Tom Maniatis, PhD
Research Interest
The primary focus of my lab during the past 10 years has been in two areas: 1. Disease mechanisms of ALS, which involves a combination of human genetic, stem cell and animal model approaches, and 2. The structure and function of the clustered protocadherin (Pcdh) genes. We have used behavioral assays in both projects to characterize the phenotypic consequences of mutations in mouse models. The ALS animal model work has involved the use of various neuromuscular behavioral studies of the SOD1 G93A mouse model, while the protocadherin project has involved studies of both motor function and affective behavior (depression and anxiety). Manuscripts describing both studies are under review. The most recent ALS work is a study of the role of autophagy in ALS disease progression, and these studies involved various studies of motor function such as the rotarod test for motor coordination and muscle strength. The protocadherin studies involve various assays for affective function (anxiety and depression), in Pcdha gene cluster deletion mice. We have shown that these mice display a cell-autonomous serotonergic wiring phenotype, and have characterized the behavioral consequences. Recent human genetic studies from other laboratories have implicated the Pcdh gene cluster in autism and other neurological diseases. We have generated a series of well-characterized deletion mutants in the Pcdh gene cluster, and are characterizing their behavioral phenotypes. Thus, the behavior core is central to our ongoing and future studies.
- BA, 1965 Biology, University of Colorado
- MS, 1967 Chemistry, University of Colorado
- PhD, 1971 Molecular Biology, Vanderbilt University
Dr. Maniatis’ research has been recognized by many awards, including:
The Eli Lilly Award in Microbiology and Immunology,
The Richard Lounsbery Award for Biology and Medicine (Awarded by the French and U.S National Academy of Sciences),
The 2012 Lasker-Koshland Special Achievement Award in Medical Science.
He is a member of the U.S. National Academy of Science, the U.S. Academy of Medicine, a fellow of the U.S. Academy of Arts and Sciences. In 2021 he received an Honorary Degree from The Rockefeller University.
- ALS Disease Mechanisms
- Development of Neural Circuits
- Protocadherin gene expression and function
- Catherine Braine, BA, Graduate Student
- Erin Flaherty, PhD, Postdoctoral Research Scientist
- Valeria Gerbino, PhD,Postdoctoral Research Scientist
- Elena Kandror, BA, Graduate Student
- Amy Kirner, BS, Tech B
- Tom Maniatis, PhD, Principal Investigator
- Lexi Peterson, BS, Lab Technician
- Abbas Rizvi, PhD, Postdoctoral Research Scientist
- Junqiang Ye, PhD, Research Associate
- Jin Zhang, PhD, Postdoctoral Fellow
- Chiamake Nwakeze, BA, Tech B
Richard Axel - Role of protocadherins in olfactory receptor neuron wiring
Tom Jessell - Astrocyte/motor neuron interactions in ALS
Charles Zuker - single cell analysis of taste receptors
Publications
https://www.biochem.cumc.columbia.edu/research/research-labs/maniatis-lab/publications
Canzio D, Nwakeze CL, Horta A, Rajkumar SM, Coffey EL, Duffy EE, Duffié R, Monahan K, O'Keeffe S, Simon MD, Lomvardas S, Maniatis T.
Cell. 2019 Apr 18;177(3):639-653.e15. doi: 10.1016/j.cell.2019.03.008. Epub 2019 Apr 4. PMID: 30955885
Mountoufaris G, Canzio D, Nwakeze CL, Chen WV, Maniatis T.
Annu Rev Cell Dev Biol. 2018 Oct 6;34:471-493. doi: 10.1146/annurev-cellbio-100616-060701. PMID: 30296392
Solid phase chemistry to covalently and reversibly capture thiolated RNA
Duffy EE, Canzio D, Maniatis T, Simon MD.
Nucleic Acids Res. 2018 Aug 21;46(14):6996-7005. doi: 10.1093/nar/gky556 PMID: 29986098
Protocadherin cis-dimer architecture and recognition unit diversity
Goodman KM, Rubinstein R, Dan H, Bahna F, Mannepalli S, Ahlsén G, Aye Thu C, Sampogna RV, Maniatis T, Honig B, Shapiro L.
Proc Natl Acad Sci U S A. 2017 Nov 14;114(46):E9829-E9837. doi: 10.1073/pnas.1713449114. Epub 2017 Oct 30. PMID: 29087338
Protocadherin cis-dimer architecture and recognition unit diversity
Goodman KM, Rubinstein R, Dan H, Bahna F, Mannepalli S, Ahlsén G, Aye Thu C, Sampogna RV, Maniatis T, Honig B, Shapiro L.
Proc Natl Acad Sci U S A. 2017 Nov 14;114(46):E9829-E9837. doi: 10.1073/pnas.1713449114. Epub 2017 Oct 30. PMID: 29087338
Distinct roles for motor neuron autophagy early and late in the SOD1 G93A mouse model of ALS
Rudnick ND, Griffey CJ, Guarnieri P, Gerbino V, Wang X, Piersaint JA, Tapia JC, Rich MM, Maniatis T.
Proc Natl Acad Sci U S A. 2017 Sep 26;114(39):E8294-E8303. doi: 10.1073/pnas.1704294114. Epub 2017 Sep 13. PMID: 28904095
Structural origins of clustered protocadherin-mediated neuronal barcoding
Rubinstein R, Goodman KM, Maniatis T, Shapiro L, Honig B.
Semin Cell Dev Biol. 2017 Sep;69:140-150. doi: 10.1016/j.semcdb.2017.07.023. Epub 2017 Jul 22. Review. PMID: 28743640
Rizvi AH, Camara PG, Kandror EK, Roberts TJ, Schieren I, Maniatis T, Rabadan R.
Nat Biotechnol. 2017 Jun;35(6):551-560. doi: 10.1038/nbt.3854. Epub 2017 May 1. PMID: 28459448
Multicluster Pcdh diversity is required for mouse olfactory neural circuit assembly
Mountoufaris G, Chen WV, Hirabayashi Y, O'Keeffe S, Chevee M, Nwakeze CL, Polleux F, Maniatis T.
Science. 2017 Apr 28;356(6336):411-414. doi: 10.1126/science.aai8801. PMID: 28450637
Pcdhαc2 is required for axonal tiling and assembly of serotonergic circuitries in mice
Chen WV, Nwakeze CL, Denny CA, O'Keeffe S, Rieger MA, Mountoufaris G, Kirner A, Dougherty JD, Hen R, Wu Q, Maniatis T.
Science. 2017 Apr 28;356(6336):406-411. doi: 10.1126/science.aal3231. PMID: 28450636
γ-Protocadherin structural diversity and functional implications
Goodman KM, Rubinstein R, Thu CA, Mannepalli S, Bahna F, Ahlsén G, Rittenhouse C, Maniatis T, Honig B, Shapiro L.
Elife. 2016 Oct 26;5. pii: e20930. doi: 10.7554/eLife.20930. PMID: 27782885
Histone and DNA Modifications as Regulators of Neuronal Development and Function
Lomvardas S, Maniatis T.
Cold Spring Harb Perspect Biol. 2016 Jul 1;8(7). pii: a024208. doi: 10.1101/cshperspect.a024208. Review. PMID: 27371659
He J, Zhou R, Wu Z, Carrasco MA, Kurshan PT, Farley JE, Simon DJ, Wang G, Han B, Hao J, Heller E, Freeman MR, Shen K, Maniatis T, Tessier-Lavigne M, Zhuang X.
Proc Natl Acad Sci U S A. 2016 May 24;113(21):6029-34. doi: 10.1073/pnas.1605707113. Epub 2016 May 9. PMID: 27162329
Structural Basis of Diverse Homophilic Recognition by Clustered α- and β-Protocadherins
Goodman KM, Rubinstein R, Thu CA, Bahna F, Mannepalli S, Ahlsén G, Rittenhouse C, Maniatis T, Honig B, Shapiro L.
Neuron. 2016 May 18;90(4):709-23. doi: 10.1016/j.neuron.2016.04.004. Epub 2016 May 5. PMID: 27161523
Glaser JB, Pau D, Maniatis T.
Ann Am Thorac Soc. 2016 Mar;13(3):447. doi: 10.1513/AnnalsATS.201512-813LE. No abstract available. PMID: 26963359
Molecular logic of neuronal self-recognition through protocadherin domain interactions
Rubinstein R, Thu CA, Goodman KM, Wolcott HN, Bahna F, Mannepalli S, Ahlsen G, Chevee M, Halim A, Clausen H, Maniatis T, Shapiro L, Honig B.
Cell. 2015 Oct 22;163(3):629-42. doi: 10.1016/j.cell.2015.09.026. Epub 2015 Oct 17. PMID: 26478182
CRISPR Inversion of CTCF Sites Alters Genome Topology and Enhancer/Promoter Function
Guo Y, Xu Q, Canzio D, Shou J, Li J, Gorkin DU, Jung I, Wu H, Zhai Y, Tang Y, Lu Y, Wu Y, Jia Z, Li W, Zhang MQ, Ren B, Krainer AR, Maniatis T, Wu Q.
Cell. 2015 Aug 13;162(4):900-10. doi: 10.1016/j.cell.2015.07.038. PMID: 26276636
Ye J, Beetz N, O'Keeffe S, Tapia JC, Macpherson L, Chen WV, Bassel-Duby R, Olson EN, Maniatis T.
Proc Natl Acad Sci U S A. 2015 Jun 9;112(23):E3020-9. doi: 10.1073/pnas.1508461112. Epub 2015 May 26. PMID: 26039991
Astrocytes in neurodegenerative disease
Phatnani H, Maniatis T.
Cold Spring Harb Perspect Biol. 2015 Apr 15;7(6). pii: a020628. doi: 10.1101/cshperspect.a020628. Review. PMID: 25877220
Exome sequencing in amyotrophic lateral sclerosis identifies risk genes and pathways
Cirulli ET, Lasseigne BN, Petrovski S, Sapp PC, Dion PA, Leblond CS, Couthouis J, Lu YF, Wang Q, Krueger BJ, Ren Z, Keebler J, Han Y, Levy SE, Boone BE, Wimbish JR, Waite LL, Jones AL, Carulli JP, Day-Williams AG, Staropoli JF, Xin WW, Chesi A, Raphael AR, McKenna-Yasek D, Cady J, Vianney de Jong JM, Kenna KP, Smith BN, Topp S, Miller J, Gkazi A; FALS Sequencing Consortium, Al-Chalabi A, van den Berg LH, Veldink J, Silani V, Ticozzi N, Shaw CE, Baloh RH, Appel S, Simpson E, Lagier-Tourenne C, Pulst SM, Gibson S, Trojanowski JQ, Elman L, McCluskey L, Grossman M, Shneider NA, Chung WK, Ravits JM, Glass JD, Sims KB, Van Deerlin VM, Maniatis T, Hayes SD, Ordureau A, Swarup S, Landers J, Baas F, Allen AS, Bedlack RS, Harper JW, Gitler AD, Rouleau GA, Brown R, Harms MB, Cooper GM, Harris T, Myers RM, Goldstein DB.
Science. 2015 Mar 27;347(6229):1436-41. doi: 10.1126/science.aaa3650. Epub 2015 Feb 19. PMID: 25700176
Resident duty-hour reform: moving beyond "change for change's sake"
Maniatis T.
CMAJ. 2015 Mar 17;187(5):309-10. doi: 10.1503/cmaj.150010.
Epub 2015 Feb 9. No abstract available. PMID: 25667251
Scheduling in the context of resident duty hour reform
Sun NZ, Maniatis T.
BMC Med Educ. 2014;14 Suppl 1:S18. doi: 10.1186/1472-6920-14-S1-S18.
Epub 2014 Dec 11. Review. PMID: 25561221
Zhang Y, Chen K, Sloan SA, Bennett ML, Scholze AR, O'Keeffe S, Phatnani HP, Guarnieri P, Caneda C, Ruderisch N, Deng S, Liddelow SA, Zhang C, Daneman R, Maniatis T, Barres BA, Wu JQ.
J Neurosci. 2014 Sep 3;34(36):11929-47. doi: 10.1523/JNEUROSCI.1860-14.2014. Erratum in: J Neurosci. 2015 Jan 14;35(2):846-6. PMID: 25186741
Thu CA, Chen WV, Rubinstein R, Chevee M, Wolcott HN, Felsovalyi KO, Tapia JC, Shapiro L, Honig B, Maniatis T.
Cell. 2014 Aug 28;158(5):1045-1059. doi: 10.1016/j.cell.2014.07.012. PMID: 25171406
- Regulation of RNA Transcription and Splicing
- The Role of Neuroinflammation in ALS
- ALS Disease Mechanisms
- Genetic Basis of Neurological Diseases