Research Summary

The McManus lab studies fundamental processes relating to the regulation of gene expression. We take high-throughput approaches, analyzing hundreds of thousands to millions of experiments at once, using unique and complex libraries coupled to deep sequencing. Our systems span from cell culture to in vivo models, focusing on a broad array of disease relevant tissues. From cancer to diabetes, we develop novel technologies to help us better understand how genes are regulated and how they function in cells. We aim to uncover the dark matter of the genome, to help unravel the beautiful genomic complexity of pathways and how genes interact in development and disease.

Research Funding

  • September 15, 2017 - August 31, 2023 - Illuminating Druggable Dark Matter , Principal Investigator . Sponsor: NIH, Sponsor Award ID: U24DK116214
  • August 10, 2017 - July 31, 2022 - The Cancer Target Discovery and Development Network at UCSF , Principal Investigator . Sponsor: NIH, Sponsor Award ID: U01CA217882
  • August 1, 2017 - July 31, 2022 - Functional Networks for Persister Cell Sensitivities , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01CA212767
  • September 15, 2018 - August 31, 2021 - Bay Area CRISPR Reporters , Principal Investigator . Sponsor: NIH, Sponsor Award ID: U42OD026647
  • September 1, 2002 - March 31, 2021 - Diabetes Research Center , Co-Investigator . Sponsor: NIH, Sponsor Award ID: P30DK063720
  • May 19, 2017 - February 28, 2021 - Regulation of developmental potency by the transposon LINE1 , Principal Investigator . Sponsor: NIH/NIGMS, Sponsor Award ID: R01GM123556
  • September 23, 2014 - August 31, 2019 - Tracing Cell Lineages , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01CA195770
  • August 15, 2014 - March 31, 2019 - Empiric deconvolution of functional RNA elements , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01GM110251
  • September 1, 2013 - August 31, 2018 - Genetic models for exRNA communication , Principal Investigator . Sponsor: NIH, Sponsor Award ID: U19CA179513
  • August 1, 2014 - July 31, 2017 - Unlocking the Hidden Kinome , Principal Investigator . Sponsor: NIH, Sponsor Award ID: U01MH105028
  • May 1, 2012 - April 30, 2017 - Bay Area Cancer Target Discovery and Development Network , Principal Investigator . Sponsor: NIH, Sponsor Award ID: U01CA168370
  • February 1, 2007 - January 31, 2014 - New Frontiers for Small RNA Therapies , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01GM080783
  • September 25, 2009 - February 29, 2012 - Whole genome RNA-interference screen for novel regulators of the insulin promoter , Principal Investigator . Sponsor: NIH, Sponsor Award ID: RC1DK086290
  • June 1, 2009 - May 31, 2011 - Resolving MicroRNA Targets , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01DA026065
  • September 29, 2006 - August 31, 2009 - The Epigenetics of Small RNAs in the Mammalian Brain , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R03DA022201

Education

Auburn University, Auburn, Alabama, B.S., 05/1991, Horticultural Science
University of Alabama at Birmingham, Ph.D., 12/2000, Biochem & Mol Genetics
Massachusetts Institute of Technology, Postdoctoral, 12/2004, Small RNA Biology

Honors & Awards

  • 2002
    Cancer Research Institute (CRI) Fellowship
  • 2003
    MIT School of Science Spot Appreciation Award
  • 2005
    Sandler Award in the Basic Sciences
  • 2006
    Integrative Science Award
  • 2006
    New Technologies Award
  • 2007-2010
    Deans Recognition for Excellence in Teaching
  • 2007
    WM Keck Award
  • 2009
    New Technologies Award
  • 2011
    Breakthrough Technologies Award
  • 2012
    UCSF IT Innovator Award
  • 2012
    NIH Cancer Target Discovery and Development Award
  • 2012
    Vincent and Stella Coates Endowed Chair
  • 2012, 2013
    Tom and Michelle Parker gift for stellar research
  • 2014
    NIH Illuminating the Druggable Genome Award
  • 2014
    NIH Transformative Research Award
  • 2016
    Coates Gift for Research Excellence

Selected Publications

  1. Xue B, Chuang CH, Prosser HM, Fuziwara CS, Chan C, Sahasrabudhe N, Kühn M, Wu Y, Chen J, Biton A, Chen C, Wilkinson JE, McManus MT, Bradley A, Winslow MM, Su B, He L. miR-200 deficiency promotes lung cancer metastasis by activating Notch signaling in cancer-associated fibroblasts. Genes Dev. 2021 08 01; 35(15-16):1109-1122.  View on PubMed
  2. Gruner HN, McManus MT. Examining the evidence for extracellular RNA function in mammals. Nat Rev Genet. 2021 07; 22(7):448-458.  View on PubMed
  3. Covarrubias S, Vollmers AC, Capili A, Boettcher M, Shulkin A, Correa MR, Halasz H, Robinson EK, O'Briain L, Vollmers C, Blau J, Katzman S, McManus MT, Carpenter S. High-Throughput CRISPR Screening Identifies Genes Involved in Macrophage Viability and Inflammatory Pathways. Cell Rep. 2020 12 29; 33(13):108541.  View on PubMed
  4. Hines MJ, Coffre M, Mudianto T, Panduro M, Wigton EJ, Tegla C, Osorio-Vasquez V, Kageyama R, Benhamou D, Perez O, Bajwa S, McManus MT, Ansel KM, Melamed D, Koralov SB. miR-29 Sustains B Cell Survival and Controls Terminal Differentiation via Regulation of PI3K Signaling. Cell Rep. 2020 12 01; 33(9):108436.  View on PubMed
  5. Bouchareychas L, Duong P, Covarrubias S, Alsop E, Phu TA, Chung A, Gomes M, Wong D, Meechoovet B, Capili A, Yamamoto R, Nakauchi H, McManus MT, Carpenter S, Van Keuren-Jensen K, Raffai RL. Macrophage Exosomes Resolve Atherosclerosis by Regulating Hematopoiesis and Inflammation via MicroRNA Cargo. Cell Rep. 2020 07 14; 32(2):107881.  View on PubMed
  6. Oguri Y, Shinoda K, Kim H, Alba DL, Bolus WR, Wang Q, Brown Z, Pradhan RN, Tajima K, Yoneshiro T, Ikeda K, Chen Y, Cheang RT, Tsujino K, Kim CR, Greiner VJ, Datta R, Yang CD, Atabai K, McManus MT, Koliwad SK, Spiegelman BM, Kajimura S. CD81 Controls Beige Fat Progenitor Cell Growth and Energy Balance via FAK Signaling. Cell. 2020 08 06; 182(3):563-577.e20.  View on PubMed
  7. Tromp AT, Van Gent M, Jansen JP, Scheepmaker LM, Velthuizen A, De Haas CJC, Van Kessel KPM, Bardoel BW, Boettcher M, McManus MT, Van Strijp JAG, Lebbink RJ, Haas PA, Spaan AN. Host-Receptor Post-Translational Modifications Refine Staphylococcal Leukocidin Cytotoxicity. Toxins (Basel). 2020 02 06; 12(2).  View on PubMed
  8. Yoneshiro T, Wang Q, Tajima K, Matsushita M, Maki H, Igarashi K, Dai Z, White PJ, McGarrah RW, Ilkayeva OR, Deleye Y, Oguri Y, Kuroda M, Ikeda K, Li H, Ueno A, Ohishi M, Ishikawa T, Kim K, Chen Y, Sponton CH, Pradhan RN, Majd H, Greiner VJ, Yoneshiro M, Brown Z, Chondronikola M, Takahashi H, Goto T, Kawada T, Sidossis L, Szoka FC, McManus MT, Saito M, Soga T, Kajimura S. BCAA catabolism in brown fat controls energy homeostasis through SLC25A44. Nature. 2019 08; 572(7771):614-619.  View on PubMed
  9. Lindtner S, Catta-Preta R, Tian H, Su-Feher L, Price JD, Dickel DE, Greiner V, Silberberg SN, McKinsey GL, McManus MT, Pennacchio LA, Visel A, Nord AS, Rubenstein JLR. Genomic Resolution of DLX-Orchestrated Transcriptional Circuits Driving Development of Forebrain GABAergic Neurons. Cell Rep. 2019 08 20; 28(8):2048-2063.e8.  View on PubMed
  10. Gagnon JD, Kageyama R, Shehata HM, Fassett MS, Mar DJ, Wigton EJ, Johansson K, Litterman AJ, Odorizzi P, Simeonov D, Laidlaw BJ, Panduro M, Patel S, Jeker LT, Feeney ME, McManus MT, Marson A, Matloubian M, Sanjabi S, Ansel KM. miR-15/16 Restrain Memory T Cell Differentiation, Cell Cycle, and Survival. Cell Rep. 2019 08 20; 28(8):2169-2181.e4.  View on PubMed
  11. Wang TA, Teo CF, Åkerblom M, Chen C, Tynan-La Fontaine M, Greiner VJ, Diaz A, McManus MT, Jan YN, Jan LY. Thermoregulation via Temperature-Dependent PGD2 Production in Mouse Preoptic Area. Neuron. 2019 Jul 17; 103(2):349.  View on PubMed
  12. Wang TA, Teo CF, Åkerblom M, Chen C, Tynan-La Fontaine M, Greiner VJ, Diaz A, McManus MT, Jan YN, Jan LY. Thermoregulation via Temperature-Dependent PGD2 Production in Mouse Preoptic Area. Neuron. 2019 07 17; 103(2):309-322.e7.  View on PubMed
  13. Mues M, Karra L, Romero-Moya D, Wandler A, Hangauer MJ, Ksionda O, Thus Y, Lindenbergh M, Shannon K, McManus MT, Roose JP. High-Complexity shRNA Libraries and PI3 Kinase Inhibition in Cancer: High-Fidelity Synthetic Lethality Predictions. Cell Rep. 2019 04 09; 27(2):631-647.e5.  View on PubMed
  14. Das S, Extracellular RNA Communication Consortium, Ansel KM, Bitzer M, Breakefield XO, Charest A, Galas DJ, Gerstein MB, Gupta M, Milosavljevic A, McManus MT, Patel T, Raffai RL, Rozowsky J, Roth ME, Saugstad JA, Van Keuren-Jensen K, Weaver AM, Laurent LC. The Extracellular RNA Communication Consortium: Establishing Foundational Knowledge and Technologies for Extracellular RNA Research. Cell. 2019 04 04; 177(2):231-242.  View on PubMed
  15. Boettcher M, Covarrubias S, Biton A, Blau J, Wang H, Zaitlen N, McManus MT. Tracing cellular heterogeneity in pooled genetic screens via multi-level barcoding. BMC Genomics. 2019 Feb 06; 20(1):107.  View on PubMed
  16. Oprea TI, Jan L, Johnson GL, Roth BL, Ma'ayan A, Schürer S, Shoichet BK, Sklar LA, McManus MT. Far away from the lamppost. PLoS Biol. 2018 12; 16(12):e3000067.  View on PubMed
  17. Elling R, Robinson EK, Shapleigh B, Liapis SC, Covarrubias S, Katzman S, Groff AF, Jiang Z, Agarwal S, Motwani M, Chan J, Sharma S, Hennessy EJ, FitzGerald GA, McManus MT, Rinn JL, Fitzgerald KA, Carpenter S. Genetic Models Reveal cis and trans Immune-Regulatory Activities for lincRNA-Cox2. Cell Rep. 2018 11 06; 25(6):1511-1524.e6.  View on PubMed
  18. Lu Y, Cao J, Napoli M, Xia Z, Zhao N, Creighton CJ, Li W, Chen X, Flores ER, McManus MT, Rosen JM. miR-205 Regulates Basal Cell Identity and Stem Cell Regenerative Potential During Mammary Reconstitution. Stem Cells. 2018 12; 36(12):1875-1889.  View on PubMed
  19. Tromp AT, Van Gent M, Abrial P, Martin A, Jansen JP, De Haas CJC, Van Kessel KPM, Bardoel BW, Kruse E, Bourdonnay E, Boettcher M, McManus MT, Day CJ, Jennings MP, Lina G, Vandenesch F, Van Strijp JAG, Lebbink RJ, Haas PA, Henry T, Spaan AN. Publisher Correction: Human CD45 is an F-component-specific receptor for the staphylococcal toxin Panton-Valentine leukocidin. Nat Microbiol. 2018 Oct; 3(10):1187.  View on PubMed
  20. Lee J, Pappalardo Z, Chopra DG, Hennings TG, Vaughn I, Lan C, Choe JJ, Ang K, Chen S, Arkin M, McManus MT, German MS, Ku GM. A Genetic Interaction Map of Insulin Production Identifies Mfi as an Inhibitor of Mitochondrial Fission. Endocrinology. 2018 09 01; 159(9):3321-3330.  View on PubMed

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