• Functional genomics for translational cancer medicine
• Cancer signaling
• Drug sensitivity and resistance mechanisms

• Instructor, Department of Systems Biology, MD Anderson Cancer Center, USA
• Postdoctoral Fellow, Department of Systems Biology, MD Anderson Cancer Center, USA
• Ph.D., The University of Hong Kong, Hong Kong
• Visiting Scholar, University of British Columbia, Canada
• B.Sc., The University of Hong Kong, Hong Kong

Deregulated signaling pathways in cancer cells drive tumorigenesis and dictate drug responses. These changes in signaling can be caused by genomic aberrations (e.g. gene mutation or copy number variation) or non-genetic network rewiring. Targeting the alterations can be effective anticancer strategies.

The overall goal of the laboratory is to identify potential molecular targets for cancer therapies. Our major focus areas include:

1. Exploring novel genome-informed therapeutic approaches. We are dedicated to: i) characterize driver genomic aberrations and the associated signaling cascades; ii) determine the therapeutic vulnerability engendered by the aberrations; and iii) identify predictive markers of therapeutic responses.
2. Deriving strategies to overcome cancer drug resistance. We investigate the molecular mechanisms by which cancer cells become resistant to pathway inhibitors.

# Corresponding author

1. Ng AS, Zhang S, Mak CY, Zhou Y, Yuen Y, Sharma R, Lu Y, Zhuang G, Zhao W, Pang HH, Cheung LW^#. AKTIP loss is enriched in ERα-positive breast cancer for tumorigenesis and confers endocrine resistance. Cell Reports 2022; 41(11):111821.
2. Li X, Lau AY, Ng AS, Aldehaiman A, Zhou Y, Ng PK, Arold ST^#, Cheung LW^#. Cancer-associated mutations in the p85α N-terminal SH2 domain activate a spectrum of receptor tyrosine kinases. Proc Natl Acad Sci USA 2021; 118(37):e2101751118.
3. Mak VC, Li X, Rao L, Zhou Y, Tsao SW, Cheung LW^#. p85β alters response to EGFR inhibitor in ovarian cancer through p38 MAPK-mediated regulation of DNA repair. Neoplasia 2021; 23(7):718-30.
4. Rao L, Mak VC, Zhou Y, Zhang D, Li X, Fung CC, Sharma R, Gu C, Lu Y, Tipoe GL, Cheung AN, Mills GB and Cheung LW^#. p85β regulates autophagic degradation of AXL to activate oncogenic signaling. Nature Communications 2020; 11(1):2291.
5. Li X, Mak VC, Zhou Y, Wang C, Wong ES, Sharma R, Lu Y, Cheung AN, Mills GB and Cheung LW^#. Deregulated Gab2 phosphorylation mediates aberrant AKT and STAT3 signaling upon PIK3R1 loss in ovarian cancer. Nature Communications 2019; 10(1):716.
6. Ng PK, Li J, Jeong KJ, Shao S, Chen H, Tsang YH, Sengupta S, Wang Z, Bhavana VH, Tran R, Soewito S, Minussi DC, Moreno D, Kong K, Dogruluk T, Lu H, Gao J, Tokheim C, Zhou DC, Zeng J, Ip CK, Ju Z, Wester M, Yu S, Li Y, Vellano C, Schultz N, Karchin R, Ding L, Lu Y, Cheung LW, Chen K,  Shaw KR, Meric-Bernstam F, Scott KL, Yi S, Sahni N, Liang H and Mills GB. Systematic Functional Annotation of Somatic Mutations in Cancer. Cancer Cell 2018; 33:450-62.
7. Takiar V, Ip CK, Gao M, Mills GB^# and Cheung LW^#. Neomorphic mutations create therapeutic challenges in cancer. Oncogene 2017; 36:1607-18.
8. Han L, Diao L, Yu S, Xu X, Li J, Zhang R, Yang Y, Werner HM, Eterovic AK, Yuan Y, Li J, Nair N, Minelli R, Tsang YH, Cheung LW, Jeong KJ, Roszik J, Ju Z, Woodman SE, Lu Y, Scott KL, Li JB, Mills GB and Liang H. The Genomic Landscape and Clinical Relevance of A-to-I RNA Editing in Human Cancers. Cancer Cell 2015; 28(4):515-28
9. Cheung LW, Walkiewicz KW, Besong TM, Guo H, Hawke DH, Arold ST and Mills GB. Regulation of the PI3K Pathway through a p85a Monomer-Homodimer Equilibrium. eLife 2015; 4:e06866.
   ▪ Featured in Editors’ Choice in Science Signaling 2015; 8(389) ec224
10. Cheung LW^#, Yu S, Zhang D, Li J, Ng PK, Panupinthu N, Mitra S, Ju Z, Yu Q, Liang H, Hawke DH, Lu Y, Broaddus RR, and Mills GB. A recurrent neomorphic p85α mutant activates the MAPK pathway dictating therapeutic response to MAPK pathway inhibitors. Cancer Cell 2014; 26:479-94. 
    ▪ Featured in Preview in Cancer Cell 2014; 26(4): 445–447.
    ▪ Research Watch in Cancer Discovery 2014 December 4; OF14.
    ▪ Editors’ Choice in Science Signaling 2014; 7(349) ec306.
    ▪ Research Highlight in Nature Review Cancer 2014;14, 766–767.
11. Cheung LW, Mak AS, Yung S, Chan TM, Leung PC and Wong AS. Targeting gonadotropin-releasing hormone receptor inhibits the early step of ovarian cancer metastasis by modulating tumor-mesothelial adhesion. Molecular Therapy 2013; 21:78-90.
12. Liang H*, Cheung LW*, Li J, Ju Z, Yu S, Stemke-Hale K, Dogruluk T, Lu Y, Liu X, Gu C, Guo W, Scherer SE, Carter H, Westin SN, Dyer MD, Verhaak RG, Zhang F, Karchin R, Liu CG, Lu KH, Broaddus RR, Scott KL, Hennessy BT, Mills GB. Whole-exome sequencing combined with functional genomics reveals novel candidate driver cancer genes in endometrial cancer. Genome Research 2012; 22:2120-9.
    * Equal contribution
12. Cheung LW*^#, Hennessy BT*, Li J, Yu S, Myers AP, Djordjevic B, Lu Y, Stemke-Hale K, Dyer MD, Zhang F, Ju Z , Cantley LC, Scherer SE, Liang H, Lu KH, Broaddus RR, and Mills GB. High frequency of PIK3R1 and PIK3R2 mutations in endometrial cancer elucidates a novel mechanism for regulation of PTEN protein stability. Cancer Discovery 2011; 1:170-85.
    * Equal contribution
    ▪ Featured article with commentary
    ▪ Most highly cited Cancer Discovery article in 2011

RGC - General Research Fund 2022/2023 (PI)
RGC - General Research Fund 2021/2022 (PI)
RGC - General Research Fund 2020/2021 (co-I)
RGC - General Research Fund 2020/2021 (co-I)
Health and Medical Research Fund 2019 (PI)
RGC - General Research Fund 2018/2019 (PI)
NSFC Science Fund for Young Scholars 2017 (PI)
RGC - Early Career Scheme 2016/2017 (PI)

• Faculty Outstanding Research Output Award, LKS Faculty of Medicine, HKU (2020)
• NSFC Excellent Young Scientists Fund (Hong Kong and Macau) (2020)
• Scholar Award for outstanding translational cancer research, The US Chinese Anti-Cancer Association (USCACA) and the Asian Fund for Cancer Research (AFCR) (2017)     
• Travel Award, Early Career Researcher Workshop: Big data at the heart of 21st Century Research, Universitas 21 (2016)
• Women in Cancer Research Scholar Award, American Association for Cancer Research (2015)
• Uterine SPORE (Special Program of Research Excellence) Career Development Award, MD Anderson Cancer Center & National Cancer Institute (2014-2015)
• Computational Cancer Biology Training Grant, Cancer Prevention and Research Institute of Texas (2012-2014)
• Citation of Excellence Award (3rd Annual Research Award), Division of Cancer Medicine, MD Anderson Cancer Center (2013)
• AMGEN Award in Basic Science Research, MD Anderson Cancer Center (2013)
• AMGEN Award in Basic Science Research, MD Anderson Cancer Center (2011)

• Mills GB, Lu Y, Liang H and Cheung LW. Invention title: Efficient functional genomics platform.