Previous Projects

These are most of the projects from my graduate training

“The only way to do great work is to love what you do.”

I remember that, the criteria for getting in the famous HHMI investigator Yi Zhang’s lab was extremely high. There are many rounds of interviews —-

(1) Round #0: I need to answer a few questions raised by Dr. Zhang, most of which asking me about my career aspiration, scientific questions I would like to address. These were great questions!
(1) Round #1: I need to write two mokc NIH style proposals to Dr. Zhang, who pre-assigned the topics and game me 1 week for each proposal. 
(2) Round #2: I need to give a 1-hr presentation on my previous works. After the presentation, all current lab members have to fill in the 1-page feedback, at last, they have to say “Y” or “N”. Only the candidates passing a 75% of “Y” will be sent to the next round, the PI. 
(3) Round #3, Dr. Zhang will decide whether he wants to offer a position or not. It was a long decision. He told me to learn some techniques before giving me the final offer. So I stayed in a lab for >6 months learning all kinds of required experimental skills.
In the end, quite dramatically, I got the offer, and started to move to the US. I remember that Dr. Zhang told me, for graduates with the papers like me, he would not give any chances for an interview, however, it was my determination, my motivation and my strong interests in science that impressed him most, these are far more important than anything else. For that, I owe my deep gratitude to him. 

(1) Research papers

Single-cell investigations on disease stages

Most of the work here are coming from my first postdoc training in the Yi Zhang lab, where I was working on several projects in a highly collaborative environments: 

  • Project 1: reveal molecular heterogeneity underlying the brain reward systems (mPFC, NAc, and VTA)  
  • Project 2: characterize Set1da in schizophrenia pathogenesis.
  • Project 3: characterize a dopamine neuron highly expressed protein in drug addiction (unpublished).

Some key figures: 

  • 2021, Nature Neuroscience, Figure 1, showing the major cell populations in the NAc
  • 2022, Science Advances, Figure 6, showing the behavioral deficits in setd1a+/- mice (which I performed all the behavioral tests in this study)
  • 2019, Nature Communications, Figure 1, showing the major cell populations in the PFC
  • 2019, Nature Communications, Figure 6, showing how chronic cocaine IVSA alters transcriptional profiles in PFC cell types (which I contributed to the cocaine IVSA and provided the brain materials for scRNA-seq)
  • 2022, Science Advances, Figure 1, showing Tac2-expressing MSN cells exhibited different responses to cocaine IVSA

Role of Glial insulin signaling in AD pathogenesis

This is from my second postdoc training in the Ronald Kahn lab, where I mainly work on two glial cell types (astrocyte and microglia) and how they are involved in AD pathogenesis:

  • Project 1 (iGIRKO/5xFAD): reveal astrocyte-specific insulin signaling in AD pathogenesis
  • Project 2 (MGIRKO): reveal microglia-specific insulin signaling in health and in diseases 
  • Project 3 (MGIRKO/5xFAD): reveal microglia-specific insulin signaling in AD pathogenesis
  • Project 4 (MG-DKO): reveal microglia-specifid insulin and IGF-1 signaling in health and in diseases 

Front-page images showing my co-first and co-author papers from the Yi Zhang lab (02/2027 – 10/2019). All the papers are related to single-cell investigation of brain diseases (substance abuse and schizophrenia). 

(2) Centered on the brain

Previous / Recent Research

Again, from the very beginning of my research career, everything I am doing is about the brain:

  • Undergraduate: brain ischemic injury 
  • M.Sc. degree: mood disorders 
  • Ph.D. degree: cognitive disorders 
  • Postdoc #1: psychiatric conditions 
  • Postdoc #2: brain insulin resistance and neurodegenerative disease 
  • Steno visit: T2D/AD patients.

Current / Future Research

The previous / recent research has shaped my vision for my future labs, where I am thrilled to be investigating the following questions/areas:

  • Disease Comorbidity: why certain brain diseases have high risk of developing other paghological conditions or disorders?
  • Biomarkers: are there fluid biomarkers that can predict disease progression or conversion to an advanced stage (AD)?
  • Functional role: what are the physiological or pathophysiological roles of these identified biomarkers? Can we manipulate tham to delay or stop disease onset?

Imaging showing amyloid-beta deposition in a SHIELD post-fixed mouse brain. Brain was cleared for 5 days in SmartClear II Pro and labeled in SmartLabel. (6-month-old, male, 5xFAD mouse). 

Image acquired by LifeCanvas.inc for my project. Note for each channel, lectin (488 nm); amyloid-beta (642 nm); GFAP (561 nm)

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