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Darius Ebrahimi-Fakhari, M.D.

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Biography
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Ruprecht-Karls Universität Heidelberg, Heidelberg, GermanyMD04/2013Medicine
Ruprecht-Karls Universität Heidelberg, Heidelberg, GermanyPhD04/2013Neurobiology
University Hospital Heidelberg, Heidelberg, Germany04/2014Pediatrics
Harvard Medical School, Boston, MA07/2016Neurobiology
Boston Children's Hospital, Boston, MA07/2018Pediatrics
Boston Children's Hospital, Boston, MA07/2021Child Neurology

Overview
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Dr. Ebrahimi-Fakhari s research interests cover childhood-onset neurogenetic, neurodegenerative, and movement disorders. He leads a translational research program that aims to discover novel therapies for childhood-onset forms of hereditary spastic paraplegia and disorders related to the autophagy pathway. Current work covers gene discovery, natural history studies in patients, disease modeling in iPSC-derived neurons and zebrafish, and high-throughput small molecule screens and CRISPR screens. Work over the last years has focused on the role of adaptor protein complex-mediated protein trafficking in neurons using AP-4-associated hereditary spastic paraplegia as a tractable model. We established that AP-4 cargo proteins, ATG9A and DAGLB, are mislocalized in AP-4 deficient cells, including in neurons derived from patients. Building on this cellular phenotype, we developed a high-throughput assay for small molecule and functional genomics screens. Ongoing work is testing the hypothesis that small molecule modulators of protein trafficking, identified using our high-content imaging platform, can restore key cellular mechanisms in AP-4-associated hereditary spastic paraplegia in vitro and in vivo.
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Available: 01/20/25, Expires: 07/01/26

https://www.def-lab.org/ Translational Research in Rare Diseases Research on rare diseases is faced with unique challenges and opportunities. Our research program combines basic science and clinical research to create and implement novel medical technologies and treatments. Our work is translational and patient-centered. Most of our research projects are inspired by patients and families we meet in the clinic. We take on areas where we see an unmet need and bring ideas from our clinical work to our laboratory (‘bedside to bench’). Vice versa, our basic science research program is targeted at understanding fundamental molecular disease mechanisms and at developing platforms for testing novel therapeutics, with the goal of ultimately implementing first-in-human and pivotal clinical studies (‘bench to bedside’). We aim to accelerate the time between laboratory research, development, and clinical application.


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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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PMC Citations indicate the number of times the publication was cited by articles in PubMed Central, and the Altmetric score represents citations in news articles and social media. (Note that publications are often cited in additional ways that are not shown here.) Fields are based on how the National Library of Medicine (NLM) classifies the publication's journal and might not represent the specific topic of the publication. Translation tags are based on the publication type and the MeSH terms NLM assigns to the publication. Some publications (especially newer ones and publications not in PubMed) might not yet be assigned Field or Translation tags.) Click a Field or Translation tag to filter the publications.
Displaying 25 of 119 total Publications Show all
  1. Quiroz V, Zubair U, Schierbaum L, Tam A, Battaglia N, Rong J, Agianda HAP, Alecu JE, Yang K, Ebrahimi-Fakhari D. Heterozygous variants in AP4S1 are not associated with a neurological phenotype. Ann Clin Transl Neurol. 2025 Jan 27. PMID: 39865903.
    Citations:
    Fields: NeuNeurology
  2. Zubair U, Yang K, Schierbaum L, Tam A, Battaglia N, Rong J, Quiroz V, Ebrahimi-Fakhari D. Blended phenotype of TECPR2-associated hereditary sensory-autonomic neuropathy and Temple syndrome. Ann Clin Transl Neurol. 2025 Jan 14. PMID: 39807687.
    Citations:
    Fields: NeuNeurology
  3. Brooks AK, Quiroz V, Schierbaum L, Tam A, Alecu JE, Ebrahimi-Fakhari D. Expanding molecular and clinical spectrum of CPT1C-associated hereditary spastic paraplegia (SPG73)-a case series. Ann Clin Transl Neurol. 2024 Dec 29. PMID: 39737739.
    Citations:
    Fields: NeuNeurology
  4. Agianda HAP, Tam A, Kunta A, Zubair U, Saffari A, Rong J, Crough M, Srouji R, Quiroz V, Yang K, Schierbaum L, Ebrahimi-Fakhari D. STUB1-Associated Autosomal-Recessive Spinocerebellar Ataxia Type 16 (SCAR16) Presenting with Gordon-Holmes Syndrome Caused by Maternal Uniparental Isodisomy. Mov Disord Clin Pract. 2024 Dec 27. PMID: 39728009.
    Citations:
    Fields: NeuNeurology
  5. Alecu JE, Tam A, Richter S, Quiroz V, Schierbaum L, Saffari A, Ebrahimi-Fakhari D. Quantitative natural history modeling of HPDL-related disease based on cross-sectional data reveals genotype-phenotype correlations. Genet Med. 2024 Dec 25; 27(3):101349. PMID: 39731469.
    Citations:
    Fields: GenGenetics, Medical
  6. French CE, Andrews NC, Beggs AH, Boone PM, Brownstein CA, Chopra M, Chou J, Chung WK, D'Gama AM, Doan RN, Ebrahimi-Fakhari D, Goldstein RD, Irons M, Jacobsen C, Kenna M, Lee T, Madden JA, Majmundar AJ, Mann N, Morton SU, Poduri A, Randolph AG, Roberts AE, Roberts S, Sampson MG, Shao DD, Shao W, Sharma A, Shearer E, Shimamura A, Snapper SB, Srivastava S, Thiagarajah JR, Whitman MC, Wojcik MH, Rockowitz S, Sliz P. Hospital-wide access to genomic data advanced pediatric rare disease research and clinical outcomes. NPJ Genom Med. 2024 Dec 02; 9(1):60. PMID: 39622807; PMCID: PMC11612168.
    Citations:
  7. Yang K, Lindsay R, Quiroz V, Srouji R, Ebrahimi-Fakhari D. Spectrum and Evolution of Movement Disorder Phenomenology in a Pediatric Powassan Encephalitis Case Series. Mov Disord Clin Pract. 2024 Dec; 11(12):1613-1619. PMID: 39435637; PMCID: PMC11647971.
    Citations:
    Fields: NeuNeurology
  8. Dafsari HS, Martinelli D, Saffari A, Ebrahimi-Fakhari D, Fanto M, Dionisi-Vici C, Jungbluth H. An update on autophagy disorders. J Inherit Metab Dis. 2025 01; 48(1):e12798. PMID: 39420677; PMCID: PMC11669743.
    Citations:
    Fields: MetMetabolism
  9. Schierbaum L, Quiroz V, Tam A, Zubair U, Tochen L, Srouji R, Yang K, Ebrahimi-Fakhari D. Biallelic Variants in COQ4 Cause Childhood-Onset Pure Hereditary Spastic Paraplegia. Mov Disord Clin Pract. 2024 Dec; 11(12):1620-1624. PMID: 39367686; PMCID: PMC11648031.
    Citations:
    Fields: NeuNeurology
  10. Wiseman JP, Scarrott JM, Alves-Cruzeiro J, Saffari A, Böger C, Karyka E, Dawes E, Davies AK, Marchi PM, Graves E, Fernandes F, Yang ZL, Coldicott I, Hirst J, Webster CP, Highley JR, Hackett N, Angyal A, Silva T, Higginbottom A, Shaw PJ, Ferraiuolo L, Ebrahimi-Fakhari D, Azzouz M. Pre-clinical development of AP4B1 gene replacement therapy for hereditary spastic paraplegia type 47. EMBO Mol Med. 2024 Nov; 16(11):2882-2917. PMID: 39358605; PMCID: PMC11554807.
    Citations:
    Fields: MolMolecular BiologyTranslation:HumansAnimalsCells
  11. Danzi MC, Powell E, Rebelo AP, Dohrn MF, Beijer D, Fazal S, Xu IRL, Medina J, Chen S, Arcia de Jesus Y, Schatzman J, Hershberger RE, Saporta M, Baets J, Falk M, Herrmann DN, Scherer SS, Reilly MM, Cortese A, Marques W, Cornejo-Olivas MR, Sanmaneechai O, Kennerson ML, Jordanova A, Silva TYT, Pedroso JL, Schierbaum L, Ebrahimi-Fakhari D, Peric S, Lee YC, Synofzik M, Tekin M, Ravenscroft G, Shy M, Basak N, Schule R, Zuchner S. The GENESIS database and tools: A decade of discovery in Mendelian genomics. Exp Neurol. 2024 Dec; 382:114978. PMID: 39357594.
    Citations:
    Fields: NeuNeurologyTranslation:Humans
  12. Quinlan A, Rodan L, Barkoudah E, Tam A, Saffari A, Shammas I, Ranatunga W, Morava-Kozicz E, Oglesbee D, Berry G, Ebrahimi-Fakhari D, Srivastava S. Case Report of Friedreich's Ataxia and ALG1 -Related Biochemical Abnormalities in a Patient With Progressive Spastic Paraplegia. Am J Med Genet A. 2025 Feb; 197(2):e63890. PMID: 39324476; PMCID: PMC11698633.
    Citations:
    Fields: GenGenetics, MedicalTranslation:HumansCells
  13. Yang K, Quiroz V, Tam A, Srouji R, Villanueva X, Amarales C, Ebrahimi-Fakhari D. Juvenile-onset Huntington's disease - Spectrum and evolution of presenting movement disorders. Ann Clin Transl Neurol. 2024 Oct; 11(10):2805-2810. PMID: 39239850; PMCID: PMC11514935.
    Citations:
    Fields: NeuNeurologyTranslation:Humans
  14. Novelli M, Tolve M, Quiroz V, Carducci C, Bove R, Ricciardi G, Yang K, Manti F, Pisani F, Ebrahimi-Fakhari D, Galosi S, Leuzzi V. Autosomal Recessive Guanosine Triphosphate Cyclohydrolase I Deficiency: Redefining the Phenotypic Spectrum and Outcomes. Mov Disord Clin Pract. 2024 Sep; 11(9):1072-1084. PMID: 39001623; PMCID: PMC11452796.
    Citations:
    Fields: NeuNeurologyTranslation:Humans
  15. Quiroz V, Planas-Serra L, Sveden A, Tam A, Kim HM, Zubair U, Resch D, Saffari A, Danzi MC, Züchner S, Chopra M, Schierbaum L, Pujol A, Eklund EA, Ebrahimi-Fakhari D. Biallelic variants in RINT1 present as early-onset pure hereditary spastic paraplegia. J Clin Invest. 2024 Jul 11; 134(17). PMID: 38990652; PMCID: PMC11364375.
    Citations:
    Fields: MedMedicine (General)Translation:Humans
  16. Dowling JJ, Pirovolakis T, Devakandan K, Stosic A, Pidsadny M, Nigro E, Sahin M, Ebrahimi-Fakhari D, Messahel S, Varadarajan G, Greenberg BM, Chen X, Minassian BA, Cohn R, Bonnemann CG, Gray SJ. AAV gene therapy for hereditary spastic paraplegia type 50: a phase 1 trial in a single patient. Nat Med. 2024 Jul; 30(7):1882-1887. PMID: 38942994; PMCID: PMC11271397.
    Citations: 4
    Fields: MedMedicine (General)MolMolecular BiologyTranslation:HumansCellsCTClinical Trials
  17. Domínguez Carral J, Reinhard C, Ebrahimi-Fakhari D, Dorison N, Galosi S, Garone G, Malenica M, Ravelli C, Serdaroglu E, van de Pol LA, Koy A, Leuzzi V, Roubertie A, Lin JP, Doummar D, Cif L, Ortigoza-Escobar JD. Dyskinetic crisis in GNAO1-related disorders: clinical perspectives and management strategies. Front Neurol. 2024; 15:1403815. PMID: 38903163; PMCID: PMC11188927.
    Citations:
  18. Akula SK, Quiroz V, D'Gama AM, Chiu MY, Koh HY, Saffari A, Zaman Z, Tam A, Srouji R, Valentine R, Wiltrout K, Pinto A, Harini C, Pearl PL, Poduri A, Ebrahimi-Fakhari D. The spectrum of movement disorders in young children with ARX-related epilepsy-dyskinesia syndrome. Ann Clin Transl Neurol. 2024 Jun; 11(6):1643-1647. PMID: 38711225; PMCID: PMC11187834.
    Citations: 1
    Fields: NeuNeurologyTranslation:Humans
  19. Afshar-Saber W, Chen C, Teaney NA, Kim K, Yang Z, Gasparoli FM, Ebrahimi-Fakhari D, Buttermore ED, Pin-Fang Chen I, Pearl PL, Sahin M. Generation and characterization of six human induced pluripotent stem cell lines (hiPSCs) from three individuals with SSADH Deficiency and CRISPR-corrected isogenic controls. Stem Cell Res. 2024 Jun; 77:103424. PMID: 38677032; PMCID: PMC11178435.
    Citations:
    Fields: CelCell BiologyTranslation:HumansCells
  20. Vogt LM, Yang K, Tse G, Quiroz V, Zaman Z, Wang L, Srouji R, Tam A, Estrella E, Manzi S, Fasano A, Northam WT, Stone S, Moharir M, Gonorazky H, McAlvin B, Kleinman M, LaRovere KL, Gorodetsky C, Ebrahimi-Fakhari D. Recommendations for the Management of Initial and Refractory Pediatric Status Dystonicus. Mov Disord. 2024 Sep; 39(9):1435-1445. PMID: 38619077.
    Citations:
    Fields: NeuNeurologyTranslation:Humans
  21. Vogt L, Quiroz V, Ebrahimi-Fakhari D. Emerging therapies for childhood-onset movement disorders. Curr Opin Pediatr. 2024 06 01; 36(3):331-341. PMID: 38655812; PMCID: PMC11047116.
    Citations: 1
    Translation:Humans
  22. Saffari A, Brechmann B, Böger C, Saber WA, Jumo H, Whye D, Wood D, Wahlster L, Alecu JE, Ziegler M, Scheffold M, Winden K, Hubbs J, Buttermore ED, Barrett L, Borner GHH, Davies AK, Ebrahimi-Fakhari D, Sahin M. High-content screening identifies a small molecule that restores AP-4-dependent protein trafficking in neuronal models of AP-4-associated hereditary spastic paraplegia. Nat Commun. 2024 Jan 17; 15(1):584. PMID: 38233389; PMCID: PMC10794252.
    Citations: 3
    Fields: BioBiologySciScienceTranslation:HumansCells
  23. Afshar-Saber W, Teaney NA, Winden KD, Jumo H, Shi X, McGinty G, Hubbs J, Chen C, Tokatly Latzer I, Gasparoli F, Ebrahimi-Fakhari D, Buttermore ED, Roullet JB, Pearl PL, Sahin M. ALDH5A1-deficient iPSC-derived excitatory and inhibitory neurons display cell type specific alterations. Neurobiol Dis. 2024 Jan; 190:106386. PMID: 38110041; PMCID: PMC10843729.
    Citations: 1
    Fields: NeuNeurologyTranslation:HumansCells
  24. Saffari A, Lau T, Tajsharghi H, Karimiani EG, Kariminejad A, Efthymiou S, Zifarelli G, Sultan T, Toosi MB, Sedighzadeh S, Siu VM, Ortigoza-Escobar JD, AlShamsi AM, Ibrahim S, Al-Sannaa NA, Al-Hertani W, Sandra W, Tarnopolsky M, Alavi S, Li C, Day-Salvatore DL, Martínez-González MJ, Levandoski KM, Bedoukian E, Madan-Khetarpal S, Idleburg MJ, Menezes MJ, Siddharth A, Platzer K, Oppermann H, Smitka M, Collins F, Lek M, Shahrooei M, Ghavideldarestani M, Herman I, Rendu J, Faure J, Baker J, Bhambhani V, Calderwood L, Akhondian J, Imannezhad S, Mirzadeh HS, Hashemi N, Doosti M, Safi M, Ahangari N, Torbati PN, Abedini S, Salpietro V, Gulec EY, Eshaghian S, Ghazavi M, Pascher MT, Vogel M, Abicht A, Moutton S, Bruel AL, Rieubland C, Gallati S, Strom TM, Lochmüller H, Mohammadi MH, Alvi JR, Zackai EH, Keena BA, Skraban CM, Berger SI, Andrew EH, Rahimian E, Morrow MM, Wentzensen IM, Millan F, Henderson LB, Dafsari HS, Jungbluth H, Gomez-Ospina N, McRae A, Peter M, Veltra D, Marinakis NM, Sofocleous C, Ashrafzadeh F, Pehlivan D, Lemke JR, Melki J, Benezit A, Bauer P, Weis D, Lupski JR, Senderek J, Christodoulou J, Chung WK, Goodchild R, Offiah AC, Moreno-De-Luca A, Suri M, Ebrahimi-Fakhari D, Houlden H, Maroofian R. The clinical and genetic spectrum of autosomal-recessive TOR1A-related disorders. Brain. 2023 08 01; 146(8):3273-3288. PMID: 36757831; PMCID: PMC10393417.
    Citations: 3
    Fields: BraBrainNeuNeurologyTranslation:Humans
  25. Alecu JE, Saffari A, Ziegler M, Jordan C, Tam A, Kim S, Leung E, Szczaluba K, Mierzewska H, King SD, Santorelli FM, Yoon G, Trombetta B, Kivisäkk P, Zhang B, Sahin M, Ebrahimi-Fakhari D. Plasma Neurofilament Light Chain Is Elevated in Adaptor Protein Complex 4-Related Hereditary Spastic Paraplegia. Mov Disord. 2023 09; 38(9):1742-1750. PMID: 37482941; PMCID: PMC10529494.
    Citations: 1
    Fields: NeuNeurologyTranslation:HumansCells
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