检索结果-内蒙古大学图书馆

Immunometabolism at the crossroads of obesity and cancer-a Keystone Symposia report

ANNALS OF THE NEW YORK ACADEMY OF SCIENCES 2023年第1期1523卷 38-50页

作者： Cable, Jennifer Rathmell, Jeffrey C. Pearce, Erika L. Ho, Ping-Chih Haigis, Marcia C. Mamedov, Murad R. Wu, Meng-Ju Kaech, Susan M. Lynch, Lydia Febbraio, Mark A. Bapat, Sagar P. Hong, Hanna S. Zou, Weiping Belkaid, Yasmine Sullivan, Zuri A. Keller, Andrea Wculek, Stefanie K. Green, Douglas R. Postic, Catherine Amit, Ido Benitah, Salvador Aznar Jones, Russell G. Reina-Campos, Miguel Torres, Santiago Valle Beyaz, Semir Brennan, Donal O'Neill, Luke A. J. Perry, Rachel J. Brenner, Dirk PhD Sci Writer New York NY 10017 USA Vanderbilt Univ Vanderbilt Ingram Canc Ctr Med Ctr Nashville TN USA Vanderbilt Univ Vanderbilt Ctr Immunobiol Med Ctr Nashville TN USA Vanderbilt Univ Dept Pathol Microbiol & Immunol Med Ctr Nashville TN USA Bloomberg Kimmel Inst Canc Immunotherapy Johns Ho Baltimore MD USA Max Planck Inst Immunobiol & Epigenet Freiburg Germany Univ Lausanne Dept Fundamental Oncol Lausanne Switzerland Univ Lausanne Ludwig Inst Canc Res Lausanne Switzerland Harvard Med Sch Blavatnik Inst Dept Cell Biol Boston MA USA Univ Calif San Francisco Gladstone UCSF Inst Genom Immunol San Francisco CA USA Univ Calif San Francisco Dept Med San Francisco CA USA Harvard Med Sch Massachusetts Gen Hosp Canc Ctr Boston MA USA Harvard Med Sch Dept Med Boston MA USA Broad Inst Harvard & MIT Cambridge MA USA Salk Inst Biol Studies NOMIS Ctr Immunobiol & Microbial Pathogenesis La Jolla CA USA Harvard Med Sch Brigham & Womens Hosp Boston MA USA Monash Univ Monash Inst Pharmaceut Sci Parkville VIC Australia Univ Calif San Francisco Diabet Ctr San Francisco CA USA Univ Calif San Francisco Dept Lab Med San Francisco CA USA Univ Michigan Dept Mol & Integrat Physiol Ann Arbor MI USA Univ Michigan Dept Surg Sch Med Ann Arbor MI USA Univ Michigan Univ Michigan Rogel Canc Ctr Ctr Excellence Canc Immunol & Immunotherapy Sch Med Ann Arbor MI USA Univ Michigan Dept Pathol Grad Program Immunol Sch Med Ann Arbor MI USA Univ Michigan Grad Program Canc Biol Sch Med Ann Arbor MI USA NIH Metaorganism Immun Sect Lab Immune Syst Biol Bethesda MD USA NIAID NIAID Microbiome Program NIH Bethesda MD USA Harvard Univ Dept Immunobiol Mol & Cellular Biol Cambridge MA USA Ohio State Univ Coll Med Dept Biol Chem & Pharmacol Columbus OH USA Ohio State Univ Arthur G James Canc Hosp Comprehens Canc Ctr Wexner Med Ctr Columbus OH USA Ctr Nacl Invest Cardiovasc CNIC Madrid Spain St Jude Childrens Res Hosp Memphis TN USA Univ Paris Cite Inst Coch

Immunometabolism considers the relationship between metabolism and immunity. Typically, researchers focus on either the metabolic pathways within immune cells that affect their function or the impact of immune cells on systemic metabolism. A more holistic approach that considers both these viewpoints is needed. On September 5-8, 2022, experts in the field of immunometabolism met for the Keystone symposium "Immunometabolism at the Crossroads of Obesity and Cancer" to present recent research across the field of immunometabolism, with the setting of obesity and cancer as an ideal example of the complex interplay between metabolism, immunity, and cancer. Speakers highlighted new insights on the metabolic links between tumor cells and immune cells, with a focus on leveraging unique metabolic vulnerabilities of different cell types in the tumor microenvironment as therapeutic targets and demonstrated the effects of diet, the microbiome, and obesity on immune system function and cancer pathogenesis and therapy. Finally, speakers presented new technologies to interrogate the immune system and uncover novel metabolic pathways important for immunity.

关键词： cancer immunity immunometabolism immunotherapy metabolism obesity

来源：评论

学校读者我要写书评

暂无评论

LGG-45. Genetic dependencies inMYB/MYBL1-driven pediatric low-grade glioma models

引用

Neuro-Oncology 2022年第SUPPLEMENT_1期24卷 i98–i98页

作者： Alexandra-Larisa Condurat Jill Jones Elizabeth Gonzalez Jeyna Doshi Kevin Zhou Jessica W Tsai Prasidda Khadka Graham B J Buchan Cecile Rouleau Kristine Pelton Tanaz Abid Amy Goodale Nicole Persky Rameen Beroukhim Keith Ligon David Root Federica Piccioni Pratiti Bandopadhayay Department of Pediatric Oncology Dana-Farber Boston Children’s Cancer and Blood Disorders Center Boston MA USA Broad Institute of MIT and Harvard Cambridge MA USA Harvard/MIT MD-PhD Program Boston MA USA Department of Cancer Biology Dana Farber Cancer Institute Boston MA USA Department of Oncologic Pathology Dana Farber Cancer Institute Boston MA USA

AIM: Pediatric low-grade gliomas (pLGGs) are a heterogenous group of tumors, diverse in their localization, histology, mutational landscape, clinical behavior, and treatment response. Genomic alterations impacting the MYB family of transcription factors were identified in two distinct pLGG subtypes: Angiocentric Gliomas (AG) and Diffuse Astrocytomas (DA). The molecular profiles and therapeutic vulnerabilities associated with these genomic alterations remain unexplored. In this study we highlight the use of genome-wide CRISPR/Cas9 knock-out screens for an unbiased identification of translatable therapeutic targets. METHODOLOGY : Given the lack of patient-derived pLGG cell lines, we engineered in vitro pLGG mouse and human neural stem cell (NSC) models to harbor pLGG-relevant genomic alterations. We performed single cell RNA sequencing to investigate the transcriptional profiles driven by these mutations and to dissect the central regulatory networks enabling tumorigenesis. Specific genetic dependencies associated with MYB/MYBL1 mutations were screened using the Brie genome-wide mouse CRISPR lentiviral knock-out pooled library, consisting of 78,637 single guide RNAs (sgRNAs) targeting 19,674 mouse genes. RESULTS : We have successfully generated in vitro NSC-based pLGG models crucial to deepening our knowledge on pLGG biology and the identification of translatable therapeutic targets. Genome-scale CRISPR/Cas9 knock-out screens in isogenic NSCs models, expressing distinct MYB/MYBL1 alterations or a control transgene, revealed several differential genetic dependencies. Among the top identified dependencies are regulators of cell-stress response, cell-cycle progression, and modulators of the ubiquitin-proteasome degradation pathway. CONCLUSION : Genome-wide CRISPR knock-out screens are a powerful tool for the unbiased identification of mutation-specific genetic dependencies that can be explored as candidates for precision medicine approaches.

关键词：

来源：评论

学校读者我要写书评

暂无评论

Aplp1 interacts with Lag3 to facilitate transmission of pathologic α-synuclein

引用

NATURE COMMUNICATIONS 2024年第1期15卷 4663页

作者： Mao, Xiaobo Gu, Hao Kim, Donghoon Kimura, Yasuyoshi Wang, Ning Xu, Enquan Kumbhar, Ramhari Ming, Xiaotian Wang, Haibo Chen, Chan Zhang, Shengnan Jia, Chunyu Liu, Yuqing Bian, Hetao Karuppagounder, Senthilkumar S. Akkentli, Fatih Chen, Qi Jia, Longgang Hwang, Heehong Lee, Su Hyun Ke, Xiyu Chang, Michael Li, Amanda Yang, Jun Rastegar, Cyrus Sriparna, Manjari Ge, Preston Brahmachari, Saurav Kim, Sangjune Zhang, Shu Shimoda, Yasushi Saar, Martina Liu, Haiqing Kweon, Sin Ho Ying, Mingyao Workman, Creg J. Vignali, Dario A. A. Muller, Ulrike C. Liu, Cong Ko, Han Seok Dawson, Valina L. Dawson, Ted M. Johns Hopkins Univ Sch Med Inst Cell Engn Neuroregenerat & Stem Cell Programs Baltimore MD 21205 USA Johns Hopkins Univ Sch Med Dept Neurol Baltimore MD 21205 USA Adrienne Helis Malvin Med Res Fdn New Orleans LA 70130 USA Chinese Acad Sci Interdisciplinary Res Ctr Biol & Chem Shanghai Inst Organ Chem 26 Qiuyue Rd Shanghai 201210 Peoples R China Univ Chinese Acad Sci 19 A Yuquan Rd Beijing 100049 Peoples R China Johns Hopkins Univ Inst NanoBioTechnol Baltimore MD 21218 USA Johns Hopkins Univ Whiting Sch Engn Dept Mat Sci & Engn Baltimore MD 21218 USA Nagaoka Univ Technol Dept Bioengn 1603-1 Kamitomiokamachi Nagaoka Niigata 9402188 Japan Heidelberg Univ Inst Pharm & Mol Biotechnol IPMB Dept Funct Genom Neuenheimer Feld 364 D-69120 Heidelberg Germany Hugo W Moser Res Inst Kennedy Krieger 707 North Broadway Baltimore MD 21205 USA Univ Pittsburgh Sch Med Dept Immunol Pittsburgh PA 15261 USA UPMC Hillman Canc Ctr Tumor Microenvironm Ctr Pittsburgh PA 15232 USA Johns Hopkins Univ Sch Med Dept Physiol Baltimore MD 21205 USA Johns Hopkins Univ Sch Med Solomon H Snyder Dept Neurosci Baltimore MD 21205 USA Johns Hopkins Univ Sch Med Dept Pharmacol & Mol Sci Baltimore MD 21205 USA Nanjing Brain Hosp Dept Neurol Nanjing 210029 Jiangsu Prov Peoples R China Yangzhou Univ Med Coll Yangzhou 225001 Jiangsu Peoples R China Sichuan Univ Res Units West China 2018RU012 West China Hosp Chinese Acad Med SciDept Anesthesiol Chengdu 610041 Sichuan Peoples R China MIT Dept Brain & Cognit Sci Cambridge MA 02139 USA Dong A Univ Dept Pharmacol Coll Med 32 Daesin Gongwon Ro Busan 49201 South Korea Chungbuk Natl Univ Dept Biol Sci & Biotechnol Cheongju 28644 Chungbuk South Korea Shandong First Med Univ & Shandong Acad Med Sci Sch Basic Med Sci Inst Basic Med Sci Dept Physiol Jinan 250000 Peoples R China Picower Inst Learning & Memory Cambridge MA 02139 USA Harvard Med Sch Harvard MIT MD PhD Program Boston MA 02115 USA

Pathologic alpha-synuclein (alpha-syn) spreads from cell-to-cell, in part, through binding to the lymphocyte-activation gene 3 (Lag3). Here we report that amyloid beta precursor-like protein 1 (Aplp1) interacts with Lag3 that facilitates the binding, internalization, transmission, and toxicity of pathologic alpha-syn. Deletion of both Aplp1 and Lag3 eliminates the loss of dopaminergic neurons and the accompanying behavioral deficits induced by alpha-syn preformed fibrils (PFF). Anti-Lag3 prevents the internalization of alpha-syn PFF by disrupting the interaction of Aplp1 and Lag3, and blocks the neurodegeneration induced by alpha-syn PFF in vivo. The identification of Aplp1 and the interplay with Lag3 for alpha-syn PFF induced pathology deepens our insight about molecular mechanisms of cell-to-cell transmission of pathologic alpha-syn and provides additional targets for therapeutic strategies aimed at preventing neurodegeneration in Parkinson's disease and related alpha-synucleinopathies. Pathologic alpha-synuclein spreads from cell-to-cell through binding to the lymphocyteactivation gene 3 (Lag3). Here, the authors demonstrate that the amyloid beta precursor-like protein 1 (Aplp1) interacts with Lag3 and facilitates the binding, internalization, transmission, and toxicity of pathologic alpha-synuclein.

关键词：

来源：评论

学校读者我要写书评

暂无评论

Advancements in Immunity and Dementia Research: Highlights from the 2023 AAIC Advancements: Immunity Conference

引用

ALZHEIMERS & DEMENTIA 2025年第1期21卷 e14291页

作者： Kloske, Courtney M. Mahinrad, Simin Barnum, Christopher J. Batista, Andre F. Bradshaw, Elizabeth M. Butts, Brittany Carrillo, Maria C. Chakrabarty, Paramita Chen, Xiaoying Craft, Suzanne Da Mesquita, Sandro Dabin, Luke C. Devanand, Davangere Duran-Laforet, Violeta Elyaman, Wassim Evans, Elizabeth E. Fitzgerald-Bocarsly, Patricia Foley, Kate E. Harms, Ashley S. Heneka, Michael T. Hong, Soyon Huang, Yu-Wen A. Jackvony, Stephanie Lai, Laijun Guen, Yann Le Lemere, Cynthia A. Liddelow, Shane A. Martin-Pena, Alfonso Orr, Anna G. Quintana, Francisco J. Ramey, Grace D. Rexach, Jessica E. Rizzo, Stacey J. S. Sexton, Claire Tang, Alice S. Torrellas, Jose G. Tsai, Andy P. van Olst, Lynn Walker, Keenan A. Wharton, Whitney Tansey, Malu Gamez Wilcock, Donna M. Alzheimers Assoc 225 N Michigan AveFloor 17 Chicago IL 60601 USA INmune Bio Inc Boca Raton FL USA Harvard Med Sch Brigham & Womens Hosp Ann Romney Ctr Neurol Dis Boston MA USA Columbia Univ Carol & Gene Ludwig Ctr Res Neurodegenerat Dept Neurol Div Translat Neurobiol New York NY USA Emory Univ Atlanta GA USA Univ Florida Dept Neurosci Ctr Translat Res Neurodegenerat Dis Gainesville FL 32610 USA Washington Univ Hope Ctr Neurol Disorders Knight Alzheimers Dis Res Ctr Dept NeurolSch Med St Louis MO USA Wake Forest Univ Alzheimers Dis Res Ctr Bowman Gray Sch Med Winston Salem NC USA Mayo Clin Dept Neurosci Jacksonville FL USA Indiana Univ Sch Med Dept Med & Mol Genet Indianapolis IN USA Indiana Univ Sch Med Stark Neurosci Res Inst Indianapolis IN 46202 USA Columbia Univ Irving Med Ctr New York NY USA Univ Massachusetts Brudnick Neuropsychiat Res Inst Dept Neurobiol Chan Med Sch Worcester MA USA Columbia Univ Dept Neurol Div Translat Neurobiol Irving Med Ctr New York NY USA Columbia Univ Taub Inst Res Alzheimers Dis & Aging Brain Irving Med Ctr New York NY USA Vaccinex Inc Rochester NY USA Rutgers New Jersey Med Sch Newark NJ USA Indiana Univ Stark Neurosci Res Inst Indianapolis IN USA Univ Alabama Birmingham Dept Neurol Birmingham AL USA Univ Luxembourg Luxembourg Ctr Syst Biomed Belval Luxembourg Univ Massachusetts Div Infect Dis & Immunol Med Sch North Worcester MA USA UCL UK Dementia Res Inst Inst Neurol London England Brown Univ Providence RI USA Weill Cornell Med Appel Alzheimers Dis Res Inst Feil Family Brain & Mind Res Inst Neurosci Grad Program New York NY USA Univ Connecticut Storrs CT USA Stanford Univ Dept Neurol & Neurol Sci Palo Alto CA USA Stanford Univ Dept Med Quantitat Sci Unit Sch Med Palo Alto CA USA Brigham & Womens Hosp Ann Romney Ctr Neurol Dis Dept Neurol Boston MA 02115 USA Harvard Med Sch Dept Neurol Boston MA USA NYU Neurosci Inst Dept Neurosci & Physiol & Ophthalmol Grossman Sch Med New

The immune system is a key player in the onset and progression of neurodegenerative disorders. While brain resident immune cell-mediated neuroinflammation and peripheral immune cell (eg, T cell) infiltration into the brain have been shown to significantly contribute to Alzheimer's disease (AD) pathology, the nature and extent of immune responses in the brain in the context of AD and related dementias (ADRD) remain unclear. Furthermore, the roles of the peripheral immune system in driving ADRD pathology remain incompletely elucidated. In March of 2023, the Alzheimer's Association convened the Alzheimer's Association International Conference (AAIC), Advancements: Immunity, to discuss the roles of the immune system in ADRD. A wide range of topics were discussed, such as animal models that replicate human pathology, immune-related biomarkers and clinical trials, and lessons from other fields describing immune responses in neurodegeneration. This manuscript presents highlights from the conference and outlines avenues for future research on the roles of immunity in neurodegenerative disorders.

关键词： Alzheimer's disease immunity inflammation microglia therapeutics

来源：评论

学校读者我要写书评

暂无评论

Outflanking immunodominance to target subdominant broadly neutralizing epitopes

引用

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 2019年第27期116卷 13474-13479页

作者： Angeletti, Davide Kosik, Ivan Santos, Jefferson J. S. Yewdell, William T. Boudreau, Carolyn M. Mallajosyula, Vamsee V. A. Mankowski, Madeleine C. Chambers, Michael Prabhakaran, Madhu Hickman, Heather D. McDermott, Adrian B. Alter, Galit Chaudhuri, Jayanta Yewdell, Jonathan W. NIAID Lab Viral Dis NIH 9000 Rockville Pike Bethesda MD 20892 USA Univ Gothenburg Dept Microbiol & Immunol Inst Biomed S-40530 Gothenburg Sweden Mem Sloan Kettering Canc Ctr Immunol Program New York NY 10065 USA Ragon Inst MGH MIT & Harvard Univ Cambridge MA 02139 USA Harvard Univ Div Med Sci PhD Program Virol Boston MA 02115 USA Stanford Univ Inst Immun Transplantat & Infect Stanford CA 94305 USA NIAID Vaccine Res Ctr NIH 9000 Rockville Pike Bethesda MD 20892 USA NIAID Lab Clin Immunol & Microbiol NIH 9000 Rockville Pike Bethesda MD 20892 USA

A major obstacle to vaccination against antigenically variable viruses is skewing of antibody responses to variable immunodominant epitopes. For influenza virus hemagglutinin (HA), the immuno-dominance of the variable head impairs responses to the highly conserved stem. Here, we show that head immunodominance depends on the physical attachment of head to stem. Stem immuno-genicity is enhanced by immunizing with stem-only constructs or by increasing local HA concentration in the draining lymph node. Surprisingly, coimmunization of full-length HA and stem alters stem-antibody class switching. Our findings delineate strategies for overcoming immunodominance, with important implications for human vaccination.

关键词： influenza immunodominance B cell hemagglutinin antibodies

来源：评论

学校读者我要写书评

暂无评论

Deciphering the impact of genomic variation on function

引用

NATURE 2024年第8028期633卷 47-+页

作者： Engreitz, Jesse M. Lawson, Heather A. Singh, Harinder Starita, Lea M. Hon, Gary C. Carter, Hannah Sahni, Nidhi Reddy, Timothy E. Lin, Xihong Li, Yun Munshi, Nikhil V. Chahrour, Maria H. Boyle, Alan P. Hitz, Benjamin C. Mortazavi, Ali Craven, Mark Mohlke, Karen L. Pinello, Luca Wang, Ting Kundaje, Anshul Yue, Feng Cody, Sarah Farrell, Nina P. Love, Michael I. Muffley, Lara A. Pazin, Michael J. Reese, Fairlie Van Buren, Eric Dey, Kushal K. Kircher, Martin Ma, Jian Radivojac, Predrag Balliu, Brunilda Williams, Brian A. Huangfu, Danwei Park, Chong Y. Quertermous, Thomas Das, Jishnu Calderwood, Michael A. Fowler, Douglas M. Vidal, Marc Ferreira, Lucas Mooney, Sean D. Pejaver, Vikas Zhao, Jingjing Gazal, Steven Koch, Evan Reilly, Steven K. Sunyaev, Shamil Carpenter, Anne E. Buenrostro, Jason D. Leslie, Christina S. Savage, Rachel E. Luo, Chongyuan Plath, Kathrin Barrera, Alejandro Schubach, Max Gschwind, Andreas R. Moore, Jill E. Ahituv, Nadav Yi, S. Stephen Hallgrimsdottir, Ingileif Gaulton, Kyle J. Sakaue, Saori Booeshaghi, Sina Mattei, Eugenio Nair, Surag Pachter, Lior Wang, Austin T. Shendure, Jay Agarwal, Vikram Blair, Andrew Chalkiadakis, Theofilos Chardon, Florence M. Dash, Pyaree M. Deng, Chengyu Hamazaki, Nobuhiko Keukeleire, Pia Kubo, Connor Lalanne, Jean-Benoit Maass, Thorben Martin, Beth McDiarmid, Troy A. Nobuhara, Mai Page, Nicholas F. Regalado, Sam Sims, Jasmine Ushiki, Aki Best, Sabrina M. Boyle, Gabe Camp, Nathan Casadei, Silvia Da, Estelle Y. Dawood, Moez Dawson, Samantha C. Fayer, Shawn Hamm, Audrey James, Richard G. Jarvik, Gail P. McEwen, Abbye E. Moore, Nick Pendyala, Sriram Popp, Nicholas A. Post, Mason Rubin, Alan F. Smith, Nahum T. Stone, Jeremy Tejura, Malvika Wang, Ziyu R. Wheelock, Melinda K. Woo, Ivan Zapp, Brendan D. Amgalan, Dulguun Aradhana, Aradhana Arana, Sophia M. Bassik, Michael C. Bauman, Julia R. Bhattacharya, Asmita Cai, Xiangmeng Shawn Chen, Ziwei Conley, Stephanie Deshpande, Salil Doughty, Benjamin R. Du, Peter P. Galante, James A. Gifford, Casey Greenleaf, William J. Guo, Kathe Stanford Univ Dept Genet Sch Med Stanford CA 94305 USA Stanford Childrens Hlth Basic Sci & Engn Initiat Betty Irene Moore Childrens Heart Ctr Stanford CA 94305 USA Broad Inst MIT & Harvard Novo Nordisk Fdn Ctr Genom Mech Dis Cambridge MA 02138 USA Broad Inst MIT & Harvard Gene Regulat Observ Cambridge MA 02138 USA Washington Univ Dept Genet St Louis MO USA Univ Pittsburgh Dept Immunol Pittsburgh PA USA Univ Pittsburgh Dept Computat & Syst Biol Pittsburgh PA USA Univ Washington Dept Genome Sci Seattle WA USA Brotman Baty Inst Precis Med Seattle WA USA Univ Texas Southwestern Med Ctr Cecil H & Ida Green Ctr Reprod Biol Sci Dallas TX USA Univ Texas Southwestern Med Ctr Dept Obstet & Gynecol Dallas TX USA Univ Texas Southwestern Med Ctr Dept Bioinformat Dallas TX USA Univ Calif San Diego Dept Med San Diego CA USA Univ Texas MD Anderson Canc Ctr Dept Epigenet & Mol Carcinogenesis Houston TX USA Univ Texas MD Anderson Canc Ctr Dept Bioinformat & Computat Biol Houston TX USA Duke Univ Med Ctr Dept Biostat & Bioinformat Durham NC USA Harvard TH Chan Sch Publ Hlth Dept Biostat Boston MA USA Harvard Univ Dept Stat Cambridge MA USA Univ North Carolina Dept Genet Chapel Hill NC USA Univ North Carolina Dept Biostat Chapel Hill NC USA Univ Texas Southwestern Med Ctr Div Cardiol Dept Internal Med Dallas TX USA Univ Texas Southwestern Med Ctr Dept Mol Biol Dallas TX USA Univ Texas Southwestern Med Ctr Eugene McDermott Ctr Human Growth & Dev Dallas TX USA Univ Texas Southwestern Med Ctr Dept Neurosci Dallas TX USA Univ Texas Southwestern Med Ctr Dept Psychiat Dallas TX USA Univ Texas Southwestern Med Ctr Ctr Genet Host Def Dallas TX USA Univ Texas Southwestern Med Ctr Peter ODonnell Jr Brain Inst Dallas TX USA Univ Michigan Dept Computat Med & Bioinformat Ann Arbor MI USA Univ Michigan Dept Human Genet Ann Arbor MI USA UC Irvine Dept Dev & Cell Biol Irvine CA USA UC Irvine Ctr Complex Biol Syst Irvine CA USA Univ Wisconsin Dept Biosta

Our genomes influence nearly every aspect of human biology-from molecular and cellular functions to phenotypes in health and disease. Studying the differences in DNA sequence between individuals (genomic variation) could reveal previously unknown mechanisms of human biology, uncover the basis of genetic predispositions to diseases, and guide the development of new diagnostic tools and therapeutic agents. Yet, understanding how genomic variation alters genome function to influence phenotype has proved challenging. To unlock these insights, we need a systematic and comprehensive catalogue of genome function and the molecular and cellular effects of genomic variants. Towards this goal, the Impact of Genomic Variation on Function (IGVF) Consortium will combine approaches in single-cell mapping, genomic perturbations and predictive modelling to investigate the relationships among genomic variation, genome function and phenotypes. IGVF will create maps across hundreds of cell types and states describing how coding variants alter protein activity, how noncoding variants change the regulation of gene expression, and how such effects connect through gene-regulatory and protein-interaction networks. These experimental data, computational predictions and accompanying standards and pipelines will be integrated into an open resource that will catalyse community efforts to explore how our genomes influence biology and disease across populations.

关键词：

来源：评论

学校读者我要写书评

暂无评论

Frontiers in cancer immunotherapy-a symposium report

引用

ANNALS OF THE NEW YORK ACADEMY OF SCIENCES 2021年第1期1489卷 30-47页

作者： Cable, Jennifer Greenbaum, Benjamin Pe'er, Dana Bollard, Catherine M. Bruni, Sofia Griffin, Matthew E. Allison, James P. Wu, Catherine J. Subudhi, Sumit K. Mardis, Elaine R. Brentjens, Renier Sosman, Jeffry A. Cemerski, Saso Zavitsanou, Anastasia-Maria Proia, Theresa Egeblad, Mikala Nolan, Garry Goswami, Sangeeta Spranger, Stefani Mackall, Crystal L. PhD Sci Writer New York NY USA Mem Sloan Kettering Canc Computat Oncol Program Computat Immunooncol Dept Epidemiol & Biostat New York NY USA Mem Sloan Kettering Canc Parker Inst Canc Immunotherapy Program Computat & Syst Biol New York NY USA Mem Sloan Kettering Canc Ctr Parker Inst Canc Immunotherapy New York NY USA George Washington Univ Natl Childrens Hosp Ctr Canc & Immunol Res Washington DC USA Consejo Nacl Invest Cient & Tecn IBYME Lab Mol Mech Carcinogenesis Buenos Aires DF Argentina Rockefeller Univ New York Lab Chem Biol & Microbial Pathogenesis New York NY USA Univ Texas MD Anderson Canc Ctr Immunotherapy Platform Houston TX 77030 USA Univ Texas MD Anderson Canc Ctr Dept Immunol Houston TX 77030 USA Dana Farber Canc Inst Dept Med Oncol Boston MA 02115 USA MIT Broad Inst 77 Massachusetts Ave Cambridge MA 02139 USA Harvard Univ Cambridge MA 02138 USA Harvard Med Sch Boston MA 02115 USA Brigham & Womens Hosp Dept Med 75 Francis St Boston MA 02115 USA Univ Texas MD Anderson Canc Ctr Dept Genitourinary Med Oncol Houston TX 77030 USA Nationwide Childrens Hosp Rasmussen Inst Genom Med Columbus OH USA Mem Sloan Kettering Canc Ctr Dept Med & Ctr Cell Engn 1275 York Ave New York NY 10021 USA Northwestern Univ Div Hematol & Oncol Dept Med Feinberg Sch Med Chicago IL 60611 USA Cue Biopharma Cambridge MA USA NYU Sch Med Dept Pathol New York NY USA AstraZeneca Waltham MA USA Canc Ctr Cold Spring Harbor Lab New York NY USA Stanford Univ Baxter Lab Stem Cell Biol Stanford CA 94305 USA Stanford Univ Dept Microbiol & Immunol Stanford CA 94305 USA Parker Inst Canc Immunotherapy San Francisco CA USA MIT Koch Inst Integrat Canc Res 77 Massachusetts Ave Cambridge MA 02139 USA MIT Dept Biol 77 Massachusetts Ave Cambridge MA 02139 USA Stanford Canc Inst Ctr Canc Cell Therapy Stanford CA USA Stanford Univ Dept Pediat Sch Med Stanford CA 94305 USA Stanford Univ Dept Med Sch Med Stanford CA 94305 USA

Cancer immunotherapy has dramatically changed the approach to cancer treatment. The aim of targeting the immune system to recognize and destroy cancer cells has afforded many patients the prospect of achieving deep, long-term remission and potential cures. However, many challenges remain for achieving the goal of effective immunotherapy for all cancer patients. Checkpoint inhibitors have been able to achieve long-term responses in a minority of patients, yet improving response rates with combination therapies increases the possibility of toxicity. Chimeric antigen receptor T cells have demonstrated high response rates in hematological cancers, although most patients experience relapse. In addition, some cancers are notoriously immunologically "cold" and typically are not effective targets for immunotherapy. Overcoming these obstacles will require new strategies to improve upon the efficacy of current agents, identify biomarkers to select appropriate therapies, and discover new modalities to expand the accessibility of immunotherapy to additional tumor types and patient populations.

关键词： cancer vaccine CAR T checkpoint inhibitors immune evasion immuno‐ oncology immunogenomics immunotherapy neoantigen T cell therapy tumor microenvironment

来源：评论

学校读者我要写书评

暂无评论

Regulation of human cerebral cortical development by EXOC7 and EXOC8, components of the exocyst complex, and roles in neural progenitor cell proliferation and survival

引用

GENETICS IN MEDICINE 2020年第6期22卷 1040-1050页

作者： Coulter, Michael E. Musaev, Damir DeGennaro, Ellen M. Zhang, Xiaochang Henke, Katrin James, Kiely N. Smith, Richard S. Hill, R. Sean Partlow, Jennifer N. Muna Al-Saffar Kamumbu, A. Stacy Hatem, Nicole Barkovich, A. James Aziza, Jacqueline Chassaing, Nicolas Zaki, Maha S. Sultan, Tipu Burglen, Lydie Rajab, Anna Al-Gazali, Lihadh Mochida, Ganeshwaran H. Harris, Matthew P. Gleeson, Joseph G. Walsh, Christopher A. Harvard Med Sch Div Genet & Genom Boston MA 02115 USA Harvard Med Sch Howard Hughes Med Inst Boston Childrens Hosp Dept Pediat Boston MA 02115 USA Harvard Med Sch Howard Hughes Med Inst Boston Childrens Hosp Dept Neurol Boston MA 02115 USA Harvard Med Sch Program Neurosci Boston MA 02115 USA Harvard Med Sch Harvard MIT MD PHD Program Boston MA 02115 USA Univ San Diego Dept Neurosci La Jolla CA 92110 USA Univ San Diego Howard Hughes Med Inst La Jolla CA 92110 USA MIT Harvard Mit Div Hlth Sci & Technol Cambridge MA 02139 USA Univ Chicago Dept Human Genet Chicago IL 60637 USA Harvard Med Sch Boston Childrens Hosp Dept Genet Div Orthoped Res Boston MA 02115 USA United Arab Emirates Univ Coll Med & Hlth Sci Dept Paediat Al Ain U Arab Emirates Univ Calif San Francisco Dept Radiol Benioff Childrens Hosp San Francisco CA USA Univ Calif San Francisco Dept Pediat Benioff Childrens Hosp San Francisco CA USA Univ Calif San Francisco Dept Neurol Benioff Childrens Hosp San Francisco CA USA Univ Calif San Francisco Dept Neurol Surg Benioff Childrens Hosp San Francisco CA USA CHU Toulouse Inst Univ Canc Toulouse Oncopole Dept Pathol Toulouse France CHU Toulouse Serv Genet Med Toulouse France Univ Toulouse UDEAR INSERM UMR 1056 Toulouse France Natl Res Ctr Human Genet & Genome Res Div Dept Clin Genet Cairo Egypt Inst Child Hlth Dept Pediat Neurol Lahore Pakistan Childrens Hosp Lahore Pakistan Sorbonne Univ Ctr Reference Malformat & Malad Congenitales Cerv Dept Genet AP HP Paris France Hop Trousseau Paris France INSERM Dev Brain Disorders Lab Imagine Inst UMR 1163 Paris France Minist Hlth Directorate Gen Hlth Affairs Natl Genet Ctr Muscat Oman Massachusetts Gen Hosp Dept Neurol Boston MA 02114 USA

Purpose The exocyst complex is a conserved protein complex that mediates fusion of intracellular vesicles to the plasma membrane and is implicated in processes including cell polarity, cell migration, ciliogenesis, cytokinesis, autophagy, and fusion of secretory vesicles. The essential role of these genes in human genetic disorders, however, is unknown. Methods We performed homozygosity mapping and exome sequencing of consanguineous families with recessively inherited brain development disorders. We modeled an EXOC7 splice variant in vitro and examined EXOC7 messenger RNA (mRNA) expression in developing mouse and human cortex. We modeled exoc7 loss-of-function in a zebrafish knockout. Results We report variants in exocyst complex members, EXOC7 and EXOC8, in a novel disorder of cerebral cortex development. In EXOC7, we identified four independent partial loss-of-function (LOF) variants in a recessively inherited disorder characterized by brain atrophy, seizures, and developmental delay, and in severe cases, microcephaly and infantile death. In EXOC8, we found a homozygous truncating variant in a family with a similar clinical disorder. We modeled exoc7 deficiency in zebrafish and found the absence of exoc7 causes microcephaly. Conclusion Our results highlight the essential role of the exocyst pathway in normal cortical development and how its perturbation causes complex brain disorders.

关键词： exocyst EXOC7 EXOC8 microcephaly developmental delay

来源：评论

学校读者我要写书评

暂无评论

Author Correction: Multiplexed CRISPR-based microfluidic platform for clinical testing of respiratory viruses and identification of SARS-CoV-2 variants

引用

Nature medicine 2024年第1期30卷 307页

作者： Nicole L Welch Meilin Zhu Catherine Hua Juliane Weller Marzieh Ezzaty Mirhashemi Tien G Nguyen Sreekar Mantena Matthew R Bauer Bennett M Shaw Cheri M Ackerman Sri Gowtham Thakku Megan W Tse Jared Kehe Marie-Martine Uwera Jacqueline S Eversley Derek A Bielwaski Graham McGrath Joseph Braidt Jeremy Johnson Felecia Cerrato Gage K Moreno Lydia A Krasilnikova Brittany A Petros Gabrielle L Gionet Ewa King Richard C Huard Samantha K Jalbert Michael L Cleary Nicholas A Fitzgerald Stacey B Gabriel Glen R Gallagher Sandra C Smole Lawrence C Madoff Catherine M Brown Matthew W Keller Malania M Wilson Marie K Kirby John R Barnes Daniel J Park Katherine J Siddle Christian T Happi Deborah T Hung Michael Springer Bronwyn L MacInnis Jacob E Lemieux Eric Rosenberg John A Branda Paul C Blainey Pardis C Sabeti Cameron Myhrvold Broad Institute of MIT and Harvard Cambridge MA USA. nicole_welch@g.harvard.edu. Harvard Program in Virology Division of Medical Sciences Harvard Medical School Boston MA USA. nicole_welch@g.harvard.edu. Broad Institute of MIT and Harvard Cambridge MA USA. Department of Biological Engineering Massachusetts Institute of Technology Cambridge MA USA. Division of Infectious Diseases Department of Medicine Massachusetts General Hospital Boston MA USA. Wellcome Sanger Institute Wellcome Genome Campus Hinxton UK. Harvard Program in Biological and Biomedical Sciences Harvard Medical School Boston MA USA. Division of Health Sciences and Technology Harvard Medical School and Massachusetts Institute of Technology Cambridge MA USA. Department of Organismic and Evolutionary Biology Harvard University Cambridge MA USA. Harvard/Massachusetts Institute of Technology MD-PhD Program Harvard Medical School Boston MA USA. Department of Systems Biology Harvard Medical School Boston MA USA. State Health Laboratories Rhode Island Department of Health Providence RI USA. Massachusetts Department of Public Health Boston MA USA. Influenza Division National Center for Immunization and Respiratory Diseases Centers for Disease Control and Prevention Atlanta GA USA. African Centre of Excellence for Genomics of Infectious Diseases Redeemer's University Ede Nigeria. Department of Biological Sciences College of Natural Sciences Redeemer's University Ede Nigeria. Molecular Biology Department and Center for Computational and Integrative Biology Massachusetts General Hospital Boston MA USA. Department of Immunology and Infectious Disease Harvard T.H. Chan School of Public Health Harvard University Boston MA USA. Department of Pathology Massachusetts General Hospital and Harvard Medical School Boston MA USA. Koch Institute for Integrative Cancer Research at Massachusetts Institute of Technology Cambridge MA USA. Broad Institute of MIT and Harvard Cambridge MA USA. pardis

来源：评论

学校读者我要写书评

暂无评论

TMET-13. SEX DIFFERENCES IN GLUCOSE METABOLISM AND mitOCHONDRIAL FUNCTION IN GLIOBLASTOMA IMPLICATE HYPOXIA-INDUCIBLE FACTOR 1 ALPHA (HIF1A) ACTIVITY

引用

Neuro-Oncology 2022年第SUPPLEMENT_7期24卷 vii264–vii264页

作者： Lu, Jianyun Sponagel, Jasmin Jones, Jill Gass, Hannah Nunez, Elena Frankfater, Cheryl Williams-McLeod, Sierra Marquez, Camryn Chinnaiyan, Prakash Rubin, Joshua Ippolito, Joseph Washington University in St. Louis School of Medicine Saint Louis USA Washington University in St. Louis School of Medicine St. Louis USA Harvard / MIT MD-PhD Program Boston MA USA Washington University in St. Louis School of Medicine Saint Louis MO USA Hampton University Hampton VA USA Beaumont Health Royal Oak USA

Glioblastoma (GBM) is the most common and aggressive primary brain tumor in adults. It is more prevalent in males and female patients have better survival. Investigating the molecular mechanisms underlying this disparity is imperative for understanding its development and progression as well as developing novel treatment paradigms. Carbohydrate (namely glucose) metabolism is a critical GBM nutrient source for biosynthesis, energetics, and reducing equivalents. Previously, our group discovered that elevated glycolytic activity uniquely predicted the outcomes of male, but not female, lower grade glioma patients. Our goal was to characterize sex differences in GBM carbohydrate metabolism and their effects on cellular phenotype. First, we discovered that male transformed murine astrocytes were more susceptible to glucose deprivation than females. We confirmed this phenotype with irreversible inhibition of hexokinase with 2-deoxyglucose as well as a GLUT1-selective inhibitor. Time-resolved stable isotope tracing of cell metabolism with carbon-13 glucose in transformed astrocytes further supported these findings; male cells had significantly higher rates of glucose uptake and metabolism than female cells. These results were validated with stable isotope metabolomics datasets from human cancer cell lines. Using additional assays of cellular metabolism, we discovered that male transformed astrocytes had a higher glycolytic rate, higher pyruvate kinase activity, higher mitochondrial respiration, and higher mitochondrial mass compared to females. This was validated by a TCGA pancancer analysis that revealed significantly higher expression of nuclear genes involved in mitochondrial regulation in males than in females. This prompted us to identify possible regulators of this metabolic phenotype. We discovered that HIF1A had robust hypoxia-inducible expression that was significantly higher in male transformed astrocytes. Moreover, HIF1A expression as well as its target transcrip

关键词：

来源：评论

学校读者我要写书评

暂无评论

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

请选择保存的检索档案：

请选择收藏分类：

通借通还

建议与咨询 留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

请选择保存的检索档案： 新增检索档案 确定 取消

请选择收藏分类： 新增自定义分类 确定 取消

通借通还

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

请选择保存的检索档案：

请选择收藏分类：