Daesung Shin PhD

Daesung Shin

Daesung Shin
PhD

Assistant Professor

Department of Biotechnical and Clinical Laboratory Sciences

Jacobs School of Medicine & Biomedical Sciences


Specialty/Research Focus

Inherited Metabolic Disorders; Metabolism; Molecular and Cellular Biology; Molecular Basis of Disease; Molecular genetics; Neurobiology; Neurodegenerative disorders; Neuropharmacology; Signal Transduction; Transcription and Translation; Transgenic organisms

Contact Information
313 Farber Hall
3435 Main Street
Buffalo, New York 14214
Phone: 716-829-5191
Fax: 716-829-3601
daesungs@buffalo.edu



Professional Summary:

Krabbe Disease (KD), also known as globoid cell Leukodystrophy, is a fatal neurodegenerative lysosomal storage disorder caused by deficiency of galactosylceramidase (GALC) that affects both central and peripheral nervous systems. KD manifests in infants in the first few months of life and presents with severe irritability, muscle rigidity and motor deterioration, which quickly progresses to overall clinical decline and death within months. Unfortunately, there is no cure for KD. Our limited understanding of the pathogenesis is based on clinical data and on the spontaneous mouse model. Hematopoietic stem cell transplantation (HSCT) partially attenuates the course of KD only if performed before the onset of symptoms, presumably because stem cell derivatives secrete GALC that is uptaken by myelinating glia via the mannose-6-phosphate receptor, so called cross-correction. However, it is not clear how efficiently cross-correction happens in vivo, if only myelin-forming glia need to be corrected and at which developmental stage. Furthermore, accumulation of the lipid psychosine due to GALC deficiency contributes to KD by killing myelin-forming glia and neurons, but the relative importance of psychosine, its origin and the sequence of pathogenic events is unclear. I recently developed a conditional Galc floxed mouse and found that: 1) A KD-like phenotype similar to twitcher, an authentic KD mouse model, is obtained when Galc ablation is induced ubiquitously [Galc-iKO] at P4 or before. In contrast, induction at P6 or later significantly delayed the phenotype and prolonged survival (~25 days). Galc deletion before P4 caused severe developmental brainstem problems that were milder if deletion was induced after P6, indicating that GALC may be required for brainstem development; 2) Oligodendrocyte (OL)-specific Galc conditional knockout [Galc-CKO] results in a phenotype that includes tremor, wasting, kyphosis, motor defects, demyelination and mild axonal degeneration, but that is not as severe as Galc-iKO mice, suggesting that Galc deficiency in OLs may be not sufficient to trigger a complete KD phenotype; and 3) GALC uptake is less efficient in Galc-null cells in vitro, and surrounding WT cells provides minimal GALC to Galc-deficient OLs in vivo, indicating inefficient cross-correction of GALC. By combining a series of in vitro experiments with the comparison of cell-specific, time–specific and constitutive deletion of Galc in vivo, I will test the following 3 hypotheses that derived from my preliminary data and from the clinical experience: 1) GALC has specific developmental roles during critical periods including P4-6 in Krabbe mice; 2) any brain cell can produce psychosine or be the target of toxicity; 3) HSCT fails to cure KD due to inefficient cross-correction of GALC. These results will help to understand the disease mechanisms of KD and the limitations of HSCT, which will allow the development of better therapies for KD and similar lysosomal, neurodegenerative and demyelinating diseases.

Education and Training:

  • PhD, Neuroscience, Korea Advanced Institute of Science and Technology (2003)
  • MS, Korea Advanced Institute of Science and Technology (1999)
  • BS, Korea Advanced Institute of Science and Technology (1997)

Employment:

  • Assistant Professor, Biotechnical and Clinical Laboratory Sciences, University at Buffalo (2020-present)
  • Principal Investigator, Hunter James Kelly Research Institute (2011–2020)
  • Post Doctoral Fellow, Neurology, University of California San Francisco / HHMI (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:

  • 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:

See all (8 more)

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)

Service Activities:

  • UK Research and Innovation; ad hoc reviewer (2023–present)
  • BCLS Faculty Search Committee; Member (2023)
  • UB Neuroscience Research Symposium; Poster Judge (2022–present)
  • Global Leukodystrophy Initiative; a key opinion leader (2022)
  • Experiential Learning Network; Faculty Mentor (2021–present)
  • Select Committee on Graduate Educational Policies in Biomedical Sciences; Committee Member (2021–present)
  • Sanfilippo Foundation; ad hoc reviewer (2021–present)
  • Neuroscience program representative to the Faculty Council; Member (2021–present)
  • PhD Program in Biomedical Sciences - Admission Committee; Member (2020–present)
  • MS Program in Biotechnology - Admission Committee; Member (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; ad hoc reviewer (2015–present)

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Contact Information

313 Farber Hall
3435 Main Street
Buffalo, New York 14214
Phone: 716-829-5191
Fax: 716-829-3601
daesungs@buffalo.edu