LEONG, David

Assistant Professor

PhD (Biology) NUS 2006
PG Dip Edn NIE, NTU 1999
B Eng (Chemical Engineering) NUS 1998

Postdoctoral fellowships
Howard Hughes Medical Institute, University of Pennsylvania 2007
Lee Kuan Yew Postdoctoral Fellow, CSIS, NUS 2008

Leong lab website

RESEARCH

Assembling nanoparticles with genetically modified micro-organisms

Organisms took millions of years to learn to incorporate inorganic materials into their organic domains, usually to bring about benefits to themselves, for example, vertebrate bone is a tightly regulated structure comprised of collagen and calcium hydroxyapatite. Much of the information required to synthesize these structures is locked in the genome of the organism of which up to now, much biological research is pursuing. Can we learn from this synergistic marriage and apply it to nanoparticle assembly? Can we use genetic engineering to circumvent the many generations of evolutionary “fit-ness” to bring about assembly of inorganic substrates? Starting from one of the “simplest” organisms known to man, the humble phage, this project aims to use classical genetic engineering and molecular cloning strategies to use the phage as a platform to build smart and application-centric design and assembly of inorganic based nanoparticles.

Biology and mechanisms of toxicity of nanoparticles

The use of nanoparticles is finding its way into increasing facets of modern living. Our understanding of their biological effects and mechanisms is unfortunately unable to keep up with the exponentially increasing variants of nanoparticles types. Preliminary research suggests cytotoxic and genotoxic effects of nanoparticles of TiO2, ZnO and GdO2 but these studies are only scratching the surface of understanding their harmful effects. Genotoxic effects of nanoparticles might explain environmental causes on increased rates of cancer occurrence in recent times despite the rapid advancement in medicine. Therefore, there is a need to characterize these effects and determine the mechanisms with the aim of making better and safer nanoparticles. We aim to understand how common nanoparticles exert their (if any) genotoxic, cellular phenotype and general cell biology disruptions.

Fluid dynamics effects on metastatic cancer cells

Metastasis or spread of cancer cells from the primary site to distal secondary sites account for about 90% of all cancer-related deaths. Cancer cells would need to have undergone many transformations and mutations to acquire the ability to circumvent the many protective mechanisms presented by the body against these rogue cells. Determining how metastatic cells of solid tumor origins can survive in the often foreign and harsh fluid environment of the vascular system is both scientifically intriguing and clinically important. We achieve this aim through modification of cancer cells with either overexpressing or knocking down genes of interest and studying the effects in a microfluidics based environment.

Applying cancer biology to cell based biologics production

Revenue from the sales of mammalian cell derived biologics reached the order of billions of US dollars per annum. One of various contributing factors to the industry’s success is the continued research in optimizing important aspects of cellular performance. Some of these characteristics include very good cell viability, robustness in the face of harsh culture conditions and high resistance to intrinsic and extrinsic apoptotic signals. The characteristics are found in cancer cells. Therefore, can we learn a trick or two from cancer cells and apply those biological alterations to cells producing biologics in a way that they acquire some of the desirable traits? Specifically, we aim to study the influences of oncogenes, tumor suppressors, epigenetics and microRNA on the biologics production performance of CHO cells. Understanding these influences will allow us to apply cancer biology to make better and safer cell variants.

SELECTED PUBLICATIONS

Setyawati M.I.; Tay C.Y.; Chia S.L.; Goh S.L.; Fang, W.; Neo, M.J.; Chong, H.C.; Tan, S.M.; Loo, S.C.; Ng, K.W.; Xie, J.P.; Ong. C.N.; Tan, N.S.; Leong, D.T*. TiO2 nanomaterials cause endothelial cell leakiness by disrupting the homophilic interaction of VE-cadherin. NATURE Communications (Accepted 27 Feb 2013).

Yuan, X.; Setyawati, M.I.; Tan, A.S.; Ong, C.N.; Leong, D.T.* and Xie, J.* “Highly Luminescent Silver Nanoclusters with Tunable Emissions: Cyclic Reduction-Decomposition Synthesis and Antimicrobial Property”, NATURE Publishing Group Asia Materials 2013, DOI: 10.1038/am.2013.3 (IF = 5.5).

Luo, Z.; Yuan, X.; Yu, Y.; Zhang, Q.; Leong, D.T.; Lee, J.Y. and Xie, J* “From Aggregation-Induced Emission of Au(I)-Thiolate Complexes to Ultra-bright Au(0)@Au(I)-Thiolate Core-Shell Nanoclusters”, Journal of the American Chemical Society 2012, 134, 16662-16670 (IF = 9.9).

Setyawati, M.I.; Fang, W.; Chia, S.L.; Leong, D.T.*. Nanotoxicology of common metal oxide based nanomaterials: their ROS-y and non-ROS-y consequences. Asia Pacific Journal of Chemical Engineering. 2012. DOI: 10.1002/apj.1680.

Wu, Y.L.; Putcha, N.; Ng, K.W.; Leong, D.T.; Lim, C.T.; Loo, S.C.; Chen, X. Biophysical Responses upon the Interaction of Nanomaterials with Cellular Interfaces. Accounts of Chemical Research. 2012. DOI: 10.1021/ar300046u. (IF = 21.640)

Tay CY, Pal M, Yu H, Leong WS, Tan NS, Ng KW, Venkatraman S, Boey F, *Leong DT, Tan LP. Bio-inspired Micropatterned Platform to Steer Stem Cell Differentiation. SMALL 2011 May 23;7(10):1416-21. (IF = 8.4)

Huang RL, Teo ZQ, Chong HC, Zhu PC, Tan MJ, Tan CK, Lam CR, Sng MK, Leong DT, Tan SM, Kersten S, Ding JL, Li HY, Tan NS. ANGPTL4 modulates vascular junction integrity by integrin a5b1-Rac/PAK signaling and the disruption of intercellular VE-cadherin and claudin-5 clusters. BLOOD 2011 Oct 6;118(14):3990-4002. (IF = 9.898)

Yun Zhao, Josephine L.C. Howe, Zhang Yu, Leong DT, Justin Jang Hann Chu, Joachim Say Chye Loo and Kee Woei Ng*. Exposure to Titanium Dioxide Nanoparticles Induces Autophagy in Primary Human Keratinocytes. SMALL 2012 Oct 23. doi: 10.1002/smll.201201363. (IF = 8.4)

Ng KW, Khoo PKS, Heng BC, Setyawati MI, Tan EC, Zhao XX, Xiong SJ, Fang WR, Leong DT*, Loo JSC*. Cellular DNA Damage Response to Zinc Oxide Nanoparticles Hinges on the Tumor Suppressor p53 Pathway. Biomaterials 2011 Nov;32(32):8218-25. (IF = 7.404)

Leong DT, Gupta A, Bai HF, Wan G, Yoong LF, Too HP, Chew FT, Hutmacher DW. Absolute quantification of gene expression in biomaterials research using real-time PCR. Biomaterials. 2007 Jan;28(2):203-10. (IF = 7.404)