Personal Profile
Zhang Hongbo, a professor and doctoral supervisor at the Zhongshan School of Medicine, Sun Yat-sen University, is a selected participant in the National High-level Talent Program for Young Talents, a "Young Pearl River Scholar" in Guangdong Province, and an outstanding young talent introduced by Sun Yat-sen University. He graduated from the Swiss Federal Institute of Technology Lausanne (EPFL) in 2016. Under the supervision of Professor Johan Auwerx, an authority in the field of metabolism, he obtained his Ph.D. degree. In 2017, he was introduced to Sun Yat-sen University through the "Hundred Talents Program".

His research work first revealed the mitochondrial imbalance mechanism in stem cell senescence, proposed the important role of mitochondrial energy metabolism in regulating the senescence of skeletal muscle stem cells, and discovered a small molecule metabolic intervention method dependent on NAD+ to delay the senescence of adult stem cells and prevent and treat skeletal muscle dystrophy diseases. Relevant achievements have been published in journals such as Science, Science Translational Medicine, Nature Reviews Endocrinology, and Kidney International. He has also been granted 3 international/domestic invention patents and 1 software copyright.

The team comprehensively uses methods such as bioinformatics and molecular cell biology to study energy metabolism, especially the regulatory role of mitochondrial function in cell fate determination during development, the maintenance of adult stem cell function, and senescence. The main research directions at the current stage are as follows:

1. Molecular mechanisms of adult stem cell senescence
Stem cells have long been considered to have immortal capabilities. However, recent studies have found that they age with the aging of individuals, but the molecular mechanisms regulating stem cell senescence are unclear. Taking skeletal muscle stem cells as a model, the team studies the senescence mechanisms of quiescent stem cells under normal physiological conditions, reveals the changes in intracellular signal pathways, mitochondrial function alterations, and the impact of cell microenvironment perturbations on stem cells, especially skeletal muscle stem cell senescence, aiming to find effective methods to delay stem cell senescence, prolong life, and promote healthy aging.

2. Cell fate determination during development
The essence of development is the precisely differentiated process of cells in specific spatiotemporal patterns, which is an ideal model for studying cell fate determination. Focusing on limb development and with the help of self-developed single-cell data analysis tools combined with in vivo and in vitro gene function verification methods, the team systematically studies the divergence process of cell fate and the determination mechanism of spatial positions during development. The ultimate goal is to provide methods and technical guidance for regenerative medicine.

3. The impact of energy metabolism and epigenetics on adult stem cell function
Mitochondrial energy metabolism is closely related to protein epigenetic modifications. Several metabolites such as NAD+ and acetyl-CoA can directly serve as substrates for protein acetylation, methylation, and other modifications. The team focuses on the impact of acetyltransferases, deacetylases, etc. on the activation, differentiation, senescence, and other cellular functions and behaviors of skeletal muscle stem cells, providing references for promoting skeletal muscle regeneration and preventing and treating diseases such as muscle atrophy and muscular dystrophy.

Academic Achievements
Papers as the first or corresponding author

*, corresponding authors; #, equal contribution

1     Zhang B#, He P#, Lawrence JEG#, Wang S#, Tuck E, Williams BA, Roberts K, Kleshchevnikov V, Mamanova L, Bolt L, Polanski K, Li T, Elmentaite R, Fasouli ES, Prete M, He X, Yayon N, Fu Y, Yang H, Liang C, Zhang H, Blain R, Chedotal A, FitzPatrick DR, Firth H, Dean A, Bayraktar OA, Marioni JC, Barker RA, Storer MA, Wold BJ, Zhang H*, Teichmann SA*. A human embryonic limb cell atlas resolved in space and time. Nature, 2023 (IF: 64.8).

2    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: 56.9，ESI高被引论文).

3     Menzies KJ#, Zhang H#, Katsyuba E & Auwerx J*. Protein acetylation in metabolism - metabolites and cofactors. Nat Rev Endocrinol, 2016 (IF: 40.5).

4     Ryu D#, Zhang H#, Ropelle ER, Sorrentino V, Mazala DA, Mouchiroud L, Marshall PL, Campbell MD, Ali AS, Knowels GM, Bellemin S, Iyer SR, Wang X, Gariani K, Sauve AA, Canto C, Conley KE, Walter L, Lovering RM, Chin ER, Jasmin BJ, Marcinek DJ, Menzies KJ & Auwerx J*. NAD+ repletion improves muscle function in muscular dystrophy and counters global PARylation. Sci transl med, 2016 (IF: 17.1).

5     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: 3.1).

6     Aging Biomarker C, Bao H, Cao J, Chen M, Chen M, Chen W, Chen X, Chen Y, …, Zhang H*, Zhang L*, Zhang W*, Zhang Y*, Zhang YW*, Zhang Z*, Zhao T*, Zhao Y*, Zhu D*, Zou W*, Pei G* & Liu GH*. Biomarkers of aging. Sci China Life Sci, 2023 (IF: 9.1，封面论文).

7     Addicks GC#, Zhang H#, Ryu D#, Vasam G, Green AE, Marshall PL, Patel S, Kang BE, Kim D, Katsyuba E, Williams EG, Renaud JM, Auwerx J* & Menzies KJ*. GCN5 maintains muscle integrity by acetylating YY1 to promote dystrophin expression. J Cell Biol, 2022 (IF: 7.8).

8     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: 5.0).

9     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: 7.3).

10   Guo F, Zhang B, Yang H, Fu Y, Wang Y, Huang J, Cheng M, Li X, Shen Z, Li L, He P, Xiang AP, Wang S* & Zhang H*. Systemic transcriptome comparison between early- And late-onset pre-eclampsia shows distinct pathology and novel biomarkers. Cell Prolif, 2021 (IF: 8.5).

11   Wang S, Zhang B, Addicks GC, Zhang H, Menzies KJ* & Zhang H*. Muscle Stem Cell Immunostaining. Curr Protoc Mouse Biol, 2018 (专著).

12   Addicks GC, Marshall P, Jasmin BJ, Renaud JM, Zhang H* & Menzies KJ*. Critical Assessment of the mdx Mouse with Ex Vivo Eccentric Contraction of the Diaphragm Muscle. Curr Protoc Mouse Biol, 2018 (专著).

13   Zhang H#, Menzies KJ & Auwerx J*. The role of mitochondria in stem cell fate and aging. Development, 2018 (IF: 4.6，ESI高被引论文).

14   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: 19.6).

Other Paper

1     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: 3.1).

2     Lai BQ, Wu RJ, Han WT, Bai YR, Liu JL, Yu HY, Yang SB, Wang LJ, Ren JL, Ding Y, Li G, Zeng X, Ma YH, Quan Q, Xing LY, Jiang B, Wang YQ, Zhang L, Chen ZH, Zhang HB, Chen YF, Zheng QJ & Zeng YS. 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: 14).

3     Lai BQ, Bai YR, Han WT, Zhang B, Liu S, Sun JH, Liu JL, Li G, Zeng X, Ding Y, Ma YH, Zhang L, Chen ZH, Wang J, Xiong Y, Wu JH, Quan Q, Xing LY, Zhang HB & Zeng YS. 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: 18.9).

4     Romani M, Sorrentino V, Oh CM, Li H, de Lima TI, Zhang H, Shong M & Auwerx J. NAD(+) boosting reduces age-associated amyloidosis and restores mitochondrial homeostasis in muscle. Cell reports, 2021 (IF: 8.8).

5     Muus C, Luecken MD, Eraslan G, Sikkema L, Waghray A, Heimberg G, Kobayashi Y, Vaishnav ED, …, 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: 82.9， ESI高被引论文).

6     Li G, Zhang B, Sun JH, Shi LY, Huang MY, Huang LJ, Lin ZJ, Lin QY, Lai BQ, Ma YH, Jiang B, Ding Y, Zhang HB, Li MX, Zhu P, Wang YQ, Zeng X & Zeng YS. 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: 18.9).

7     Sungnak W, Huang N, Becavin C, Berg M, Queen R, Litvinukova M, Talavera-Lopez C, Maatz H, Reichart D, Sampaziotis F, Worlock KB, Yoshida M, Barnes JL & Network HCALB. SARS-CoV-2 entry factors are highly expressed in nasal epithelial cells together with innate immune genes. Nat Med, 2020 (IF: 82.9，ESI高被引论文).

8     Litvinukova M, Talavera-Lopez C, Maatz H, Reichart D, Worth CL, Lindberg EL, Kanda M, Polanski K, Heinig M, Lee M, Nadelmann ER, Roberts K, Tuck L, Fasouli ES, DeLaughter DM, McDonough B, Wakimoto H, Gorham JM, Samari S, Mahbubani KT, Saeb-Parsy K, Patone G, Boyle JJ, Zhang H, Zhang H, Viveiros A, Oudit GY, Bayraktar OA, Seidman JG, Seidman CE, Noseda M, Hubner N & Teichmann SA. Cells of the adult human heart. Nature, 2020 (IF: 64.8，ESI高被引论文).

9     Chen YP, Yin JH, Li WF, Li HJ, Chen DP, Zhang CJ, Lv JW, Wang YQ, Li XM, Li JY, Zhang PP, Li YQ, He QM, Yang XJ, Lei Y, Tang LL, Zhou GQ, Mao YP, Wei C, Xiong KX, Zhang HB, Zhu SD, Hou Y, Sun Y, Dean M, Amit I, Wu K, Kuang DM, Li GB, 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: 44.1).

10   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: 20.1).

11   Lahiri S, Kim H, Garcia-Perez I, Reza MM, Martin KA, Kundu P, Cox LM, Selkrig J, Posma JM, 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. Sci transl med, 2019 (IF: 17.1，ESI高被引论文).

12   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 LA, Gariani K, Kutalik Z, Schoonjans K, Radcliffe RA, Prins P, Morgenthaler S, Williams RW & Auwerx J. An Integrated Systems Genetics and Omics Toolkit to Probe Gene Function. Cell Syst, 2018 (IF: 9.3).

13   Sorrentino V, Romani M, Mouchiroud L, Beck JS, 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: 64.8，ESI高被引论文).

14   Gariani K, Ryu D, Menzies KJ, Yi HS, Stein S, Zhang H, Perino A, Lemos V, Katsyuba E, Jha P, Vijgen S, Rubbia-Brandt L, Kim YK, Kim JT, Kim KS, Shong M, Schoonjans K & Auwerx J. Inhibiting poly ADP-ribosylation increases fatty acid oxidation and protects against fatty liver disease. J hepat, 2017 (IF: 25.7).

15   Rabhi N, Denechaud PD, Gromada X, Hannou SA, 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: 8.8).

16   Gariani K, Menzies KJ, Ryu D, Wegner CJ, Wang X, Ropelle ER, Moullan N, Zhang H, Perino A, Lemos V, Kim B, Park YK, Piersigilli A, Pham TX, Yang Y, Ku CS, Koo SI, Fomitchova A, Canto C, Schoonjans K, Sauve AA, Lee JY & Auwerx J. Eliciting the mitochondrial unfolded protein response by nicotinamide adenine dinucleotide repletion reverses fatty liver disease in mice. Hepatology, 2016 (IF: 13.5，Highly Cited Papers in ESI).

17   Ryu D, Jo YS, Lo Sasso G, Stein S, Zhang H, Perino A, Lee JU, Zeviani M, Romand R, Hottiger MO, Schoonjans K & Auwerx J. A SIRT7-dependent acetylation switch of GABPbeta1 controls mitochondrial function. Cell metab, 2014 (IF: 29.0).

18   Pirinen E, Canto C, Jo YS, Morato L, Zhang H, Menzies KJ, Williams EG, 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 AA, Schoonjans K & Auwerx J. Pharmacological Inhibition of poly(ADP-ribose) polymerases improves fitness and mitochondrial function in skeletal muscle. Cell metab, 2014 (IF: 29.0).

Textbooks and Monographs
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. Authorized PCT patent, 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. Authorized PCT patent, WO2017042196, (2017).
3. Zhang Hongbo, Wang Shuaiyu, Zhang Bao, Yang Hao. Screening method for placenta-related disease markers and the markers. Authorized Chinese invention patent, ZL 2020 1 0908665.8, (2023).
4. Zhang Hongbo, Zhang Bao, Wang Shuaiyu. PLOGS software [abbreviated as: Python package software for gene pseudotime expression analysis]. Authorized software copyright, 5091728, (2020).

Awards and Honors
2020: National High-level Talent Program for Young Talents;
2018: "Young Pearl River Scholar" in Guangdong Province;
2016: Swiss Young Investigator Award;
2016: The Lausanne Integrative Metabolism and Nutrition Alliance travel grant;
2014: Fellowship award for stem cell research (CARIGEST Stem Cell Research Award).