Epub 2018 Jun 7.

The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA. Electronic address:

NusG/RfaH/Spt5 transcription elongation factors are the only transcription regulators conserved across all life. Bacterial NusG regulates RNA polymerase (RNAP) elongation complexes (ECs) across most genes, enhancing elongation by suppressing RNAP backtracking and coordinating ρ-dependent termination and translation. The NusG paralog RfaH engages the EC only at operon polarity suppressor (ops) sites and suppresses both backtrack and hairpin-stabilized pausing. Read More

Cell 2018 May 28. Epub 2018 May 28.

Howard Hughes Medical Institute, Massachusetts General Hospital, Boston, MA, USA; Department of Molecular Biology, Massachusetts General Hospital, Boston, MA, USA; Department of Genetics, Harvard Medical School, Boston, MA, USA. Electronic address:

Mammalian chromosomes are partitioned into A/B compartments and topologically associated domains (TADs). The inactive X (Xi) chromosome, however, adopts a distinct conformation without evident compartments or TADs. Here, through exploration of an architectural protein, structural-maintenance-of-chromosomes hinge domain containing 1 (SMCHD1), we probe how the Xi is reconfigured during X chromosome inactivation. Read More

Cell 2018 May 24. Epub 2018 May 24.

Department of Microbiology and Immunobiology and Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02115, USA. Electronic address:

Visceral adipose tissue (VAT) hosts a population of regulatory T (Treg) cells, with a unique phenotype, that controls local and systemic inflammation and metabolism. Generation of a T cell receptor transgenic mouse line, wherein VAT Tregs are highly enriched, facilitated study of their provenance, dependencies, and activities. We definitively established a role for T cell receptor specificity, uncovered an unexpected function for the primordial Treg transcription-factor, Foxp3, evidenced a cell-intrinsic role for interleukin-33 receptor, and ordered these dependencies within a coherent scenario. Read More

Cell 2018 May 23. Epub 2018 May 23.

Department of Medicine, University of California San Francisco (UCSF), San Francisco, CA 94143, USA; Department of Microbiology & Immunology, University of California San Francisco (UCSF), San Francisco, CA 94143, USA; Howard Hughes Medical Institute, UCSF. Electronic address:

The small intestinal tuft cell-ILC2 circuit mediates epithelial responses to intestinal helminths and protists by tuft cell chemosensory-like sensing and IL-25-mediated activation of lamina propria ILC2s. Small intestine ILC2s constitutively express the IL-25 receptor, which is negatively regulated by A20 (Tnfaip3). A20 deficiency in ILC2s spontaneously triggers the circuit and, unexpectedly, promotes adaptive small-intestinal lengthening and remodeling. Read More

Cell 2018 May 23. Epub 2018 May 23.

Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; The Wistar Institute, Philadelphia, PA 19104, USA; Ludwig Institute for Cancer Research, New York, NY 10017, USA. Electronic address:

Recent reports indicate that hypoxia influences the circadian clock through the transcriptional activities of hypoxia-inducible factors (HIFs) at clock genes. Unexpectedly, we uncover a profound disruption of the circadian clock and diurnal transcriptome when hypoxic cells are permitted to acidify to recapitulate the tumor microenvironment. Buffering against acidification or inhibiting lactic acid production fully rescues circadian oscillation. Read More

Cell 2018 May 31;173(6):1552-1552.e1. Epub 2018 May 31.

Institut Curie, 91405 Orsay, France.

Post-translational modification of tubulin offers a mechanism for functional diversification of microtubules and regulation in a variety of physiological contexts. This SnapShot recaps the current state of understanding of tubulin posttranslational modifications and their functions in the regulation of biological processes. To view this SnapShot, open or download the PDF. Read More

Cell 2018 May 31;173(6):1549-1550. Epub 2018 May 31.

Cell 2018 May 31;173(6):1549. Epub 2018 May 31.

Cell 2018 May 31;173(6):1520-1534.e20. Epub 2018 May 31.

(Epi)genomics of Animal Development Unit, Department of Developmental and Stem Cell Biology, Institut Pasteur, 75015 Paris, France; CNRS, UMR3738, 25 Rue du Dr Roux, 75015 Paris, France. Electronic address:

The emergence and diversification of cell types is a leading factor in animal evolution. So far, systematic characterization of the gene regulatory programs associated with cell type specificity was limited to few cell types and few species. Here, we perform whole-organism single-cell transcriptomics to map adult and larval cell types in the cnidarian Nematostella vectensis, a non-bilaterian animal with complex tissue-level body-plan organization. Read More

Cell 2018 May 31;173(6):1439-1453.e19. Epub 2018 May 31.

Center for Cellular Immunotherapies, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA; Division of Hematology-Oncology, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA. Electronic address:

The absence of cancer-restricted surface markers is a major impediment to antigen-specific immunotherapy using chimeric antigen receptor (CAR) T cells. For example, targeting the canonical myeloid marker CD33 in acute myeloid leukemia (AML) results in toxicity from destruction of normal myeloid cells. We hypothesized that a leukemia-specific antigen could be created by deleting CD33 from normal hematopoietic stem and progenitor cells (HSPCs), thereby generating a hematopoietic system resistant to CD33-targeted therapy and enabling specific targeting of AML with CAR T cells. Read More

Cell 2018 May 31;173(6):1370-1384.e16. Epub 2018 May 31.

Université Libre de Bruxelles (ULB), Institute for Interdisciplinary Research (IRIBHM) and ULB Neuroscience Institute (UNI), 1070 Brussels, Belgium; VIB-KULeuven Center for Brain & Disease Research, 3000 Leuven, Belgium; Department of Neurosciences, Leuven Brain Institute, KUL, 3000 Leuven, Belgium; WELBIO, ULB, B-1070 Brussels, Belgium. Electronic address:

The cerebral cortex underwent rapid expansion and increased complexity during recent hominid evolution. Gene duplications constitute a major evolutionary force, but their impact on human brain development remains unclear. Using tailored RNA sequencing (RNA-seq), we profiled the spatial and temporal expression of hominid-specific duplicated (HS) genes in the human fetal cortex and identified a repertoire of 35 HS genes displaying robust and dynamic patterns during cortical neurogenesis. Read More

Cell 2018 May 31;173(6):1356-1369.e22. Epub 2018 May 31.

UC Santa Cruz Genomics Institute, Santa Cruz, CA, USA; Howard Hughes Medical Institute, UC Santa Cruz, Santa Cruz, CA, USA. Electronic address:

Genetic changes causing brain size expansion in human evolution have remained elusive. Notch signaling is essential for radial glia stem cell proliferation and is a determinant of neuronal number in the mammalian cortex. We find that three paralogs of human-specific NOTCH2NL are highly expressed in radial glia. Read More

Cell 2018 May 31;173(6):1343-1355.e24. Epub 2018 May 31.

Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA; Program in Neuroscience, Harvard Medical School, Boston, MA 02115, USA. Electronic address:

Numerous well-defined classes of retinal ganglion cells innervate the thalamus to guide image-forming vision, yet the rules governing their convergence and divergence remain unknown. Using two-photon calcium imaging in awake mouse thalamus, we observed a functional arrangement of retinal ganglion cell axonal boutons in which coarse-scale retinotopic ordering gives way to fine-scale organization based on shared preferences for other visual features. Specifically, at the ∼6 μm scale, clusters of boutons from different axons often showed similar preferences for either one or multiple features, including axis and direction of motion, spatial frequency, and changes in luminance. Read More

Cell 2018 May 31;173(6):1323-1327. Epub 2018 May 31.

Institut Curie, PSL Research University, CNRS UMR3348, Orsay, France; Université Paris Sud, Université Paris-Saclay, CNRS UMR3348, Orsay, France. Electronic address:

Tubulin posttranslational modifications are currently emerging as important regulators of the microtubule cytoskeleton and thus have a strong potential to be implicated in a number of disorders. Here, we review the latest advances in understanding the physiological roles of tubulin modifications and their links to a variety of pathologies. Read More

Cell 2018 May 31;173(6):1320-1322. Epub 2018 May 31.

Department of Plant Science, McGill University, Macdonald Campus, 21111 Lakeshore, Ste-Anne-de-Bellevue, Québec H9X 3V9, Canada. Electronic address:

The detachment of plant organs is highly choreographed, requiring the enzymatic dissolution of the middle lamella between cell layers at the base of the detaching organ. Now, Lee et al. demonstrate that abscission efficiency and plant health rely on the spatial confinement of enzymatic activity and mechanical features that ensure a smooth separation. Read More

Cell 2018 May 31;173(6):1318-1319. Epub 2018 May 31.

University of Navarra, Center for Applied Medical Research (CIMA), Pamplona 31008, Spain; Institute of Health Research of Navarra (IdiSNA), Pamplona 31008, Spain. Electronic address:

The role of the noncoding genome in cancer biology is continually expanding. Cho et al. reveal a new and unexpected mechanism for the regulation of MYC expression mediated by the promoter sequence of its neighbor gene PVT1. Read More

Cell 2018 May 31;173(6):1316-1317. Epub 2018 May 31.

Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, Los Angeles, CA 90095, USA; Parker Institute for Cancer Immunotherapy Center at UCLA, Los Angeles, CA 90095, USA. Electronic address:

Chimeric antigen receptor (CAR) T cells offer a promising treatment option for advanced cancers resistant to standard therapy. Here, Cho et al. report a split-CAR design that enables the engineering of multi-feature CAR-T cells, aiming to address current challenges limiting the safety and efficacy of CAR-T cells for cancer treatment. Read More

Cell 2018 May 31;173(6):1314-1315. Epub 2018 May 31.

Department of Biology, Indiana University, Bloomington, IN 47405 USA. Electronic address:

Salicylic acid (SA) is a potent inducer of defense gene expression in plants, but how SA activates transcription has been controversial. In this issue of Cell, Ding et al. show that the SA-binding proteins NPR3 and NPR4 function as transcriptional co-repressors, with this activity being blocked by SA. Read More

Cell 2018 May 31;173(6):1311-1313. Epub 2018 May 31.

The power of CRISPR is undeniable, but where is the field heading? Cell's April Pawluk caught up with Jia Chen, Weizhi Ji, and Prashant Mali to discuss the successes and challenges we can expect in the coming years. Annotated excerpts from this conversation are presented below, and the full conversation is available with the article online. Read More

Cell 2018 May 31;173(6):1309. Epub 2018 May 31.

Cell 2018 May 15. Epub 2018 May 15.

Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA. Electronic address:

The seven-transmembrane-spanning protein Smoothened is the central transducer in Hedgehog signaling, a pathway fundamental in development and in cancer. Smoothened is activated by cholesterol binding to its extracellular cysteine-rich domain (CRD). How this interaction leads to changes in the transmembrane domain and Smoothened activation is unknown. Read More

Cell 2018 May 18. Epub 2018 May 18.

Howard Hughes Medical Institute; Program in Cellular and Molecular Medicine, Boston Children's Hospital, and Department of Genetics, Harvard Medical School, Boston, MA 02115, USA. Electronic address:

RAG endonuclease initiates antibody heavy chain variable region exon assembly from V, D, and J segments within a chromosomal V(D)J recombination center (RC) by cleaving between paired gene segments and flanking recombination signal sequences (RSSs). The IGCR1 control region promotes DJ intermediate formation by isolating Ds, Js, and RCs from upstream Vs in a chromatin loop anchored by CTCF-binding elements (CBEs). How Vs access the DJRC for V to DJ rearrangement was unknown. Read More

Cell 2018 May 18. Epub 2018 May 18.

Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Biochemistry, Stanford University School of Medicine, Stanford, CA 94305, USA; Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA 94305, USA. Electronic address:

Ribonucleoprotein enzymes require dynamic conformations of their RNA constituents for regulated catalysis. Human telomerase employs a non-coding RNA (hTR) with a bipartite arrangement of domains-a template-containing core and a distal three-way junction (CR4/5) that stimulates catalysis through unknown means. Here, we show that telomerase activity unexpectedly depends upon the holoenzyme protein TCAB1, which in turn controls conformation of CR4/5. Read More