Janghoo Lim, PhD
Research & Publications
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Research Summary
There are two main research interests in our laboratory: 1) understanding the molecular basis of cellular pathology in neurodegenerative diseases, and 2) understanding the mechanisms of brain development, function and its associated neurological disorders
In particular, we have a long-standing interest in neurodegenerative disease research, both in understanding the molecular and cellular mechanisms that are responsible for neurodegeneration, and ultimately, translating these findings into the development of therapeutics. Our approach to understanding these diseases involves utilizing multiple different model systems, including mice, flies, and human patient-derived induced pluripotent stem cells, to comprehensively examine disease mechanisms. We focus on several specific neurodegenerative diseases including the polyglutamine diseases. Polyglutamine diseases are dominantly inherited neurodegenerative conditions caused by an expansion of the glutamine tract in the respective disease-causing proteins. Polyglutamine expansion makes the host protein toxic, resulting in the formation of mutant protein aggregates and cell death. We study two distinct polyglutamine diseases, named spinocerebellar ataxia type 1 (SCA1) and spinal and bulbar muscular atrophy (SBMA). SCA1 is a dominantly inherited disease characterized by the progressive degeneration of neurons, specifically those in the cerebellum and brainstem. SBMA is an X-linked progressive neuromuscular disease. There is no current cure or effective therapeutics for both of these diseases. In addition to studying the polyglutamine diseases, we also investigate the molecular and cellular mechanisms underlying pathogenesis in Alzheimer’s disease (AD) and related disorders using various model systems, including mice and patient-derived stem cell models.
Specialized Terms: Mechanisms of neural development; Neurological disorders; Neurodegenerative diseases
Coauthors
Research Interests
Mental Disorders; Developmental Disabilities; Neuromuscular Diseases; Motor Neuron Disease; Neurodegenerative Diseases; Spinocerebellar Ataxias
Selected Publications
- Longitudinal single-cell transcriptional dynamics throughout neurodegeneration in SCA1Tejwani L, Ravindra N, Lee C, Cheng Y, Nguyen B, Luttik K, Ni L, Zhang S, Morrison L, Gionco J, Xiang Y, Yoon J, Ro H, Haidery F, Grijalva R, Bae E, Kim K, Martuscello R, Orr H, Zoghbi H, McLoughlin H, Ranum L, Shakkottai V, Faust P, Wang S, van Dijk D, Lim J. Longitudinal single-cell transcriptional dynamics throughout neurodegeneration in SCA1. Neuron 2023, 112: 362-383.e15. PMID: 38016472, PMCID: PMC10922326, DOI: 10.1016/j.neuron.2023.10.039.
- Dysregulation of alternative splicing in spinocerebellar ataxia type 1Olmos V, Thompson E, Gogia N, Luttik K, Veeranki V, Ni L, Sim S, Chen K, Krause D, Lim J. Dysregulation of alternative splicing in spinocerebellar ataxia type 1. Human Molecular Genetics 2023, 33: 138-149. PMID: 37802886, PMCID: PMC10979408, DOI: 10.1093/hmg/ddad170.
- Reduction of Nemo-like kinase increases lysosome biogenesis and ameliorates TDP-43-related neurodegenerationTejwani L, Jung Y, Kokubu H, Sowmithra S, Ni L, Lee C, Sanders B, Lee P, Xiang Y, Luttik K, Soriano A, Yoon J, Park J, Ro H, Ju H, Liao C, Tieze S, Rigo F, Jafar-Nejad P, Lim J. Reduction of Nemo-like kinase increases lysosome biogenesis and ameliorates TDP-43-related neurodegeneration. Journal Of Clinical Investigation 2023, 133: e138207. PMID: 37384409, PMCID: PMC10425213, DOI: 10.1172/jci138207.
- A Novel Missense Mutation in ERCC8 Co-Segregates with Cerebellar Ataxia in a Consanguineous Pakistani FamilyGauhar Z, Tejwani L, Abdullah U, Saeed S, Shafique S, Badshah M, Choi J, Dong W, Nelson-Williams C, Lifton RP, Lim J, Raja GK. A Novel Missense Mutation in ERCC8 Co-Segregates with Cerebellar Ataxia in a Consanguineous Pakistani Family. Cells 2022, 11: 3090. PMID: 36231052, PMCID: PMC9564319, DOI: 10.3390/cells11193090.
- Identifying Disease Signatures in the Spinocerebellar Ataxia Type 1 Mouse CortexLuttik K, Olmos V, Owens A, Khan A, Yun J, Driessen T, Lim J. Identifying Disease Signatures in the Spinocerebellar Ataxia Type 1 Mouse Cortex. Cells 2022, 11: 2632. PMID: 36078042, PMCID: PMC9454518, DOI: 10.3390/cells11172632.
- Differential effects of Wnt-β-catenin signaling in Purkinje cells and Bergmann glia in spinocerebellar ataxia type 1Luttik K, Tejwani L, Ju H, Driessen T, Smeets CJLM, Edamakanti CR, Khan A, Yun J, Opal P, Lim J. Differential effects of Wnt-β-catenin signaling in Purkinje cells and Bergmann glia in spinocerebellar ataxia type 1. Proceedings Of The National Academy Of Sciences Of The United States Of America 2022, 119: e2208513119. PMID: 35969780, PMCID: PMC9407543, DOI: 10.1073/pnas.2208513119.
- The extra-cerebellar effects of spinocerebellar ataxia type 1 (SCA1): looking beyond the cerebellumOlmos V, Gogia N, Luttik K, Haidery F, Lim J. The extra-cerebellar effects of spinocerebellar ataxia type 1 (SCA1): looking beyond the cerebellum. Cellular And Molecular Life Sciences 2022, 79: 404. PMID: 35802260, PMCID: PMC9993484, DOI: 10.1007/s00018-022-04419-7.
- Exploring the Role of Posttranslational Modifications in Spinal and Bulbar Muscular AtrophyGogia N, Ni L, Olmos V, Haidery F, Luttik K, Lim J. Exploring the Role of Posttranslational Modifications in Spinal and Bulbar Muscular Atrophy. Frontiers In Molecular Neuroscience 2022, 15: 931301. PMID: 35726299, PMCID: PMC9206542, DOI: 10.3389/fnmol.2022.931301.
- Chapter 8 Exploring the role of protein quality control in aging and age-associated neurodegenerative diseasesGogia N, Olmos V, Haidery F, Luttik K, Tejwani L, Lim J. Chapter 8 Exploring the role of protein quality control in aging and age-associated neurodegenerative diseases. 2022, 139-171. DOI: 10.1016/b978-0-323-90235-9.00012-4.
- Microglia regulate brain Progranulin levels through the endocytosis-lysosomal pathwayDong T, Tejwani L, Jung Y, Kokubu H, Luttik K, Driessen TM, Lim J. Microglia regulate brain Progranulin levels through the endocytosis-lysosomal pathway. JCI Insight 2021, 6: e136147. PMID: 34618685, PMCID: PMC8663778, DOI: 10.1172/jci.insight.136147.
- Genetic Risk of Autism Spectrum Disorder in a Pakistani PopulationKhalid M, Raza H, Driessen T, Lee P, Tejwani L, Sami A, Nawaz M, Baig S, Lim J, Raja G. Genetic Risk of Autism Spectrum Disorder in a Pakistani Population. Genes 2020, 11: 1206. PMID: 33076578, PMCID: PMC7602870, DOI: 10.3390/genes11101206.
- Pathogenic mechanisms underlying spinocerebellar ataxia type 1Tejwani L, Lim J. Pathogenic mechanisms underlying spinocerebellar ataxia type 1. Cellular And Molecular Life Sciences 2020, 77: 4015-4029. PMID: 32306062, PMCID: PMC7541529, DOI: 10.1007/s00018-020-03520-z.
- Nemo-like Kinase Reduces Mutant Huntingtin Levels and Mitigates Huntington’s DiseaseJiang M, Zhang X, Liu H, LeBron J, Alexandris A, Peng Q, Gu H, Yang F, Li Y, Wang R, Hou Z, Arbez N, Ren Q, Dong JL, Whela E, Wang R, Ratovitski T, Troncoso JC, Mori S, Ross CA, Lim J, Duan W. Nemo-like Kinase Reduces Mutant Huntingtin Levels and Mitigates Huntington’s Disease. Human Molecular Genetics 2020, 29: 1340-1352. PMID: 32242231, PMCID: PMC7254850, DOI: 10.1093/hmg/ddaa061.
- Molecular pathway analysis towards understanding tissue vulnerability in spinocerebellar ataxia type 1Driessen TM, Lee PJ, Lim J. Molecular pathway analysis towards understanding tissue vulnerability in spinocerebellar ataxia type 1. ELife 2018, 7: e39981. PMID: 30507379, PMCID: PMC6292693, DOI: 10.7554/elife.39981.
- Association of CACNA1C with bipolar disorder among the Pakistani populationKhalid M, Driessen TM, Lee JS, Tejwani L, Rasool A, Saqlain M, Shiaq PA, Hanif M, Nawaz A, DeWan AT, Raja GK, Lim J. Association of CACNA1C with bipolar disorder among the Pakistani population. Gene 2018, 664: 119-126. PMID: 29684488, PMCID: PMC5970093, DOI: 10.1016/j.gene.2018.04.061.
- Nemo-like kinase is a novel regulator of spinal and bulbar muscular atrophyTodd TW, Kokubu H, Miranda HC, Cortes CJ, La Spada AR, Lim J. Nemo-like kinase is a novel regulator of spinal and bulbar muscular atrophy. ELife 2015, 4: e08493. PMID: 26308581, PMCID: PMC4577982, DOI: 10.7554/elife.08493.
- Polyglutamine Disease Toxicity Is Regulated by Nemo-like Kinase in Spinocerebellar Ataxia Type 1Ju H, Kokubu H, Todd TW, Kahle JJ, Kim S, Richman R, Chirala K, Orr HT, Zoghbi HY, Lim J. Polyglutamine Disease Toxicity Is Regulated by Nemo-like Kinase in Spinocerebellar Ataxia Type 1. Journal Of Neuroscience 2013, 33: 9328-9336. PMID: 23719801, PMCID: PMC3710458, DOI: 10.1523/jneurosci.3465-12.2013.
- Dorsoventral boundary for organizing growth and planar polarity in the Drosophila eyeSingh A, Lim J, Choi K. Dorsoventral boundary for organizing growth and planar polarity in the Drosophila eye. 2005, 14: 59-90. DOI: 10.1016/s1574-3349(05)14004-6.
- dAtaxin-2 mediates expanded Ataxin-1-induced neurodegeneration in a Drosophila model of SCA1Al-Ramahi I, Perez A, Lim J, Zhang M, Sorensen R, de Haro M, Branco J, Pulst S, Zoghbi H, Botas J. dAtaxin-2 mediates expanded Ataxin-1-induced neurodegeneration in a Drosophila model of SCA1. PLOS Genetics 2005, preprint: e234. DOI: 10.1371/journal.pgen.0030234.eor.