Assoc Prof Tan Nguan Soon, Andrew
Telephone: 6316 2941
- B.Sc., B.Sc (Hon), Ph.D National University of Singapore
- 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)
Impaired wound repair is a major complication of diabetes, resulting in substantial morbidity, lost productivity, and healthcare expenditures. A cardinal feature of non-healing skin wounds is a prolonged inflammatory response at the wound site, in which case progression of the repair response culminates in excessive scar formation. The scarring response rapidly replaces the missing tissue, but the skin function, biomechanical properties and aesthetic quality of the scar tissue are compromised. Thus, scarring is also a major cause of physical and psychological morbidity. Despite the enormous impact of these chronic wounds, effective therapies remain lacking. Effective management of these problems will require a thorough understanding of the interplay among different cell types and microenvironment during wound healing. The multitude of complex biological processes that occurs during wound healing depends on the collaborative efforts of several cell types like macrophages, keratinocytes and fibroblasts. However, the mechanisms integrating and coordinating these efforts are still poorly known. There is increasing body of evidence for the important roles of matricellular proteins in wound healing. Matricellular proteins reside at the crossroads of cell–matrix and cell-cell communication, modulating several key regulatory networks. Presumably, the regulatory pathways consist of complex networks, creating many opportunities for the compensatory adjustments required for wound repair. My research concerns the heterotypic cell-cell communication during skin repair. We use various approaches, such as skin organotypic culture, knockdown technology and appropriate animal models to understand the interplay of different cell types. New insights will led to a better understanding of skin biology and aid in the development of better treatment and clinical injury management.
Cancer is the leading cause of death worldwide with metastasis accounting for more than 90% of its mortality rate. Metastasis is a multi-step process characterized by invasive cancer cells that breach the tumor basement membrane and intravasate into the systemic circulation to spread to distal organs. This complex nature of metastasis makes it a difficult therapeutic target. The pivotal and early event in metastasis resembles the epithelial-to-mesenchymal transition (EMT) that occurs during embryogenesis and wound healing. Tumor microenviromental stresses such as hypoxia, low pH and an inflammatory milieu exert a selective pressure on cancer cells to exploit the adverse microenvironment and modify their behaviour for tumor progression. Interestingly, the microenvironmental stresses that transform the cancer cells into a highly aggressive phenotype can also alter the bioenergetics of cancer cells. Metastasis and reprogramming energy metabolism have been identified as hallmarks in cancer cells. Cancer cells make adjustments to their energy production to sustain uncontrolled proliferation. However, little is known about the mechanism that coordinates this metabolic reprogramming during EMT. Anoikis is a programmed cell death induced upon cell detachment from extracellular matrix, behaving as a critical mechanism in preventing adherent-independent cell growth and attachment to an inappropriate matrix, thus avoiding colonizing of distant organs. Thus, anoikis resistance is an essential feature of metastatic cancer cells. However, the mechanism by which anoikis resistance is acquired remains an unsolved problem in cancer biology. As anoikis resistance and EMT are vital steps during metastatic colonization, they have attracted much attention from the scientific community. My research focus is to identify molecular drivers of EMT and anoikis resistance. Conceivably, genes that confer anoikis resistance and regulate the energy demand during EMT transition will be critical drivers for the extensive cellular changes required during these events, and thus are potential therapeutic targets.