Huanxing SU 蘇煥興

1. Drug Discovery and Validation in Cross-Species ALS Models
Amyotrophic lateral sclerosis (ALS) is a fast-progressing and devastating neurodegenerative disease. Despite extensive studies on ALS over the past decades, there is still no cure for this fatal disease. My lab has successfully developed a suite of cross-species ALS models including, C. elegans, mice, and patient derived iPSCs, which enable comprehensive exploration of the pathogenesis of ALS and facilitate screening for effective candidate drugs.
Representative publications:
1) Li A, Huang S, Cao SQ, Lin J, Zhao L, Yu F, Huang M, Yang L, Xin J, Wen J, Yan L, Zhang K, Jiang M, Le W, Li P, Liu YU, Qin D, Lu J, Lu G, Shen H, Yao X*, Fang EF*, Su H*. Isoginkgetin antagonizes ALS pathologies in its animal and patient iPSC models via PINK1-Parkin-dependent mitophagy. EMBO Mol Med. 2025 Oct 15. doi: 10.1038/s44321-025-00323-2
2) Wen J, Li Y, Qin Y, Yan L, Zhang K, Li A, Wang Z, Yu F, Lai J, Yang W, Liu YU*, Qin D*, Su H*. Lycorine protects motor neurons against TDP-43 proteinopathy-induced degeneration in cross-species models with amyotrophic lateral sclerosis. Pharmacol Res. 2024 Dec; 210:107518.
3) Huang M, Liu YU, Yao X*, Qin D*, Su H*. Variability in SOD1-associated amyotrophic lateral sclerosis: geographic patterns, clinical heterogeneity, molecular alterations, and therapeutic implications. Transl Neurodegener. 2024 May 29;13(1):28.

2. Targeting glymphatic function and blood-brain barrier integrity to treat dementia
Targeting the glymphatic system and blood-brain barrier integrity offers a promising therapeutic strategy for various forms of dementia including Alzheimer’s disease and vascular dementia by clearing toxic proteins and maintaining brain homeostasis. Over the past decade, my lab is looking for pharmacological agents that can be used in long term to promote glymphatic function and protect BBB integrity without obvious side effects.
Representative publications:
1) Yan L, Xu K, Liu C, Yu F, Guo J, Hou L, Feng Y, Yang M, Gong Q, Qin D, Qin M, Wang Y, Su H*, Lu Y*. Polymer-Formulated Nerve Growth Factor Shows Effective Therapeutic Efficacy for Cerebral Microinfarcts. Adv Mater. 2025 Jan;37(3): e2412843.
2) Wen J, Satyanarayanan SK, Li A, Yan L, Zhao Z, Yuan Q, Su KP*, Su H*. Unraveling the impact of Omega-3 polyunsaturated fatty acids on blood-brain barrier (BBB) integrity and glymphatic function. Brain Behav Immun. 2024 Jan;115:335-355.
3) Yan L, Xie Y, Satyanarayanan SK, Zeng H, Liu Q, Huang M, Ma Y, Wan JB, Yao X, Su KP, Su H*. Omega-3 polyunsaturated fatty acids promote brain-to-blood clearance of β-Amyloid in a mouse model with Alzheimer’s disease. Brain Behav Immun. 2020 Mar; 85:35-45.
4) Luo C, Ren H, Yao X, Shi Z, Liang F, Kang JX, Wan JB, Pei Z, Su KP, Su H*. Enriched Brain Omega-3 Polyunsaturated Fatty Acids Confer Neuroprotection against Microinfarction. EBioMedicine. 2018 Jun; 32:50-61.

3. Exploring physiological functions of D-granules
Aberrant regulation of biomolecular condensates, including their formation, dynamics and biophysical properties could lead to protein misfolding and aggregation events underlying various neurodegenerative diseases and other aging-related diseases. My lab has identified DIAPH3, an actin nucleator, as a scaffold protein to initiate liquid-liquid phase separation (LLPS) and forms protein-only D-granules when cells are subjected to stress. Building upon this finding, we are devoted to exploring the biophysical properties and physiological functions of D-granules in maintaining cellular homeostasis.
Representative publications:
1)  Zhang K, Huang M, Li A, Wen J, Yan L, Li Y, Guo L, Senthil KS, Zhou Y, Chen G, Liu Y, Zhang X, Yao X, Qin D, Su H*. DIAPH3 condensates formed by liquid-liquid phase separation act as a regulatory hub for stress-induced actin cytoskeleton remodeling. Cell Rep. 2023 Jan 10;42(1):111986.

Dr. Su obtained his medical degree (MD) from Zhejiang University, an MPhil from the Chinese University of Hong Kong, and a PhD from the University of Hong Kong. He is currently a Full Professor at the University of Macau. His research primarily focuses on identifying and validating effective pharmacological strategies for the treatment of neurodegenerative diseases, including Alzheimer’s disease and amyotrophic lateral sclerosis. Dr. Su has authored nearly 100 peer-reviewed publications as corresponding author in high-impact journals in his discipline, with more than 11,000 citations in Scopus and over 25,956 citations on Google Scholar. He also serves as an Associate Editor for Aging and Disease and is an editorial board member of Brain Behavior and Immunity. His research continues to integrate multidisciplinary approaches spanning neuropharmacology, molecular neuroscience, and regenerative medicine, aiming to identify safe and effective long-term therapeutics for neurodegenerative and aging-related disorders.

For his complete list of publications, please visit his PubMed profile “https://pubmed.ncbi.nlm.nih.gov/?term=huanxing+su&sort=date”.

(1). Mechanistic studies on cell cycle and cell division during cell reprograming (Ministry of Science and Technology 973 program of China; Project Code: 2012CB966802; Duration: 2012, 01-2016, 12). PI.

(2). Application of induced pluripotent stem cells in treatment of multiple sclerosis (Start-up Research Grant (SRG) 2012; Project Code: SRGO14.ICMS12-SHX; Duration: 2012, 01-2012, 12). PI.

(3). Using patient-derived induced pluripotent stem cells for drug screens for efficacy and preclinical predictive toxicology (Multi-year research grant from the University of Macau; Project Code: MYRG122 (Y1-L3)-ICMS12-SHX; Duration: 2012, 06-2015, 05). PI.

(4). Therapeutic potentials of ginsenoside and neural progenitor cell transplantation in stroke (Multi-year research grant from the University of Macau; Project Code: MYRG110 (Y1-L2)-ICMS13-SHX; Duration: 2013, 05-2016, 04). PI.

(5). Therapeutic potentials of a combination of ginsenoside Rd administration and neural progenitor cell transplantation in stroke (Macao Science and Technology Development Fund; Project Code: FDCT 003/2012/A; Duration: 2012, 10-2014, 04). PI.

(6). Using patient-specific induced pluripotent stem cells to establish drug screening platforms for neurodegenerative diseases (Macao Science and Technology Development Fund; Project Code: FDCT 018/2013/A1; Duration: 2014, 01-2016, 12). PI.

(7). Driving metabolite clearance from the brain to maintain its homeostasis via activating the Glymphatic System and exploring its underlying mechanisms (Macao Science and Technology Development Fund; Project Code: FDCT 063/2015/A2; Duration: 2016, 01-2018, 06). PI.

(8). Mechanistic studies on the development of cerebral small vessel diseases and therapeutic potentials of omega-3 polyunsaturated fatty acids in the treatment of cerebral small vessel diseases and vascular cognition impairment (Macao Science and Technology Development Fund; Project Code: FDCT 020/2017/A1; Duration: 2017, 08-2020, 07). PI.

(9). Driving metabolite clearance from the brain to maintain its homeostasis via activating the Glymphatic System (Multi-year research grant from the University of Macau; Project Code: MYRG2016-00184-ICMS-QRCM; Duration: 2017, 01-2019, 12). PI.

(10). Roles and action mechanisms of SENP3 in autism (FDCT-NSFC; Project Code: FDCT 039/2017/AFJ; Duration: 2018, 01-2020, 12). PI.

(11). Study of neprilysin gene therapy targeting the glymphatic pathway for the treatment of Alzheimer’s disease and cerebral amyloid angiopathy (Multi-year research grant from the University of Macau; Project Code: MYRG2018-00242-ICMS; 2018, 09-2021, 08). PI.

(12). Mechanistic studies on clearance of amyloid beta in the brain and therapeutic roles of glymphatic pathways in prevention and treatment of neurodegenerative diseases (Macao Science and Technology Development Fund; Project Code: FDCT 049/2019/A1; Duration: 2019, 07-2022, 06). PI.

(13). Study of pathophysiological mechanisms and cognitive consequences of microinfarcts and beneficial effects of omega-3 polyunsaturated fatty acids on attenuating microinfarcts and improving vascular dementia (Multi-year research grant from the University of Macau; Project Code: MYRG2019-00160-ICMS; 2020, 01-2021, 12). PI.

Peng Y, Shi Z, Kumaran Satyanarayanan S, He C, Li P, Wan JB, Su H*. Fish oil alleviates LPS-induced inflammation and depressive-like behavior in mice via restoration of metabolic impairments. Brain Behav Immun. 2020 Nov;90:393-402.

Tong J, Satyanarayanan SK, Su H*. Nutraceuticals and probiotics in the management of psychiatric and neurological disorders: A focus on microbiota-gut-brain-immune axis. Brain Behav Immun. 2020 Nov;90:403-419.

Ke M, Chong CM, Zeng H, Huang M, Huang Z, Zhang K, Cen X, Lu JH, Yao X, Qin D*, Su H*. Azoramide protects iPSC-derived dopaminergic neurons with PLA2G6 D331Y mutation through restoring ER function and CREB signaling. Cell Death Dis. 2020 Feb 18;11(2):130.

Liu Q, Yan L, Huang M, Zeng H, Satyanarayanan SK, Shi Z, Chen D, Lu JH, Pei Z, Yao X, Su H*. Experimental alcoholism primes structural and functional impairment of the glymphatic pathway. Brain Behav Immun. 2020 Mar;85:106-119.

Yan L, Xie Y, Satyanarayanan SK, Zeng H, Liu Q, Huang M, Ma Y, Wan JB, Yao X, Su KP, Su H*.  Omega-3 polyunsaturated fatty acids promote brain-to-blood clearance of β-Amyloid in a mouse model with Alzheimer’s disease. Brain Behav Immun. 2020 Mar;85:35-45.

Tan Y, Ke M, Huang Z, Chong C, Cen X, Lu JH, Yao X*, Qin D*, Su H*. Hydroxyurea facilitates manifestation of disease relevant phenotypes in patients-derived iPSCs-based modeling of late-onset Parkinson’s disease. Aging and disease. 2019 Oct 1;10(5):1037-1048.

Chong CM, Ke M, Tan Y, Huang ZJ, Zhang K, Ai N, Ge W, Qin DJ, Lu JH, Su H*. Presenilin 1 deficiency suppresses autophagy in human neural stem cells through reducing γ-secretase-independent ERK/CREB signaling. Cell Death Dis. 2018 Aug 29;9(9):879.

Luo C, Ren H, Yao X, Shi Z, Liang F, Kang JX, Wan JB, Pei Z, Su KP, Su H*. Enriched Brain Omega-3 Polyunsaturated Fatty Acids Confer Neuroprotection against Microinfarction. EBioMedicine. 2018 Jun;32:50-61.

Luo C, Liang F, Ren H, Yao X, Liu Q, Li M, Qin D, Yuan TF, Pei Z, Su H*. Collateral blood flow in different cerebrovascular hierarchy provides endogenous protection in cerebral ischemia. Brain Pathology. 2017 Nov;27(6):809-821.

Ren H, Yang Z, Luo C, Zeng H, Li P, Kang JX, Wan JB, He C, Su H*. Enriched Endogenous Omega-3 Fatty Acids in Mice Ameliorate Parenchymal Cell Death After Traumatic Brain Injury. Mol Neurobiol. 2017 Jul;54(5):3317-3326.

Huang X, Chen Y-Y, Shen Y, Cao Y,  Li A, Liu Q, Li Z, Zhang L-B, Dai W, Tan T, Arias-Carrion O, Xue Y-X, Su H* and Yuan T-F*. Methamphetamine abuse impairs motor cortical plasticity and function. Molecular Psychiatry 2017 Sep;22(9):1274-1281.

Ren H, Luo C, Feng Y, Yao X, Shi Z, Liang F, Kang JX, Wan JB, Pei Z, Su H*. Omega-3 polyunsaturated fatty acids promote amyloid-β clearance from the brain through mediating the function of the glymphatic system. FASEB J, 2017 Jan;31(1):282-293.

Luo C, Yao X, Li J, He B, Liu Q, Ren H, Liang F, Li M, Lin H, Peng J, Yuan TF, Pei Z, Su H*. Paravascular pathways contribute to vasculitis and neuroinflammation after subarachnoid hemorrhage independently of glymphatic control. Cell Death Dis. 2016 Mar 31;7:e2160.

Editorial Board Member: Brain, Behavior, and Immunity

Editorial Board Member: Aging and disease