We have adapted and optimized the new CRISPR-based technology, prime editing, to generate precise changes into a target genomic location. 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. The challenge is now to understand how these pathways intersect and cooperate, as it is not clear if some pathways regulate the activity of others, or if they act concomitantly. bioRxiv 2023.02.20.529262; doi: Copyright 2023 The President and Fellows of Harvard College. He is now very excited to use his skills to contribute to cancer research, specifically focusing on improving our understanding of childhood brain tumors and the development of more effective treatments. 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. Studying the neuronal functions of circular RNA. Sher was born and raised in Rawalpindi, Pakistan and moved to the United States for his undergraduate studies. Lic. Chikne V.*, Doniger T.*, Bartok O. Im a Masters student studying the expression of Ultradian Genes and their role in Canton-S flies. *, Afik S., Menet J., Wolfson V., Weissbein U., Haimovich D., Gafni C., Friedman N., Rosbash M. and Kadener S. . Protocol. Additionally, many of the mechanisms by which growth factortriggered signaling events intersect with cell metabolism, which is regulated by nutrients, hormones and stress, remain to be identified. This collection is available to the community through the Bloomington Drosophila Stock Center. ), we have identified and validated novel mechanisms of how stem cells adjust their rate of proliferation/differentiation to meet the demand for tissue regeneration. Proximity Labeling: Characterizing the proteome composition of organelles and subcellular regions of living cells can facilitate the understanding of cellular organization as well as protein interactome networks. J. Biol. Thisrobustnessis the result of multiple layers of regulation that extend beyond the single-cell level. Understanding how circadian rhythms are generated, maintained, and adapted to changing conditions is key, as several diseases such as cancer and depression are associated with misalignment of the circadian clock with the environment. 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. Zaffagni M, Kadener S. NEAT1 is overexpressed in Parkinson's disease substantia nigra and confers drug-inducible neuroprotection from oxidative stress. Derr A, Yang C, Zilionis R, Sergushichev A, Blodgett DM, Redick S, Bortell R, Luban J, Harlan DM, Kadener S, Greiner DL, Klein A, Artyomov MN, Garber M. End Sequence Analysis Toolkit (ESAT) expands the extractable information from single-cell RNA-seq data. Coordination between transcription and pre-mRNA processing. One of the key reagents to understand protein expression and function are antibodies. Rabin A, Zaffagni M, Ashwal-Fluss R, Patop IL, Jajoo A, Shenzis S, Carmel L, Kadener S. Extensive tissue-specific expression variation and novel regulators underlying circadian behavior. In the Bandopadhayay Lab, Michelle is interested in using computational efforts to better characterize pediatric brain tumors. A Biblioteca Virtual em Sade uma colecao de fontes de informacao cientfica e tcnica em sade organizada e armazenada em formato eletrnico nos pases da Regio Latino-Americana e do Caribe, acessveis de forma universal na Internet de modo compatvel com as bases internacionais. Nogues G., Kadener S., Cramer P., Bentley D. and Kornblihtt A.R. For example, we identified a number of ion channels that either directly or indirectly regulate stem cell proliferation. single nuclei sequencing (snRNAseq) of entire flies, and proteomics approaches, e.g. Circadian clocks are also exceptionallyplasticas they can quickly and specifically adjust to specific environmental cues. Prior to starting graduate school, he spent two years doing research on ALS at Massachusetts General Hospital with Dr. Lagier-Tourenne. CircRNAs expression levels are not correlated with the expression of their linear isoforms, indicating a potentially widespread layer of previously unknown gene regulation. Moreover, we also showed that the neural and molecular circadian systems compensate and interact with each other. Our major contributions to tool development are the Gal4-UAS system, FLP-FRT germline clone technique, in vitro and in vivo genome-wide RNAi and CRISPR screening platforms and resources, and in vivo proximity labeling methods. Zaffagni M, Kadener S. NEAT1 is overexpressed in Parkinson's disease substantia nigra and confers drug-inducible neuroprotection from oxidative stress. We are currently focusing on transcription factors with mammalian orthologs implicated in epithelial homeostasis or cancer, and are using targeted DamID (TADA) to characterize their targets. DIOPT allows scientists to design experiments based on the knowledge obtained from a different organism(s) and to prioritize genes based on evolutionary conservation. My diverse. She also loves bagels and is always on the hunt for the best bagel. Selected for Faculty of 1000 (Factor 6 Must Read). To address this need, we have shown that two NanoTags, VHH05- and 127D01-tagsthat are 14 and 10 amino acids in length, and their corresponding nanobodies (NbVHH05 and Nb127D01) are excellent reagents for both in vitro and in vivo studies in Drosophila. 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. 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. Pamudurti N., Bartok O., Jens O., Ashwal-Fluss R., Stottmeister C., Ruhe L., Hanan M., Wyler E., Perez-Hernandez D., Ramberger E., Shenzis S., Samson M., Dittmar G., Landthaler M., Chekulaeva M., Rajewsky N. and Kadener S. Translation of circRNAs. Title. Dr. Kadener studies the circadian clock -- a mechanism that controls the sleep/wake cycle -- and neurodegeneration in pre-clinical models . Sebastian Kadener. Or do you know how to improve StudyLib UI? Clonally stable VK allelic choice instructs IgK repertoire. leptin), neural development, and behavior are conserved, . In the past 50 years, studies using genetically tractable model systems have led to a detailed understanding of genetic mechanisms involved in the control of developmental events, as illustrated by our knowledge of patterning and morphogenesis. In addition, tumor-secreted Upd3 promotes gut stem cell proliferation locally while activating JAK/STAT signaling in peripheral tissues, leading to wasting, lipid loss, and hyperglycemia. Selected for Faculty of 1000 (Factor 3 Recommended). . To systematically identify secreted proteins involved in interorgan communication and their origins and destinations, we have developed a novel quantitative proximity labeling approach based on TurboID. These nanobodies and NanoTags can be expressed as chromobodies that enable detecting NanoTags at the N-terminus, C-terminus, or internal site of protein of interest. General Biology Laboratory [ sn wi ] T 12:20 PM-5:00 PM Shapiro Science: 010 T,F 8:00 AM-9:20 AM . . RNA biology Neurosciences. For his honors thesis, Sher characterized the role of the MAPK/ERK signaling modulator SPRY2 in regulating the transcriptome of the HL-60 Acute Myeloid Leukemia cell line. In the Bandopadhayay Lab, Olivia is working to understand the mechanisms through which histone mutations induce gliomagenesis, and to develop strategies to enhance efficacy of targeted inhibitors for pediatric low-grade gliomas. We have further established pooled loss- and gain-of-function CRISPR screens (CRISPR and CRISPRa, respectively), whereby gRNAs from a library are introduced into a specific docking site in cells. For doing this, we study the circadian clock from a systemic point of view, including studies at the molecular and neural levels. Selected for Faculty of 1000 (Factor 3.0 Recommended). Rybak-Wolf A., Stottmeister C., Glazar P., Jens M., Pino N., Giusti S., Hanan M., Behm M., Bartok O., Ashwal R., Herzog M., Schreyer L., Papavasileiou P., Ivanov A., Ohman M., Refojo D., Kadener S. and Rajewsky N. Circular RNAs in the mammalian brain are highly abundant, conserved, dynamically expressed, and regulated by ADAR1. In a collaboration with Sebastian Kadener's lab at Brandeis, we generated a new set of PspCas13b and RfxCas13d expression constructs that can be used to target RNA in cells and in vivo. She also loves sleeping in, making guacamole, and reading about art history. 312. Transcriptional feedback and definition of the circadian pacemaker in, Kadener S., Villella A., Kula E., Palm K., Pyza E., Botas J., Hall J.C. and Rosbash M. Neurotoxic protein expression reveals connections between the circadian clock and mating behavior in. , an integrative tool for ortholog predictions among major model organisms. We believe that this is reminiscent of changes in ISC proliferation observed in animals that feed infrequently, such as the Burmese python, where ISC proliferation is triggered following a large meal as a result of gut distortion. These lines can be combined with tissue-specific delivery of Cas9 to generate clones of cells (mosaics) or combined with germline expression of Cas9 to generate null mutations. Now, in an article published in the journal Molecular Cell, the lab of Dr. Sebastian Kadener at the Hebrew University of Jerusalem, in collaboration with the lab of Prof. Nikolaus Rajewsky at the . Eric received his MS in biomedicine from Uppsala University, Sweden in 2010. Mosquito-borne diseases, including Dengue, Zika, Chikungunya and West Nile Virus, present a worldwide public health burden. Cramer P., Srebrow A., Kadener S., Werbajh S., de la Mata M., Melen G., Nogues G. and Kornblihtt AR. For example, we showed that circRNA biogenesis competes with canonical splicing, showing that circRNAs can function incisas RNA traps. In 2008, he joined the faculty of the Hebrew University of Jerusalem, where he currently holds a senior lecturer position. Hanan M, Simchovitz A, Yayon N, Vaknine S, Cohen-Fultheim R, Karmon M, Madrer N, Rohrlich TM, Maman M, Bennett ER, Greenberg DS, Meshorer E, Levanon EY, Soreq H, Kadener S. Past, present, and future of circRNAs. Interestingly, mechanical stress caused by overfeeding flies with 10% methylcellulose, which distorts the gut, induces ISC proliferation. Selected for Faculty of 1000 (Factor 9 Exceptional). Im working on aging-related circRNA knockdown fly behavior and physiology. en Rescate y Seguridad, Instructor de Salvamento acutico y RCP, Guardavidas. Sebastian Kadener. Lacadie S.A., Tardiff D.F., Kadener S. and Rosbash M. In vivo commitment to yeast cotranscriptional splicing is sensitive to transcription elongation mutants. Among the next significant questions to address are how complex phenotypes arise in the context of the whole organism and how the programs regulating these phenotypes are influenced by genetic background and environment. 1 / 3 Looking for Postdoctoral researchers Gut tumors can be induced in adult flies by overexpressing an active form of the transcriptional co-activator yorkie/YAP using the intestinal stem cell driver escargot-GAL4. Chikne V.*, Doniger T.*, Bartok O. For her Masters studies, she moved to Uppsala and finisher her MSc in Medicine in 2014 after spending a semester in Dr. Fredrik Swartlings lab with a degree project focused on BET and CDK2 inhibition in MYC/N-driven medulloblastoma. Over the years, we have added a number of screening reagents and developed bioinformatics tools to improve the platform. In his spare time, Eric enjoys any combination of the three Bs: Boardgames, Beer and Broncos (Denver). Transcriptional activators differ in their abilities to control alternative splicing. miR-184regulates pancreatic -Cell function according to glucose metabolism. Selected for Faculty of 1000 (Factor 3 Recommended). 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. Lic. We have developed a series of bioinformatics tools that provide the research community with well-designed, user-friendly resources that impact research at all stages, from project design to data analysis and integration. Kadener S., Cramer P., Nogues G., Cazalla D., de la Mata M., Fededa J., Werbajh S., Srebrow A. and Kornblihtt A. Articles Cited by Public access Co-authors. Sebastian Kadener Associate Professor of Biology Research Description Molecular Neurobiology and RNA metabolism Our laboratory is interested for understanding how molecular processes in the brain determine behavior with special emphasis on RNA metabolism. How do circRNAs work at the molecular level? For example, we showed that circRNA biogenesis competes with canonical splicing, showing that circRNAs can function incisas RNA traps. The tagged endogenous proteins can then be isolated for further analysis by MS. To analyze protein-protein interactions or identify components that localize to discrete subcellular compartments, we developed tools based on. * Corresponding authors. Kadener S., Fededa J.P., Rosbash M. and Kornblihtt A.R. Molecular Neurobiology and RNA metabolism. Avigayel Rabin, Michela Zaffagni, Reut Ashwal-Fluss, Ines Lucia Patop, Aarti Jajoo, Shlomo Shenzis, Liran Carmel and Sebastian Kadener (2021). SRCP: a comprehensive pipeline for accurate annotation and quantification of circRNAs. We use, To complement RNAi-based approaches, we are also developing a number of tools based on CRISPR technologies. Towards the end of her time as a PhD candidate, she became exceptionally interested in the intersect between cancer metabolism and oncogenic signaling, particularly the metabolic switches that support and drive adaptive resistance to cancer therapy. She is the Co-Director of Research for a non-profit, the STEM Advocacy Institute, which is focused on building a future where there is equitable access and exposure to science for all people. Associate Professor, Brandeis University. Second, we identified 53 transcription factors, specifically expressed or enriched in the ISCs, and are characterizing how they cooperate to integrate signal inputs. Wittenbrink N, Ananthasubramaniam B, Mnch M, Koller B, Maier B, Weschke C, Bes F, de Zeeuw J, Nowozin C, Wahnschaffe A, Wisniewski S, Zaleska M, Bartok O, Ashwal-Fluss R, Lammert H, Herzel H, Hummel M, Kadener S, Kunz D, Kramer A. Levin-Klein R., Fraenkel S., Lichtenstein M., Matheson L., Bartok O., Nevo Y., Kadener S., Corcoran A., Cedar H., Bergman Y. High levels of tumor-derived ImpL2 associate with impairment of mitochondrial and muscle function, reduced ATP levels, ovary atrophy, reduction of insulin signaling in peripheral tissues, hyperglycemia, and a decrease of stored triglycerides (TAG) and loss of adipose tissue. * Corresponding authors. Selected for Faculty of 1000 (Factor 3 Recommended). Sebastian Kadener. This plasticity is the result of the existence of very efficient input pathways that convey the external signals into the core oscillator machinery. Bartok O., Teesalu M., Pandey V., Hanan M., Poukkula M., Havula E., Moussaieff A., Vodala S., Nahmias Y., Kadener S.* and Hietakangas V.* Cabut-dependent repressive branch of the sugar sensing transcriptional network regulates glyceroneogenesis. I am interested in studying circular RNAs and neurological disorders. Our Funds. I am researching the role of circular RNAs (circRNAs) in aging processes in Drosophila melanogaster. Further, our work and that of others has suggested functions of these moleculesin vivo. He also enjoys playing handball and online chess. In this context, the most important question looking forward are: Afik S. 1, Bartok O. 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. Now the stage is set for the most exciting questions, which we are currently working in the lab, by combining molecular, computational and RNA biology with advances techniques in genetics and neurosciences. 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. Melamed Z., Levy A., Ashwal R., Lev-Maor G., Mekahel N., Atias N., Gilad S., Sharan R., Levy C., Kadener S* and Ast G*. This plasticity is the result of the existence of very efficient input pathways that convey the external signals into the core oscillator machinery. There, she studied the oncogenic role of certain signaling molecules in the Hedgehog signaling pathway, and became extremely interested in advancing cancer therapy research. Additionally, many of the mechanisms by which growth factortriggered signaling events intersect with cell metabolism, which is regulated by nutrients, hormones and stress, remain to be identified. 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. Dana joined the Bandopadhayay Lab in 2021 where is she working to apply single-cell methods to evaluate the heterogeneity of pediatric gliomas, and to understand spatial associations. I am in the Class of 2024 studying neuroscience and biology. . Articles Cited by Public access Co-authors. Andranik Ivanov and Sebastian Meczmack (Prof. Rajewsky's . PERIOD1-associated proteins modulate the negative limb of the mammalian circadian oscillator. Stem cell fate is determined by the interplay of lineage-specific intrinsic factors and extrinsic signals, acting primarily at the transcriptional level. Understanding how circadian rhythms are generated, maintained, and adapted to changing conditions is key, as several diseases such as cancer and depression are associated with misalignment of the circadian clock with the environment. Thermosensitive alternative splicing senses and mediates temperature adaptation in Drosophila. We chose to use peripheral blood monocytes as source material for gene expression profiling, because (a) blood is an easily accessible source of human cells and (b) monocytes constitute a homogenous blood cell population and have been shown to possess a high-amplitude circadian clock ( 24, 25) in contrast to other PBMCs, such as B or T cells. 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