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Sandra Cristina Vicente Almeida PhD

TitleAssistant Professor
InstitutionUMass Chan Medical School
DepartmentNeurology
AddressUMass Chan Medical School
366 Plantation Street NERB N5-1085
Worcester MA 01605
Phone774-455-4716
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    Other Positions
    InstitutionT.H. Chan School of Medicine
    DepartmentNeurology

    InstitutionT.H. Chan School of Medicine
    DepartmentNeuroNexus Institute

    InstitutionMorningside Graduate School of Biomedical Sciences
    DepartmentInterdisciplinary Graduate Program

    InstitutionMorningside Graduate School of Biomedical Sciences
    DepartmentNeuroscience

    InstitutionMorningside Graduate School of Biomedical Sciences
    DepartmentTranslational Science


    Collapse Biography 
    Collapse education and training
    University of Coimbra, Coimbra, , PortugalBSBiochemistry
    University of Coimbra, Coimbra, , PortugalPHDCell Biology

    Collapse Overview 
    Collapse Summary
    Dr. Almeida’s primary focus is elucidating the molecular mechanisms of frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS) and Alzheimer’s disease (AD). Her main strategy employs patient-derived, induced pluripotent stem cell (iPSC) lines to generate disease-relevant neuronal cells.
    Collapse overview
    My primary research focus is on understanding the molecular mechanisms of frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS) and Alzheimer disease (AD). Our strategy involves the use of patient derived cellular models. To date we have generated induced pluripotent stem cell (iPSC) lines from FTD and ALS/FTD patients carrying mutations in progranulin, C9ORF72, TDP-43 and MAPT, as well as lines from healthy controls. I have differentiated these iPSCs into post-mitotic cortical and motor neurons and applied a variety of approaches to uncover underlying molecular and cellular defects. This approach allows the interrogation of patient-derived neurons in the appropriate, differentiated context, leading to a better understanding of how ALS/FTD mutations impact cellular physiology, resulting in their pathogenic consequences. We are also using a gene editing approach to create CHMP2B mutant iPSCs that can be differentiated into a cellular model for the study of AD cellular pathogenesis. I am particularly interested in exploring and testing potential therapeutic interventions to halt or slow the progression of these and related diseases.


    Collapse Bibliographic 
    Collapse selected publications
    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
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    1. Halim DO, Krishnan G, Hass EP, Lee S, Verma M, Almeida S, Gu Y, Kwon DY, Fazzio TG, Gao FB. The exocyst subunit EXOC2 regulates the toxicity of expanded GGGGCC repeats in C9ORF72-ALS/FTD. Cell Rep. 2024 07 23; 43(7):114375. PMID: 38935506.
      Citations:    
    2. Fang M, Deibler SK, Nana AL, Vatsavayai SC, Banday S, Zhou Y, Almeida S, Weiss A, Brown RH, Seeley WW, Gao FB, Green MR. Loss of TDP-43 function contributes to genomic instability in amyotrophic lateral sclerosis. Front Neurosci. 2023; 17:1251228. PMID: 37849894.
      Citations:    
    3. Rojas F, Aguilar R, Almeida S, Fritz E, Corval?n D, Ampuero E, Abarz?a S, Garc?s P, Amaro A, Diaz I, Arredondo C, Cortes N, Sanchez M, Mercado C, Varela-Nallar L, Gao FB, Montecino M, van Zundert B. Mature iPSC-derived astrocytes of an ALS/FTD patient carrying the TDP43A90V mutation display a mild reactive state and release polyP toxic to motoneurons. Front Cell Dev Biol. 2023; 11:1226604. PMID: 37645251.
      Citations:    
    4. Lorenzini I, Alsop E, Levy J, Gittings LM, Lall D, Rabichow BE, Moore S, Pevey R, Bustos LM, Burciu C, Bhatia D, Singer M, Saul J, McQuade A, Tzioras M, Mota TA, Logemann A, Rose J, Almeida S, Gao FB, Marks M, Donnelly CJ, Hutchins E, Hung ST, Ichida J, Bowser R, Spires-Jones T, Blurton-Jones M, Gendron TF, Baloh RH, Van Keuren-Jensen K, Sattler R. Moderate intrinsic phenotypic alterations in C9orf72 ALS/FTD iPSC-microglia despite the presence of C9orf72 pathological features. Front Cell Neurosci. 2023; 17:1179796. PMID: 37346371.
      Citations:    
    5. Van't Spijker HM, Almeida S. How villains are made: The translation of dipeptide repeat proteins in C9ORF72-ALS/FTD. Gene. 2023 Mar 30; 858:147167. PMID: 36621656.
      Citations: 3     Fields:    Translation:AnimalsCells
    6. Arredondo C, Cefaliello C, Dyrda A, Jury N, Martinez P, D?az I, Amaro A, Tran H, Morales D, Pertusa M, Stoica L, Fritz E, Corval?n D, Abarz?a S, M?ndez-Ruette M, Fern?ndez P, Rojas F, Kumar MS, Aguilar R, Almeida S, Weiss A, Bustos FJ, Gonz?lez-Nilo F, Otero C, Tevy MF, Bosco DA, S?ez JC, K?hne T, Gao FB, Berry JD, Nicholson K, Sena-Esteves M, Madrid R, Varela D, Montecino M, Brown RH, van Zundert B. Excessive release of inorganic polyphosphate by ALS/FTD astrocytes causes non-cell-autonomous toxicity to motoneurons. Neuron. 2022 05 18; 110(10):1656-1670.e12. PMID: 35276083.
      Citations: 16     Fields:    Translation:HumansAnimalsCells
    7. van 't Spijker HM, Stackpole EE, Almeida S, Katsara O, Liu B, Shen K, Schneider RJ, Gao FB, Richter JD. Ribosome profiling reveals novel regulation of C9ORF72 GGGGCC repeat-containing RNA translation. RNA. 2022 02; 28(2):123-138. PMID: 34848561.
      Citations: 9     Fields:    Translation:HumansCells
    8. Lu Y, Almeida S, Gao FB. TBK1 haploinsufficiency in ALS and FTD compromises membrane trafficking. Acta Neuropathol. 2021 07; 142(1):217-221. PMID: 34081168.
      Citations: 4     Fields:    Translation:HumansCells
    9. Lampasona A, Almeida S, Gao FB. Translation of the poly(GR) frame in C9ORF72-ALS/FTD is regulated by cis-elements involved in alternative splicing. Neurobiol Aging. 2021 09; 105:327-332. PMID: 34157654.
      Citations: 5     Fields:    Translation:HumansAnimalsCells
    10. Krishnan G, Zhang Y, Gu Y, Kankel MW, Gao FB, Almeida S. CRISPR deletion of the C9ORF72 promoter in ALS/FTD patient motor neurons abolishes production of dipeptide repeat proteins and rescues neurodegeneration. Acta Neuropathol. 2020 07; 140(1):81-84. PMID: 32266467.
      Citations: 17     Fields:    Translation:HumansCells
    11. Yuva-Aydemir Y, Almeida S, Krishnan G, Gendron TF, Gao FB. Transcription elongation factor AFF2/FMR2 regulates expression of expanded GGGGCC repeat-containing C9ORF72 allele in ALS/FTD. Nat Commun. 2019 11 29; 10(1):5466. PMID: 31784536.
      Citations: 29     Fields:    Translation:HumansAnimalsCells
    12. Almeida S, Krishnan G, Rushe M, Gu Y, Kankel MW, Gao FB. Production of poly(GA) in C9ORF72 patient motor neurons derived from induced pluripotent stem cells. Acta Neuropathol. 2019 12; 138(6):1099-1101. PMID: 31624870.
      Citations: 17     Fields:    Translation:HumansCells
    13. Choi SY, Lopez-Gonzalez R, Krishnan G, Phillips HL, Li AN, Seeley WW, Yao WD, Almeida S, Gao FB. C9ORF72-ALS/FTD-associated poly(GR) binds Atp5a1 and compromises mitochondrial function in vivo. Nat Neurosci. 2019 06; 22(6):851-862. PMID: 31086314.
      Citations: 108     Fields:    Translation:HumansAnimalsCells
    14. Yuva-Aydemir Y, Almeida S, Gao FB. Insights into C9ORF72-Related ALS/FTD from Drosophila and iPSC Models. Trends Neurosci. 2018 07; 41(7):457-469. PMID: 29729808.
      Citations: 31     Fields:    Translation:HumansAnimalsCells
    15. Gao FB, Almeida S, Lopez-Gonzalez R. Dysregulated molecular pathways in amyotrophic lateral sclerosis-frontotemporal dementia spectrum disorder. EMBO J. 2017 10 16; 36(20):2931-2950. PMID: 28916614.
      Citations: 97     Fields:    Translation:HumansAnimals
    16. Lee CW, Stankowski JN, Chew J, Cook CN, Lam YW, Almeida S, Carlomagno Y, Lau KF, Prudencio M, Gao FB, Bogyo M, Dickson DW, Petrucelli L. The lysosomal protein cathepsin L is a progranulin protease. Mol Neurodegener. 2017 07 25; 12(1):55. PMID: 28743268.
      Citations: 49     Fields:    Translation:HumansCells
    17. Lopez-Gonzalez R, Lu Y, Gendron TF, Karydas A, Tran H, Yang D, Petrucelli L, Miller BL, Almeida S, Gao FB. Poly(GR) in C9ORF72-Related ALS/FTD Compromises Mitochondrial Function and Increases Oxidative Stress and DNA Damage in iPSC-Derived Motor Neurons. Neuron. 2016 Oct 19; 92(2):383-391. PMID: 27720481.
      Citations: 217     Fields:    Translation:HumansCells
    18. Silva MC, Cheng C, Mair W, Almeida S, Fong H, Biswas MHU, Zhang Z, Huang Y, Temple S, Coppola G, Geschwind DH, Karydas A, Miller BL, Kosik KS, Gao FB, Steen JA, Haggarty SJ. Human iPSC-Derived Neuronal Model of Tau-A152T Frontotemporal Dementia Reveals Tau-Mediated Mechanisms of Neuronal Vulnerability. Stem Cell Reports. 2016 09 13; 7(3):325-340. PMID: 27594585.
      Citations: 45     Fields:    Translation:HumansCells
    19. Biswas MHU, Almeida S, Lopez-Gonzalez R, Mao W, Zhang Z, Karydas A, Geschwind MD, Biernat J, Mandelkow EM, Futai K, Miller BL, Gao FB. MMP-9 and MMP-2 Contribute to Neuronal Cell Death in iPSC Models of Frontotemporal Dementia with MAPT Mutations. Stem Cell Reports. 2016 09 13; 7(3):316-324. PMID: 27594586.
      Citations: 14     Fields:    Translation:HumansCells
    20. Kramer NJ, Carlomagno Y, Zhang YJ, Almeida S, Cook CN, Gendron TF, Prudencio M, Van Blitterswijk M, Belzil V, Couthouis J, Paul JW, Goodman LD, Daughrity L, Chew J, Garrett A, Pregent L, Jansen-West K, Tabassian LJ, Rademakers R, Boylan K, Graff-Radford NR, Josephs KA, Parisi JE, Knopman DS, Petersen RC, Boeve BF, Deng N, Feng Y, Cheng TH, Dickson DW, Cohen SN, Bonini NM, Link CD, Gao FB, Petrucelli L, Gitler AD. Spt4 selectively regulates the expression of C9orf72 sense and antisense mutant transcripts. Science. 2016 Aug 12; 353(6300):708-12. PMID: 27516603.
      Citations: 78     Fields:    Translation:HumansAnimalsCells
    21. Swartz EW, Baek J, Pribadi M, Wojta KJ, Almeida S, Karydas A, Gao FB, Miller BL, Coppola G. A Novel Protocol for Directed Differentiation of C9orf72-Associated Human Induced Pluripotent Stem Cells Into Contractile Skeletal Myotubes. Stem Cells Transl Med. 2016 Nov; 5(11):1461-1472. PMID: 27369896.
      Citations: 22     Fields:    
    22. Almeida S, Gao FB. Lost & found: C9ORF72 and the autophagy pathway in ALS/FTD. EMBO J. 2016 06 15; 35(12):1251-3. PMID: 27154207.
      Citations: 7     Fields:    Translation:Humans
    23. Almeida S, Gao F, Coppola G, Gao FB. Suberoylanilide hydroxamic acid increases progranulin production in iPSC-derived cortical neurons of frontotemporal dementia patients. Neurobiol Aging. 2016 06; 42:35-40. PMID: 27143419.
      Citations: 8     Fields:    Translation:HumansCells
    24. Woehlbier U, Colombo A, Saaranen MJ, P?rez V, Ojeda J, Bustos FJ, Andreu CI, Torres M, Valenzuela V, Medinas DB, Rozas P, Vidal RL, Lopez-Gonzalez R, Salameh J, Fernandez-Collemann S, Mu?oz N, Matus S, Armisen R, Sagredo A, Palma K, Irrazabal T, Almeida S, Gonzalez-Perez P, Campero M, Gao FB, Henny P, van Zundert B, Ruddock LW, Concha ML, Henriquez JP, Brown RH, Hetz C. ALS-linked protein disulfide isomerase variants cause motor dysfunction. EMBO J. 2016 Apr 15; 35(8):845-65. PMID: 26869642.
      Citations: 43     Fields:    Translation:HumansAnimalsCells
    25. Burguete AS, Almeida S, Gao FB, Kalb R, Akins MR, Bonini NM. GGGGCC microsatellite RNA is neuritically localized, induces branching defects, and perturbs transport granule function. Elife. 2015 Dec 09; 4:e08881. PMID: 26650351.
      Citations: 60     Fields:    Translation:HumansAnimalsCells
    26. Tran H, Almeida S, Moore J, Gendron TF, Chalasani U, Lu Y, Du X, Nickerson JA, Petrucelli L, Weng Z, Gao FB. Differential Toxicity of Nuclear RNA Foci versus Dipeptide Repeat Proteins in a Drosophila Model of C9ORF72 FTD/ALS. Neuron. 2015 Sep 23; 87(6):1207-1214. PMID: 26402604.
      Citations: 115     Fields:    Translation:HumansAnimals
    27. Freibaum BD, Lu Y, Lopez-Gonzalez R, Kim NC, Almeida S, Lee KH, Badders N, Valentine M, Miller BL, Wong PC, Petrucelli L, Kim HJ, Gao FB, Taylor JP. GGGGCC repeat expansion in C9orf72 compromises nucleocytoplasmic transport. Nature. 2015 Sep 03; 525(7567):129-33. PMID: 26308899.
      Citations: 451     Fields:    Translation:HumansAnimalsCells
    28. Yang D, Abdallah A, Li Z, Lu Y, Almeida S, Gao FB. FTD/ALS-associated poly(GR) protein impairs the Notch pathway and is recruited by poly(GA) into cytoplasmic inclusions. Acta Neuropathol. 2015 Oct; 130(4):525-35. PMID: 26031661.
      Citations: 81     Fields:    Translation:HumansAnimalsCells
    29. Gascon E, Lynch K, Ruan H, Almeida S, Verheyden JM, Seeley WW, Dickson DW, Petrucelli L, Sun D, Jiao J, Zhou H, Jakovcevski M, Akbarian S, Yao WD, Gao FB. Alterations in microRNA-124 and AMPA receptors contribute to social behavioral deficits in frontotemporal dementia. Nat Med. 2014 Dec; 20(12):1444-51. PMID: 25401692.
      Citations: 92     Fields:    Translation:AnimalsCells
    30. Lee WC, Almeida S, Prudencio M, Caulfield TR, Zhang YJ, Tay WM, Bauer PO, Chew J, Sasaguri H, Jansen-West KR, Gendron TF, Stetler CT, Finch N, Mackenzie IR, Rademakers R, Gao FB, Petrucelli L. Targeted manipulation of the sortilin-progranulin axis rescues progranulin haploinsufficiency. Hum Mol Genet. 2014 Mar 15; 23(6):1467-78. PMID: 24163244.
      Citations: 45     Fields:    Translation:HumansCells
    31. Zhang Z, Almeida S, Lu Y, Nishimura AL, Peng L, Sun D, Wu B, Karydas AM, Tartaglia MC, Fong JC, Miller BL, Farese RV, Moore MJ, Shaw CE, Gao FB. Downregulation of microRNA-9 in iPSC-derived neurons of FTD/ALS patients with TDP-43 mutations. PLoS One. 2013; 8(10):e76055. PMID: 24143176.
      Citations: 72     Fields:    Translation:HumansCells
    32. Almeida S, Gascon E, Tran H, Chou HJ, Gendron TF, Degroot S, Tapper AR, Sellier C, Charlet-Berguerand N, Karydas A, Seeley WW, Boxer AL, Petrucelli L, Miller BL, Gao FB. Modeling key pathological features of frontotemporal dementia with C9ORF72 repeat expansion in iPSC-derived human neurons. Acta Neuropathol. 2013 Sep; 126(3):385-99. PMID: 23836290.
      Citations: 188     Fields:    Translation:HumansAnimalsCells
    33. Silva AC, Almeida S, La?o M, Duarte AI, Domingues J, Oliveira CR, Janu?rio C, Rego AC. Mitochondrial respiratory chain complex activity and bioenergetic alterations in human platelets derived from pre-symptomatic and symptomatic Huntington's disease carriers. Mitochondrion. 2013 Nov; 13(6):801-9. PMID: 23707479.
      Citations: 16     Fields:    Translation:HumansCells
    34. Almeida S, Zhang Z, Coppola G, Mao W, Futai K, Karydas A, Geschwind MD, Tartaglia MC, Gao F, Gianni D, Sena-Esteves M, Geschwind DH, Miller BL, Farese RV, Gao FB. Induced pluripotent stem cell models of progranulin-deficient frontotemporal dementia uncover specific reversible neuronal defects. Cell Rep. 2012 Oct 25; 2(4):789-98. PMID: 23063362.
      Citations: 81     Fields:    Translation:HumansCells
    35. Almeida S, Delaloy C, Liu L, Gao FB. Protocols for investigating microRNA functions in human neural progenitor cells. Methods Mol Biol. 2012; 916:387-402. PMID: 22914955.
      Citations:    Fields:    Translation:HumansAnimalsCells
    36. Almeida S, Zhou L, Gao FB. Progranulin, a glycoprotein deficient in frontotemporal dementia, is a novel substrate of several protein disulfide isomerase family proteins. PLoS One. 2011; 6(10):e26454. PMID: 22028881.
      Citations: 31     Fields:    Translation:HumansAnimalsCells
    37. Kuo TC, Chen CT, Baron D, Onder TT, Loewer S, Almeida S, Weismann CM, Xu P, Houghton JM, Gao FB, Daley GQ, Doxsey S. Midbody accumulation through evasion of autophagy contributes to cellular reprogramming and tumorigenicity. Nat Cell Biol. 2011 Sep 11; 13(10):1214-23. PMID: 21909099.
      Citations: 142     Fields:    Translation:HumansAnimalsCells
    38. Rosenstock TR, de Brito OM, Lombardi V, Louros S, Ribeiro M, Almeida S, Ferreira IL, Oliveira CR, Rego AC. FK506 ameliorates cell death features in Huntington's disease striatal cell models. Neurochem Int. 2011 Oct; 59(5):600-9. PMID: 21703318.
      Citations: 15     Fields:    Translation:HumansAnimalsCells
    39. Cenik B, Sephton CF, Dewey CM, Xian X, Wei S, Yu K, Niu W, Coppola G, Coughlin SE, Lee SE, Dries DR, Almeida S, Geschwind DH, Gao FB, Miller BL, Farese RV, Posner BA, Yu G, Herz J. Suberoylanilide hydroxamic acid (vorinostat) up-regulates progranulin transcription: rational therapeutic approach to frontotemporal dementia. J Biol Chem. 2011 May 06; 286(18):16101-8. PMID: 21454553.
      Citations: 85     Fields:    Translation:HumansCells
    40. Ferreira IL, Nascimento MV, Ribeiro M, Almeida S, Cardoso SM, Grazina M, Pratas J, Santos MJ, Janu?rio C, Oliveira CR, Rego AC. Mitochondrial-dependent apoptosis in Huntington's disease human cybrids. Exp Neurol. 2010 Apr; 222(2):243-55. PMID: 20079354.
      Citations: 16     Fields:    Translation:HumansCells
    41. Almeida S, Cunha-Oliveira T, La?o M, Oliveira CR, Rego AC. Dysregulation of CREB activation and histone acetylation in 3-nitropropionic acid-treated cortical neurons: prevention by BDNF and NGF. Neurotox Res. 2010 May; 17(4):399-405. PMID: 19779956.
      Citations: 5     Fields:    Translation:AnimalsCells
    42. Almeida S, La?o M, Cunha-Oliveira T, Oliveira CR, Rego AC. BDNF regulates BIM expression levels in 3-nitropropionic acid-treated cortical neurons. Neurobiol Dis. 2009 Sep; 35(3):448-56. PMID: 19555760.
      Citations: 17     Fields:    Translation:AnimalsCells
    43. Almeida S, Sarmento-Ribeiro AB, Janu?rio C, Rego AC, Oliveira CR. Evidence of apoptosis and mitochondrial abnormalities in peripheral blood cells of Huntington's disease patients. Biochem Biophys Res Commun. 2008 Oct 03; 374(4):599-603. PMID: 18625199.
      Citations: 27     Fields:    Translation:HumansCells
    44. Domingues A, Almeida S, da Cruz e Silva EF, Oliveira CR, Rego AC. Toxicity of beta-amyloid in HEK293 cells expressing NR1/NR2A or NR1/NR2B N-methyl-D-aspartate receptor subunits. Neurochem Int. 2007 May; 50(6):872-80. PMID: 17403555.
      Citations: 25     Fields:    Translation:HumansCells
    45. Oliveira JM, Chen S, Almeida S, Riley R, Gon?alves J, Oliveira CR, Hayden MR, Nicholls DG, Ellerby LM, Rego AC. Mitochondrial-dependent Ca2+ handling in Huntington's disease striatal cells: effect of histone deacetylase inhibitors. J Neurosci. 2006 Oct 25; 26(43):11174-86. PMID: 17065457.
      Citations: 55     Fields:    Translation:AnimalsCells
    46. Almeida S, Brett AC, G?is IN, Oliveira CR, Rego AC. Caspase-dependent and -independent cell death induced by 3-nitropropionic acid in rat cortical neurons. J Cell Biochem. 2006 May 01; 98(1):93-101. PMID: 16365893.
      Citations: 8     Fields:    Translation:AnimalsCells
    47. Almeida S, Domingues A, Rodrigues L, Oliveira CR, Rego AC. FK506 prevents mitochondrial-dependent apoptotic cell death induced by 3-nitropropionic acid in rat primary cortical cultures. Neurobiol Dis. 2004 Dec; 17(3):435-44. PMID: 15571979.
      Citations: 20     Fields:    Translation:AnimalsCells
    48. Brito O, Almeida S, Oliveira CR, Rego AC. Bcl-2 prevents loss of cell viability and caspase activation induced by 3-nitropropionic acid in GT1-7 cells. Ann N Y Acad Sci. 2003 Dec; 1010:148-52. PMID: 15033710.
      Citations:    Fields:    Translation:HumansCells
    49. Gil J, Almeida S, Oliveira CR, Rego AC. Cytosolic and mitochondrial ROS in staurosporine-induced retinal cell apoptosis. Free Radic Biol Med. 2003 Dec 01; 35(11):1500-14. PMID: 14642398.
      Citations: 31     Fields:    Translation:AnimalsCells
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