Details of Research Projects:
Autophagy-lysosome dysfunctions in neurons and glial cells in the pathogenesis of neurodegenerative diseases
We propose to elucidate the cell-type-specific autophagy-lysosome pathways, focusing on neurons and microglia, under both physiological (young and old) and pathological conditions (Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease). Employing a systematic approach, we will incorporate multiple genetic mutant lines of mice, human-induced neuron lines (hiN), quantitative proteomics, and molecular and cell biology techniques to identify autophagy cargo and receptors in neurons and microglia. Furthermore, we will investigate the distinct mechanisms responsible for the degradation of multiple disease-associated proteins such as tau, alpha-synuclein (aSyn), and huntingtin. The findings of our study hold the potential to uncover novel biomarkers and therapeutic targets for autophagy-lysosomes in the treatment of Alzheimer’s, Parkinson’s, and Huntington’s diseases, thereby paving the way for innovative therapeutic interventions.
Dysfunctional AKAP11-PKA signaling underlying the pathogenic mechanism and in modeling psychiatric disease condition (schizophrenia and bipolar)
Recent human genetic study has identified AKAP11 as a definitive causal gene for bipolar disorder and enhanced risk factor for schizophrenia. Our study demonstrated AKAP11 is an autophagy receptor that mediates selective degradation of PKA-RI complex through autophagy. Our goal is to dissect the pathogenic mechanism whereby AKAP11 deficiency contributes to the psychiatric illness by characterizing genetic animal models and induced human neuron (iNeuron) models. We will test the new therapeutic ideas by targeting AKAP11-PKA signaling and activity.
Technical Duties:
- Flow-cytometry
- ELISA
- WB
- ELISPOT
- qPCR
- CyTOF data analyses
- Mouse genetics,
- molecular and cellular biology approaches,
- primary neuron/glia cultures, cellular imaging (both live and fixed),
- transcriptomics (including single-cell RNA sequencing and spatial transcriptomics),
- proteomics, bioinformatics, and animal pathology/behavioral studies.
Qualifications
Educational and other Requirements for the position: MD or PhD
Experience Required: Extensive training in basic neuroscience, molecular and cellular biology, animal models, and neurological disorder mechanism research.
Goals/Outcomes of the Research Project: The goal is to develop the skills and independence in neurological disease research and to become successful researchers. The fellow will improve their analytic thinking, public presentation, and professional writing. The fellow is expected to publish research results in professional journals, secure funding/fellowship, teach and mentor junior researchers, and develop leadership and management skills.
