- wenqiang.chen@joslin.harvard.edu
- wenqiang.chen.01@regionh.dk
Projects
Here I will introduce what I have been performed and involved in the past.
I try not to repeat what have been described in the section of “Publications“.
Below are the parts that I am mostly enjoyed!
My statements:
- It is not good to have too many projects, but one must be capable of multi-tasking.
- Both roles in supporting (i.e., collaborative) and leading (i.e., independent) are equally important.
This graphic summarizes my major projects during postdoc training, including molecular neurobiology and brain metabolism.
(1) Molecular heterogeneity of the brain reward systems
Tools: scRNA-seq & in vivo imaging / manipulation
During my first postdoc training in the Yi Zhang lab, I have made the following achievements / contributions:
- Established in vivo Ca2+ imaging at single-cell resolution during motivated behaviors (Inscopix nVoke)
- Established manipulation methods in selected brain cell types (DREADDS and optogenetics)
- Used mouse cocaine self-administration to profile brain reward systems at single-cell level (10X genomics)
- Performed behavioral characterization of Setd1a+/- mouse model (schizophrenia)
- Identified a novel cell type that mediates cocaine addiction (Tac2+ NAc cells)
- Identified a molecularly distinct cell type in midbrain to regulate mouse aggression (dmPAGTac2+ cells)
Major outputs related to this project:
Bhattacherjee A*, Djekidel M*, Chen R*, Chen W*, Tuesta L, Zhang Y. (2019) Cell type-specific transcriptional programs in mouse prefrontal cortex during adolescence and addiction. Nature Communications. 13;10(1):4169 |
Chen RC*, Blooser TR*, Djekidel MN*, Hao J, Bhattacherjee A, Chen W, Tuesta LM, Zhuang X#, Zhang Y#. (2021) Decoding structural and functional heterogeneity of nucleus accumbens with high-throughput scRNA-seq and MERFISH. Nature Neuroscience 24(12):1757-1771 |
Chen RC*, Liu YQ*, Djekidel MN*, Chen W, Bhattacherjee A, Chen ZY, Scolnick E, Zhang Y. (2021) Cell type-specific mechanism of Setd1a heterozygosity in schizophrenia pathogenesis. Science Advances 8(9):eabm1077. |
Zhao ZD, Han X, Chen RC, Liu YQ, Bhattacherjee A, Chen W, Zhang Y. (2022) A molecularly defined D1 medium spiny neuron subtype negatively regulates cocaine addiction. Science Advances Aug 12;8(32):eabn3552 |
Chen W, Tang M. (2020) An introduction to single-cell RNA-seq analysis and its applications. Systems Medicine: Integrative, Qualitative and Computational Approaches Vol. 1: 116-128 (10.1016/B978-0-12-801238-3.11592-2) |
Tang M, Kui L, Lu GY, Chen W#. (2020) Disease-associated circular RNAs: from biology to computational identification. BioMed Research International (#corresponding author) |
Note: *co-first authors, #corresponding author
(2) Brain glial cell type-specific insulin action in health and in AD
Tools: Cre/LoxP system, CLARITY, RiboTag, AD mouse model
During my second postdoc training with Dr. C Ronald Kahn, I have made the following achievements / contributions:
- Established dual-disease mouse models to study comorbidity of diabetes and AD (astrocyte- and microglia-specific insulin signaling)
- Established RiboTag profiling to study cell type-specific translatome regulated by insulin/IGF1 signaling in health and during AD pathogenesis
- Developed whole-brain CLARITY to study Aβ deposition (SHIELD technology)
- Analyzed Aβ uptake in astrocyte and microglia using FACS and Incucyte
- Examined microglial metabolism in murine microglia and human iPS cell-differentiated microglia
Major outputs related to this project:
Chen W, Cai W, Hoover B, Kahn CR. (2022) Insulin Action in the Brian: Cell types, Circuits, and Diseases. Trends in Neurosciences 45(5):384-400. |
Chen W, Huang Q, Lazdon EK, Gomes A, Wong M, Stephens E, Royal TG, Frankel D, Cai W, Kahn CR. (2023) Loss of insulin signaling in astrocytes exacerbates Alzheimer-like phenotypes in a 5xFAD mouse model. PNAS 120(21):e2220684120. |
Zhou S, Chen W#, Yang H#. (2024) Hormone of the Month: Dopamine. Trends in Endocrinology & Metabolism. Accepted and In Press. (#co-corresponding author) |
Chen W, Liu X, Munoz V, Kahn CR#. (2024) Loss of Insulin Signaling in Microglia Impairs Cellular Uptake of Ab and Neuroinflammatory Response Exacerbating Alzheimer-like Neuropathology. (Submitted, Cell Metabolism) |
Note: *co-first authors, #corresponding author
(3) a molecularly distinct cell type in midbrain for aggression behaviors
Tools: fiber photometry, DREADDs, TRAP-seq
In a collaborative project, in which I serve as a co-corresponding author (also a submiting author), I have made the following achievements/contributions:
- Designed and initiated a project mainly involving neural circuit and molecular characterization
- Narrowed down to an anatomically restricted brain region (dmPAG) based on preliminary screening
- Established G-deleted rabies tracing tool to reveal mono-synaptic inputs projecting to dmPAG Tac2-expressing cells
- Established viral tool-assisted TRAP-seq
- Co-supervised a Ph.D. candidate during her entire PhD training
Major outputs related to this project:
Li C, Miao C, Wu J, Ge Y, Gao P, Yin S, Zhang P, Tian B, Chen W#, Chen XQ#. (2024) A molecularly distinct cell type in the dmPAG regulates intermale aggression behaviors in mice. (Under Review) (#co-corresponding author) bioRxiv: doi: https://doi.org/10.1101/2023.10.19.562724 |
Note: *co-first authors, #corresponding author
Update on August 15:
The reviewers’ comments are back, and it is very helpful and addressable.
(4) Biomarker identification in AD patients with/without diabetes
Tools: mass spectrometry, clinical cohorts
Under the support of my Novo Nordisk Foundation grant, I will explore the following questoins:
(1) to identify microglia-secreted extracellular vesicles in vitro using microglia without intact insulin signaling;
(2) to identify insulin-regulated metabolic pathways in microglia that confer AD risk, by performing simultaneous multi-omics (lipidomics, metabolomics, proteomics) in minimally required CSF samples in a curated cohort with AD and T2D that the host lab has participated in.
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