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Draft:Michael T. McManus (biologist)

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Michael T. McManus (biologist)
NationalityAmerican
Alma materAuburn University (B.S.), University of Alabama at Birmingham (Ph.D.), Massachusetts Institute of Technology (postdoc)
Known forRNA interference, microRNA research, gene regulation
AwardsWM Keck Award, NIH Transformative Research Award, Robert J. Kleberg, Jr. and Helen C. Kleberg Award
Scientific career
FieldsSynthetic Biology, Immunology, RNA Biology
InstitutionsUniversity of California, San Francisco
Academic advisorsStephen L. Hajduk, Phillip A. Sharp

Michael T. McManus is an American professor of Microbiology and Immunology at the University of California, San Francisco (UCSF), where he holds the Vincent and Stella Coates Endowed Chair. He is the Director of the Keck Center for Noncoding RNAs and Core Director of the UCSF ViraCore facility. His research focuses on RNA biology, gene regulation, immunology, and high-throughput screening. Dr. McManus is also an Investigator at the Chan Zuckerberg Biohub.[1]

Early Life and Education

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Michael T. McManus earned his Bachelor of Science (B.S.) in Horticultural Science from Auburn University in 1991. He completed his Ph.D. in Biochemistry and Molecular Genetics at the University of Alabama at Birmingham in 2000, under the mentorship of Dr. Stephen L. Hajduk. During his doctoral research, he identified candidate mitochondrial RNA editing ligases from Trypanosoma brucei, providing support for an enzymatic model for insertional/deletional RNA editing.[2]

He then conducted postdoctoral research in mammalian RNA interference (RNAi) and microRNA at the Massachusetts Institute of Technology (MIT) under Nobel Laureate Phillip A. Sharp.[3] where he provided early evidence of small interfering RNA (siRNA)-mediated gene silencing in primary cells.[4] In 2002, Dr. McManus and colleagues independently developed short hairpin RNA (shRNA) techniques, facilitating advances in gene silencing and lentiviral delivery systems.[5][6][7][8]

Career

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Dr. McManus began his independent research career at UCSF in 2004 as an Assistant Professor at the Department of Microbiology and Immunology and the UCSF Diabetes Center. He was promoted to Associate Professor in 2010 and Full Professor in 2016, and he has held the Vincent and Stella Coates Endowed Chair since 2012[9]

He is the Director of the Keck Center for Noncoding RNAs and the Core Director of the UCSF ViraCore facility. Since 2022, Dr. McManus has served as an Investigator at the Chan Zuckerberg Biohub.[10] He is also a member of the UCSF Helen Diller Family Comprehensive Cancer Center and has held memberships at the Innovative Genomics Institute[11] and the Eli & Edythe Broad Center for Regeneration Medicine and Stem Cell Research. His work integrates computational and synthetic biology approaches to address questions related to human disease, particularly through gene regulation and high-throughput screening techniques.[1]

Research Contributions

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Dr. McManus’s research has focused on RNA biology, noncoding RNAs, gene regulation, immunology, and high-throughput screening. His contributions include:

  • Developed RNA interference technologies, including shRNA technologies[12][13][14]
  • Developed deep sequencing methods to analyze high-throughput gene perturbation screens, now a standard approach in the field.[15]​
  • Investigated the role of noncoding RNAs and epigenetic regulation in gene expression, advancing understanding of complex genomic pathways in development and disease.[16][17]
  • Developed the first CRISPR interference (CRISPRi) mouse model by using a catalytically inactive Cas9 fused to a transcriptional repressor, thereby enabling rapid and efficient gene suppression in vivo.[18]​[19][20][21][22][23]
  • Developed high-throughput methods to study genetic epistasis and determine biological pathway directionality.[24][25]
  • Discovered that drug-tolerant persister cancer cells are vulnerable to GPX4 inhibition, indicating a potential therapeutic strategy for targeting these resilient cancer cell populations.[26]

Awards and Honors

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In 2006, McManus received the WM Keck Award for establishing a Center for Noncoding RNAs.[27] In 2014, he received the NIH Transformative Research Award for his project on tracing cell lineages, focusing on developing high-throughput lineage tracing technologies.[28] In 2019, he received the Robert J. Kleberg, Jr. and Helen C. Kleberg Award for his work on engineering cell-based mRNA delivery therapies.[29] Additional honors listed on his university's official website.[30]

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References

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  1. ^ a b Bashyam, Hema (2008). "Michael T. McManus: Interrupting biology". Journal of Experimental Medicine. 205 (3): 506–507. doi:10.1084/jem.2053pi. PMC 2275373. PMID 18347104.
  2. ^ McManus, MT; Shimamura, M; Grams, J; Hajduk, SL (2001). "Identification of candidate mitochondrial RNA editing ligases from Trypanosoma brucei". RNA. 7 (2): 167–175. doi:10.1017/s1355838201002072. PMC 1370075. PMID 11233974.
  3. ^ McManus, M.; Sharp, P. (2002). "Gene silencing in mammals by small interfering RNAs". Nature Reviews Genetics. 3 (10): 737–747. doi:10.1038/nrg908. PMID 12360232. Retrieved March 31, 2025.
  4. ^ McManus, MT; Haines, BB; Dillon, CP; Whitehurst, CE; van Parijs, L; Chen, J; Sharp, PA (2002). "Small interfering RNA-mediated gene silencing in T lymphocytes". Journal of Immunology. 169 (10): 5754–5760. doi:10.4049/jimmunol.169.10.5754. PMID 12421955.
  5. ^ Paddison PJ, Caudy AA, Bernstein E, Hannon GJ, Conklin DS (April 2002). "Short hairpin RNAs (shRNAs) induce sequence-specific silencing in mammalian cells". Genes & Development. 16 (8): 948–58. doi:10.1101/gad.981002. PMC 152352. PMID 11959843.
  6. ^ Brummelkamp TR, Bernards R, Agami R (April 2002). "A system for stable expression of short interfering RNAs in mammalian cells". Science. 296 (5567): 550–3. Bibcode:2002Sci...296..550B. doi:10.1126/science.1068999. hdl:1874/15573. PMID 11910072.
  7. ^ McManus MT, Petersen CP, Haines BB, Chen J, Sharp PA (June 2002). "Gene silencing using micro-RNA designed hairpins". RNA. 8 (6): 842–850. doi:10.1017/S1355838202022025 (inactive 1 April 2025). PMC 137036. PMID 12088155.{{cite journal}}: CS1 maint: DOI inactive as of April 2025 (link)
  8. ^ Rubinson, Douglas A.; Dillon, Christopher P.; Kwiatkowski, Adam V.; Sievers, Claudia; Yang, Lili; Kopinja, Johnny; Rooney, Dina L.; Zhang, Mingdi; Ihrig, Melanie M.; McManus, Michael T.; Gertler, Frank B.; Scott, Martin L.; Van Parijs, Luk (March 2003). "A lentivirus-based system to functionally silence genes in primary mammalian cells, stem cells and transgenic mice by RNA interference". Nature Genetics. 33 (3): 401–406. doi:10.1038/ng1117. PMID 12590264.
  9. ^ "Michael T. McManus, PhD - UCSF Profiles". UCSF Profiles. Retrieved March 30, 2025.
  10. ^ "Investigators - Chan Zuckerberg Biohub". Chan Zuckerberg Biohub. Retrieved March 30, 2025.
  11. ^ "IGI Funds 24 New Research Projects". Innovative Genomics Institute. March 29, 2025. Retrieved March 30, 2025.
  12. ^ Paddison PJ, Caudy AA, Bernstein E, Hannon GJ, Conklin DS (April 2002). "Short hairpin RNAs (shRNAs) induce sequence-specific silencing in mammalian cells". Genes & Development. 16 (8): 948–58. doi:10.1101/gad.981002. PMC 152352. PMID 11959843.
  13. ^ Brummelkamp TR, Bernards R, Agami R (April 2002). "A system for stable expression of short interfering RNAs in mammalian cells". Science. 296 (5567): 550–3. Bibcode:2002Sci...296..550B. doi:10.1126/science.1068999. hdl:1874/15573. PMID 11910072.
  14. ^ McManus MT, Petersen CP, Haines BB, Chen J, Sharp PA (June 2002). "Gene silencing using micro-RNA designed hairpins". RNA. 8 (6): 842–850. doi:10.1017/S1355838202022025 (inactive 1 April 2025). PMC 137036. PMID 12088155.{{cite journal}}: CS1 maint: DOI inactive as of April 2025 (link)
  15. ^ Bassik, Michael C.; LeProust, Emily M.; Ebert, Benjamin L.; Rosenberg, Samuel; Ely, Alex; Holmes, Andrew; Jacobs, H. William; Greenside, Paul G.; Schuldiner, Maya; Scherens, Bruno; Weissman, Jonathan S.; McManus, Michael T. (2009). "Rapid creation and quantitative monitoring of high coverage shRNA libraries". Nature Methods. 6 (6): 443–445. doi:10.1038/nmeth.1330. PMC 2783737. PMID 19448642.
  16. ^ Roadmap Epigenomics Consortium; Kundaje, Anshul; Meuleman, Wouter; Ernst, Jason; Bilenky, Misha; Yen, Angela; Heravi-Moussavi, Alireza; Kheradpour, Pouya; Zhang, Zhiping; Wang, Jian; Ziller, Michael J.; Amin, Vishal; Whitaker, John W.; Schultz, Matthew D.; Ward, Lucas D.; Sarkar, Anshul; Quon, Gerald; Sandstrom, Richard S.; Eaton, Matthew L.; Wu, Yuan; Pfenning, Andrea R.; Wang, Xiao; Claussnitzer, Melina; Liu, Yun; Coarfa, Christian; Harris, Robert A.; Shoresh, Noam; Epstein, Charles B.; Gjoneska, Elizabeta; Leung, Diana; Xie, Wei; Hawkins, R. David; Lister, Ryan; Hong, Chun; Gascard, Philippe; Mungall, Andrew J.; Moore, Richard; Chuah, Eric; Tam, Angela; Canfield, Terence K.; Hansen, R. Scott; Kaul, Rajinder; Sabo, Peter J.; Bansal, Manish S.; Carles, Aleix; Dixon, Jesse R.; Farh, Kai-How; Feizi, Shahin; Karlic, Radoje; Kim, Alice R.; Kulkarni, Ameya; Li, Dan; Lowdon, Rebecca; Elliott, Graham; Mercer, Timothy R.; Neph, Shane J.; Onuchic, Vineet; Polak, Pascal; Rajagopal, Nisha; Ray, Pratap; Sallari, Richard C.; Siebenthall, Kyle T.; Sinnott-Armstrong, Naomi A.; Stevens, Michael; Thurman, Robert E.; Wu, Jian; Zhang, Beisi; Zhou, Xiaoyu; Beaudet, Arthur E.; Boyer, Laurie A.; De Jager, Philip L.; Farnham, Peggy J.; Fisher, Steven J.; Haussler, David; Jones, Steven J. M.; Li, Wei; Marra, Marco A.; McManus, Michael T.; Sunyaev, Shamil; Thomson, James A.; Tlsty, Thea D.; Tsai, Lili H.; Wang, Wei; Waterland, Robert A.; Zhang, Michael Q.; Chadwick, Lisa H.; Bernstein, Bradley E.; Costello, Joseph F.; Ecker, Joseph R.; Hirst, Martin; Meissner, Alexander; Milosavljevic, Aleksandar; Ren, Bing; Stamatoyannopoulos, John A.; Wang, Taiyuan; Kellis, Manolis (February 2015). "Integrative analysis of 111 reference human epigenomes". Nature. 518 (7539): 317–330. Bibcode:2015Natur.518..317.. doi:10.1038/nature14248. PMC 4530010. PMID 25693563.
  17. ^ Hangauer, Michael J.; Vaughn, Isaac W.; McManus, Michael T. (June 2013). "Pervasive transcription of the human genome produces thousands of previously unidentified long intergenic noncoding RNAs". PLOS Genetics. 9 (6): e1003569. doi:10.1371/journal.pgen.1003569. PMC 3688513. PMID 23818866.
  18. ^ "CRISPR interference Mouse Modeltm1(CAG-mCherry,-cas9/ZNF10*)Mtm/J". The Jackson Laboratory.
  19. ^ Martin, EW; Rodriguez Y Baena, A; Reggiardo, RE; Worthington, AK; Mattingly, CS; Poscablo, DM; Krietsch, J; McManus, MT; Carpenter, S; Kim, DH; Forsberg, EC (2023). "Dynamics of Chromatin Accessibility During Hematopoietic Stem Cell Differentiation Into Progressively Lineage-Committed Progeny". Stem Cells. 41 (5): 520–539. doi:10.1093/stmcls/sxad022. PMC 10183972. PMID 36945732.
  20. ^ 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 (2020). "CD81 Controls Beige Fat Progenitor Cell Growth and Energy Balance via FAK Signaling". Cell. 182 (3): 563–577.e20. doi:10.1016/j.cell.2020.06.021. PMC 7415677. PMID 32615086.
  21. ^ 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; McManus, MT; Saito, M; Soga, T; Kajimura, S (2019). "BCAA Catabolism in Brown Fat Controls Energy Homeostasis Through SLC25A44". Nature. 572 (7771): 614–619. Bibcode:2019Natur.572..614Y. doi:10.1038/s41586-019-1503-x. PMC 6715529. PMID 31435015.
  22. ^ Wang, TA; Teo, CF; Åkerblom, M; Chen, C; Tynan-La Fontaine, M; Greiner, VJ; Diaz, A; McManus, MT; Jan, YN; Jan, LY (2019). "Thermoregulation via Temperature-Dependent PGD2 Production in Mouse Preoptic Area". Neuron. 103 (2): 309–322.e7. doi:10.1016/j.neuron.2019.04.035. PMC 6639135. PMID 31151773.
  23. ^ 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 (2019). "Genomic Resolution of DLX-Orchestrated Transcriptional Circuits Driving Development of Forebrain GABAergic Neurons". Cell Reports. 28 (8): 2048–2063.e8. doi:10.1016/j.celrep.2019.07.022. PMC 6750766. PMID 31433982.
  24. ^ Boettcher, Michael; Tian, Ruilin; Blau, James A.; Markegard, Evan; Wagner, Ryan T.; Wu, David; Mo, Xiulei; Biton, Anne; Zaitlen, Noah; Fu, Haian; McCormick, Frank; Kampmann, Martin; McManus, Michael T. (February 2018). "Dual gene activation and knockout screen reveals directional dependencies in genetic networks". Nature Biotechnology. 36 (2): 170–178. doi:10.1038/nbt.4062. PMC 6072461. PMID 29334369.
  25. ^ Bassik, Michael C.; Kampmann, Martin; Lebbink, Robert Jan; Wang, Shuyi; Hein, Marco Y.; Poser, Ina; Weibezahn, Jimena; Horlbeck, Max A.; Chen, Siyuan; Mann, Matthias; Hyman, Anthony A.; LeProust, Emily M.; McManus, Michael T.; Weissman, Jonathan S. (February 2013). "A systematic mammalian genetic interaction map reveals pathways underlying ricin susceptibility". Cell. 152 (4): 909–922. doi:10.1016/j.cell.2013.01.030. PMC 3652613. PMID 23394947.
  26. ^ Hangauer, MJ; Viswanathan, VS; Ryan, MJ; Bole, D; Eaton, JK; Matov, A (2017). "Drug-tolerant persister cancer cells are vulnerable to GPX4 inhibition". Nature. 551 (7679): 247–250. Bibcode:2017Natur.551..247H. doi:10.1038/nature24297. PMC 5933935. PMID 29120424.
  27. ^ "Michael McManus, PhD". UCSF Helen Diller Family Comprehensive Cancer Center. Retrieved March 29, 2025.
  28. ^ "Funded Research - Transformative Research Award". NIH Common Fund. Retrieved March 30, 2025.
  29. ^ "The Robert J. Kleberg, Jr. and Helen C. Kleberg Foundation". Kleberg Foundation. Retrieved March 30, 2025.
  30. ^ "Awards and Honors". McManus Lab - UCSF. Retrieved March 30, 2025.
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