• Genome engineering
• CRISPR technology
• Protein engineering
• Synthetic biology
• Functional genomics
• Combinatorial genetics
• Combination therapy
• Cancer therapeutics development

• Postdoctoral Fellow/Associate, MIT Synthetic Biology Center, Research Laboratory of Electronics, Massachusetts Institute of Technology, USA (2012-2016)
• Ph.D., The Hong Kong University of Science and Technology, Hong Kong (2007-2011)
• M.Phil., The Chinese University of Hong Kong, Hong Kong (2005-2007)
• B.Sc., The Chinese University of Hong Kong, Hong Kong (2002-2005)

Many human diseases are caused by multigenic perturbations. Our research takes an integrative approach leveraging on various techniques in synthetic biology, CRISPR-based genome engineering, high-throughput sequencing, molecular biology, and genetics to decode the complex genetic bases of human diseases including cancers and neurodegenerative disorders. Our laboratory aims to develop and apply new technologies to interrogate and understand the complex biological systems, and rationally design and engineer genetic circuits for providing new biomedical and biotechnological solutions.

Research topics will focus on developing and applying cutting-edge technologies (e.g. CombiGEM, CombiGEM-CRISPR, and CombiSEAL) for studying complex disease biology, devising new therapeutic strategies, and engineering new proteins. Interested candidates are encouraged to contact Dr. Wong and our lab webpage (https://awhku.github.io) for more details.

Research Articles

1. Thean, D.*, Chu, H.Y.*, Fong J.H.C., Chan, K.C.B., Zhou, P., Kwok, C.C.S., Chan, Y.M., Mak, S.Y.L., Choi, G.C.G., Ho, J.W.K., Zheng, Z., Wong, S.L.A.# Machine learning-coupled combinatorial mutagenesis enables resource-efficient engineering of CRISPR-Cas9 genome editor activities. Nature Communications 13(1), 2219 (2022) (* Equal contributions; #Corresponding author)
2. Yuen, C*., Thean, D.G.*, Chan, B.K.C.*, Zhou, P.*, Kwok, C.S.C.*, Chu, H.Y., Cheung, M., Wang, B., Chan, Y.M. ,Mak, S., Leung, A.Y.L., Choi, G.C.G., Zheng, Z., Wong, S.L.A.#. High-fidelity KKH variant of Staphylococcus aureus Cas9 nucleases with improved base mismatch discrimination. Nucleic Acids Research 50(3): 1650-1660 (2022) (* Equal contributions; #Corresponding author)
3. Wang, T, Long, K., Zhou, Y., Jiang, X., Liu, J., Fong, J.H.C., Wong, S.L.A., Ng, W.L., Wang, W. Optochemical control of mTOR signaling and mTOR-dependent autophagy. ACS Pharmacology & Translational Science 5(3), 149-155 (2022).
4. Xu, F.*, Tong, M.*, Tong, S.W.C., Chan, K.C.B., Chu, H.Y., Wong, T.L., Fong, H.C.J., Cheung S.H.M., Mak, H.M.K., Pardeshi, L., Huang, Y., Wong, K.H., Choi, C.G.G., Ma, S.#, Wong, S.L.A.#. A combinatorial CRISPR-Cas9 screen identifies ifenprodil as an adjunct to sorafenib for liver cancer treatment. Cancer Research 81(24):6219-6232 (2021) (* Equal contributions; #Corresponding authors)
5. Cao, J., Novoa, E.M., Zhang, Z., Chen, W.C.W., Liu, D., Choi, G.C.G, Wong, S.L.A., Wehrspaun, C., Kellis, M., Lu, T.K. High-throughput 5′ UTR engineering for enhanced protein production in non-viral gene therapies. Nature Communications 12: 4138 (2021)
6. Zhou, P., Chan, K.C.B., Wan, Y.K., Yuen, T.L.C., Choi, C.G.G., Li, X., Tong, S.W.C., Zhong, S.W.S., Sun, J., Bao, Y., Mak, Y.L.S., Chow, Z.Y.M., Khaw, J.V., Leung, S.Y., Zheng, Z., Cheung, W.T.L., Tan, K., Wong, K.H., Chan, H.Y.E., Wong, S.L.A.# Three-way combinatorial CRISPR screen for analysing interactions among druggable targets. Cell Reports 32(6), 108020 (2020) (#Corresponding author)
7. Li, X., Yang, K.Y., Chan, V., Leung, K.T., Zhang, X.B., Wong, S.L.A., Chong, C., Wang, C.C., Ku, M., Lui, K.O.. Single cell RNA-Seq reveals that CD9 is a negative marker of glucose-responsive pancreatic beta-like cells derived from human pluripotent stem cells. Stem Cell Reports S2213-6711(20): 30384-2 (2020)
8. Choi, C.G.G., Zhou, P., Yuen, T.L.C., Chan, K.C.B., Xu, F., Bao, S., Chu, H.Y., Thean, D., Tan, K., Wong, K.H., Zheng, Z., Wong, S.L.A.# Combinatorial mutagenesis en masse optimizes SpCas9’s genome-editing activities. Nature Methods 16(8), 722-730 (2019) (#Corresponding author)
9. Leung, C.S., Li ,J., Xu, F., Wong, S.L.A., Lui, K.O. Ectopic expression of recipient CD47 inhibits mouse macrophage-mediated immune rejection against human stem cell transplants. FASEB J. 33(1): 484-493 (2019).
10. Wong, S.L.A.*, Choi, C.G.G.*, Cui, C.H.*, Pregernig, G., Milani, P., Adam, M., Perli, S.D., Kazer, S.W., Gaillard, A., Hermann, M., Shalek, A.K., Fraenkel, E., Lu, T.K. Multiplexed barcoded CRISPR-Cas9 screening enabled by CombiGEM. Proceedings of National Academy of Sciences 113(9), 2544-2549 (2016). (*Equal contributions)
11. Wong, S.L.A., Choi, C.G.G., Cheng, A.A., Purcell, O., Lu, T.K. Massively parallel high-order combinatorial genetics in human cells. Nature Biotechnology 33(9), 952-961 (2015).
12. Lai, K.O., Wong, S.L.A., Cheung, M.C., Xu, P., Liang, Z., Lok, K.C., Xie, H., Palkos, M.E., Yung, W.H., Tessarollo, L., Cheung, Z.H., Ip, N.Y. TrkB phosphorylation by Cdk5 is required for activity-dependent structural plasticity and spatial memory. Nature Neuroscience 15(11), 1506-1515 (2012).
13. Wong, S.L.A., Lee, R.H.K., Cheung, A.Y., Yeung, P.K., Chung, S.K., Cheung, Z.H. and Ip, N.Y. Cdk5-mediated phosphorylation of endophilin B1 is required for induced autophagy in models of Parkinson’s disease. Nature Cell Biology 13(5), 568-579 (2011).
14. Wong, S.L.A., Chan, W. M. and Chan, H.Y.E. Sodium dodecyl sulfate-insoluble oligomers are involved in polyglutamine degeneration. FASEB J. 22(9), 3348-3357 (2008).
15. Wong, S.L.A., Chen, Y.W., Chan, C.M., Chan, C.S.M., Chan, P.K.S., Chui, Y.L., Fung, K.P., Waye, M.M.Y., Tsui, S.K.W. and Chan, H.Y.E. In vivo functional characterization of the SARS Coronavirus 3a protein in Drosophila. Biochem. Biophy. Res. Comm. 337, 720-729 (2005).

Book Chapters/ Reviews/ Protocols/ Commentaries 

1. Kellogg E.H., Gootenberg J., Abudayyeh O., Wong, S.L.A., Dahlman J., Lapinaite A., Myhrvoid C., Liu C.C., Hsu P.D., Mali P., Qi L.S. What are the current bottlenecks in development and applying CRISPR technologies? Cell Systems 13(8): 589-593 (2022)

2. Chu, H.Y. Wong, S.L.A.# Facilitating Machine Learning-Guided Protein Engineering with Smart Library Design and Massively Parallel Assays. Advanced Genetics 2100038 (2021) (#Corresponding author)
3. Thean D.G.L., Wong, S.L.A#. Combinatorial genetics methods for discovering high-order regulatory combinations and engineering genetic drivers for neural differentiation. Neural Regeneration Research 16, 2403-2404 (2021) (#Corresponding author)
4. Zhou P., Wan Y.K., Chan K.C., Choi C.G.G., Wong S.L.A#. Extensible combinatorial CRISPR screening in mammalian cells. STAR Protocols, 2(10): 100255 (2021) (#Corresponding author)
5. Wan Y.K., Choi C.G.G., Wong, S.L.A#. High-Throughput Protein Engineering by Massively Parallel Combinatorial Mutagenesis. In: Chen Y.W., Yiu CP.B. (eds) Structural Genomics. Methods in Molecular Biology, vol 2199. Humana, New York, NY. (2021) (#Corresponding author)
6. Wong, S.L.A., Choi, C.G.G., Lu, T.K. Deciphering combinatorial genetics. Annual Review of Genetics 50, 515-538 (2016).
7. Wong, S.L.A., Cheung, Z.H. and Ip, N.Y. Molecular machinery of macroautophagy and its deregulation in diseases. Biochimica et Biophysica Acta – Molecular Basis of Disease 1812(11), 1490-1479 (2011).
8. Huen, N.Y.M., Wong, S.L.A. and Chan, H.Y.E. Transcriptional malfunctioning of heat shock protein gene expression in spinocerebeller ataxias. The Cerebellum 6(2), 111-117 (2006).

• am730 健康專欄: “CRISPR基因編輯技術 改良基因手術刀” (May 23, 2022)
• Croucher Foundation News: “High fidelity genome editing technique developed” (March 13, 2022)
• 大公報-港聞:“港大研發新型基因编輯工具”(March 10, 2022)
• HKU and HKUMed press releases: “港大醫學院成功研發 　具有可分辨單鹼基突變的CRISPR-Cas9基因編輯酶 　可用於精準基因治療”(March 10, 2022)
• Mirage News: “HKUMed engineers highly accurate SaCas9 enzymes with single-base precision for therapeutic genome editing” (March 9, 2022)
• Topick.hket.com: “港大醫學院研發新型基因編輯工具 有助醫治更多遺傳疾病”(March 9, 2022)
• 星島日報-港聞:“港大醫學院成功研發篩選治療肝癌新藥物組合療法”(December 20, 2021)
• 有線新聞:“港大新藥物組合治肝癌　血管藥配標靶藥遏癌細胞複製力”(December 20, 2021)
• 信報 -港聞:“港大醫學院篩選出治療肝癌新藥物組合療法”(December 20, 2021)
• 頭條日報 -港聞:“港大醫學院成功研發篩選治療肝癌新藥物組合療法”(December 20, 2021)
• 東網即時:“ 港大醫學院研新藥物組合　成功篩選治療肝癌新療法”(December 20, 2021)
• Healthy:D:“ 港大醫學院成功開發治療新肝癌藥物組合療法”(December 21, 2021)
• HKUMed press releases: “港大醫學院研究團隊通過CRISPR-Cas9多基因剔除技術平台成功篩選出治療肝癌的新藥物組合療法”(December 20, 2021)
• (星島日報)– 透視未來醫學》基因編輯系列 - [專題] 基因編輯掀科學革命, 遺傳病人迎曙光改 (Dec 23, 2020) 
• Feature Story of Research and Innovation: “HKUMed researchers create a screening platform to discover new combination therapies for ovarian cancer and Parkinson’s disease”, School of Biomedical Sciences (SBMS) Newsletter Issue 02, LKS Faculty of Medicine, HKU (Dec, 2020)
• Croucher Foundation News: “Accelerating next-generation protein engineering” (August 9, 2019)
• 成報 -港聞:“港大開發蛋白質優化平台節省成本⋯” (July 18, 2019)
• HKU and HKUMed press releases: “香港大學開發首個蛋白質優化平台,提升基因編輯酶的準確性和效率”(July 17, 2019)    
• Story of Research and Innovation: Across the divide - “Straddling Medicine and Engineering”, The Review 2017, HKU (2017)
• 東網即時–: “研治癌及改善骨質疏鬆新技術, 學者獲嘉許⋯” (Oct 26, 2016)
• 大公報 – 教育: “15人奪「傑青學者」獎⋯” (Oct 27, 2016)
• 星島日報– 教育: “⋯學者探索治療卵巢癌⋯” (Oct 27, 2016)
• 文匯報 - 新聞透視眼: “⋯黃兆麟快找治癌藥『最佳組合』⋯”  (Oct 27, 2016)
• Croucher Foundation News: “Looking for treatments in the gene: Dr Alan Wong decodes disease genetics” (August 20, 2016)

• RGC – General Research Fund (GRF) 2022/23 (PI)
• RGC – General Research Fund (GRF) 2022/23 (Co-I)
• Health@InnoHK - Centre for Oncology and Immunology, Innovation and Technology Commission of the HKSAR, 2020 (Team Leader in Functional Genomics)
• RGC - Research Impact Fund (RIF) 2020/21 (Co-PI)
• RGC – Theme-based Research Scheme 2020/2021 (Co-PI)
• RGC – General Research Fund (GRF) 2020/21 (PI)
• RGC – General Research Fund (GRF) 2019/20 (PI)
• CRF – Collaborative Research Fund (CRF) 2019/2020 (Co-PI)
• Karolinska Institutet – MWLC Associate Membership Fund 2019, Karolinska Institutet, HK (PI)
• CRF – Collaborative Research Fund (CRF) 2018/2019 (Co-PI)
• ITF – Innovation and Technology Fund (ITF) Tier 3 2018/2019 (PI)
• RGC – General Research Fund (GRF) 2018/2019 (PI)
• RGC – General Research Fund (GRF) 2018/2019 (Co-I)
• RGC – Theme-based Research Scheme 2016/2017 (Co-I)
• RGC – Early Career Scheme (ECS) 2016/2017 (PI)
• Health and Medical Research Fund (HMRF) 2015 (PI)
• Croucher Startup Allowance (PI)

• Faculty Outstanding Research Output Award 2020, LKS Faculty of Medicine, HKU
• NSFC Excellent Young Scientists Fund (Hong Kong and Macau) 2020 (PI)
• Early Career Award, Research Grant Council, Hong Kong (2016/2017)
• Croucher Fellowship (2012-2014)
• Young Scientist Award in Life Science, Hong Kong Institution of Science (2011)
• Postgraduate Achievement Award, Division of Life Science, HKUST (2010)
• Best Teaching Assistant Award in Biochemistry of Nucleic Acid, HKUST (2009/2010)
• Croucher Research Studentship (2008-2010)
• Butterfield-Croucher Studentship (2008/2009)
• Sir Edward Youde Memorial Fellowship (2008/2009)
• Essex Bio-Technology Limited Scholarship (2007/2008)
• Kwok Ching Tong Scholarship (2004/2005)
• Wu Chung Scholarship (2003/2004)
• Ho Tim Scholarship (2002/2003)
• United College Endowment Fund Prize, CUHK (2002/2003)

• Ms. Maggie CHEUNG (Technical Officer)
• Mr. Frederic FUNG (Technical Officer)
• Dr. Singuang CHEN (PDF)
• Dr. Athena CHU (PDF)
• Dr. Ricky POON (PDF)
• Dr. Chu ZHANG (PDF)
• Dr. Peng ZHOU (PDF)
• Ms. Becky CHAN (PhD student; UPF awardee)
• Mr. Charles CHAN (PhD student; UPF awardee)
• Mr. John FONG (PhD student; HKPF and HKU-PS awardee)
• Ms. Bei WANG (PhD student)
• Ms. Chaya YUEN (PhD student)
• Ms. Dawn THEAN (Research Assistant)
• Mr. Yuanbiao MOU (Research Assistant)