Principal Investigators
Principal Investigators
Principal Investigator
Structural Pharmacology, Medicinal Chemistry
huangjian@smart.org.cn
Dr. Jian Huang’s research group employs a multidisciplinary approach that incorporates structural biology, medicinal chemistry, and molecular cell biology to investigate the working mechanisms and ligand modulation of disease-related membrane proteins. By integrating structural insights with functional activity analysis, the group aims to design and optimize modulators that precisely target these proteins. Their goal is to achieve precise regulation of target proteins, drive drug innovation, and develop effective therapies for disease prevention and treatment.
Membrane transport is crucial for maintaining cellular homeostasis, energy conversion, and signal transduction. Dysfunctions or dysregulations of membrane transport proteins are associated with various diseases, making them primary targets for therapeutic interventions. Understanding their structure-function relationship is essential for advancing our understanding of their working and disease mechanisms. Recently, Dr. Jian Huang has focused on two representative types of membrane transport proteins—glucose transporters and voltage-gated ion channels—to elucidate the molecular mechanisms of drug action, identify critical pharmacological sites, and drive forward structure-based drug discovery:
1. Structure-Based Rational Drug Design
Dr. Huang has developed a series of compounds targeting both the orthosteric and allosteric sites of PfHT1 simultaneously. These compounds selectively inhibit PfHT1 over human glucose transporters and effectively impede the proliferation of multiple P. falciparum strains. This represents the first successful case of dual-site targeting of a transporter. (Cell, 2020; PNAS, 2021).
2. Structural Pharmacology of Voltage-Gated Ion Channels
Through systematic studies of the mechanisms of action (MOAs) of drugs and natural toxins on voltage-gated ion channels, Dr. Huang and his colleagues have provided structural mapping of all known ligand binding sites on VGICs and proposed a letter-coded nomenclature system to illustrate these druggable sites in three-dimensional space. This work is expected to facilitate the structure-based rational design or optimization of drugs targeting VGICs. (Nature Communications, 2023a, 2023b; PNAS, 2023a, 2023b; Cell Research, 2024; Nature Reviews Molecular Cell Biology, 2024; Cell Chemical Biology, 2024).
2024-Present Principal Investigator, Shenzhen Medical Academy of Research and Translation (SMART)
2021-2024 Postdoctoral Fellow, Department of Molecular Biology, Princeton University, NJ, USA
2016-2021 Ph.D. in Chemistry, Tsinghua University, Beijing, China
2012-2016 B.S. in Chemical Biology, Tsinghua University, Beijing, China
First Prize, 16th Chinese Pharmaceutical Association Science and Technology Award (2021)
Cell Press Best Paper Award (2020)
First Prize Scholarship, Tsinghua University (2020)
Advanced Innovation Award for Graduate Students, Beijing Advanced Innovation Center for Structural Biology at Tsinghua University (2020)
Best Student Presentation Award, 2nd Frontier Graduate Forum of Chemical Biology (2020)
Best Student Presentation Award, 11th National Congress of Chemical Biology (2019)
Outstanding Undergraduate Award, Tsinghua University (2016)
National Scholarship, Chinese Ministry of Education (2014, 2015)
Third Prize, “HACH” 9th National Environmental-friendly Science & Technology Competition (2014)
Second Prize, 7th National University Student Contest on Energy Saving & Emission Reduction (2014)
Second Prize, 30th National Physics Competition for College Students in China (2013)
First Prize, 25th National Chemistry Olympiad (2011)
Second Prize, National High School Mathematics League (2010)
(# denotes equal contribution; * denotes corresponding authors)
1. Huang, J.; *Pan, X.; *Yan, N. “Structural biology and molecular pharmacology of voltage-gated ion channels”, Nat Rev Mol Cell Biol. 2024, doi: 10.1038/s41580-024-00763-7.
2. Jiang, X.#; Yuan, Y.#; Huang, J.#; Zhang, S.#; Luo, S.; Wang, N.; Pu, D.; Zhao, N.; Tang, Q.; Hirata, K.; Yang, X.; Jiao, Y.; Sakata-Kato, T.; Wu, J.W.; Yan, C.; Kato, N.; *Yin, H.; *Yan, N. “Structural Basis for Blocking Sugar Uptake into the Malaria Parasite Plasmodium falciparum”, Cell 2020, 183(1): 258-268.
3. Huang, J.#; *Fan, X.#; Jin, X.#; Lyu, C.; Guo, Q.; Liu, T.; Chen, J.; Davakan, A.; Lory, P.; *Yan, N. “Structural basis for human Cav3.2 inhibition by selective antagonists”, Cell Res. 2024, 34(6): 440-450.
4. Huang, J.#; Yuan, Y.#; Zhao, N.#; Pu, D.; Tang, Q.; Zhang, S.; Luo, S.; Yang, X.; Wang, N.; Xiao, Y.; Zhang, T.; Liu, Z.; Sakata-Kato, T.; *Jiang, X.; *Kato, N.; *Yan, N.; *Yin, H. “Orthosteric-allosteric dual inhibitors of PfHT1 as selective anti-malarial agents”, Proc Natl Acad Sci U S A. 2021, 118(3): e2017749118.
5. Huang, J.#; Fan, X.#; Jin, X.; Jo, S.; Zhang H. B.; Fujita, A.; *Bean P. B.; *Yan, N. “Cannabidiol inhibits Nav channels through two distinct binding sites”, Nat Commun. 2023, 14(1): 3613.
6. Huang, J.#; *Fan, X.#; Jin, X.; Teng, L.; *Yan, N. “Dual-pocket inhibition of Nav channels by the antiepileptic drug lamotrigine”, Proc Natl Acad Sci U S A. 2023, 120(41): e2309773120.
7. Wu, Q.#; *Huang, J.#; *Fan, X.#; Wang, K.#; Jin, X.#; Huang, G.; Li, J.; *Pan, X.; *Yan, N. “Structural mapping of Nav1.7 antagonists”, Nat Commun. 2023, 14(1): 3224.
8. *Fan, X.#; Huang, J.#; Jin, X.; *Yan, N. “Cryo-EM structure of human voltage-gated sodium channel Nav1.6”, Proc Natl Acad Sci U S A. 2023, 120(5): e2220578120.
9. *Jin, X.#; *Huang, J.#; Wang, H.#; Wang, K.; *Yan, N. “A versatile residue numbering scheme for Nav and Cav channels”, Cell Chem Biol. 2024, 31(8): 1394-1404.
