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Kanaga Sabapathy



Professor Kanaga Sabapathy obtained his B.Sc (Hons) degree in Zoology from the NUS, and then his Ph.D. in Molecular & Cellular Immunology from the IMCB, Singapore, in 1995. His post-doctoral work was conducted at the Institute of Molecular Pathology in Vienna with Dr Erwin Wagner, studying the c-Jun-N-terminal kinase stress signaling pathway, using genetically-engineered mice. He moved to the National Cancer Centre Singapore (NCCS) in late 1999 as the Principal Investigator of the Laboratory of Molecular Carcinogenesis, and since 2013, is the overall Head of the Division of Cellular & Molecular Research, overseeing NCCS’ research activities. 

Professor Sabapathy is the Deputy Program Director and Professor with the Cancer and Stem Cell Biology Program at Duke-NUS.  He is also the Research Director of the Academic Clinical Program in Oncology at SingHealth, a joint Professor with the Department of Biochemistry at NUS and a joint Research Director at the IMCB.  

Professor Sabapathy is a Fellow to the Royal College of Pathologists (UK), and was awarded the inaugural National Research Foundation Investigatorship award (Class of 2015) in recognition of his work, to further his investigations on ground-breaking, high-risk research.

The Sabapathy lab ( is focused (i) on understanding the mechanistic basis of cellular transformation, and resistance to cancer therapy, by investigating the key p53/p73 tumor-suppressor pathway; & (ii) on generating novel therapeutic strategies to develop tumor- and mutation-specific therapeutic molecules.


The p53/p73 family of tumor-regulators

Cancer genome sequencing efforts have led to the identification of major alterations that occur in a wide variety of genes. Of these, some – especially those that code for enzymes - have been deemed “druggable” and hence, intensely pursued, albeit being of relevance to a small population. On the other hand, many genetic mutations have not received significant attention from the drug discovery perspective, simply due to the perception that they are “undruggable”. One such gene family is the p53 family of tumor suppressors, which are transcription factors. While p53 is the most mutated gene in cancers, its homologue p73 is often overexpressed in cancers. Studies have demonstrated a critical role for mutant p53 and overexpressed p73 in tumor promotion and resistance to therapy. While these molecules could be potential therapeutic targets of enormous benefit to patients, they have not been subjected to major drug discovery efforts due to the difficulties in targeting transcription factors.


Over the years, we have performed systematic analyses to understand the functions of mutant p53, and have demonstrated that p53 mutants may have both common and differing properties, indicating that any targeting effort should be aimed at generating “specific-mutant-p53”-targteing molecules (rather than pan-mutant p53). In this aspect, we are embarking on a program to identify novel molecules that would target mutant p53 expression without having an effect on the WT allele, using a multitude of novel screening strategies.


p73 is a homologue of p53 and belongs to the same family of tumor suppressors. It exists as 2 major forms: the full-length TAp73 from (similar to p53), and the amino-terminal truncated DNp73 (similar to p47). However, unlike p53, it is hardly mutated, but both forms are often variably over-expressed in many cancers, suggesting that p73 may have other differing roles in regulating tumorigenesis. While absence of TAp73 promotes tumor formation in mice – albeit weakly, highlighting a role in tumor suppression, its role in supporting tumor growth had been controversial. Our work over the years has focused on understanding this property, and we had earlier shown that TAp73 is capable of driving cellular proliferation in specific contexts, through the regulation of AP-1 target genes. Recently, we have demonstrated that TAp73 is capable of inducing the expression of angiogeneic genes, especially in hypoxic conditions that are prevalent in tumors. Thus, TAp73 appears to be utilizing multiple mechanisms to promote cancer cell growth, implying that these tumor-promoting pathways may be targetable for improving therapeutic response. We have therefore embarked on identifying key molecular determinants of the TAp73 pathway through high-throughput whole-genome siRNA screens and proteomics approaches, with the eventual goal of inhibiting them to reduce angiogenesis and proliferation of cancer cells. In addition, given the diametrically opposite roles of TAp73 in both promoting and suppressing tumor formation, we are now poised to address the question on how a transcription factor like TAp73 is able to regulate these seemingly opposite cell fate outcomes. We have therefore started answering this question of cell fate, using novel screening technology and next-generation animal models to study the spatial and temporal role of TAp73 both within the tumor exclusively, as well as in the stromal compartments.


Mouse models for hepatocellular carcinoma, liver fibrosis and liposarcoma

Another major effort in the laboratory is to develop mouse models that would recapitulate the human cancer conditions as best as possible, using state-of-the-art genetic engineering technology. This will enable the identification of novel biomarkers for early detection, as well as potential molecular targets for timely-intervention. In this regard, we have been working on modeling hepatocellular carcinoma (HCC), and liver fibrosis, and have generated mouse models that recapitulate human HCC, both molecularly and histologically. Moreover, we have established the liver fibrosis model in mice, using carbon-tetrachloride, where the fibrotic symptoms could regress upon withdrawal of treatment. We are now interrogating the critical aspects of the fibrotic process, through the analysis of the functions of several transcription factors that are major regulators of liver development and pathology, through their deletion in multiple cells types of the liver.


Other efforts are also ongoing to establish mouse models for liposarcoma, tumors that arise from fat cells (adipocytes) in soft tissues. Though surgery is the main mode of treatment, the understanding of this disease is limited due it being not a common cancer, and hence, treatment modalities have been restricted. While the process of adipogenesis has been well studied, knowledge of the transformation of an adipocyte to liposarcomas is limiting due to the lack of effective model systems to study the development and progression of this disease. Mdm2, the negative regulator of the tumor suppressor p53, is often amplified in all types of sarcomas. Thus, we are generating mouse models in which selective genetic changes are introduced in the germ-line conditionally to follow the transformation of the adipocytes, which will provide a paradigm for studying the biology of liposarcomas, and could open up new opportunities for treatment.


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Prospective students to apply through Duke-NUS (, SINGA ( and NUS ( PhD program scholarships.


Interested A*STAR scholars and post-doctoral fellows to contact the PI directly.

Selected Publications: 

  1. “Distinct roles for JNK1 and JNK2 in regulating JNK activity and c-Jun-dependent cell proliferation”. Sabapathy K*, Hochedlinger K, Nam SY, Bauer A, Karin M, Wagner EF. Molecular Cell. 2004.15(5):713-25. 
  2. “p73 supports cellular growth through c-Jun-dependent AP-1 transactivation”. Vikhansyaka F, Toh WH, Dulloo I, Wu Q, Boominathan L, Ng HH, Vousden K, Sabapathy K. Nature Cell Biol. 2007.9:698-705.
  3. “The anti-apoptotic DeltaNp73 is degraded in a c-Jun-dependent manner upon genotoxic stress through the antizyme-mediated pathway”. Dulloo I, Gopalan G, Melino G, Sabapathy K. Proc Nat Acad Sci. 2010. 107:4902-7.
  4. “Cell-type, dose and mutation-type specificity dictate mutant p53 functions in vivo.” Lee MK, Teoh WW, Phang BH, Tong WM, Wang ZQ and Sabapathy K. Cancer Cell. 2012. 22(6):751-64.
  5. “Hypoxia-inducible TAp73 regulates the angiogenic transcriptome and supports tumorigenesis.” Dulloo I, Phang BH, Othman R, Tan SY, Vijayaraghavan A, Goh LK, Martin-Lopez M, Marques MM, Li CW, Wang DY, Marin MC, Xian W, McKeon F and Sabapathy K. Nature Cell Biol. 2015. 17(4):511-23.
  6. “Molecular characterization of hepatocarcinogenesis using mouse models.” Teoh WW, Xie M, Vijayaraghavan A, Yaligar J, Tong WM, Goh LK and Sabapathy K. Disease Models and Mechanisms. 2015. 8(7):743-53.
  7. “Amino-terminal p53 mutations lead to expression of apoptosis proficient p47 and prognosticate better survival, but predispose to tumorigenesis”.   Phang BH, Othman R, Bougeard G, Chia RH, Frebourg T, Tang CL, Cheah PY, Sabapathy K.  Proc Natl Acad Sci U S A. 2015. 112(46):6349-6358.
  8. “Genome-wide AFB1-induced mutational signatures in cells, mice and human tumors – implications for molecular epidemiology”.  Huang MN, Yi W, Teoh WW, Ardin M, Jusakul A, Ng A, Abedi-Ardekani B, Villar S, Myint SS, Othman R, Poon SL, Heguy A, Olivier M, Hollstein M, Tan P, Teh BT,  Sabapathy K*, Zavadil J*, Rozen SG*. Genome Biology. 2017. 27(9):1475-1486.
  9. “Therapeutic targeting of p53: all mutants are equal, but some mutants are more equal than others”.   Sabapathy K, Lane DP. Nature Review Clinical Oncology. 2018. 15(1):13-30.
  10. “Novel tools for precision medicine - monoclonal antibodies against specific p53 hot-spot mutants”.  Hwang LA, Phang BH, Liew OW, Iqbal J, Koh XH, Koh XY, Othman R, Xue Y, Richards AM, Lane DP*, Sabapathy K*. Cell Reports. 2018. 22:299-312.
  11. “Cancer therapeutic targeting using mutant-p53-specific siRNAs”.  Ubby I, Krueger C, Rosato R, Qian W, Chang J, Sabapathy K. Oncogene. 2019. 38:3415-3427.
  12. “Functional interaction between macrophages and hepatocytes dictate the outcome of liver fibrosis.” Xie M, Chia RH, Li D, Teo FX, Krueger C, Sabapathy K. Life Sci Alliance. 2021 4(4):e202000803.
  13. “Cancer Cells Shuttle Extracellular Vesicles Containing Oncogenic Mutant p53 Proteins to the Tumor Microenvironment.” Bhatta B, Luz I, Krueger C, Teo FX, Lane DP, Sabapathy K, Cooks T. Cancers (Basel). 2021 13(12):2985.