Department of Pathology

Research Interest

My research focuses on leveraging patient-derived gastrointestinal (GI) cancer organoids to advance precision oncology and therapeutic development. We established the first local GI organoid culture platform, generating over 100 pairs of tumor and normal organoids from patients with GI cancers, as well as organoids from pre-neoplastic lesions, such as intestinal metaplasia (IM), adenoma, and dysplasia (Cell Stem Cell 2018; GUT 2020, 2023, 2025). This platform has enabled significant discoveries, including the role of RHOA mutations and ARHGAP fusions in downregulating RHO signaling and conferring anoikis resistance (Nature Genetics 2014; GUT 2023), and the functional impact of RNF43 hotspot mutations (GUT 2017) using CRISPR/Cas9. Additionally, I modeled ganciclovir-induced mutations in organoids to investigate cancer risk in transplant patients (Genome Medicine 2022).

We aim to advance GI cancer treatment discovery by integrating biobanking, multi-omic analyses, and large-scale chemical and genetic screens. Our mechanistic studies focus on elucidating molecular connections between drug sensitivity and cancer subtypes to optimize combination therapies and overcome resistance. To enhance our organoid platform, we are developing co-cultures with fibroblasts and immune cells to better recapitulate tumor microenvironments and predict treatment responses. Furthermore, we utilize pre-neoplastic organoids to explore lineage plasticity and fetal reversion, aiming to develop innovative cancer prevention strategies.

Research Grants

InnoHK fund (2020)
Research Grant Council- General Research Fund (2016, 2019)
Health and Medical Research Fund (2015, 2017)

Student Supervision

Chan Nok Man (MPhil): 2024 – Present
Lee Chi Ho (MPhil): 2022 – 2024
Choy Hiu Ching (MPhil): 2021 – 2024
Or Chung Sze (MPhil): 2018 – 2020
Yue Siu Kuen Sarah (PhD): 2016 – 2021
Postgraduate positions are available. Please send email to Dr. Helen Yan yanhelen@hku.hk for more details.

Awards and Honors

Research Output Prize, HKU (2019)
Faculty Outstanding Research Output Award, HKU (2015, 2017, 2021, 2023)

Selected Publications

Click here for detail publication list on ORCID

Coorens THH, Collord G, Jung H, Wang Y, Moore L, Hooks Y, Mahbubani K, Law SYK, Yan HHN, Yuen ST, Saeb-Parsy K, Campbell PJ, Martincorena I, Leung SY, Stratton MR. The somatic mutation landscape of normal gastric epithelium. (2025) Nature, doi: 10.1038/s41586-025-08708-6. PMID: 40108450. Impact factor: 50.5
Yue SSK, Tong Y, Siu HC, Ho SL, Law S, Tsui WY, Chan D, Huang Y, Chan ASY, Yun SW, Hui HS, Choi JE, Hsu MSS, Lai PL, Chan AS, Yuen ST, Clevers H, Leung SY#, Yan HHN#. Divergent lineage trajectories and genetic landscapes in human gastric intestinal metaplasia organoids associated with early neoplastic progression. (2025) GUT, 74(4):522-538. PMID: 39572083. Impact factor: 23.1. # Corresponding authors
Yan HHN#, Chan AS, Lai FPL, Leung SY#. Organoid cultures for cancer modelling. (2023) Cell Stem Cell, 30:917-937. PMID: 37315564. Impact factor: 19.8. Citation: 27. # Corresponding authors
Tong Y, Cheng PSW, Or CS, Yue SSK, Siu HC, Ho SL, Law S, Tsui WY, Chan D, Ma SKY, Lee SP, Chan ASY, Chan AS, Yun SW, Hui HS, Yuen ST, Leung SY#, Yan HHN#. Escape from cell-cell and cell matrix adhesion dependence underscores disease progression in gastric cancer organoid models. (2023) GUT, 72:242-255. PMID: 35705367. Impact factor: 23.1. Citation: 10. # Corresponding authors
• Awarded the 2023 Outstanding Research Output Award, Faculty of Medicine, HKU
Lee BCH, Robinson P, Coorens T, Yan HHN, Olafsson S, Lee-Six H, Sanders M, Siu HC, Hewinson J, Yue SSK, Tsui WY, Chan ASY, Chan AKW, Ho SL, Campbell P, Martincorena I, Buczacki S, Yuen ST, Leung SY, Stratton M. Mutational landscape of normal epithelial cells in Lynch Syndrome patients. (2022) Nat Commun, 13:2710. PMID: 35581206. Impact factor: 14.7. Citation: 25.
Fang H*, Yan HHN*, Bilardi RA*, Flensburg C, Yang H, Barbour JA, Siu HC, Turski M, Chew E, Xu Z, Lam ST, Sharma R, Xu M, Li J, Ip HW, Cheung CYM, Huen MSY, Sweet-Cordero EA, Majewski IJ, Leung SY, Wong JWH. Ganciclovir-induced mutations are present in a diverse spectrum of post-transplant malignancies. (2022) Genome Medicine, 14:124. PMID: 36316687. Impact factor: 10.4. Citation: 8. *Co-first authors contributed equally to this work.
^Yan HHN#, Siu HC, Ho SL, Yue SSK, Gao Y, Tsui WY, Chan D, Chan AS, Wong JWH, Man AHY, Lee BCH, Chan ASY, Chan AKW, Hui HS, Cheung AKL, Law WL, Lo OSH, Yuen ST, Clevers H, Leung SY#. Organoid cultures of early-onset colorectal cancers reveal distinct and rare genetic profiles. (2020) GUT, 69: 2165-2179. PMID: 32217638. Impact factor: 23.1. Citation: 67. # Corresponding authors
•Awarded the 2021 Outstanding Research Output Award, Faculty of Medicine, HKU
Yan HHN#, Siu HC, Law S, Ho SL, Yue SSK, Tsui WY, Chan D, Chan AS, Ma S, Lam KO, Bartfeld S, Man AHY, Lee BCH, Chan ASY, Wong JWH, Cheng PSW, Chan AKW, Zhang J, Shi J, Fan X, Kwong DLW, Mak TW, Yuen ST, Clevers H, Leung SY#. A comprehensive human gastric cancer organoid biobank captures tumor subtype heterogeneity and enables therapeutic screening. (2018) Cell Stem Cell, 23:882-897. PMID: 30344100. Impact factor: 19.8. Citation: 484. # Corresponding authors

• As of Sept/Oct 2024, this highly cited paper received enough citations to place it in the top 1% of the academic field of Molecular Biology & Genetics based on a highly cited threshold for the field and publication year. Data from Essential Science Indicators

• Awarded the 2019 Research Output Award, HKU
Yan HHN*, Lai JCW*, Ho SL, Leung WK, Law WL, Lee JFY, Chan AKW, Tsui WY, Chan ASY, Lee BCH, Yue SSK, Man AHY, Clevers H, Yuen ST, Leung SY. RNF43 germline and somatic mutation in serrated neoplasia pathway and its association with BRAF mutation. (2017) GUT, 66:1645-1656. PMID: 27329244. Impact factor: 23.1. Citation: 145. *Authors contributed equally to this work.
Wang K*, Yuen ST*, Xu JC*, Lee SP*, Yan HHN*, Shi ST, Siu HC, Deng S, Chu KM, Law S, Chan KH, Chan ASY, Tsui WY, Ho SL, Chan AKW, Man JLK, Foglizzo V, Ng MK, Chan AS, Ching YP, Cheng GHW, Xie T, Fernandez J, Li VS W, Clevers H, Rejto PA, Mao M, Leung SY. Whole-genome sequencing and comprehensive molecular profiling identify new driver mutations in gastric cancer. (2014) Nature Genetics, 46:573-82. Impact factor 31.8. PMID: 24816253. Citation: 843. *Co-first authors contributed equally to this work.

• As of Sept/Oct 2024, this highly cited paper received enough citations to place it in the top 1% of the academic field of Molecular Biology & Genetics based on a highly cited threshold for the field and publication year. Data from Essential Science Indicators

• Awarded the 2015 Outstanding Research Output Award, Faculty of Medicine, HKU