Investigator Profile: Lei Sun, PhD


Key Points

  • Lei Sun, PhD, is a Professor in the Department of Biomedical Engineering at Hong Kong Polytechnic University.
  • He shares his research on sonogenetics and nanoparticle-mediated, cell-type-specific ultrasound neuromodulation.

Lei Sun, PhD, is a Professor in the Department of Biomedical Engineering at Hong Kong Polytechnic University. He received his bachelor’s degree from the University of Science and Technology of China (USTC) and his PhD from Pennsylvania State University (Penn State). He then conducted postdoctoral research at the University of Southern California (USC). Dr. Sun joined Hong Kong Polytechnic University in 2008 and was promoted to Professor in 2022.

Focused Ultrasound Work

When and how did you get interested in focused ultrasound?
I started my journey with focused ultrasound during my PhD study under the late Professor Nadine Smith at Penn State, where I conducted MR-guided high-intensity focused ultrasound (HIFU) for treating prostate cancer. The recent wave of ultrasound neuromodulation research inspired me mostly, and I began to pursue methodologies for precise and accurate ultrasound neuromodulation.

What are your areas of interest in focused ultrasound?
Our group studies the biological mechanisms and possible translational strategies of using ultrasound to modulate cellular activities (i.e., neuromodulation or immunotherapy), investigates the potential of using ultrasonic bioeffects for cancer therapy and diabetes, and develops multimodality molecular imaging and theranostics. Specifically, we develop (1) “sonogenetics,” a cell-type-specific and spatiotemporally accurate ultrasound modulation method; and (2) nanoparticle-mediated ultrasound modulation for cell-type-specific and accurate neural circuit activation of targeted neurons for distinct behaviors. Our studies are based on the understanding and identification of responsible molecular mechanisms of ultrasound modulation, especially the role of mechanosensitive ion channels. We also include other ultrasound-responsive cells into our studies, such as immune cells and beta cells.

What mechanisms and clinical indications do you study?
We primarily focus on the role of mechanosensitive ion channels as a main cellular mechanism to understand how low-intensity ultrasound modulates cells.

What is the goal of your work?
The ultimate goal of our research is to translate the technologies we develop to disease therapy for clinical use. Our specific objectives include developing therapies to battle Parkinson’s disease, depression, and epilepsy by demonstrating utility in small and large animal models.

What are your funding sources?
We have received financial support from the Hong Kong government through various funding schemes, including the Innovation Technology Fund (ITF), General Research Fund (GRF), and Health Medical Research Fund. Funding from the mainland China government has been granted through the National Natural Science Foundation of China (NSFC), Guangdong Science and Technology Department, and Shenzhen Municipal Science and Technology Commissioner.

Research Details

Who are your team members?
Our team is multidisciplinary and includes neuroscientists, biologists, biomedical engineers, clinicians, physicists, and nanotechnologists.

Who are your internal and external collaborators?
We have a long collaboration history with Professors Hairong Zheng and Weibao Qiu at Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, in ultrasound transducers and instrumentation. We also extensively collaborate with Professors Baojun Li and Yao Zhang in optical nanotechnology. Collaboration with Prof. Dawei Wu from Nanjing University of Aeronautics and Astronautics and Prof. Chunlong Fei from Xidan University has been fruitful in understanding the acoustics behind ultrasound neuromodulation.

What are your greatest achievements? Any major disappointments?
We are proud of our work to understand the mechanosensitive ion channel’s role in ultrasound neuromodulation, which has allowed us to create neuronal manipulation accurately and precisely with sonogenetics and nanotechnology.

On the other hand, it has never been a smooth ride for a new research topic. Difficulties are always there; we like to consider them as surprises rather than disappointments.

What do you see as impediments to your success?
It is still a long journey for ultrasound to be applied clinically and extensively. Although I am confident, there are still obstacles that need to be solved. For instance, understanding the biophysical mechanisms would be a major one for its future utility.

What is on your research wish list?
We would like to demonstrate the treatment potential of our neuromodulation method for Parkinson’s disease, depression, and epilepsy.

Has the US-based Foundation played a role in your work?
The Foundation has been an information hub for different kinds of activities in focused ultrasound, from research to clinics. Its biennial meeting and annual [State of the Field] report have been particularly useful in understanding the current situation.

Looking Ahead

Do you have any follow-up funding opportunities?
We are seeking funding support to develop a sonogenetic approach to inhibit a cell instead of exciting one.

What comes next?
We plan to demonstrate accurate neural circuit manipulation through sonogenetics and nanotechnology for distinct advanced animal behavior.

Recent Key Publications

  1. Tianyi Liu, Dongmin He, Mi Hyun Choi, Quanxiang Xian, Jiejun Zhu, Xuandi Hou, Jinghui Guo, Kim Butts Pauly, Lei Sun*, Zhihai Qiu* Sonogenetics: Recent Advances and Future Directions. Brain Stimulation (accepted)
  2. J Guo†*, Y Wu†, …, Y Li*, Y Zhang*, L Sun*. Photonic nanojet-mediated optogenetics. Advanced Science 20 Feb 2022, DOI: 10.1002/advs.202104140.
  3. L Song, X Hou, KF Wong, Y Yang, Z Qiu, S Kala, S Hou, Y Wu, C Fei, J Guo, L Sun*. Gas-filled Protein Nanostructures as Cavitation Nuclei for Molecule-Specific Sonodynamic Therapy. Acta Biomaterialia DOI:10.1016/j.actbio.2021.09.010
  4. X Hou, Z Qiu, Q Xian, S Kala, J Jing, KF Wong, J Zhu, J Guo, T Zhu, M Yang, L Sun*. Precise ultrasound neuromodulation in a deep brain region using nanobubble actuators. Advanced Science 2021, Nov, 8 (21):2101934, doi:10.1002/advs.202101934
  5. Q Xian, Z Qiu, S Kala, KF Wong, J Guo, L Sun*. Behavioral and functional assessment of ultrasound neuromodulation on Caenorhabditis elegans. IEEE Transactions on Ultrasonics Ferroelectrics Frequency Control 2021 68(6) 2150-2154, doi:10.1109/TUFFC.2021.3057873
  6. Q Xian, Z Qiu, S Kala, J Guo, J Zhu, KF Wong, S Guo, T Zhu, X Hou, L Sun*. Protocol for the sonogenetic stimulation of mouse brain by non-invasive ultrasound. STAR Protocol Vol 2, Issue 2, Mar 2021, DOI: 10.1016/j.xpro.2021.100393
  7. Z Qiu, S Kala, J Guo, Q Xian, J Zhu, T Zhu, X Hou, KF Wong, M Yang, H Wang, L Sun*. Targeted neuronal stimulation in mouse brains using non-invasive ultrasound Cell Reports:32(7), 18 August 2020, DOI:10.1016/j.celrep.2020.108033
  8. L Song, G Wang, X Hou, S Kala, Z Qiu, KF Wong, F Cao, L Sun*. Biogenic nanobubbles for effective oxygen delivery and enhanced photodynamic therapy of cancer. Acta Biomaterialia 2020 DOI:10.1016/j.actbio.2020.03.034
  9. G Wang, L Song, X Hou, S Kala, KF Wong, L Tang, Y Dai, L Sun*. Surface-modified GVs as nanosized contrast agents for molecular ultrasound imaging of tumor. Biomaterials. 2020 DOI: 10.1016/j.biomaterials.2020.119803
  10. Z Qiu, J Guo, S Kala, J Zhu, Q Xian, W Qiu, G Li, L Meng, HC Chan, H Zheng*, L Sun*. The mechanosensitive ion channel Piezo1 significantly mediates in vitro ultrasonic stimulation of neurons. iScience 21, 448-457, Nov 22 2019 doi: 10.1016/j.isci.2019.10.037
  11. Song L, Huang Y, Hou X, Yang Y, Kala S, Qiu Z, Zhang R, Sun L*. PINK1/Parkin mediated mitophagy promotes resistance to sonodynamic therapy. Cellular Physiology and Biochemistry 2018;49(5):1825-1839