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Tan Nguan Soon, Andrew

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Tan Nguan Soon, Andrew

Tan Nguan Soon, Andrew
Associate Professor

Office: 02s-60
Telephone: 6316 2941
Email: NSTan@ntu.edu.sg

 

Education

  • B.Sc., B.Sc (Hon), Ph.D National University of Singapore

Professional Experience

  • Lee Kong Chian School of Medicine, NTU (2016-now)
  • Adjunct-PI, Institute of Molecular and Cell Biology, A*STAR (2016-now)
  • Joint Scientist, KK Women's and Children's Hospital, SingHealth (2013-now)
  • Joint-SPI, Institute of Molecular and Cell Biology, A*STAR(2012-2016)

Research Interest

Wound Repair

Poor healing wounds represent a silent epidemic that affects a large fraction of the world population and carries a heavy socioeconomic burden. Despite the enormous impact of these poor-healing wounds, effective therapies remain lacking. Effective management of these problems will require better understanding of the healing process to allow the creation of a salubrious environment conducive to healing.

Over the past decade, our lab has worked extensively to understand the transcriptional regulation of skin wound healing and particularly the interplay among different cell types during wound healing. In wound keratinocytes, we showed that nuclear receptor PPARβ/δ inhibits keratinocyte apoptosis at wound edges to maintain a sufficient number of viable wound keratinocytes for re-epithelialization. In fibroblasts, PPARβ/δ controls IL-1 signaling and thereby contributes to the homeostatic control of keratinocyte proliferation. Experimental animal studies showed that the controlled release of PPARβ/δ agonist improves diabetic wound healing through redox modulation of wound microenvironment. We also identified ANGPTL4, a PPAR target gene, as a novel matricellular protein that is essential for proper wound healing. Hyperproliferative wound keratinocytes secrete high amount of ANGPTL4 which plays a major role in cell-cell communication, and cell-matrix interactions during wound healing The ANGPTL4 modulates cell adhesion, migration (movie), differentiation and angiogenesis to facilitate wound closure. We showed that wound healing in ANGPTL4-knockout mice are delayed and share many characteristics of poor healing wounds, including increased/prolonged inflammation, impaired wound-related angiogenesis and ruined extracellular matrix. A cardinal feature of poor healing wounds is a persistent inflammatory response at the wound site. Thus, our future studies will investigate the role of immune-associated reactive oxygen species on wound healing, particularly on tissue remodeling, scar formation and fibrosis. We will develop various mutant mice as physiologically more relevant model for wound healing and fibrosis.

TARGETING METASTASIS

Metastasis accounts for more than 90% of cancer mortality. Once metastasis occurs, surgical excision of the primary tumor no longer guarantees disease free survival and the probability of cancer relapse in distal organs increases significantly. Although most cancer deaths are the result of metastases, cancer research has mainly focused on the primary tumor. In recent years, reactive oxygen species (ROS) which are by-products of aberrant cancer cell metabolism and mitochondrial defect have come to the forefront as potent modifiers of cancer cell behavior. However, very little is known about the precise involvement of ROS in metastatic spread. Over the past decade, my lab has actively interrogated the molecular changes in tumor epithelia at various critical points during tumor metastasis.

Copyright belongs to A/P Andrew Tan Nguan Soon

Our findings have established several paradigms in oxidative stress-driven metastasis. We revealed that non-canonical TGFβ pathways involving TAK1 was a crucial mediator of epithelial-mesenchymal transition. The loss of TAK1 accelerated EMT of cancer cells via an integrin:Rac-induced ROS mechanism. We found that many metastatic tumors upregulated their expression of the matricellular protein, angiopoietin-like 4 (ANGPTL4). This has significant consequences on metastatic escape from the primary tumor as well as extravasation for the formation of secondary micrometastases. Subsequently, our interest on how cancer cells survived in the circulation led to our discovery of an ANGPTL4-Nox1-ROS axis responsible for conferring anoikis resistance. ANGPTL4 also stimulated STAT3-mediated inducible nitric oxide synthase expression and enhanced angiogenesis. Thus, ANGPTL4 is an important redox player in metastasis and a potential therapeutic target. Our lab has developed a neutralizing monoclonal antibody against ANGPTL4 that displays potent in vivo anticancer effects. These findings underscore the role of ROS in multiple events during metastasis and highlight redox therapeutics as a potential adjunctive treatment to existing anticancer regiments. Our future studies will incorporate the effects of ROS on field cancerization and the seed-soil concept into the global view of metastasis. We seek to address how a radial spread of ROS impacts the adjacent normal epithelia and native stroma. Another question we seek to answer is how secondary micrometastases enact field cancerization to corrupt the new "soil". This will provide us with a holistic understanding of how cancer cells leverage on ROS to develop a niche that acts as a "springboard" to EMT and escape from the primary tumor.