Laboratory of Applied Human Genetics

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The Laboratory of Applied Human Genetics was conceived in 2013 under the leadership of Associate Professor Ong. A/Prof Ong pursued his PhD at the University of Cambridge, UK, as an NRF-MOH Research Scholar in 2009. As a returning scientist with an aspiration to become a surgeon–scientist, he quickly resumed cancer research and has been under the mentorship of Prof. Kon since 2016. 

Our laboratory is an interdisciplinary laboratory, with a specific focus on peritoneal and sarcoma malignancies. 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. We are a group of young and enthusiastic team of researchers with a vision of making an impact on patients’ lives through sound scientific research and to harness technology to transit scientific research to clinical care beyond proof of concept. 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) generation of in vivo mouse models of human samples. Our approach to solving clinical questions with translational relevance and addressing hypotheses is illustrated in Figure 1. 

There are three main pillars to our laboratory - translational therapeutics, innovation and academic pursuits. 

Translational Therapeutics

The research that our laboratory has been tirelessly working on for the past 7 years was published in Cell Reports Medicine and was selected as one of the flagship articles for the February 2022 issue, with its message featured as the cover image of the reputable journal. We detail the identification of a key paracrine factor (PAI-1) found within the fluid microenvironment of the peritoneal cavity, which can be directly targeted via ligand inhibition, providing proof of concept of therapeutic perturbation in peritoneal carcinomatosis (Hendrikson et al., 2022). Building upon this, we have also included paracrine inhibition as a key therapeutic strategy in tackling peritoneal carcinomatosis in our review article in Journal of Clinical Oncology (Gwee et al., 2022).

Innovation

Our work in the use of biomarkers for molecular stratification of peritoneal carcinomatosis patients to predict response to PAI-1 ligand inhibition have also been filed for a Patent Cooperation Treaty (PCT) application (PCT/SG2020/050177) in March 2020, and is currently in the National phase review in 5 countries (China, USA, Europe, Singapore and Taiwan). 

Academic Pursuits

Academically, our team has published extensively in the field of peritoneal disease and sarcomas. To date, we have published close to 60 articles including publications in high impact factor or Top 10 and 20% 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 highly committed in nurturing the next generation of scientists and clinician scientists. Within our laboratory, we have formulated an informal program to stimulate the interests of surgical residents and junior doctors to pursue scientific research that can accommodate their hectic schedules. We have had significant success in this area; we have mentored more than 33 residents, junior doctors and medical students, many of which have published in Top 10/ 20% journals and presented in local and international conferences by working together with us. 

Collaborations

As part of our efforts to push the frontiers of translational science, we actively seek collaborations with numerous disciplines and institutions to synergize our strengths in different expertise. To this end, we have established several scientific collaborations to advance our research, including 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 one of the founding members of the Singapore Peritoneal Oncology Study (SPOS) Group, which was set up to address the multiple challenges in the management of patients with peritoneal carcinomatosis in Singapore. These collaborations will further enhance the three pillars of our laboratory, i.e. translational therapeutics, innovation and academic pursuits. 

Grants and Awards

Since the inception of our laboratory, we have been awarded 36 grants, including eight 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 2019. Our PI, A/Prof Ong, was also awarded the NMRC Clinician Scientist-Individual Research Grant (CS-IRG) in 2021 and NMRC Clinician Scientist Award (CSA) in 2022. The team has received numerous awards, including International Conference Travel Award, Best Oral Presentation Award, Young Investigator Award, Distinguished Young Researcher Award and an NMRC Transition Award.

Selected Publications

1. Zhou J, Toh SH-M, Tan TK, Balan K, Tan TZ, Xiong S, Jia Y, Ng S-B, Peng Y, Jeyasekharan AD, Fan S, Lim ST, Ong C-AJ, Ong CK, Sanda T, Chng W-J (2023) Super-enhancer-driven TOX2 mediates oncogenesis in Natural Killer/T cell lymphoma. Mol Cancer 22(2): 69 
2. Zhao H, Pan S, Natalia A, Wu X, Ong C-AJ, Teo MCC, So JBY, Shao H (2023) A hydrogel-based mechanical metamaterial for the interferonic profiling of extracellular vesicles in patient samples. Nat Biomed Eng 7(2): 135-148 
3. Liu Y*, Ng WH*, Zhu H-Y, Tan QX, Hendrikson J, Tan JWS, Ng G, Lim WK, Ong C-AJ (2022) Generating patient-derived ascites-dependent xenograft mouse models of peritoneal carcinomatosis. STAR Protoc 3(3): 101548 (* Equal contribution) 
4. Joanito I, Wirapati P, Zhao N, Nawaz Z, Yeo G, Lee F, Eng CLP, Macalinao DC, Kahraman M, Srinivasan H, Lakshmanan V, Verbandt S, Tsantoulis P, Gunn N, Venkatesh PN, Poh ZW, Nahar R, Oh HLJ, Loo JM, Chia S, Cheow LF, Cheruba E, Wong MT, Kua L, Chua C, Nguyen A, Golovan J, Gan A, Lim W-J, Guo YA, Yap CK, Tay B, Hong Y, Chong DQ, Chok A-Y, Park W-Y, Han S, Chang M, Seow-En I, Fu C, Mathew R, Toh E-L, Hong LZ, Skanderup AJ, DasGupta R, Ong C-AJ, Lim KH, Tan EKW, Koo S-L, Leow WQ, Tejpar S, Prabhakar S, Tan IB (2022) Single-cell and bulk transcriptome sequencing identifies two epithelial tumour cell states and refines the consensus molecular classification of colorectal cancer. Nat Genet 54(7): 963-975
   
5. Gwee YX, Chia DKA, So J, Yong WP, Tan P, Ong C-AJ*, Sundar R* (2022) Integration of genomic biology into therapeutic strategies of gastric cancer. J Clin Oncol 40(24): 2830 (* Co-corresponding authors)
   
6. Hendrikson J*, Liu Y*, NG WH, Lee JY, Lim AH, Loh JW, Ng CCY, Ong WS, Tan JWS, Tan QX, Ng G, Shannon NB, Lim WK, Lim TKH, Chua C, Wong JSM, Tan GHC, So JBY, Yeoh KG, Teh BT, Chia CS, Soo KC, Kon OL, Tan IBH, Chan JY, Teo MCC, Ong C-AJ, Singapore Peritoneal Oncology Study (SPOS) Group and Singapore Gastric Cancer Consortium (SGCC) (2022) Ligand-mediated PAI-1 inhibition in a mouse model of peritoneal carcinomatosis. Cell Rep Med 3(2): 100526 (* Equal contribution) 
   
7. Shannon NB*, Tan QX*, Tan JWS, Hendrikson J, Ng WH, Ng G, Liu Y, Tan GHC, Wong JSM, Soo KC, Teo MCC, Chia CS, Ong C-AJ (2021) Gene expression changes associated with dedifferentiation in liposarcoma predict overall survival. Cancers (Basel)13(12): 3049 (* Equal contribution) 
8. Wang Z, Zhao H, Zhang Y, Natalia A, Ong C-AJ, Teo MCC, So JBY, Shao H (2021) Surfactant-guided spatial assembly of nano-architecture for molecular profiling of extracellular vesicles. Nat Commun12(1): 4039 
9. Lek SM, Li K, Tan QX, Shannon NB, Ng WH, Hendrikson J, Tan JWS, Lim HJ, Chen Y, Koh KKN, Skanthakumar T, Kwang XL, Chong FT, Leong HS, Tay G, Putri NE, Lim TKH, Hwang JSG, Ang MK, Tan DSW, Tan NC, Tan HK, Kon OL, Soo KC, Iyer NG, Ong C-AJ (2020) Pairing a prognostic target with potential therapeutic strategy for head and neck cancer. Oral Oncol111: 105035 
10. Wu X, Zhao H, Natalia A, Lim CZJ, Ho NRY, Ong C-AJ, Teo MCC, So JBY, Shao H (2020) Exosome-templated nanoplasmonics for multiparametric molecular profiling. Sci Adv6(19): eaba2556 
    
11. Wang Z, Sun X, Natalia A, Tang CSL, Ang CBT, Ong C-AJ, Teo MCC, So JBY, Shao H (2020) Dual-selective magnetic analysis of extracellular vesicle glycans. Matter2: 1-17