Kang Lab Research Focus

1. Neurodegenerative diseases (PD and AD)

2. Genomics (Wet bench research)

3. Molecular circadian rhythms & NDs

- Molecular neurodegeneration

Neurodegeneration is the overarching term for conditions with progressive loss of function and eventually death of neurons participating in motor, sensory or cognitive functions.

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         he aetiology of Parkinson’s is still unclear. Loss of pigmented dopaminergic
       neurons of the  substantia
nigra pars compacta occurs most prominently in the ventral lateral substantia nigra. Approximately 60-80% of dopaminergic neurons are lost before the motor signs of Parkinson’s emerge. Dopamine depletion is believed to result from degeneration of dopamine nigrostriatal system. The presence of Lewy bodies (LB) and Lewy neuritis (LN) have been hypothesised to represent the pre-symptomatic phase of Parkinson. Their prevalence increases with age, but they are specific to Parkinson’s and are found in some cases of atypical parkinsonism and other disorders such as dementia with Lewy bodies with dementia (LBD), Parkinson’s disease dementia (PDD), and Progressive supranuclear palsy (PSP).

Kang Lab has been focusing on the development of an early diagnosis of Parkinson’s (PD) and Alzheimer’s disease (AD) through an understanding of cell-type and region-specific molecular mechanisms. 

- Single-Cell Genomics 

To identify major key hubs from complexity of neurodegeneration as well as druggable target candidates, I have developed a highly efficient and cost-effective single-cell sequencing methods, highly efficient single nuclei RNA sequencing (HiF snRNA-seq) and highly efficient single nuclei assay for transposase-accessible chromatin using sequencing (HiF snATAC-seq), which are compatible with the frozen and fixed tissue samples. These dataset compared with transcriptome profiles from mouse is evaluated for further research design. Dr.Kang has led a research team for development of experimental techniques using genetically engineered mouse lines and post-mortem brain tissues with analytic pipelines.

- Epigenomics in Parkinson's Disease

The nature of Parkinson’s Disease is progressive, meaning that it gets worse over time. The development of effective therapies for Parkinson’s disease (PD) proved challenging due to the dearth of known targetable aberrations. Responses to traditional anti-parkinsonian therapies such as L-dopa treatment are limited and heterogeneous both within and across different PD stages. More importantly, patients exhibiting PD symptoms have already undergone significant dopaminergic neuronal loss before the clinical diagnosis. As a consequence, current medical practice focuses strongly on managing the symptoms, instead of treating PD, and has a vast room for improvement. Toward this end, a research which intensively focuses on early epigenetic signaling pathways is crucial, augmented by a PD rodent model induced by α-syn PFFs and patients with PD (or DLB), to identify potential signaling pathway of early-stage PD or patients at high risk for developing PD.

 

Kang Lab research has focused on: (1) comprehensively investigate phenotype-specific alterations that occur during genome-wide remodeling of the PD methylome, (2) associate these epigenetic changes with PD progression, (3) identify unique DNA methylation regions that help track the onset and progression of PD, (4) define methylation patterns at particular genomic locations which would serve as potential druggable targets

 -Bioinformatics & Machine learning (Dry bench research)

Neurodegenerative disorders have been shown to exhibit substantial interconnectedness with circadian rhythmicity. Alzheimer’s patients exhibit high degradation of the SCN, the central endogenous circadian timekeeper, and Parkinson’s patients have highly disrupted peripheral clock gene expression. Disrupted sleep patterns are highly evident in patients with neurodegenerative diseases; fragmented sleep has been shown to affect tau-protein accumulation in Alzheimer’s patients, and REM behavioral disorder is observed in a significant amount of Parkinson’s patients.

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1) Bioinformatics and development of unique analytic algorithms 

- to be updated..

2) Machine learning toward the identification of biomarkers and
  potential druggable targets

Although numerous studies exist analyzing the mechanisms of neurodegeneration and circadian rhythm function independently, molecular mechanisms establishing a specific link between the two must be explored further.

- Gut-Brain axis: 

- to be updated..

- Animal models

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        hough neurodegenerative disorders have no clear genetic causes, the field has been
      guided by the discovery of
mutated genes that deterministically drive these disorders, as well as genetic variants that alter risk. These genetic guideposts, along with the biochemical identification of proteins defining the pathological hallmarks of these diseases such, as α-synuclein, amyloid-β (Aβ), and tau have provided essential insights into the pathophysiology of neurodegenerative disorders and provided the opportunity to create animal models for these diseases.

#Kang Lab; #Dat-Cre/H2B-GFP; #Zeiss Lightsheet Z.1; #Tg model 

(Imaging by Fatih Akruti) 

- to be updated..

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- Stem Cell (ESCs, iPSCs) models

AAV-GFP (Gut injection)

AAV-GFP; Gut-injection; Gut-Brain axis; α-syn PFF

(Image by Fatih Akruti)

Gut-injection; Gut-Brain axis; Immune response

(Imaging by Fatih Akrutih)

Genomic Landscape of Parkinson's Disease

(Video  by I-Hsun Wu)

#Kang Lab; #Dat-Cre/H2B-GFP; #Zeiss Lightsheet Z.1; #Tg model 

(Imaging by Fatih Akruti) 

- to be updated..

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