Daesung Shin PhD
Daesung Shin
PhD
Associate Professor
Department of Biotechnical and Clinical Laboratory Sciences
Jacobs School of Medicine & Biomedical Sciences
Specialty/Research Focus
Glia - Physiology & Pathophysiology; Lysosomal Storage Diseases; Myelin Diseases; Neurodevelopmental Disorders
Professional Summary:
Krabbe disease (KD), or globoid cell leukodystrophy, is a fatal neurodegenerative lysosomal storage disorder caused by a deficiency in galactosylceramidase (GALC), impacting both the central and peripheral nervous systems. Early-infantile KD typically manifests within the first few months of life with severe irritability, muscle rigidity, and rapid motor decline, inevitably progressing to terminal clinical decay within months. Currently, no cure exists.
Our understanding of KD pathogenesis remains limited, largely constrained by clinical observation and spontaneous animal models. While hematopoietic stem cell transplantation (HSCT) can partially attenuate disease progression, its efficacy is strictly limited to pre-symptomatic intervention. This therapy relies on cross-correction—the mechanism by which stem cell derivatives secrete functional GALC that is internalized by recipient glia via mannose-6-phosphate receptors. However, critical questions remain regarding the in vivo efficiency of cross-correction, the precise cell types requiring restoration, and the developmental window during which intervention must occur. Furthermore, while GALC deficiency causes toxic accumulation of the lysolipid psychosine—driving oligodendrocyte, Schwann cell, and neuronal death—the relative contribution of psychosine toxicity, its primary cellular sources, and the precise cascade of pathogenic events remain unresolved.
To address these critical gaps, we generated a novel conditional Galc floxed mouse allele. Utilizing targeted in vivo and in vitro conditional knockout models, we are elucidating the cell-autonomous and non-cell-autonomous mechanisms driving KD, as well as the mechanistic constraints of HSCT cross-correction. By dissecting both the primary loss-of-function defects and downstream secondary pathogenic pathways, our goal is to identify novel therapeutic targets for Krabbe disease and related neurodegenerative and demyelinating leukodystrophies.
Education and Training:
- PhD, Neuroscience, Korea Advanced Institute of Science and Technology (2003)
- MS, Genetics, Korea Advanced Institute of Science and Technology (1999)
- BS, Biological Sciences, Korea Advanced Institute of Science and Technology (1997)
Employment:
- Principal Investigator, Hunter James Kelly Research Institute (2011–2020)
- Post Doctoral Fellow, Neurogenetics, University of California San Francisco / Howard Hughes Medical Institute (2005–2011)
Awards and Honors:
- Travel Stipend Award - Gordon Conference (Lysosomal disease) (2019)
- Young Investigator Award - Neurobiology of Disease in Children Symposium (2017)
- Travel Fellowship Award - American Neurological Association (2010)
Grants and Sponsored Research:
- December 2024–December 2029
Selective galactosylceramidase ablation to study the pathogenesis of Krabbe leukodystrophy
NIH
Role: Principal Investigator
$2,013,407 - November 2024–January 2027
Modulating Oligodendroglial NFkB as a Therapeutic Strategy for Krabbe Disease
The Rosenau Family Research Foundation
Role: Principal Investigator
$250,000 - November 2025–October 2026
Role of SERPINA3 in Krabbe leukodystrophy
Research and Economic Development Grant Resubmission Program
Role: Principal Investigator
$15,000 - June 2024–November 2025
Selective galactosylceramidase ablation to study the pathogenesis of Krabbe leukodystrophy
SUNY Research Seed Grant Program
Role: Principal Investigator
$40,000 - February 2019–January 2025
The peripheral nervous system: A window into Krabbe disease
NIH-NINDS
Role: Co-Investigator
$2,129,163 - December 2019–November 2024
Selective galactosylceramidase ablation to study the pathogenesis of Krabbe leukodystrophy
NIH-NINDS
Role: Principal Investigator
$1,395,624 - December 2018–November 2019
Selective galactosylceramidase ablation to study the pathogenesis of Krabbe leukodystrophy
NIH-NINDS
Role: Principal Investigator
$398,750 - September 2014–August 2016
Clinical variability and Cell autonomy of Krabbe leukodystrophy
NIH-NINDS
Role: Principal Investigator
$159,084 - July 2014–June 2015
Study of clinical variability of Krabbe disease using oligodendrocytes differentiated from patient iPSCs
New York Stem Cell Foundation
Role: Principal Investigator
$6,000
Journal Articles:
- Narayan Dhimal, Aditya Sidharth, Jiajun Zhang, Trina Rudra, Edward Hurley, Pablo M. Paez, Fraser J. Sim, Daesung Shin [Correspondence], and M. Laura Feltri. (2026) Schwann cell-specific ATG7-dependent autophagy protects myelin in a mouse model of Krabbe disease. Glia (Oct), 74(12): e70244. doi:10.1002/glia.70244
- Aditya Sidharth and Daesung Shin. (2026) The role of SUMOylation in regulating proteins that drive neuronal disease progression. Biochemistry and Biophysics Reports (Jun), 47: 102687. doi:10.1016/j.bbrep.2026.102687
- Diego Zelada, Natalia Saldivia, Ashna Konjeti, Shayla Samano, Michael S. Marshall, Rima Rebiai, Pearl Sutter, Zachary Zurawski, Daniel Simchuck, Ruth Muchiri, Richard van Breemen, Daesung Shin, Maria I. Givogri, Stephen J. Crocker, Simon T. Alford, and Ernesto R. Bongarzone. (2025) Impaired docking and recycling of synaptic vesicles in inherited lysosomal sphingolipidoses. Cell Communication and Signaling (Dec) doi:10.1186/s12964-025-02560-x
- Jacob Favret, Malabika Maulik, Rayan Masoom, Meghana Kushwaha, Devin Thompson, Richard Browne, and Daesung Shin. (2024) Ablation of lipocalin-2 reduces neuroinflammation in a mouse model of Krabbe disease. Scientific Reports (Dec), 14(1): 31822. doi:10.1038/s41598-024-82927-1
- Jacob Favret, Mohammed Haseeb Nawaz, Mayuri Patel, Hamid Khaledi, Michael Gelb, and Daesung Shin. (2024) Perinatal loss of galactosylceramidase in both oligodendrocytes and microglia is crucial for the pathogenesis of Krabbe disease in mice. Molecular Therapy (Jul), 32(7): 2207-2222. doi:10.1016/j.ymthe.2024.05.019
- Conlan Kreher, Jacob Favret , Nadav I. Weinstock, Malabika Maulik, Xinying Hong, Michael H. Gelb, Lawrence Wrabetz, M. Laura Feltri, and Daesung Shin. (2022) Neuron-specific ablation of the Krabbe disease gene galactosylceramidase in mice results in neurodegeneration. PLoS Biology (Jul), 20(7): e3001661. doi:https://doi.org/10.1371/journal.pbio.3001661
- M. Laura Feltri, Nadav I. Weinstock, Jacob Favret, Narayan Dhimal, Lawrence Wrabetz, and Daesung Shin. (2021) Mechanisms of demyelination and neurodegeneration in globoid cell leukodystrophy. Glia (Apr)1-23. doi:https://doi.org/10.1002/glia.24008
- Conlan Kreher, Jacob Favret, Malabika Maulik, and Daesung Shin. (2021) Lysosomal Functions in Glia Associated with Neurodegeneration. Biomolecules (Mar), 11(3): 400.
- Nadav I. Weinstock, Conlan Kreher, Jacob Favret, Duc Nguyen, Ernesto R. Bongarzone, Lawrence Wrabetz, M. Laura Feltri, and Daesung Shin. (2020) Brainstem development requires galactosylceramidase and is critical for pathogenesis in a model of Krabbe disease. Nature Communications (Oct), 11(1): 5356.
- N.I. Weinstock*, D. Shin*, N. Dhimal, X. Hong, E. E. Irons, N. Silvestri, C.B. Reed, D. Nguyen, O. Sampson, Y.C. Cheng, J.T.Y. Lau, E. Bongarzone, J. Kofler, M. Escolar, M. Gelb, L. Wrabetz, M.L. Feltri. (2020) Macrophages Expressing GALC Improve Peripheral Krabbe Disease by a Mechanism Independent of Cross-Correction. Neuron (Jul), 107(1): 65-81.
- Jacob M Favret, Nadav I Weinstock, M Laura Feltri, Daesung Shin. (2020) Pre-clinical Mouse Models of Neurodegenerative Lysosomal Storage Diseases. Front Mol Biosci (Apr), 7(57).
- Weinstock NI, Wrabetz L, Feltri ML, Shin D. (2016) Metabolic profiling reveals biochemical pathways and potential biomarkers associated with the pathogenesis of Krabbe disease. J Neurosci Res (Nov), 94(11): 1094-1107.
- Shin D, Feltri ML, Wrabetz L. (2016) Altered Trafficking and Processing of GALC Mutants Correlates with Globoid Cell Leukodystrophy Severity. J Neurosci (Feb), 36(6): 1858-1870.
- Daesung Shin , Shu-Ting Lin, Ying-Hui Fu, Louis J Ptácek. (2013) Very large G protein-coupled receptor 1 regulates myelin-associated glycoprotein via Gas/Gaq-mediated protein kinases A/C. Proc Natl Acad Sci U S A (Nov), 110(47): 19101-19106.
- D Shin, S Y B Howng, L J Ptácek, Y-H Fu. (2012) miR-32 and its target SLC45A3 regulate the lipid metabolism of oligodendrocytes and myelin. Neuroscience (Jun), 213: 29-37.
- Shao Y, Kim SY, Shin D, Kim MS, Suh HW, Piao ZH, Jeong M, Lee SH, Yoon SR, Lim BH, Kim WH, Ahn JK, Choi I. (2010) TXNIP regulates germinal center generation by suppressing BCL-6 expression. Immunology letters (Apr), 129(2): 78-84.
- Daesung Shin, Ji-Yeon Shin, Michael T McManus, Louis J Ptácek, Ying-Hui Fu. (2009) Dicer ablation in oligodendrocytes provokes neuronal impairment in mice. Annals of Neurology (Dec), 66(6): 843-857.
- Chaeyoung Lee, Changhoon Kim, Sooan Shin, Daesung Shin, Joohyun Kang, and Chankyu Park. (2008) The dopamine D4 receptor polymorphism affects the canine fearfulness. Animal Cells and Systems (Nov), 12(2)
- Shin D, Jeon JH, Jeong M, Suh HW, Kim S, Kim HC, Moon OS, Kim YS, Chung JW, Yoon SR, Kim WH, Choi I. (2008) VDUP1 mediates nuclear export of HIF1alpha via CRM1-dependent pathway. Biochimica et biophysica acta (May), 1783(5): 838-48.
- Kim I, Kim E, Yoo S, Shin D, Min B, Song J, Park C. (2004) Ribose utilization with an excess of mutarotase causes cell death due to accumulation of methylglyoxal. Journal of bacteriology (Nov), 186(21): 7229-35. doi:10.1128/JB.186.21.7229-7235.2004
- Werner P, Raducha MG, Shin D, Ostrander EA, Kirkness E, Patterson DF, Henthorn PS. (2004) Assignment of 10 canine genes to the canine linkage and comparative maps. Animal genetics (Jun), 35(3): 249-51.
- Shin D, Park C. (2004) N-terminal extension of canine glutamine synthetase created by splicing alters its enzymatic property. The Journal of biological chemistry (Jan), 279(2): 1184-90.
- Shin D, Park S, Park C. (2003) A splice variant acquiring an extra transcript leader region decreases the translation of glutamine synthetase gene. The Biochemical journal (Aug), 374(Pt 1): 175-84. doi:10.1042/BJ20030132
Abstracts:
- Daesung Shin, Nadav Weinstock, M. Laura Feltri, and Lawrence Wrabetz. (2018) Temporal Galc deletion reveals a critical vulnerable period in the pathogenesis of Krabbe leukodystrophy. Mol. Genet. Metab, (Feb)
Presentations:
- "NF-kB activation in oligodendrocytes attenuates interferon-gamma response and cell death in Krabbe leukodystrophy" Neurobiology of Brain Disorders, Gordon Research Conferences (2026)
- "Cell autonomous roles of galactosylceramidase in Krabbe disease" Invited seminar, Chiesi Global Rare Diseases (2025)
- "Cell-autonomous roles of galactosylceramidase and their contribution to Krabbe disease" Lysosomes Storage Diseases, Gordon Research Conferences (2025)
- "Quest to cure Krabbe disease" Dyne Therapeutics, Inc. Invited Seminar (2024)
- "Study on the molecular mechanisms of Krabbe Disease" Neuroscience program seminar, University at Buffalo (2024)
- "Cell-autonomous roles of galactosylceramidase: Novel insights into the progression Krabbe disease" Lysosomes Storage Diseases, Gordon Research Conferences (2023)
- "Molecular mechanisms and Preclinical study of Krabbe disease" BK21 International Symposium on Neurodegeneration (2023)
- "Molecular pathogenesis of Krabbe leukodystrophy" Global Leukodystrophy Initiative Conference, Children’s Hospital of Philadelphia (2022)
Service Activities:
- Special Emphasis Panel, NIH study section; ad hoc grant reviewer (2026)
- Fondazione Telethon ETS; ad hoc grant reviewer (2026)
- European Leukodystrophy Association International Research Grant; ad hoc grant reviewer (2026)
- Biotechnical and Clinical Laboratory Sciences Staff; Search Committee (2026)
- Krabbe Translational Research Network Round Table Workshops; Panel (2026)
- Tenure, Promotion & Privileges Committee; Faculty Senator (2025–present)
- European Leukodystrophy Association International Research Grant; ad hoc grant reviewer (2025)
- 17th Annual Buffalo Neuroscience Research Day; Facilitator (2024)
- UB Budget Priorities Committee; Faculty Senator (2024–2025)
- Search Committee for a Biotechnical and Clinical Laboratory Sciences Staff; Committee (2024)
- 16th Annual Buffalo Neuroscience Research Day; Judge (2023)
- UK Research and Innovation; ad hoc grant reviewer (2023–present)
- On-site Research discussion committee for MD-PhD candidates; Committee (2023)
- Search Committee for a Biotechnical and Clinical Laboratory Sciences faculty; Committee (2023–2024)
- 15th Annual Buffalo Neuroscience Research Day; Judge (2022)
- Global Leukodystrophy Initiative; a key opinion leader (2022–present)
- Select Committee on Graduate Educational Policies in Biomedical Sciences; Committee (2021–present)
- Sanfilippo Foundation; ad hoc grant reviewer (2021–present)
- Neuroscience program representative to the Faculty Council; Committee (2021–present)
- Experimental Learning Network Program; Faculty Mentor (2021–present)
- PhD Program in Biomedical Sciences - Admission Committee; Member (2020–present)
- MS Program in Biotechnology - Admission Committee; Admission Committee (2020–present)
- Undergraduate Program in Biotechnology - Admission Committee; Admission Committee (2020–present)
- Biotechnology Undergraduate Program; Associate Program Director (2020–present)
- Journal of Neuroscience / Journal of Neuroscience Research / Cerebral Cortex / Journal of Visualized Experiments / Journal of Inherited Metabolic Disease / Disease Models and Mechanisms / Brain Communications / International Journal of Molecular Sciences / PLoS Biology / Neurochemical Research; ad hoc reviewer (2015–present)