Marcel Daadi, Ph.D.
Associate Professor
Department of Cell Systems and Anatomy
Leader of Regenerative Medicine & Aging Unit
Dr. Marcel Daadi is an expert in neural stem cell biology and regulated translational research, especially in stem cell therapeutic applications for Parkinson’s disease and brain injuries. He discovered growth and differentiation conditions to direct human neural stem cells toward the dopaminergic lineage. This work produced two hallmark studies, both of scientific importance and therapeutic application for Parkinson’s disease.
In an industrial setting (NeuroSpheres Ltd. and Layton Biosciences Inc.), he developed therapeutic neural stem cell lines for clinical use in stroke, Parkinson’s disease and other diseases and injuries. He is involved in the development of the world’s first cryopreserved neural product manufactured under current Good Manufacturing Practices and transplanted into patients afflicted with stroke at Layton Biosciences Inc., Sunnyvale CA.
At the University of California San Francisco, he was involved in pivotal Investigational New Drug-enabling gene therapy nonhuman primate studies that allowed Avigen, Inc. to conduct clinical trials for treating patients with Parkinson’s disease. At Stanford University, he started and led the human embryonic stem cell program focused on developing therapeutic stem cell lines for treating ischemic stroke. He also discovered and patented a novel methods for engineering neural stem cells from human pluripotent stem cells that is currently in development for treating patients with Parkinson's disease, traumatic brain injury and stroke.
Daadi's laboratory is devoted to the modeling and understanding of neurological disorders and to discovery and development of therapeutics including small molecules, cell and gene therapy for the treatment of Parkinson’s disease in particular. Our laboratory uses a wide array of neurobehavioral tests, multimodal imaging, induced pluripotent stem cell-based models, in vitro cell assays, single cell multi-omics and immunohistopathological approaches to investigate cellular diversity, aging and neural networks neuroplasticity in health and diseases
Dr. Daadi's current research is centered on the following areas:
1. Development of technologies to establish pluripotent stem cells, isolate self-renewable multipotent NSCs and generate specific neuronal lineages, such as dopaminergic neurons for treating Parkinson’s disease.
2. Reprogramming and genome-editing technologies to model neurological disorders in vitro and to understand mechanisms mediating disease development and degenerative processes following injury or disease.
3. Developing therapeutic stem cell lines for clinical use.
4. Preclinical development using nonhuman primates models of a variety of diseases and applying cell delivery and multimodal molecular imaging approaches for monitor the safety and efficacy.
5. Genetic engineering of NSCs to investigate the role of optogenetics on their fate after grafting. These studies will help determine the mechanisms mediating stem cell graft–host interactions in enhancing neuro-regeneration and restoring function.
Results from our studies are the foundation of translational research aimed at repairing diseased or injured brain through transplantation of highly purified NSCs or stimulation of endogenous repair mechanisms.
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Publications
Daadi EW, Daadi ES, Oh T, Li M, Kim J, Daadi MM. Combining physical & cognitive training with iPSC-derived dopaminergic neuron transplantation promotes graft integration & better functional outcome in parkinsonian marmosets. Exp. Neurol. 2024; 374:114694. Epub 20240123. doi: 10.1016/j.expneurol.2024.114694. PubMed PMID: 38272159
Kim J, Daadi EW, Daadi ES, Oh T, Deleidi M, Daadi MM. LRRK2 Attenuates Antioxidant Response in Familial Parkinson's Disease Derived Neural Stem Cells. Cells. 2023 Oct 31;12(21):2550
Kim J, Daadi EW, Oh T, Daadi ES, Daadi MM. Human Induced Pluripotent Stem Cell Phenotyping and Preclinical Modeling of Familial Parkinson's Disease. Genes (Basel). 2022 Oct 25;13(11):1937
Ma S, Skarica M, Li Q, Xu C, Risgaard RD, Tebbenkamp ATN, Mato-Blanco X, Kovner R, Krsnik Ž, de Martin X, Luria V, Martí-Pérez X, Liang D, Karger A, Schmidt DK, Gomez-Sanchez Z, Qi C, Gobeske KT, Pochareddy S, Debnath A, Hottman CJ, Spurrier J, Teo L, Boghdadi AG, Homman- Ludiye J, Ely JJ, Daadi EW, Mi D, Daadi M, Marín O, Hof PR, Rasin MR, Bourne J, Sherwood CC, Santpere G, Girgenti MJ, Strittmatter SM, Sousa AMM, Sestan N., Molecular and cellular evolution of the primate dorsolateral prefrontal cortex. Science. 2022 Sep 30;377(6614):eabo7257.
Oh T, Daadi ES, Kim J, Daadi EW, Chen PJ, Roy-Choudhury G, Bohmann J, Blass BE, Daadi MM. Dopamine D3 Receptor Ligand Suppresses the Expression of Levodopa-Induced Dyskinesia in Nonhuman Primate Model of Parkinson’s Disease. Exp Neurol. 2022 Jan; 347: 113920 .
Daadi MM. Isolation and Purification of Self-Renewable Human Neural Stem Cells from iPSCs for Cell Therapy in Experimental Model of Ischemic Stroke. Methods Mol Biol. 2022; 2389: 165-175.
Singh P, Bahr T, Zhao X, Hu P, Daadi M, Huang T, Bai Y. Creating Cell Model 2.0 Using Patient Samples Carrying a Pathogenic Mitochondrial DNA Mutation: iPSC Approach for LHON. Methods Mol Biol. 2021 Oct 21.
Li Y, Xing Z, Yu T, Pao A, Daadi M, Yu YE. Coat Color-Facilitated Efficient Generation and Analysis of a Mouse Model of Down Syndrome Triplicated for All Human Chromosome 21 Orthologous Regions. Genes (Basel). 2021 Aug 6;12(8):1215.
Lizarraga S., Daadi E.W., Roy-Choudhury G., Daadi M.M. Age-Related Cognitive Decline in Baboons: Modeling the Prodromal Phase of Alzheimer's Disease and Related Dementias. Aging (Albany NY) 2020; 19,12(11):10099-10116.
Boltze J., Modo M.M., Mays R.W., Taguchi A., Jolkkonen J., Savitz S.I. and STEPS 4 Consortium. Stem Cells as an Emerging Paradigm in Stroke 4: Advancing and Accelerating Preclinical Research. Stroke. 2019; 50(11):3299-3306.
Kim J., Daadi M.M. (2019). Non-Cell Autonomous Mechanism of Parkinson’s Disease Pathology Caused by G2019S LRRK2 Mutation in Ashkenazi Jewish Patient: Single Cell Analysis. Brain Res. 2019 Nov 1;1722:146342.
Daadi M.M. (2019). Generation of Neural Stem Cells From Induced Pluripotent Stem Cells. Methods Mol. Biol. 1919: 1-7.
Daadi M.M. (2019). Differentiation of Neural Stem Cells Derived from Induced Pluripotent Stem Cells into Dopaminergic Neurons. Methods Mol. Biol. 1919: 89-96.
Hong H., Daadi M.M. (2019). Generating Neural Stem Cells from iPSCs with Dopaminergic Neurons Reporter Gene. Methods Mol. Biol. 1919: 119-128.
Kim J., Daadi M.M. (2019). Single-Cell Library Preparation of iPSC-derived Neural Stem Cells. Methods Mol. Biol. 1919: 129-143.
Kim J., Daadi M.M. (2019). Bioinformatics Analysis of Single-Cell RNA-Seq Raw Data From iPSC-Derived Neural Stem Cells. Methods Mol. Biol. 1919: 145-159.
Roy-Choudhury G., Daadi M.M. (2019). Assay for Assessing Mitochondrial Function In iPSC-Derived Neural Stem Cells and Dopaminergic Neurons. Methods Mol. Biol. 1919: 161-173.
Yang G., Hong H., Torres A., Malloy K.E., Choudhury G.R., Kim J., Daadi M.M. (2019). Reference Transcriptome for Deriving Nonhuman Primate Induced Pluripotent Stem Cells. Methods Mol. Biol. 1919: 175-186.
Hong H., Roy-Choudhury G., Kim J., Daadi M.M. (2019). Isolation and Differentiation of Self-Renewable Neural Stem Cells from Marmoset Induced Pluripotent Stem Cells. Methods Mol. Biol. 1919: 199-204.
Choudhury G.R., Daadi M.M. (2018). Charting the onset of Parkinson-like motor and non-motor symptoms in nonhuman primate model of Parkinson's disease. PLoS One. 2018 Aug 23; 13(8):e0202770..
Yang G., Hong H., Torres A., Malloy K.E., Choudhury G.R., Kim J., Daadi M.M. (2018) Standards for Deriving Nonhuman Primate-Induced Pluripotent Stem Cells, Neural Stem Cells and Dopaminergic Lineage. (2018). Int J Mol Sci. 2018 Sep 17; 19(9).
Malloy K., Li J., Choudhury G., Torres A., Gupta S., Kantorak C., Goble T., Fox P., Clarke G., Daadi M.M.MRI Guided Delivery of Neural Stem Cells into the Basal Ganglia of Nonhuman Primates. STEM CELLS Translational Medicine. 2017, 6(3):877-885.
McEntire CR, Choudhury GR, Torres A, Steinberg GK, Redmond DE Jr, Daadi M.M. Impaired Arm Function and Finger Dexterity in a Nonhuman Primate Model of Stroke: Motor and Cognitive Assessments. Stroke. 2016, 47(4):1109-16.
Choudhury G., Kim J., Frost P.A., Bastarrachea R.A., Daadi M.M.(2016). Nonhuman Primate Model in Clinical Modeling of Diseases for Stem Cell Therapy. BRAIN CIRCULATION. 2016, 2(3):141-145
Daadi M.M., Barberi T, Shi Q, Lanford RE. (2014) Nonhuman primate models in translational regenerative medicine.Stem Cells Dev. 23, Suppl 1:83-7.
Daadi M.M.,Grueter B.A., MalenkaR.C., Redmond DE, Steinberg G.K. (2012) Dopaminergic Neurons from Midbrain-Specified Human Embryonic Stem Cell-Derived Neural Stem Cells Engrafted in a Monkey Model of Parkinson's Disease. PLoS ONE, 2012;7(7):e41120.
Daadi M.M., Hu S., Klausner J.Q., Li Z., Sofilos M., Sun G., Wu J.C. and Steinberg G.K. (2013) Imaging Neural Stem Cell Graft-Induced Structural Repair in Stroke. Cell Transplantation, 2013;22(5):881-92.
Daadi M.M. (2011) Novel paths towards neural cellular products for neurological disorders. Regenerative Medicine 6(6 Suppl):25-30.
Daadi M.M. (2011) Engineering Therapeutic Neural Stem Cell Lines For Parkinson’s Disease. In Embryonic Stem Cells - Recent Advances in Pluripotent Stem Cell-Based Regenerative Medicine. (Craig Atwood, ed.) InTech Publisher, ISBN 978-953-307-198-5.
Daadi M.M. (2010) The Common path: Tumor suppression in the generation of iPS cells and cancer stem cells. Regenerative Medicine 5:21-22.
Martinez-Cerdeno V, Noctor SC, Espinosa A, Ariza J, Parker P, Orasji S, Daadi M.M, Bankiewicz K, Alvarez-Buylla A, Kriegstein AR (2010) Embryonic MGE precursor cells grafted into adult rat striatum integrate and ameliorate motor symptoms in 6-OHDA-lesioned rats. Cell Stem Cell 6:238-250
Daadi M.M., Davis A., Arac A., Li Z., Maag A.L., Bhatnagar R., Guohua S., Wu J.C. and Steinberg G.K. (2010) Human neural stem cell grafts modify microglial response and enhance axonal sprouting in neonatal hypoxic-ischemic brain injury. Stroke 41:516-523.