( a) Simplified overview of three stages of the gypsy retrotransposon life cycle, (i) parent insertion in the genome, (ii) the transcribed RNA (genomic RNA), and (iii) the new copy inserted in the genome. Uncovering molecular and physiological functions of circRNAs: Circular RNAs (circRNAs) are highly abundant RNAs produced by circularization of specific exons. Adam grew up in Ethiopia and moved to Bremen, Germany where he received his B.Sc and M.Sci in Biochemistry and Cell Biology from Jacobs University which was his very first exposure to the exciting field of epigenetics. In the Bando Lab, Adam is studying how alterations in chromatin factors lead to pediatric gliomagenesis with the ultimate goal of discovering novel therapeutic approaches. Lacadie S.A., Tardiff D.F., Kadener S. and Rosbash M. In vivo commitment to yeast cotranscriptional splicing is sensitive to transcription elongation mutants. Ashwal-Fluss R., Meyer M., Pamudurti N.R., Ivanov A., Bartok O., Evantal N., Hanan M., Memczak S., Rajewsky N.* and Kadener S.* CircRNA biogenesis and canonical splicing compete with each other. 178: In mature animals, cells and organs interact to maintain homeostasis and coordinate their physiological roles. Portal D., Lobo G.S., Kadener S., Prasad J., Espinosa J.M., Pereira C.A., Tang Z., Lin R.J., Manley J.L., Kornblihtt A.R., Flawia M.M. In addition, we are extending our studies to additional tumor models. These esg>yki gut tumors induce organ wasting by secreting the insulin binding protein ImpL2 into the hemolymph, which reduces insulin signaling in peripheral tissues. We are using CRISPR to mutate or engineer cell lines that can be used for screening, and have developed efficient protocols in Drosophila cells, which are particularly challenging as they are polyploid and difficult to grow following single-cell isolation. Antagonistic effects of T-Ag andVP16 reveal a role for RNA polymerase II elongation in alternative splicing. Portal D., Lobo G.S., Kadener S., Prasad J., Espinosa J.M., Pereira C.A., Tang Z., Lin R.J., Manley J.L., Kornblihtt A.R., Flawia M.M. Cold Spring Harbor Laboratory Online. Contact. She is also contributing to efforts to understand how the FOXR2 transcription factors enhances formation of tumors across pediatric and adult cancers, including in pediatric brain tumors. Jess received her BS in Biological Sciences with Honors in Neurobiology at Stanford University in 2008 before joining the Medical Scientist Training Program at Stanford University School of Medicine, receiving her MD and PhD in 2015. SRCP: a comprehensive pipeline for accurate annotation and quantification of circRNAs. Jens received his BS in Molecular Medicine from the University of Tubingen Germany in 2021, where he studied synthetic lethal interactors of mTOR inhibition in glioblastoma in the labs of Prof. Ghazaleh Tabatabai and Dr. Daniel Merk. Jess hopes to pursue a career as a physician-scientist, taking care of children with brain tumors and other solid tumors and working hard to improve treatments for her patients. Articles Cited by Public access Co-authors. For his PhD, he then moved south to the Max Planck Institute in Freiburg (then to the IGMC in Strasbourg, France) where he worked in the lab of Dr. Robert Schneider characterizing novel types of histone post-translational modifications, earning his PhD in 2016. Are circRNAs involved in neurodevelopmental and neurodegenerative diseases? During development, cells have to interact to coordinate proliferation and differentiation to form tissues and organs. Finally, as an alternative to RNAi for partial loss-of-function screens using a Cas system, we have shown that Cas13 is an effective tool for CRISPRi in Drosophila cells. Fun fact:April does not drink coffee or tea (which perplexes Mimi) and loves milk and the whole lab likes to make fun of her for it. In the Bandopadhayay Lab, Jess is applying genomic approaches to optimize novel treatment approaches for pediatric brain tumors, and is also working to characterize the role long non-coding RNAs play in the formation of Diffuse Intrinsic Pontine Gliomas. Followers. An early ancestor in the evolution of splicing: a. Nogues G., Kadener S., Cramer P., de la Mata M., Fededa J.P., Blaustein M., Srebrow A. and Kornblihtt A.R. Andranik Ivanov and Sebastian Meczmack (Prof. Rajewsky's . Cramer P., Cceres J.F., Cazalla D., Kadener S., Muro, A., Baralle F. and Kornblihtt A. Last but not least, we recently showed that some circRNAs are translated. I am interested in understanding how proteins and miRNAs regulate and can be regulated by circRNAs. Mezan S., Feuz JD, Deplancke B. and Kadener S. PDF signaling is an integral part of the. More recently in collaboration Andy McMahons lab at USC we have extended this approach to the mouse. Maddie received her MS and BS in Biology from Brandeis University in 2021. 178: Proximity labeling-based methods coupled with mass spectrometry (MS) offer a high-throughput approach for systematic analysis of spatially-restricted proteomes. We continue to evaluate and create new methods for genome engineering. Allada R., Kadener S., Nandakumar N. and Rosbash M. A recessive mutant of, Portal D., Espinosa J.M., Lobo G.S., Kadener S., Pereira C.A., de la Mata M., Tang Z., Lin R.J., Kornblihtt A.R., Baralle F.E., Flawia M.M. We showed that their translation is mediated by IRES-like sequences, is enhanced in response to starvation and happens in association with membranes and in synapses. Ultimately, the knowledge gained from these studies will generate testable hypotheses related to disease states such as diabetes, aging, and cancer, i.e., how biological processes observed in one tissue/organ (e.g., decreased cellular metabolism, mitochondrial dysfunction) may influence processes observed in a different tissue/organ. We are particularly interested on the role of circular RNAs (circRNAs) at the molecular and neural levels as well as the mechanisms underlying circadian clocks. * Corresponding authors. He also enjoys playing handball and online chess. Media. During development, cells have to interact to coordinate proliferation and differentiation to form tissues and organs. Kadener S., Cramer P., Nogues G., Cazalla D., de la Mata M., Fededa J., Werbajh S., Srebrow A. and Kornblihtt A. Murugan et al. We showed that miRNAs have a key role in providing robustness to the circadian system both during development and in adults. There, she studied the oncogenic role of certain signaling molecules in the Hedgehog signaling pathway, and became extremely interested in advancing cancer therapy research. Jens is co-mentored by Dr. David Jones at the DKFZ. Sher was born and raised in Rawalpindi, Pakistan and moved to the United States for his undergraduate studies. Community support Reprint. Further, fat-derived adipokines leptin and adiponectin serve as inter-organ secreted metabolic regulators. Patop, Ines Lucia; Kadener, Sebastian . Fun fact: Outside the lab, Adam is an avid soccer fan and enjoys watching the English Premier League. Metazoan MicroRNAs (2018) David P. Bartel CELL Non-canonical functions of microRNA pathway enzymes - Drosha, DGCR8, Dicer and Ago proteins Studying the neuronal functions of circular RNA. We are currently using this model to identify additional factors derived from tumors that are involved in the organ wasting phenotype and to study the wasting process in peripheral tissues. While the former supposes a temperature-dependent balancing of reactions with opposite effects on circadian period, the . We showed that miRNAs have a key role in providing robustness to the circadian system both during development and in adults. Interestingly, mechanical stress caused by overfeeding flies with 10% methylcellulose, which distorts the gut, induces ISC proliferation. Sher is now contributing to efforts to characterize FGFR alterations in pediatric gliomas, and to develop methods to optimize TP53 reactivation in Diffuse Midline Gliomas. Stelzer Y., Bar S., Bartok O., Afik S., Ronen D., Kadener S.* and Benvenisty N.* Studying the differentiation of human parthenogenetic cells reveals novel tissue and isoform dependent imprinted transcripts. These experiments will provide a system-wide understanding of the factors originating from tumors and how they perturb systemic energy balance, and how peripheral organs in turn respond to initiate cachectic phenotypes. This dual reporter can be used in either fixed or live tissues to monitor spatio-temporal activity of signaling pathways at an unprecedented resolution. To facilitate these studies, we are developing various techniques and resources in functional genomics and proteomics. I am a junior who is majoring in biochemistry. Second, we identified 53 transcription factors, specifically expressed or enriched in the ISCs, and are characterizing how they cooperate to integrate signal inputs. Kadener S., Fededa J.P., Rosbash M. and Kornblihtt A.R. He is returning to Brandeis as an Associate Professor of Biology. Adam then moved to Boston for his postdoc in the lab of Dr. Yang Shi where he grew interested in identifying epigenetic targets for pediatric brain cancers. I am in the Class of 2024 studying neuroscience and biology. In addition, skeletal muscles produce various myokines that influence metabolic homeostasis, lifespan, and the progression of age-related diseases and aging in non-muscle tissues. As an underlying mechanism, the balance or critical reaction hypothesis have been proposed. Molecular Interaction Search Tool) for mining, visualization and analysis of network data, for mining protein post-translational modification (PTM) data and comparison of PTM data across species and. Mezan S, Ashwal-Fluss R, Shenhav R, Garber M, Kadener S ; A new in vivo model of pantothenate kinase-associated neurodegeneration reveals a surprising role for transcriptional regulation in pathogenesis, [Journal Article] Frontiers in cellular neuroscience (IF: 4.300) (2013) Pandey V, Turm H, Bekenstein U, Shifman S, Kadener S Molecular Neurobiology and RNA metabolism. Further, our work and that of others has suggested functions of these moleculesin vivo. Jens joined the Bando Lab in 2023 as a visiting graduate student to understand how distinct histone mutations influence gliomagenesis and also aims to exploit the dependence of pLGGs on the MAPK pathway. de la Mata M., Alonso C.R., Kadener S., Fededa J.P., Blaustein M., Pelisch F., Cramer P., Bentley D. and Kornblihtt A.R. Bartok O., Kyriacou C., Levine J., Sehgal A. and Kadener S. Adaptation of molecular circadian clockwork to environmental changes: a role for alternative splicing and miRNAs. Sayan is a graduate student in the Molecular and Cell Biology program at Brandeis and he is investigating the role of circRNA in aging and neurodegeneration. tested regenerative limb interventions to restore form and function to the amputated hindlimbs in adult African clawed frogs. We have also generated stable nuclease-dead Cas9 activator (dCas9a) cell lines that can be used, after transfection with gRNAs, to perform overexpression screens - thus complementing loss of function screens. Litovchenko M, Meireles-Filho ACA, Frochaux MV, Bevers RPJ, Prunotto A, Anduaga AM, Hollis B, Gardeux V, Braman VS, Russeil JMC, Kadener S, Dal Peraro M, Deplancke B. Host-derived circular RNAs display proviral activities in Hepatitis C virus-infected cells. In the lab of Dr. William Kinlaw, Leslie studied lipid metabolism in breast cancer cells. *, Bartok O. Fun fact: Adams passions expand beyond the lab and include weightlifting, hot yoga, singing acappella, heading to the ballpark for a game, and visiting craft breweries. First, we developed a new method to visualize the dynamic activation of pathway activities. What are the key functions of these molecules in the brain and during aging? Fun fact: Like many Swedish people, Eric has completed Vasaloppet, a 60-mile cross-country skiing race (twice!). Selected for Faculty of 1000 (Factor 9 Exceptional). Sebastian Kadener. Before joining the Bando Lab, John worked as a High Frequency Trader. One of these translated circRNAs is circMbl. Cramer P., Srebrow A., Kadener S., Werbajh S., de la Mata M., Melen G., Nogues G. and Kornblihtt AR. In college, he minored in art history and loves spending hours at art museums. Laboratory Profile Principal Investigator: Sebastian Kadener A systemic view of circadian clocks: from gene expression to neuronal networks and behavior. . For example, little is understood about how the simultaneous growth and differentiation of different tissues and organs are coordinated and how the development of different cell types and tissues is integrated within an organ. RNA biology Neurosciences. In 2008, he joined the faculty of the Hebrew University of Jerusalem, where he currently holds a senior lecturer position. More. Advantages of CRISPRi as compared with RNAi are that the level of knockdown can be more tightly controlled and the system appears to have reduced off-target effects. Our Funds. PERIOD1-associated proteins modulate the negative limb of the mammalian circadian oscillator. Sebastian Kadener Activities Collapse all Works (11) sort Sort The chromatin factor ROW cooperates with BEAF 32 in regulating longrange inducible genes EMBO reports 2022-12-06 | Journal article DOI: 10.15252/embr.202254720 Contributors : Neta Herman; Sebastian Kadener; Sagiv Shifman Show more detail Source : Crossref Brown S.A., Ripperger J., Kadener S., Fleury-Olela F., Vilbois F., Rosbash M. and Schibler U. In the Bandopadhayay Lab, Anna will be expanding her skills to apply genomic approaches to understand the mechanisms through which gliomas develop, and to develop strategies to overcome therapeutic resistance. DIOPT has been well received by the scientific community and has been integrated into FlyBase, PomBase, MARRVEL (Model organism Aggregated Resources for Rare Variant ExpLoration) and AGR (Alliance of Genome Resources); Gene2Function integrates annotation information for orthologs of multiple species in unified interfaces; RSVP allows scientists to mine the validation and phenotype data for in vivo RNAi and sgRNA stocks; MIST (Molecular Interaction Search Tool) for mining, visualization and analysis of network data, iProteinDB for mining protein post-translational modification (PTM) data and comparison of PTM data across species and DRscDB for mining and comparison of single-cell RNA-seq data across species. Simchovitz A, Hanan M, Niederhoffer N, Madrer N, Yayon N, Bennett ER, Greenberg DS, Kadener S, Soreq H. Thermosensitive alternative splicing senses and mediates temperature adaptation in, Reconfiguration of a Multi-oscillator Network by Light in the. DIOPT allows scientists to design experiments based on the knowledge obtained from a different organism(s) and to prioritize genes based on evolutionary conservation. A polar mechanism coordinates different regions of alternative splicing within a single gene. Our main accomplishments regarding biological questions have been in the areas of canonical signaling pathway organization, cell polarity establishment, gut regeneration and homeostasis, and inter-organ communication. single nuclei sequencing (snRNAseq) of entire flies, and proteomics approaches, e.g. Regulation of RNA metabolism is emerging as a major regulatory hub for gene expression control in tissues like the brain and the muscle, which don't undergo cel. * Corresponding authors. Following. We use Drosophila as a model system to characterize the mechanisms underlying communication between cells, tissues, and organs. Thermosensitive alternative splicing senses and mediates temperature adaptation in Drosophila. Sayan is originally from India where he completed his undergraduate training in Electrical Engineering at Jadavpur University, Kolkata. Pathways that are misregulated in animals that develop organ wasting in the context of these various tumor models are identified using a combination of transcriptomics, e.g. We demonstrated that shRNAs are more efficient and specific than long dsRNA when expressed as transgenes, and generated a genome scale collection of >13,000 lines covering 75% of the genome in our optimized VALIUM vectors (85% of highly conserved genes). Bartok O., Kyriacou C., Levine J., Sehgal A. and Kadener S. Adaptation of molecular circadian clockwork to environmental changes: a role for alternative splicing and miRNAs. Usc we have extended this approach to the mouse adipokines leptin and adiponectin serve as inter-organ secreted regulators! Developed a new method to visualize the dynamic activation of pathway activities various techniques resources. 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