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Laboratory of Applied Human Genetics

Synonym(s):

 

Principal Investigator: ​Associate Professor Ong Chin-Ann Johnny
Research team:

Dr Clara Chong

Dr Florence Chan

Dr Liu Ying

Dr Vinothkumar Rethineswaran

Ananya Rajesh

Gillian Ng

Guo Wanyu

Fionicca Teo

Joey Tan

Josephine Hendrikson

Oris Chen

Qiu Xuan Tan

Clinical team (SPRinT):

Prof Soo Khee Chee (Visiting Consultant) 

Clinical A/Prof Claramae Chia Shulyn

Clinical A/Prof Jolene Wong

Dr Jane Seo Chin Jin

Dr Cai Mingzhe

The Laboratory of Applied Human Genetics was established in 2013 under the leadership of Associate Professor Ong Chin-Ann Johnny. A/Prof Ong completed his PhD at the University of Cambridge, UK, as an NRF-MOH Research Scholar in 2009. Upon returning to Singapore with the aspiration of becoming a surgeon-scientist, he resumed his cancer research journey and has been under the mentorship of Professor Kon Oi Lian since 2016.

Our laboratory is an interdisciplinary translational research laboratory with a strong focus on peritoneal and sarcoma malignancies. We are a passionate and driven team of clinicians, scientists, and researchers united by a common goal – to improve patient outcomes through rigorous scientific discovery and meaningful clinical innovation. Beyond proof-of-concept research, we strive to develop technologies and therapeutic strategies that can ultimately impact real-world patient care. The dual-hatting of surgeon–scientists in the Department of Sarcoma, Peritoneal and Rare Tumours (SPRinT) gives our laboratory an intrinsic advantage by combining our clinical practice with laboratory research, effectively paving the way for bench-to-bedside translational research.Our laboratory’s area of expertise harnesses this advantage, allowing for a) multi-sampling of surgically collected samples to correct for intra-tumoral heterogeneity, b) rapid transfer of tissues to prevent degradation, and c) development of clinically relevant in vivo mouse models of human samples. Our approach to solving clinical questions with translational relevance and addressing hypotheses is illustrated in Figure 1.

Our laboratory focuses on three key pillars:Translational Therapeutics, Innovation and Academic Pursuits.

Translational Therapeutics

Our laboratory’s work on the peritoneal tumour microenvironment was published in Cell Reports Medicine and selected as a flagship article for the February 2022 issue, with the study featured on the journal cover. In this work, we identified PAI-1 as a key paracrine factor within the peritoneal cavity that could be directly targeted through ligand inhibition, providing proof-of-concept evidence for therapeutic perturbation in peritoneal metastasis (PM) (Hendrikson et al., 2022). Building upon these findings, we further highlighted paracrine inhibition as a key therapeutic strategy for PM in our review published in Journal of Clinical Oncology (Gwee et al., 2022). More recently, in 2025, our team identified actionable molecular signatures in colorectal PM and demonstrated that in vitro inhibition of colorectal PM cells with one of our novel biologics reduced IL2-STAT5 and TGF-β pathway activity while decreasing cell viability (Ong et al., 2025).

Innovation

Our translational efforts have led to multiple international patent filings. Our work on biomarker-driven molecular stratification to predict response to PAI-1 ligand inhibition was filed under an international Patent Cooperation Treaty (PCT) application in March 2020 (PCT/SG2020/050177), which is currently undergoing national phase review in China, USA, Europe, Singapore and Taiwan. In June 2025, we further expanded our innovation portfolio with the filing of a second international PCT application (PCT/EP2025/066468) covering our novel PAI-1 biologics. Our team is currently working on the development of GMP-grade therapeutics for peritoneal metastases based on this IP.

Academic Pursuits

Our laboratory has established a strong publication track record in the fields of peritoneal malignancies and sarcoma research. To date, we have published more than 40 peer-reviewed articles including publications in high-impact and top-tier journals, such as Nature Communications, Journal of Clinical Oncology, npj Precision Oncology, Oral Oncology, Annals of Surgical Oncology and European Journal of Surgical Oncology.

We are also deeply committed to nurturing the next generation of clinician-scientists and researchers. Our laboratory has developed a flexible and supportive mentorship environment that encourages surgical residents, junior doctors and medical students to pursue scientific research alongside their clinical responsibilities. Over the years, we have mentored more than 40 trainees, many of whom have published in top-tier journals and presented their work at both local and international conferences.

Collaborations

Advancing translational science requires strong interdisciplinary collaboration. Our laboratory actively partners with institutions and research groups across Singapore to synergise expertise and accelerate scientific discovery. Our collaborators include: Singapore Gastric Cancer Consortium, Duke-NUS Medical School, BIGHEART (NUS), Department of Biochemistry (NUS), EDDC (A*STAR), IMCB (A*STAR) and GIS (A*STAR). We are also a founding member of the Singapore Peritoneal Oncology Study (SPOS) Group, established to address the clinical and scientific challenges associated with peritoneal metastases in Singapore. Through these collaborations, we continue to strengthen our laboratory’s three pillars of translational therapeutics, innovation and academic excellence.

Grants and Awards

Since its establishment, our laboratory has secured multiple research grants, including 12 national grants from National Medical Research Council (NMRC), Experimental Drug Development Centre (EDDC) in A*STAR and National Health Innovation Centre (NHIC). Our team is also part of the Singapore Gastric Cancer Consortium (SGCC), which was awarded $25 million under the Open Fund-Large Collaborative Grant programme in 2025. Our PI, A/Prof Ong, has received multiple prestigious national awards, including the NMRC Clinician Scientist-Individual Research Grant (CS-IRG) in 2021 and 2024, as well as NMRC Clinician Scientist Award (CSA) in 2023 and 2025. Members of the laboratory have also received numerous accolades, including International Conference Travel Award, Best Oral Presentation Award, Young Investigator Award, Distinguished Young Researcher Award and NMRC Research Training Fellowship.

Selected Publications
  1. Wu KZ, Ding RH, Zhao Z et al. (2025) Hydrogel-mediated preservation of live tumor explants for drug development in peritoneal metastases. Adv Cancer 37(33): e2418647
  2. Ong C-AJ, Zhao JJ, Liu Y et al. (2025) Spatial heterogeneity, stromal phenotypes, and therapeutic vulnerabilities in colorectal cancer peritoneal metastasis. Clin Cancer Res 31(12): 2515-2529
  3. Zhao JJ, Ong C-AJ, Srivatsava S et al. (2024) Spatially resolved niche and tumor microenvironmental alterations in gastric cancer peritoneal metastases. Gastroenterology 167(7): 1384-1398.e4
  4. Chong YY, Thiagarajan S, Tan QX et al. (2024) The immunomodulatory role of paracrine signalling factor VSIG4 in peritoneal metastases. Sci Rep 14(1): 17522
  5. Tan QX, Shannon NB, Lim WK et al. (2024) Transcriptomic convergence despite genomic divergence drive field cancerization in synchronous squamous tumours. Front Oncol 14: 1272432
  6. Liu Y, Ng WH, Zhu H-Y et al. (2022) Generating patient-derived ascites-dependent xenograft mouse models of peritoneal carcinomatosis. STAR Protoc 3(3): 101548
  7. Gwee YX, Chia DKA, So J et al. (2022) Integration of genomic biology into therapeutic strategies of gastric cancer. J Clin Oncol 40(24): 2830
  8. Hendrikson J, Liu Y, NG W H et al. (2022) Ligand-mediated PAI-1 inhibition in a mouse model of peritoneal carcinomatosis. Cell Rep Med 3(2): 100526
  9. Shannon NB, Tan QX, Tan JWS et al. (2021) Gene expression changes associated with dedifferentiation in liposarcoma predict overall survival. Cancers (Basel) 13(12): 3049
  10. Lek SM, Li K, Tan QX et al. (2020) Pairing a prognostic target with potential therapeutic strategy for head and neck cancer. Oral Oncol 111: 105035