个人简介/Brief introduction

      张宏波，中山大学中山医学院教授、博士生导师，国家级人才工程青年项目入选者，广东省青年珠江学者、中山大学引进青年杰出人才。2016年毕业于瑞士联邦理工大学（EPFL），师从代谢领域权威Johan Auwerx 教授获得博士学位，2017年中山大学“百人计划”项目引进。团队研究通过单细胞多组学技术结合分子细胞生物学、模式动物和临床样本研究个体衰老的基本调节机制，并以发育为借鉴，寻求提高衰老组织再生能力的新策略。前期研究构建了首个人类肢体发育和骨骼肌衰老的单细胞图谱；揭示了线粒体对维持干细胞功能的重要作用，提出线粒体代谢失衡是导致干细胞衰老的重要原因。相关成果发表于Nature、Science、Nature Aging、Science Translational Medicine等期刊，并受邀为Nature Reviews Endocrinology、Science Bulletin等撰写综述，获授权国际/国内发明专利3项，软件著作权3项。

      现阶段主要研究方向如下：
      1. 成体干细胞衰老的分子机制。干细胞长期被认为具备永生能力，近年的研究发现其会随着个体衰老而衰老，但调节干细胞衰老的分子机制不明。团队以骨骼肌干细胞为模型，研究静息干细胞在正常生理条件下的衰老机制，揭示细胞内源性信号通路的变化、线粒体功能改变、细胞微环境扰动对干细胞，尤其是骨骼肌干细胞衰老的影响，以寻找到延缓干细胞衰老、延长寿命、促进老年健康的有效方法。

      2. 发育过程中的细胞命运决定。发育的本质是细胞在特定时空精确分化的过程，是研究细胞命运决定的理想模型。团队以肢体发育为重点，借助自主开发的单细胞数据分析工具，并结合体内外基因功能验证方法，系统性研究发育过程中细胞命运的歧化过程和和空间位置的确定机制，最终目的在于为组织高质量再生提供方法和技术指引。

      3. 能量代谢和表观遗传对成体干细胞功能的影响。线粒体能量代谢与蛋白质表观遗传修饰存在密切联系，若干代谢物如NAD+、乙酰辅酶A等可以直接作为蛋白质乙酰化、甲基化等修饰的底物。团队关注乙酰化转移酶、去乙酰化酶等对骨骼肌干细胞活化、分化、衰老等细胞功能和行为的影响，为促进骨骼肌再生，防治肌萎缩和肌肉营养不良等疾病提供借鉴。

      Hongbo Zhang is a Professor and PhD supervisor at the Zhongshan School of Medicine, Sun Yat-sen University. He is a recipient of China’s national-level youth talent program, a Guangdong Pearl River Young Scholar, and a Sun Yat-sen University Distinguished Young Talent. He earned his PhD in 2016 from the Swiss Federal Institute of Technology Lausanne (EPFL), where he studied under Professor Johan Auwerx, a leading scientist in metabolism. In 2017, he was recruited through Sun Yat-sen University's “Hundred Talents” Program.

      His research group integrates single-cell multi-omics with molecular and cellular biology, model organisms, and clinical samples to investigate the fundamental regulatory mechanisms of aging. Drawing insights from developmental biology, they aim to develop novel strategies to enhance regenerative capacity in aged tissues. The team has previously constructed the first single-cell atlases of human limb development and skeletal muscle aging. Their studies revealed the critical role of mitochondria in maintaining stem cell function and proposed mitochondrial metabolic imbalance as a key driver of stem cell aging. Related findings have been published in Nature, Science, Nature Aging, and Science Translational Medicine. He has also been invited to write reviews for journals such as Nature Reviews Endocrinology and Science Bulletin, and holds three granted international/domestic invention patents and three software copyright.

Current Main Research Directions:
Molecular Mechanisms of Adult Stem Cell Aging
      Stem cells were long thought to possess immortal properties. However, recent studies show that they undergo aging alongside the organism. The molecular mechanisms regulating this process remain unclear. Using skeletal muscle stem cells as a model, the team investigates how aging occurs in quiescent stem cells under physiological conditions, focusing on changes in endogenous signaling pathways, mitochondrial function, and disturbances in the cellular microenvironment. The goal is to identify effective strategies to delay stem cell aging, extend lifespan, and promote healthy aging.

Cell Fate Determination During Development
      Development is essentially a process of precise spatial and temporal cell differentiation, making it an ideal model to study cell fate decisions. Focusing on limb development, the team applies self-developed single-cell data analysis tools along with in vivo and in vitro gene function validation to systematically study how cell fates diversify and spatial positions are established during development. The ultimate goal is to provide methodological and technological guidance for high-quality tissue regeneration.

Impact of Energy Metabolism and Epigenetics on Adult Stem Cell Function
      Mitochondrial energy metabolism is closely linked to epigenetic modifications of proteins. Metabolites such as NAD⁺ and acetyl-CoA serve as substrates for acetylation and methylation. The group explores how enzymes like acetyltransferases and deacetylases affect stem cell activation, differentiation, and aging in skeletal muscle. These insights aim to contribute to improving muscle regeneration and treating conditions such as muscle atrophy and muscular dystrophy.

学术论文/Publications

第一或通讯作者论文/fist or corresponding author papers

*, corresponding authors; #, equal contribution

1. Zhang B#, He P#, Lawrence J#, Wang S#, Tuck E, Williams B, Roberts K, Kleshchevnikov V, Mamanova L, Bolt L, Polanski K, Li T, Elmentaite R, Fasouli E, Prete M, He X, Yayon N, Fu Y, Yang H, Liang C, Zhang H, Blain R, Chedotal A, FitzPatrick D, Firth H, Dean A, Bayraktar O, Marioni J, Barker R, Storer M, Wold B, Zhang H* & Teichmann S* . A human embryonic limb cell atlas resolved in space and time. Nature, 2024 (IF: 48.5).

2. Kedlian V#, Wang Y#, Liu T#, Chen X, Bolt L, Tudor C, Shen Z, Fasouli E, Prigmore E, Kleshchevnikov V, Pett J, Li T, Lawrence J, Perera S, Prete M, Huang N, Guo Q, Zeng X, Yang L, Polanski K, Chipampe N, Dabrowska M, Li X, Bayraktar O, Patel M, Kumasaka N, Mahbubani K, Xiang A, Meyer K, Saeb-Parsy K*, Teichmann S* & Zhang H*. Human skeletal muscle aging atlas. Nat Aging, 2024 (IF: 19.4, ESI高被引).

3. Zhang H#, Ryu D, Wu Y, Gariani K, Wang X, Luan P, D'Amico D, Ropelle ER, Lutolf MP, Aebersold R, Schoonjans K, Menzies KJ & Auwerx J. NAD(+) repletion improves mitochondrial and stem cell function and enhances life span in mice. Science, 2016 (IF: 45.8, ESI高被引).

4. Zhang B. & Zhang H*. The human limb cell atlas: charting uncharted territories and setting sail on the new voyage of limb development research. Sci Bull, 2025 (IF: 21.1).

5. Menzies KJ#, Zhang H#, Katsyuba E & Auwerx J. Protein acetylation in metabolism - metabolites and cofactors. Nat Rev Endocrinol, 2016 (IF: 40, ESI高被引). 

6. Ryu D#, Zhang H#, Ropelle E, Sorrentino V, Mazala D, Mouchiroud L, Marshall P, Campbell M, Ali A, Knowels G, Bellemin S, Iyer S, Wang X, Gariani K, Sauve A, Canto C, Conley K, Walter L, Lovering R, Chin E, Jasmin B, Marcinek D, Menzies K & Auwerx J. NAD+ repletion improves muscle function in muscular dystrophy and counters global PARylation. Sci Transl Med, 2016 (IF: 14.6).

7. Guo F#, Zhang B#, Yang H#, Fu Y, Wang Y, Huang J, Cheng M, Li X, Shen Z, Li L, He P, Xiang P, Wang S* & Zhang H*. Systemic transcriptome comparison between early- And late-onset pre-eclampsia shows distinct pathology and novel biomarkers. Cell Prolif, 2021 (IF: 5.6).

8. Peng B, Wang Y & Zhang H*. Mitonuclear Communication in Stem Cell Function. Cell Prolif, 2024 (IF: 5.6).

9. Aging Biomarker C#, Huang N#, …, Zhang H*, Zhang W*, Liu G*, Pei G*, Liu Y*, Zhu D*, Dong B*. A framework of biomarkers for skeletal muscle aging: a consensus statement by the Aging Biomarker Consortium. Life Med, 2024 (IF: 6.0).

10. Aging Biomarker C#, Bao H#, Cao J#, Chen M#, Chen M#, Chen W#, Chen X#, Chen Y#, …, Zhang H*,…, Pei G* & Liu GH*. Biomarkers of aging. Sci China Life Sci, 2023 (IF: 9.5, ESI高被引, 封面论文). 

11. Chen Y#, Zhang B#, Liu T, Chen X, Wang Y* & Zhang H*. T Cells With Activated STAT4 Drive the High-Risk Rejection State to Renal Allograft Failure After Kidney Transplantation. Front Immunol, 2022 (IF: 5.9).

12. Yang H#, Guo F#, Guo Q, Wang Y, He P, Zhang H* & Wang S*. The clinical value of PlGF and the sFlt1/PlGF ratio in the management of hypertensive pregnancy disorders: A retrospective real-world study in China. Clin Chim Acta, 2022 (IF: 2.9).

13. Peng B, Chen Y, Wang Y, Fu Y, Zeng X, Zhou H, Abulaiti Z, Wang S & Zhang H*. BTG2 acts as an inducer of muscle stem cell senescence. Biochem Biophys Res Commun, 2023 (IF: 2.2).

14. Wang S, Zhang B, Addicks GC, Zhang H, K JM* & Zhang H*. Muscle Stem Cell Immunostaining. Curr Protoc Mouse Biol, 2018 (专著).

15. Addicks G, Marshall P, Jasmin B, Renaud J, Zhang H* & Menzies K*. Critical Assessment of the mdx Mouse with Ex Vivo Eccentric Contraction of the Diaphragm Muscle. Curr Protoc Mouse Biol, 2018 (专著).

16. Zhang H#, Menzies K & Auwerx J. The role of mitochondria in stem cell fate and aging. Development, 2018 (IF: 3.6).

17. Addicks G#, Zhang H#, Ryu D, Vasam G, Green A, Marshall P, Patel S, Kang B, Kim D, Katsyuba, E, Williams E, Renaud J, Auwerx J & Menzies K. GCN5 maintains muscle integrity by acetylating YY1 to promote dystrophin expression. J Cell Biol, 2022 (IF: 6.4).

18. Spichtig D#, Zhang H#, Mohebbi N, Pavik I, Petzold K, Stange G, Saleh L, Edenhofer I, Segerer S, Biber J, Jaeger P, Serra AL & Wagner CA. Renal expression of FGF23 and peripheral resistance to elevated FGF23 in rodent models of polycystic kidney disease. Kidney Int, 2014 (IF: 12.6).

其他论文/other publications

1. Ning Y, Duo S, Lin X, Zhang H, Fei J, Zhang B, Zeng Y, Xie, D, Chen J, Liu X. & Han C. Transcription factor PBX4 regulates limb development and haematopoiesis in mice. Cell Prolif, 2024 (IF: 5.6).

2. Li G, Huang L, Zhang B, Liu S, Liang J, Ding Y, Zeng X, Lai B, Ma Y, Wang Y, Wang R, Zhang H, Zeng Y. The LINGO-1-deficient neural stem cell-derived neural tissueoid showed enhanced retention and neuronal relay in the transected spinal cord. Chem Eng J, 2024 (IF: 13.2).

3. Ren J, Song M, Zhang W, Cai J, Cao, F, Cao Z, …, Zhang H, Zhang L, Zhang X, Zhang Y, Zhang Y, Zhang Z, Zhao T, Zhao Y, ZHou Z, Zhu D, Zou W, Pei G, Liu G. The Aging Biomarker Consortium represents a new era for aging research in China. Nat Med, 2023 (IF: 50.0).

4. Liu T, Chen X, Peng B, Liang C, Zhang H & Wang S. A novel prognostic model based on immunogenic cell death-related genes for improved risk stratification in hepatocellular carcinoma patients. J Cancer Res Clin Oncol, 2023 (IF: 2.8).

5. Lai B, Wu R, Han W, Bai Y, Liu J, Yu H, Yang S, Wang L, Ren J, Ding Y, Li G, Zeng X, Ma Y, Quan Q, Xing L, Jiang B, Wang Y, Zhang L, Chen Z, Zhang H, Chen Y, Zheng Q & Zeng Y*. Tail nerve electrical stimulation promoted the efficiency of transplanted spinal cord-like tissue as a neuronal relay to repair the motor function of rats with transected spinal cord injury. Biomaterials, 2023 (IF: 12.9).

6. Lai B, Bai Y, Han W, Zhang B, Liu S, Sun J, Liu J, Li G, Zeng X, Ding Y, Ma Y, Zhang L, Chen Z, Wang J, Xiong Y, Wu J, Quan Q, Xing L, Zhang H & Zeng Y*. Construction of a niche-specific spinal white matter-like tissue to promote directional axon regeneration and myelination for rat spinal cord injury repair. Bioact Mater, 2022 (IF: 20.3).

7. Romani M, Sorrentino V, Oh C, Li H, de Lima T, Zhang H, Shong M & Auwerx J. NAD(+) boosting reduces age-associated amyloidosis and restores mitochondrial homeostasis in muscle. Cell reports, 2021 (IF: 6.9).

8. Muus C, Luecken M, Eraslan G, Sikkema L, Waghray A, Heimberg G, Kobayashi Y, Vaishnav E, …, Consortium NL & Human Cell Atlas Lung Biological N. Single-cell meta-analysis of SARS-CoV-2 entry genes across tissues and demographics. Nat Med, 2021 (IF: 50.0, ESI高被引).

9. Li G, Zhang B, Sun J, Shi L, Huang M, Huang L, Lin Z, Lin Q, Lai B, Ma Y, Jiang B, Ding Y, Zhang H, Li M, Zhu P, Wang Y, Zeng X & Zeng Y. An NT-3-releasing bioscaffold supports the formation of TrkC-modified neural stem cell-derived neural network tissue with efficacy in repairing spinal cord injury. Bioact Mater, 2021 (IF: 20.3).

10. Sungnak W, Huang N, Becavin C, Berg M, Queen R, Litvinukova M, Talavera-Lopez C, Maatz H, Reichart D, Sampaziotis F, Worlock K, Yoshida M, Barnes J & Network HCALB. SARS-CoV-2 entry factors are highly expressed in nasal epithelial cells together with innate immune genes. Nat Med, 2020 (IF: 50.0, ESI高被引). 

11. Litvinukova M, Talavera-Lopez C, Maatz H, Reichart D, Worth CL, Lindberg EL, Kanda M, Polanski K, Heinig M, Lee M, Nadelmann E, Roberts K, Tuck L, Fasouli E, DeLaughter D, McDonough B, Wakimoto H, Gorham J, Samari S, Mahbubani K, Saeb-Parsy K, Patone G, Boyle J, Zhang H, Zhang H, Viveiros A, Oudit G, Bayraktar O, Seidman J, Seidman C, Noseda M, Hubner N & Teichmann S. Cells of the adult human heart. Nature, 2020 (IF: 48.5, ESI高被引). 

12. Chen Y, Yin J, Li W, Li H, Chen D, Zhang C, Lv J, Wang Y, Li X, Li J, Zhang P, Li Y, He Q, Yang X, Lei Y, Tang L, Zhou G, Mao Y, Wei C, Xiong K, Zhang H, Zhu S, Hou Y, Sun Y, Dean M, Amit I, Wu K, Kuang D, Li G, Liu N & Ma J. Single-cell transcriptomics reveals regulators underlying immune cell diversity and immune subtypes associated with prognosis in nasopharyngeal carcinoma. Cell Res, 2020 (IF: 25.9).

13. Zhu X, Shen W, Yao K, Wang H, Liu B, Li T, Song L, Diao D, Mao G, Huang P, Li C, Zhang H, Zou Y, Qiu Y, Zhao Y, Wang W, Yang Y, Hu Z, Auwerx J, Loscalzo J, Zhou Y & Ju Z. Fine-Tuning of PGC1alpha Expression Regulates Cardiac Function and Longevity. Circ Res, 2019 (IF: 16.2).

14. Lahiri S, Kim H, Garcia-Perez I, Reza M, Martin K, Kundu P, Cox L, Selkrig J, Posma J, Zhang H, Padmanabhan P, Moret C, Gulyas B, Blaser MJ, Auwerx J, Holmes E, Nicholson J, Wahli W & Pettersson S. The gut microbiota influences skeletal muscle mass and function in mice. Science Transl Med, 2019 (IF: 14.6, ESI高被引). 

15. Li H, Wang X, Rukina D, Huang Q, Lin T, Sorrentino V, Zhang H, Bou Sleiman M, Arends D, McDaid A, Luan P, Ziari N, Velazquez-Villegas L, Gariani K, Kutalik Z, Schoonjans K, Radcliffe R, Prins P, Morgenthaler S, Williams RW & Auwerx J. An Integrated Systems Genetics and Omics Toolkit to Probe Gene Function. Cell Syst, 2018 (IF: 7.7).

16. Sorrentino V, Romani M, Mouchiroud L, Beck J, Zhang H, D'Amico D, Moullan N, Potenza F, Schmid AW, Rietsch S, Counts SE & Auwerx J. Enhancing mitochondrial proteostasis reduces amyloid-beta proteotoxicity. Nature, 2017 (IF: 48.5, ESI高被引). 

17. Gariani K, Ryu D, Menzies K, Yi H, Stein S, Zhang H, Perino A, Lemos V, Katsyuba E, Jha P, Vijgen S, Rubbia-Brandt L, Kim Y, Kim J, Kim K, Shong M, Schoonjans K & Auwerx J. Inhibiting poly ADP-ribosylation increases fatty acid oxidation and protects against fatty liver disease. J Hepatol, 2017 (IF: 33.0).

18. Rabhi N, Denechaud P, Gromada X, Hannou S, Zhang H, Rashid T, Salas E, Durand E, Sand O, Bonnefond A, Yengo L, Chavey C, Bonner C, Kerr-Conte J, Abderrahmani A, Auwerx J, Fajas L, Froguel P & Annicotte JS. KAT2B Is Required for Pancreatic Beta Cell Adaptation to Metabolic Stress by Controlling the Unfolded Protein Response. Cell Rep, 2016 (IF: 6.9).

19. Gariani K, Menzies K, Ryu D, Wegner C, Wang X, Ropelle E, Moullan N, Zhang H, Perino A, Lemos V, Kim B, Park Y, Piersigilli A, Pham T, Yang Y, Ku C, Koo S, Fomitchova A, Canto C, Schoonjans K, Sauve A, Lee J & Auwerx J. Eliciting the mitochondrial unfolded protein response by nicotinamide adenine dinucleotide repletion reverses fatty liver disease in mice. Hepatology, 2016 (IF: 12.9, ESI高被引). 

20. Ryu D, Jo Y, Lo Sasso G, Stein S, Zhang H, Perino A, Lee J, Zeviani M, Romand R, Hottiger M, Schoonjans K & Auwerx J. A SIRT7-dependent acetylation switch of GABPbeta1 controls mitochondrial function. Cell Metab, 2014 (IF: 30.9).

21. Pirinen E, Canto C, Jo Y, Morato L, Zhang H, Menzies K, Williams E, Mouchiroud L, Moullan N, Hagberg C, Li W, Timmers S, Imhof R, Verbeek J, Pujol A, van Loon B, Viscomi C, Zeviani M, Schrauwen P, Sauve A, Schoonjans K & Auwerx J. Pharmacological Inhibition of poly(ADP-ribose) polymerases improves fitness and mitochondrial function in skeletal muscle. Cell Metab, 2014 (IF: 30.9).

其他成果/Other academic contributions

专利和软著/Patents and Software Copyrights

1   Zhang, H., Menzies, K. J., Auwerx, J. Ryu, D. Agents and methods using thereof for the prevention and treatment of stem cells senescence. 已授权PTC专利, WO2017042198, (2017). 
2   Zhang, H., Menzies, K. J., Auwerx, J. Ryu, D. Agents and methods using thereof for the prevention and treatment of stem cell muscle disorders. 已授权PTC专利, WO2017042196, (2017).
3  张宏波，王帅玉，张宝，杨浩. 胎盘相关疾病标志物的筛选方法及标志物. 已授权中国发明专利, ZL 2020 1 0908665.8, (2023).
4  张宏波，张宝，王帅玉. 基因拟时序表达分析Python包软件[简称：PLOGS软件]. 已授权软件著作权，5091728，(2020).
5  张宏波，孙萌. 生物学中HE与荧光图配准软件(RBMIC) [简称:RBMIC]. 已授权软件著作权， 14171926，(2024).
6  张宏波，孙萌. 生物学中针对罕见细胞类型的聚类可视化软件(RCI-SCORE) [简称:RCI-SCORE]. 已授权软件著作权， 14171935，(2024).

获奖及荣誉/Honors

2020  国家级人才工程青年项目；
2018  广东省青年“珠江学者”；
2016  瑞士青年科学家奖（Swiss Young Investigator Award）；
2016  The Lausanne Integrative Metabolism and Nutrition Alliance travel grant;
2014  CARIGEST  干细胞研究奖（fellowship award for stem cell research）