Dr. Huang Junting is currently an associate professor, principal investigator (PI), and doctoral supervisor at the Zhongshan School of Medicine, Sun Yat-sen University. He obtained his Ph.D. from the University of Nottingham, UK in 2015. Since then, he has been conducting postdoctoral research at the Hotchkiss Brain Institute, University of Calgary, Canada. His co-supervisor is Professor Gerald Zamponi, an internationally renowned scholar in the fields of pain and calcium channel research. He is now a talent introduced under the "Hundred Talents Program" of Sun Yat-sen University.

He is mainly engaged in research on the brain's pain neural circuits (encoding, conduction, and regulation of pain signals) and the neural-immune regulatory mechanisms of pain. As the first author and co-corresponding author, he has published a series of high-level academic papers in journals such as Nature Neuroscience, Cell Reports (2 papers), Arthritis & Rheumatology, and Current Biology.

Academic Achievements

Important Academic Research Achievements and Contributions

1. Neural circuits for encoding, conduction, and regulation of pain signals in the brain
   The prefrontal cortex (PFC) plays an important role in cognitive functions, emotional control, and social behaviors. The reduced activity of pyramidal cells in the PFC under pain conditions is a common phenomenon, but the causes and underlying mechanisms remain unclear.

By establishing a mouse model of sciatic nerve pain and applying techniques such as optogenetics, chemogenetics, and in vivo fiber photometry, we have: 1) revealed the causes of the reduced activity of pyramidal cells in the PFC during sciatic nerve pain (inhibited by parvalbumin interneurons in the same region and loss of CB1 receptors), 2) identified the important role of a new neural circuit, the basolateral amygdala (BLA)-PFC-ventrolateral periaqueductal gray (vlPAG), in the encoding and regulation of sciatic nerve pain, and 3) confirmed that spinal 5-HT1/2 and α2 adrenergic receptors are involved in the regulation of pain neural circuits and are effective targets for pain treatment (Huang et al., Nature Neuroscience, 2019). We were also invited to write a review article on pain neural circuits (Huang et al., Current Biology, 2020).

At the same time, we found that in addition to receiving neural projections from the PFC, the vlPAG also receives projections from the ventrolateral orbitofrontal cortex (vlOFC). It is speculated that the vlOFC may be involved in pain regulation. Subsequent experiments confirmed that: 1) the activity of vlOFC GABAergic neurons increased during sciatic nerve pain and inhibited the signal output from vlOFC-vlPAG, 2) activating vlOFC glutamatergic neurons or vlOFC-vlPAG alleviated sciatic nerve pain, and 3) the vlOFC receives neural projections from the ventromedial thalamus (VM), and optogenetic activation of VM-vlOFC alleviated sciatic nerve pain. Thus, a new mechanism for the regulation of sciatic nerve pain by the VM-vlOFC-vlPAG circuit was elucidated (Huang et al., Cell Reports, 2021).

These studies are of great significance for understanding how the brain precisely encodes, conducts, and regulates pain signals, and provide targets and new treatment strategies for non-invasive treatment of sciatic nerve pain.

2. Neural-immune regulation of pain
   Tissue injury in the body often induces pain, and host immune defense plays an important role. The involvement of innate immune Toll-like receptors (TLRs) in pain regulation has been confirmed more than a decade ago. In recent years, inflammasomes have also been reported to be involved in pain regulation. However, these studies were isolated, and the connection and mechanisms of action of TLRs and inflammasomes in the occurrence and development of pain are still unclear.

Using various mouse pain models, calcium imaging, molecular biology techniques, and behavioral tests, we have: 1) found that innate immune TLRs are significantly elevated in pain, and activation of TLR2/6 induces pain, 2) revealed that innate immunity mediates the occurrence and development of pain through TLR2-NLRP3-IL33, and 3) confirmed that blocking TLR2 or IL33 alleviates inflammatory pain. Thus, we were the first to reveal the important function of excessive activation of innate immunity in inflammatory pain (Huang et al., Cell Reports, 2020), providing new insights and perspectives on how pathogen infection causes pain and leads to the chronic development of pain. Further research found that knocking out TLR2 or NLRP3 does not alleviate neuropathic pain caused by sciatic nerve injury, while blocking IL33 can (Huang et al., Molecular Brain, 2021), further confirming the wide application of IL33 in pain treatment.

Resolvins are endogenous anti-inflammatory mediators secreted during the resolution of inflammation. We found that treatment with resolvin precursors alleviates osteoarthritis pain and elucidated its mechanism of action (inhibiting the activity of spinal astrocytes and the release of resolvin D2) (Huang et al., Arthritis & Rheumatology, 2017). Since resolvins are endogenous anti-inflammatory mediators with no obvious side effects, they have potential clinical translational value and provide new targets for pain treatment.

Our laboratory is currently recruiting full-time research staff (distinguished/associate research fellows, postdoctoral fellows), doctoral and master's students. We warmly welcome outstanding young scholars at home and abroad who are interested in neuroscience and pain science research to join our team and jointly promote the development of the discipline. Please contact Dr. Huang Junting at huangjt56@mail.sysu.edu.cn if interested.

Academic Works and Textbooks

1. Huang J*, Zhang Z, Gambeta E, Chen L, Zamponi GW *. An orbitofrontal cortex to midbrain projection modulates hypersensitivity after peripheral nerve injury. Cell Rep. 2021. Apr 27; 35(4):109033
2. Huang J* , Gadotti VM, Zhang Z, Zamponi GW. The IL33 receptor ST2 contributes to mechanical hypersensitivity in mice with neuropathic pain. Mol Brain. 2021 Feb 17; 14(1):35.
3. Huang J*, Gandini MA, Chen L, M'Dahoma S, Stemkowski PL, Chung H, Muruve DA, Zamponi GW*. Hyperactivity of innate immunity triggers pain via IL33-mediated neuroimmune crosstalk. Cell Rep. 2020 Oct 6;33(1):108233
4. Huang J, Zhang Z, Zamponi GW. Pain: Integration of Sensory and Affective Aspects of Pain. Curr Biol. 2020;30(9): R393-R395.
5. Huang J, Gadotti VM, Chen L, Souza IA, Huang S, Wang D, Ramakrishnan C, Deisseroth K, Zhang Z, Zamponi GW. A neuronal circuit for activating descending modulation of neuropathic pain. Nat Neurosci. 2019 Oct;22(10):1659-1668.
6. Huang J, Burston JJ, Li L, Ashraf S, Mapp PI, Bennett AJ, Ravipati S, Pousinis P, Barrett DA, Scammell BE1, Chapman V. Targeting the D-series resolvin receptor system for the treatment of osteoarthritic pain. Arthritis&Rheumatol. 2017; 69(5):996-1008.
7. Huang J, Zamponi GW. Regulation of voltage gated calcium channels by GPCRs and post-translational modification. Curr Opin Pharmacol. 2017; 32:1-8.
8. Gaifullina AS, Lazniewska J, Gerasimova EV, Burkhanova GF, Rzhepetskyy Y, Tomin A, Rivas-Ramirez P, Huang J, Cmarko L, Zamponi GW, Sitdikova GF, Weiss N. A potential role for T-type calcium channels in homocysteinemia-induced peripheral neuropathy. Pain. 2019;160(12):2798-2810.
9. Garcia-Caballero A, Zhang FX, Chen L, M'Dahoma S, Huang J, Zamponi GW. SUMOylation regulates USP5-Cav3.2 calcium channel interactions. Mol brain 2019;12(1):73. doi: 10.1186.
10. Gadotti VM, Zhang Z, Huang J, Zamponi GW. Analgesic effects of optogenetic inhibition of basolateral amygdala inputs into the prefrontal cortex in nerve injured female mice. Mol brain. 2019;12(1):105. doi: 10.1186/s13041-019-0529-1.
11. Garcia-Caballero A, Zhang FX, Hodgkinson V, Huang J, Chen L, Souza IA, Cain S, Kass J, Alles S, Snutch TP, Zamponi GW. T-type calcium channels functionally interact with spectrin (α/β) and ankyrin B. Mol Brain. 2018; 11(1):24.
12. Kim JH, Jeong HR, Jung DW, Yoon HB, Kim SY, Kim HJ, Lee KT, Gadotti VM, Huang J, Zhang FX, Zamponi GW, Lee JY6. Synthesis and biological evaluation of fluoro-substituted 3,4-dihydroquinazoline derivatives for anticancer and analgesic effects. Bioorg Med Chem, 2017; 25(17):4656-4664.
13. Teleb M, Zhang FX, Huang J, Gadotti VM, Farghaly AM, AboulWafa OM, Zamponi GW, Fahmy H. Synthesis and biological evaluation of novel N3-substituted dihydropyrimidine derivatives as T-type calcium channel blockers and their efficacy as analgesics in mouse models of inflammatory pain. Bioorg Med Chem.2017; 25(6):1926-1938.
14. Kelly S, Chapman RJ, Woodhams S, Sagar DR, Turner J, Burston JJ, Bullock C, Paton K, Huang J, Wong A, McWilliams DF, Okine BN, Barrett DA, Hathway GJ, Walsh DA, Chapman V. Increased function of pro-nociceptive TRPV1 at the level of the joint in a rat model of osteoarthritis pain. Ann Rheum Dis. 2015; 74(1):252-9.
15. Luo T , Zhang H, Zhang WW, Huang JT, Song EL, Chen SG, He F, Xu J and Wang HQ. Neuroprotective effect of Jatrorrhizine on hydrogen peroxide-induced cell injury and its potential mechanisms in PC12 cells. Neurosci.Lett. 2011; 498(3):227-31.
16. Song EL, Hou YP, Yu SP, Chen SG, Huang JT, Luo T, Kong LP, Xu J, Wang HQ. EFEMP1 expression promotes angiogenesis and accelerates the growth of cervical cancer in vivo. Gynecologic Oncology, 2011; 121(1):174-80.
17. Book chapter: The Color Specimen Atlas of Medical Anatomy (bilingual version). Beijing: Beijing Science and Technology Press, 2008:23-35.

Awards and Honors

As the first author and co-corresponding author, he has published a series of high-level academic papers in journals such as Nature Neuroscience, Cell Reports (2 papers), Arthritis & Rheumatology, and Current Biology.

Our research group will establish mouse pain models and use techniques such as neural tracing, optogenetics/chemogenetics, in vivo fiber photometry/two-photon imaging, electrophysiology, and behavioral tests to conduct in-depth research on: 1) the neural network mechanisms for encoding, conducting, and regulating pain signals; 2) the brain-immune regulatory mechanisms of pain; and 3) pain-related mental and psychological disorders. Through research in the above directions, we are committed to identifying molecular markers of brain pain signals, exploring potential targets and innovative therapies for pain treatment, promoting the transformation of scientific research results, and driving the development of pain discipline research and treatment.