• Postdoctoral Research Fellow, Department of Radiation Oncology, Mayo Clinic, Minnesota, USA
• Postdoctoral Research Fellow, Department of Therapeutic Radiology, Yale University, Connecticut, USA

DNA repair is fundamental to life. Failing to launch DNA repair in the right place at the right time compromises genome stability, which in turn can lead to a wide range of devastating human diseases, including cancers and developmental disorders. Emerging evidence also implicate DNA repair as a key process that underlies learning and memory, highlighting the diverse roles of DNA metabolism in brain and cognitive sciences. As such, research in DNA repair mechanisms advances our understanding of the molecular bases of genome instability-associated human syndromes. Indeed, not only does DNA repair research aid in disease risk assessment, it also provides invaluable insight in rational drug design and discovery, as exemplified by the recent development of PARP inhibitors as promising therapeutics for the treatment of BRCA-related breast and ovarian cancers.

My research goal aims to define DNA damage detection and repair processes by identifying key players and events that drive genome integrity protection. Aside its direct implications in human health and disease, insight in the regulation of DNA repair also contributes to the operational framework of emerging methodologies in genome-editing and gene replacement therapies.

• DNA Damage Detection and Repair Control

Research Articles:

1. Dong C, An L, Yu CH, Huen MS. A DYRK1B-dependent pathway suppresses rDNA transcription in response to DNA damage. Nucleic Acids Res 2021; 49(3): 1485-1496.
2. Dong C, West KL, Tan XY, Li J, Ishibashi T, Yu CH, Sy SM, Leung JW, Huen MS. Screen identifies DYRK1B network as mediator of transcription repression on damaged chromatin. PNAS 2020; 117(29): 17019-17030.
3. Chen Y, Li J, Cao F, Lam J, Cheng CC, Yu CH, Huen MS. Nucleolar residence of the Seckel Syndrome protein TRAIP is coupled to ribosomal DNA transcription. Nucleic Acids Res 2018; 46(19): 10119-10131.
4. An L, Dong C, Li J, Chen J, Yuan J, Huang J, Chan KM, Yu CH, Huen MS. RNF169 limits 53BP1 deposition at DSBs to stimulate single-strand annealing repair. PNAS 2018; 115(35): E8286-8295.
5. An L, Jiang Y, Ng HH, Man EP, Chen J, Khoo US, Gong Q, Huen MS. Dual-utility NLS drives RNF169-dependent DNA damage responses. PNAS 2017; 114(4): E2872-2881.
6. Guo Y, An L, Ng HM, Sy SM, Huen MS. An E2-guided E3 screen identifies the RNF17-UBE2U pair as regulator of the RIDDLE syndrome protein RNF168. J Biol Chem 2017; 292(3):967-978.
7. Feng W, Guo Y, Huang J, Deng Y, Zang J, Huen MS. TRAIP regulates replication fork recovery and progression via PCNA. Cell Discovery 2016; 2:16016.
8. Ng HM, Wei L, Lan L, Huen MS. The K63-Deubiquitylating enzyme BRCC36 limits DNA break processing and repair. J Biol Chem 2016; 291(31):16197-207.
9. Guo Y, Feng W, Sy SM, Huen MS. ATM-dependent phosphorylation of the Fanconi anemia protein PALB2 promotes the DNA Damage Response. J Biol Chem 2015; 290(46):27545-56.
10. Sy SM, Jiang J, O WS, Deng Y, Huen MS. The Ubiquitin Specific Protease USP34 promotes ubiquitin signaling at DNA double-strand breaks. Nucleic Acids Res 2013; 41(18):8572-80.
11. Chen J, Feng W, Jiang J, Deng Y, Huen MS. Ring Finger Protein RNF169 antagonizes the ubiquitin-dependent signaling cascade at sites of DNA damage. J Biol Chem 2012; 278(33):27715-22.
12. Lok GT, Sy SM, Dong S, Ching YP, Tsao SW, Thomson TM, Huen MS. Differential regulation of RNF8-mediated Lys48- and Lys63-based poly-ubiquitylation. Nucleic Acids Res 2012; 40(1): 196-205.
13. Sy SM, Jiang J, Dong S, Lok GT, Wu J, Cai H, Yeung ES, Huang J, Chen J, Deng Y, Huen MS. Critical roles of Ring Finger Protein RNF8 in replication stress responses. J Biol Chem 2011; 286(25): 22355-22361.
14. Huen MS, Huang J, Leung JW, Sy SM, Leung KM, Ching YP, Tsao SW, Chen J. Regulation of chromatin architecture by the PWWP domain-containing DNA damage responsive factor EXPAND1. Mol Cell 2010; 37:1-11.
15. Huen MS, Huang J, Yuan J, Yamamoto M, Akira S, Ashley C, Xiao W, Chen J. Non-canonical E2 variant-independent function of UBC13 in promoting checkpoint protein assembly. Mol Cell Biol. 2008;28(19):6104-12.
16. Huen MS, Sy SM, van Deursen JM, Chen J. Direct interaction between SET8 and PCNA couples H4-K20 methylation with DNA replication. J Biol Chem 2008; 283(17):11073-7.
17. Huen MS, Grant R, Manke I, Minn K, Yu X, Yaffe MB, Chen J. RNF8 transduces the DNA-damage signal via histone ubiquitylation and checkpoint protein assembly. Cell 2007; 131(5):901-14.

Commentaries & Reviews:

1. Tan XY, Huen MS. Perfecting DNA double-strand break repair on transcribed chromatin. Essays Biochem 2020; EBC20190094.
2. Huen MS, Chen J. H1 provides the missing link. Cell Res 2016; 26(1):5-6
3. Huen MS, Chen J. ATM creates a veil of transcriptional silence. Cell 2010; 141:924-6.
4. Huen MS, Sy SM, Chen J. BRCA1 and its toolbox for the maintenance of genome integrity. Nat Rev Mol Cell Biol 2010; 11(2):138-48.
5. Huen MS, Chen J. Assembly of checkpoint and repair machineries at DNA damage sites. Trends Biochem Sci 2010; 35(2):101-8.
6. Huen MS, Chen J. When loose ends finally meet. Nat Struct Mol Biol 2008;15(12):1241-2.
7. Huen MS, Chen J. The DNA damage response pathways: at the crossroad of protein modifications. Cell Res 2008; 18(1):8-16.

1. 晴報 Sky Post (2020-07-08): 港大揭新DNA修復網絡　助治癌症
2. HKU Press Release (2020-07-07): HKUMed uncovers novel DNA repair network as promising cancer drug targets
3. 明報 (2020-07-07): 港大破解DNA修復機制　助研治癌
4. 星島日報 (2020-07-07): 港大解構DNA　有望檢測癌病變
5. TOPick 新聞 (2020-07-07): 港大團隊發現全新DNA修復網絡　助未來癌症治療開拓新路向
6. 文匯報 (2020-07-07): 港大發現全新DNA修復網絡助抗癌
7. HK01 (2020-07-07): 港大發現新蛋白助修復基因損傷　為延緩癌病變及治療提供研究方向
8. 香港仔 (2020-07-07): 港大揭新DNA修復網絡助治癌
9. 頭條日報 (2020-07-07): 港大解構DNA　有望檢測癌病變
10. 經濟日報 (2020-07-07): 港大揭新DNA修復治癌　解長壽之謎
11. 巴士的報 (2020-07-07): 香港大學解構DNA　有望檢測癌症病變
12. am730 (2020-07-07): 解構DNA修復網絡　港大研究作為癌症藥物新標靶
13. healthy:D (2020-07-07): 港大解構DNA修復機制　有望早期癌症病變檢測
14. 《健康創富》 (2017-05-21): DNA修復機制新發現有助抗癌藥物發展
15. HKU Press Release (2017-03-23): HKU and USTC Scientists Discover New Strategy to DNA Repair Control
16. 文匯報 (2017-03-24): 港大揭修復DNA關鍵機制
17. 《醫‧藥‧人》醫藥健康雜誌 (2017-03-23): 港大與中國科大發現DNA修復機制
18. 蘋果日報 (2015-10-08): 港大研DNA修復失效基因

1. Research Grants Council - General Research Fund 2020/21, Project Title: A study of the DYRK1A-ARIP4 complex in DNA damage response control (Funded: HKD1,174,620)
2. Research Grants Council - General Research Fund 2021/22, Project Title: Dissecting regulatory pathways for transcription restart following DNA double-strand break repair (Funded: HKD1,134,732)
3. Research Grants Council - General Research Fund 2022/23, Project Title: Role of nuclear phosphoinositides in DNA damage detection and repair control (Funded: HKD1,144,812)
4. Research Grants Council - General Research Fund 2023/24, Project Title: Regulation of Transcription Recovery on the Damaged Chromatin (Funded: HKD1,596,000)

1. Endowed Professorship (2022-2027)
2. Outstanding Young Researcher Award 2014-15, The University of Hong Kong
3. Early Career Award 2012-13, Research Grants Council, Hong Kong
4. Anna Fuller Fund Fellow 2007-2009, Yale University, Connecticut, USA

• Carman Leung (Senior Lab Technician)
• Mengya Xu (PhD Student 2021-)
• Nancy Xiong (PhD Student 2022-)
• Jing Yi (Research Assistant II 2023-)
• Sherry Li (Research Assistant I 2024-)
• Raissa Ng (Research Assistant I 2024-)
• Jung-Eun Kim (Research Assistant II 2024-)