Harvard Catalyst Profiles

Ruprecht-Karls Universität Heidelberg, Heidelberg, Germany	MD	04/2013	Medicine
Ruprecht-Karls Universität Heidelberg, Heidelberg, Germany	PhD	04/2013	Neurobiology
University Hospital Heidelberg, Heidelberg, Germany		04/2014	Pediatrics
Harvard Medical School, Boston, MA		07/2016	Neurobiology
Boston Children's Hospital, Boston, MA		07/2018	Pediatrics
Boston Children's Hospital, Boston, MA		07/2021	Child Neurology

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.

• Translational Medical Research
• Neuroscience
• Neurobiology, Molecular
• Neurology
• Cell Biology
• Neurodegenerative Disorders
• Drug Screening
• Molecular Targeted Therapy
• Gene Discovery
• Clinical Research
• Movement Disorders
• Neurobiology
• Zebrafish
• IPS Cells