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Alison Goate

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Alison Goate
CitizenshipBritish
EducationOxford University (DPhil 1983)
Known forAlzheimer's disease, addiction
AwardsPotamkin Prize (1993)
Metlife Foundation Award (1994)
Alzheimer's Association Lifetime Achievement Award (2015)
Rainwater Prize(2022)
Piepenbrock-DZNE Prize (2023)
Scientific career
FieldsNeurology, Genetics
InstitutionsIcahn School of Medicine
Washington University in St. Louis

Alison Mary Goate is the Jean C. and James W. Crystal Professor and Chair of the Department of Genetics and Genomic Sciences and Director of the Loeb Center for Alzheimer's Disease at Icahn School of Medicine at Mount Sinai, New York City.[1][2] She was previously professor of genetics in psychiatry, professor of genetics, and professor of neurology at Washington University School of Medicine.[3]

The Goate Lab studies the genetics and molecular bases of Alzheimer's disease, frontotemporal dementia, and alcoholism.[4]

Education and early career

[edit]

After receiving her undergraduate degree in biochemistry at the University of Bristol (UK) and her graduate training at Oxford University (UK), Goate studied under Professors Theodore Puck, Professor Louis Lim and Dr. John Hardy. She received a Royal Society University Research Fellowship to conduct research at St. Mary's Hospital Medical School in London.[5]

Awards and affiliations

[edit]

She has received the Potamkin Prize from the American Academy of Neurology (1993), the Zenith Award from the Alzheimer's Association, Senior Investigator Award from the Metropolitan Life Foundation, the St. Louis Academy of Science Innovation Award, Carl and Gerty Cori Faculty Achievement Award at Washington University in St. Louis. (1994), and a Lifetime Achievement Award from the Alzheimer's Association (2015).[6] She is a fellow of the American Association for the Advancement of Science.[1] She also serves on the faculty of the Hope Center for Neurological Disorders[7] and is an elected member of the National Academy of Medicine.[8] Dr. Goate received the Rainwater Prize for Innovation in Neurodegeneration from the Rainwater Charitable Foundation in 2022. [9] Dr. Goate was the first female to be awarded the Piepenbrock-DZNE Prize for Neurodegenerative disease research in 2023. [10]

Research

[edit]

Goate's research centers on the genetics of Alzheimer's disease and related dementias that led to the development of animal and cellular models and the development of anti-amyloid and anti-tau therapies. She has been the principal investigator on four grants and has co-invented and awarded six patents.

Patents

[edit]
  • APP770 mutant in alzheimer's disease, (1999).[11]
  • Mutant S182 genes, (1999).[12]
  • Method for elucidation and detection of polymorphisms, splice variants, and proximal coding mutations using intronic sequences of the Alzheimer's S182 gene, (2000).[13]
  • Transgenic mouse expressing an APP-FAD DNA sequence, (2001).[14]
  • Pathogenic Tau mutations, (2002).[15]
  • Markers for addiction, (2011).[16]

Grants

[edit]

Partial list:[17]

Funding Source, Project Title & Number Role in Project Dates Direct Costs
NIH/NIA/Columbia University

National Institute on Aging Alzheimer's Disease Family-Based Study (NIA-AD FBS) U24AG056270[18]

Subaward PI (MPI) 8/1/2022 - 4/30/2027 $151,653
NIH/NIA

Neuroprotective Signaling and Transcriptional Pathways in Microglia Associated with Alzheimer's Disease R01AG072489[19]

MPI 2/1/2022 - 11/30/2026 $5,972,363
NIH/NINDS

Uncovering the Genetic Mechanisms of the Chromosome 17q21.31 Tau haplotype on Neurodegeneration Risk in FTD and PSP U54NS123746[20]

MPI 9/1/2021 - 8/31/2026 $9,278,441
The JPB Foundation

Integrative approaches to the identification of AD risk genes and novel therapeutics 2023-4265

Principal Investigator 9/1/2023 - 8/31/2026 $2,250,000
NIH/NIA/Mayo Clinic

Biology and Pathobiology of ApoE in Aging and Alzheimer's Disease U19AG069701[21]

Subaward PI (MPI) 6/1/2021 - 5/31/2026 $1,885,527
Cure Alzheimer's Foundation

Investigating MEF2C transcription factor as therapeutic targets to reprogram pathological microglial states in Alzheimer's disease[22]

Principal Investigator 1/14/2024 - 1/13/2026 $201,250
Rainwater Charitable Foundation

Using unbiased proteomics to validate iPSC models of FTD-MAPT and discover novel biomarkers

MPI 8/1/2023 - 7/31/2025 $200,000
NIH/NIA/Massachusetts Institute of Technology

Development of PU.1 Inhibitory Modulators as Novel Therapeutics for Alzheimer's Disease U01AG066757[23]

Subaward PI (MPI) 5/15/2020 - 4/30/2025 $1,364,375
NIH/NIA/Banner Health

APOE in the Predisposition to, Protection from and Prevention of Alzheimer's Disease R01AG069453[24]

Subaward PI (MPI) 7/1/2020 - 3/31/2025 $71,390
NIH/NIA/University of Pennsylvania

Alzheimer's Disease Genetics Consortium U01AG032984[25]

Subaward PI 3/6/2020 - 8/31/2024 $1,021,752
NIH/NINDS/University of Miami

Reducing Disparities in Dementia and VCID Outcomes in a Multicultural Rural Population[26] R01NS101483

Subaward PI 4/15/2020 - 3/31/2025 $78,593
NIH/NIAAA/SUNY

Collaborative Study on the Genetics of Alcoholism (COGA) U10AA008401[27]

Subaward PI 9/1/2019 - 8/31/2024 $2,175,426
M.D. Anderson

Understanding the mechanism of MS4A-dependent AD risk AGR-13139

Principal Investigator 8/7/2017 - 8/31/2024 $3,562,500
NIH/NIA

Genomic Approach to Identification of Microglial Networks Involved in Alzheimer's Disease Risk U01AG058635[28]

Principal Investigator 8/1/2018 - 7/31/2024 $4,799,685
NIH/NIA/Washington University

DIAN Genetics Core U19AG032438[29]

Subaward PI and Core Leader 7/1/2019 - 6/30/2024 $651,291
Rainwater Charitable Foundation

Investigating rare and common mechanisms underlying tauopathy risk

Principal Investigator 11/1/2022 - 4/30/2024 $230,000

Publications

[edit]

Semantic Scholar lists 483 publications, 22,943 citations and 1,808 influential citations of Goate's peer-reviewed and original contribution as of 2019.[30]

Partial list:

  • Goate, A.; et al. (1991). "Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease". Nature. 349 (6311): 704–706. Bibcode:1991Natur.349..704G. doi:10.1038/349704a0. PMID 1671712. S2CID 4336069. Cited by 5017 as of October 18, 2019.[31]
  • De Strooper, B.; et al. (1999). "A presenilin-1-dependent gamma-secretase-like protease mediates release of Notch intracellular domain". Nature. 398 (6727): 518–22. Bibcode:1999Natur.398..518D. doi:10.1038/19083. PMID 10206645. S2CID 4346474. Cited by 2274 as of October 18, 2019.[31]
  • Saccone, S. F.; et al. (2007). "Cholinergic nicotinic receptor genes implicated in a nicotine dependence association study targeting 348 candidate genes with 3713 SNPS". Human Molecular Genetics. 16 (1): 36–49. doi:10.1093/hmg/ddl438. PMC 2270437. PMID 17135278. Cited by 793 as of October 18, 2019[31]
  • Bierut, L. J.; et al. (2007). "Novel genes identified in a high-density genome wide association study for nicotine dependence". Human Molecular Genetics. 16 (1): 24–35. doi:10.1093/hmg/ddl441. PMC 2278047. PMID 17158188. Cited by 604 as of October 18, 2019.[31]
  • Kehoe, P.; et al. (1999). "A full genome scan for late onset Alzheimer's disease". Human Molecular Genetics. 8 (2): 237–45. doi:10.1093/hmg/8.2.237. PMID 9931331. Cited by 419 as of October 18, 2019[31]
  • Foroud, T.; et al. (2000). "Alcoholism susceptibility loci: Confirmation studies in a replicate sample and further mapping". Alcoholism: Clinical and Experimental Research. 24 (7): 933–45. doi:10.1111/j.1530-0277.2000.tb04634.x. PMID 10923994. Cited by 275 as of October 18, 2019.[31]
  • Bierut LJ et al. (2012) "ADH1B is associated with alcohol dependence and alcohol consumption in populations of European and African ancestry." Mol Psychiatry PMCID: PMC3252425.[32]
  • Hutton M., et al. (1998) "Association of missense and 5’-splice-site mutations in tau with inherited dementia FTDP-17." Nature PMID 9641683. [33]
  • Gitcho M, et al. (2008) "TDP-43 A 315T mutation in familial motor neuron disease." Ann Neurol PMCID: PMC2747362 [34]
  • Kauwe JSK, et al. (2008). "Variation in MAPT is associated with cerebrospinal fluid tau levels in the presence of amyloid-beta deposition." Proc Natl Acad Science PMCID: PMC2430357. [35]
  • Bierut L J, et al. (2008). "Variants in nicotinic receptors and risk for nicotine dependence." Am J Psychiatry PMCID: PMC2574742 [36]
  • Guerreiro R et al.; (2013) "TREM2 Variants in Alzheimer's Disease" NEJM PMCID: PMC3631573.[37]
  • Cruchaga C. et al.; (2013) "GWAS of Cerebrospinal Fluid Tau Levels Identifies Risk Variants for Alzheimer's Disease." Neuron PMCID: PMC3664945 [38]
  • Cruchaga C. (2014). "Rare coding variants in the phospholipase D3 gene confer risk for Alzheimer's disease." Nature PMCID: PMC4050701. [39]
  • Kauwe JS. et al. (2014) "Genome-Wide Association Study of CSF Levels of 59 Alzheimer's Disease Candidate Proteins: Significant Associations with Proteins Involved in Amyloid Processing and Inflammation." PLoS Genet. PMCID: PMC4207667. [40]
  • Huang KL, et al. (2017). "A common haplotype lowers PU.1 expression in myeloid cells and delays onset of Alzheimer's disease." Nat Neuroscience PMCID: PMC5759334. [41]
  • Kapoor M, et al. (2019). "Analysis of whole genome-transcriptomic organization in brain to identify genes associated with alcoholism." Transl Psychiatry PMCID: PMC6376002. [42]
  • Novikova G, et al. (2021). "Integration of Alzheimer's disease genetics and myeloid genomics identifies disease risk regulatory elements and genes." Nat Commun PMID: 33712570. [43]
  • Kapoor M, et al. (2021). "Multi-omics integration analysis identifies novel genes for alcoholism with potential overlap with neurodegenerative diseases." Nat Commun. PMID: 34417470. [44]
  • Bowles KR, et al. (2021). "ELAVL4, splicing, and glutamatergic dysfunction precede neuron loss in MAPT mutation cerebral organoids." Cell. PMID: 34314701.[45]
  • Tcw J, et al. (2022). "Cholesterol and matrisome pathways dysregulated in astrocytes and microglia." Cell. PMID 35750033. [46]
  • Podleśny-Drabiniok A, et al. (2024) "BHLHE40/41 regulate microglia and peripheral macrophage responses associated with Alzheimer's disease and other disorders of lipid-rich tissues." Nat Commun. PMID 38448474. [47]

References

[edit]
  1. ^ a b "Alison M Goate". Icahn School of Medicine at Mount Sinai. Archived from the original on 23 October 2018. Retrieved 23 October 2018.
  2. ^ "Huffington Center on Aging celebrates 30th anniversary". BCM Family. 5 November 2018. Archived from the original on 18 October 2019. Retrieved 18 October 2019.
  3. ^ Goate, Alison (2008). "Interview". Biomarkers in Medicine. 2 (6). Future Medicine Ltd: 541–545. doi:10.2217/17520363.2.6.541. ISSN 1752-0363. PMID 20477443.
  4. ^ Icahn School of Medicine at Mount Sinai. "Goate Lab". Icahn School of Medicine at Mount Sinai. Archived from the original on 2 September 2019. Retrieved 26 August 2019.
  5. ^ Goate, Alison (December 2008). "Interview". Biomarkers in Medicine. 2 (6): 541–545. doi:10.2217/17520363.2.6.541. PMID 20477443. Archived from the original on 19 October 2019. Retrieved 19 October 2019.
  6. ^ Goate, Alison (2 December 2008). "Interview with Alison Goate". Biomarkers in Medicine. 2 (6): 541–545. doi:10.2217/17520363.2.6.541. ISSN 1752-0371. PMID 20477443.
  7. ^ "Announcements: Bob Lane Receives Lifetime Achievement Award". 1998. doi:10.1037/e404572005-032. {{cite journal}}: Cite journal requires |journal= (help)
  8. ^ "National Academy of Medicine Elects 80 New Members". National Academy of Medicine. 17 October 2016. Archived from the original on 6 January 2017. Retrieved 18 October 2019.
  9. ^ "RCF Announces Third-Annual Rainwater Prize Winners for Neurodegenerative Research". 14 December 2021.
  10. ^ "Award for Dementia Researcher from New York City".
  11. ^ US 5877015, Hardy, John Anthony; Chartier-Harlin, Marie-Christine & Goate, Alison Mary et al., "APP770 mutant in Alzheimer's disease", published 1999-03-02, assigned to Imperial College of Science, Technology and Medicine 
  12. ^ US 5973133, Hardy, John A. & Goate, Alison M., "Mutant S182 genes", published 1999-10-26, assigned to Washington University and University of South Florida 
  13. ^ US 6083694, Hardy, John & Goate, Alison M., "Method for elucidation and detection of polymorphisms, splice variants, and proximal coding mutations using intronic sequences of the Alzheimer's S182 gene", published 2000-07-04, assigned to Washington University and University of South Florida 
  14. ^ US 6300540, Hardy, John Anthony; Chartier-Harlin, Marie-Christine & Goate, Alison Mary et al., "Transgenic mouse expressing an APP-FAD DNA sequence", published 2001-10-09, assigned to Elan Pharmaceuticals Inc. 
  15. ^ "Espacenet – search results". worldwide.espacenet.com. Archived from the original on 16 March 2023. Retrieved 16 March 2023.
  16. ^ US 8080371, Ballinger, Dennis; Konvicka, Karel & Bierut, Laura Jean et al., "Markers for addiction", published 2011-12-20, assigned to Washington University in St. Louis 
  17. ^ "Alison M. Goate, PhD - US grants". Neurotree. Archived from the original on 16 March 2023. Retrieved 15 September 2019.
  18. ^ "RePORT ⟩ RePORTER".
  19. ^ "RePORT ⟩ RePORTER".
  20. ^ "RePORT ⟩ RePORTER".
  21. ^ "RePORT ⟩ RePORTER".
  22. ^ "Investigating MEF2C Transcription Factor as a Therapeutic Target to Reprogram Pathological Microglial States in Alzheimer's Disease".
  23. ^ "RePORT ⟩ RePORTER".
  24. ^ "RePORT ⟩ RePORTER".
  25. ^ "RePORT ⟩ RePORTER".
  26. ^ "RePORT ⟩ RePORTER".
  27. ^ "RePORT ⟩ RePORTER".
  28. ^ "RePORT ⟩ RePORTER".
  29. ^ "RePORT ⟩ RePORTER".
  30. ^ "Alison M. Goate - Semantic Scholar". www.semanticscholar.org. Archived from the original on 18 October 2019. Retrieved 18 October 2019.
  31. ^ a b c d e f "Google Scholar". scholar.google.com. Archived from the original on 16 March 2023. Retrieved 18 October 2019.
  32. ^ Bierut, LJ (2012). "ADH1B is associated with alcohol dependence and alcohol consumption in populations of European and African ancestry". Mol Psychiatry. 17 (4): 445–450. doi:10.1038/mp.2011.124. PMC 3252425. PMID 21968928.
  33. ^ Hutton, M.; et al. (1998). "Association of missense and 5'-splice-site mutations in tau with the inherited dementia FTDP-17". Nature. 393 (6686): 702–705. Bibcode:1998Natur.393..702H. doi:10.1038/31508. PMID 9641683.
  34. ^ Gitcho, M. A.; Baloh, R. H.; Chakraverty, S.; Mayo, K.; Norton, J. B.; Levitch, D.; Hatanpaa, K. J.; White Cl, 3rd; Bigio, E. H.; Caselli, R.; Baker, M.; Al-Lozi, M. T.; Morris, J. C.; Pestronk, A.; Rademakers, R.; Goate, A. M.; Cairns, N. J. (2008). "TDP-43 A315T mutation in familial motor neuron disease". Annals of Neurology. 63 (4): 535–538. doi:10.1002/ana.21344. PMC 2747362. PMID 18288693.{{cite journal}}: CS1 maint: numeric names: authors list (link)
  35. ^ Kauwe, John S. K.; Cruchaga, Carlos; Mayo, Kevin; Fenoglio, Chiara; Bertelsen, Sarah; Nowotny, Petra; Galimberti, Daniela; Scarpini, Elio; Morris, John C.; Fagan, Anne M.; Holtzman, David M.; Goate, Alison M. (2008). "Variation in MAPT is associated with cerebrospinal fluid tau levels in the presence of amyloid-beta deposition". Proceedings of the National Academy of Sciences. 105 (23): 8050–8054. Bibcode:2008PNAS..105.8050K. doi:10.1073/pnas.0801227105. PMC 2430357. PMID 18541914.
  36. ^ Bierut, L. J.; et al. (2008). "Variants in nicotinic receptors and risk for nicotine dependence". The American Journal of Psychiatry. 165 (9): 1163–1171. doi:10.1176/appi.ajp.2008.07111711. PMC 2574742. PMID 18519524.
  37. ^ Guerreiro, R (2013). "TREM2 Variants in Alzheimer's Disease". NEJM. 368 (2): 117–127. doi:10.1056/NEJMoa1211851. PMC 3631573. PMID 23150934.
  38. ^ Cruchaga, C (2013). "GWAS of Cerebrospinal Fluid Tau Levels Identifies Risk Variants for Alzheimer's Disease". Neuron. 78 (2): 256–268. doi:10.1016/j.neuron.2013.02.026. PMC 3664945. PMID 23562540.
  39. ^ Cruchaga, C (2014). "Rare coding variants in the phospholipase D3 gene confer risk for Alzheimer's disease". Nature. 505 (7484): 550–554. doi:10.1038/nature12825. PMC 4050701. PMID 24336208.
  40. ^ Kauwe, JS (2014). "Genome-Wide Association Study of CSF Levels of 59 Alzheimer's Disease Candidate Proteins: Significant Associations with Proteins Involved in Amyloid Processing and Inflammation". PLOS Genetics. 10 (10): e1004758. doi:10.1371/journal.pgen.1004758. PMC 4207667. PMID 25340798.
  41. ^ Huang, Kuan-lin; et al. (2017). "A common haplotype lowers PU.1 expression in myeloid cells and delays onset of Alzheimer's disease". Nature Neuroscience. 20 (8): 1052–1061. doi:10.1038/nn.4587. PMC 5759334.
  42. ^ Kapoor, Manav; Wang, Jen-Chyong; Farris, Sean P.; Liu, Yunlong; McClintick, Jeanette; Gupta, Ishaan; Meyers, Jacquelyn L.; Bertelsen, Sarah; Chao, Michael; Nurnberger, John; Tischfield, Jay; Harari, Oscar; Zeran, Li; Hesselbrock, Victor; Bauer, Lance; Raj, Towfique; Porjesz, Bernice; Agrawal, Arpana; Foroud, Tatiana; Edenberg, Howard J.; Mayfield, R. Dayne; Goate, Alison (2019). "Analysis of whole genome-transcriptomic organization in brain to identify genes associated with alcoholism". Translational Psychiatry. 9. doi:10.1038/s41398-019-0384-y. hdl:20.500.12648/7935. PMID 30765688.
  43. ^ Novikova, Gloriia; Kapoor, Manav; Tcw, Julia; Abud, Edsel M.; Efthymiou, Anastasia G.; Chen, Steven X.; Cheng, Haoxiang; Fullard, John F.; Bendl, Jaroslav; Liu, Yiyuan; Roussos, Panos; Björkegren, Johan LM; Liu, Yunlong; Poon, Wayne W.; Hao, Ke; Marcora, Edoardo; Goate, Alison M. (2021). "Integration of Alzheimer's disease genetics and myeloid genomics identifies disease risk regulatory elements and genes". Nature Communications. 12: 1610. Bibcode:2021NatCo..12.1610N. doi:10.1038/s41467-021-21823-y. PMC 7955030. PMID 33712570.
  44. ^ Kapoor, M.; et al. (2021). "Multi-omics integration analysis identifies novel genes for alcoholism with potential overlap with neurodegenerative diseases". Nature Communications. 12 (1): 5071. Bibcode:2021NatCo..12.5071K. doi:10.1038/s41467-021-25392-y. PMC 8379159. PMID 34417470.
  45. ^ Bowles, K. R.; Silva, M. C.; Whitney, K.; Bertucci, T.; Berlind, J. E.; Lai, J. D.; Garza, J. C.; Boles, N. C.; Mahali, S.; Strang, K. H.; Marsh, J. A.; Chen, C.; Pugh, D. A.; Liu, Y.; Gordon, R. E.; Goderie, S. K.; Chowdhury, R.; Lotz, S.; Lane, K.; Crary, J. F.; Haggarty, S. J.; Karch, C. M.; Ichida, J. K.; Goate, A. M.; Temple, S. (2021). "ELAVL4, splicing, and glutamatergic dysfunction precede neuron loss in MAPT mutation cerebral organoids". Cell. 184 (17): 4547–4563.e17. doi:10.1016/j.cell.2021.07.003. PMC 8635409. PMID 34314701.
  46. ^ Tcw, J.; Qian, L.; Pipalia, N. H.; Chao, M. J.; Liang, S. A.; Shi, Y.; Jain, B. R.; Bertelsen, S. E.; Kapoor, M.; Marcora, E.; Sikora, E.; Andrews, E. J.; Martini, A. C.; Karch, C. M.; Head, E.; Holtzman, D. M.; Zhang, B.; Wang, M.; Maxfield, F. R.; Poon, W. W.; Goate, A. M. (2022). "Cholesterol and matrisome pathways dysregulated in astrocytes and microglia". Cell. 185 (13): 2213–2233.e25. doi:10.1016/j.cell.2022.05.017. PMC 9340815. PMID 35750033.
  47. ^ Podleśny-Drabiniok, Anna; Novikova, Gloriia; Liu, Yiyuan; Dunst, Josefine; Temizer, Rose; Giannarelli, Chiara; Marro, Samuele; Kreslavsky, Taras; Marcora, Edoardo; Goate, Alison Mary (2024). "BHLHE40/41 regulate microglia and peripheral macrophage responses associated with Alzheimer's disease and other disorders of lipid-rich tissues". Nature Communications. 15: 2058. Bibcode:2024NatCo..15.2058P. doi:10.1038/s41467-024-46315-7. PMC 10917780. PMID 38448474.
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