Tan Suet Mien
Telephone: 6316 2834
- BSc (1st Class Hons), MSc, National University of Singapore
- D.Phil., Oxford University, UK
- Singapore Society for Biochemistry and Molecular Biology Medal, NUS, 1995
- The Lijen Industrial Development Medal, NUS, 1995
- Arthritis Research Campaign Scholarship, UK, 1998
- Assistant Professor, School of Biological Sciences (SBS), NTU, 2001
- Sub-Dean (Academic) 2005-2006
- Assistant Chair (Academic) 2006-2008
- Nanyang Award for Excellence in Teaching, NTU, 2006
- Associate Chair (Academic), School of Biological Sciences, NTU, 1st July 2011 – 30th June 2014
- National Day Honours (2013)
- The Public Administration Medal (Bronze)
My research group has a long-standing
understanding the molecular mechanisms of cell adhesion and migration
underpinning normal and pathological conditions, including inflammation and
cancer. We focus on two families of molecules – integrins and kindlins. Integrins
are heterodimeric transmembrane proteins that mediate cell-cell,
cell-extracellular matrix, and cell-virus interactions. Integrin ligand-binding
is regulated by its conformational change that is dependent on the interactions
between its cytoplasmic domain and cytosolic proteins. These cytosolic proteins
can either be positive or negative regulators of integrin function. Currently,
my research group and in collaboration with others seek to define the molecular
basis of cross-talks between these regulators, and how they modulate integrin
ligand-binding, signaling and cytoskeletal re-modelling under normal and
pathological conditions, such as chronic inflammation and cancer metastasis.
Kindlins are a small
family of FERM-domain-containing cytoplasmic proteins. Three kindlin paralogs
have been identified with dissimilar tissue expression profiles. Over the last
few years, kindlins emerged as key regulators of integrin activation and
signaling. The importance of kindlins is underscored by diseases Kindler
syndrome, leukocyte adhesion deficiency III, and cancer. In addition to
integrin-affinity regulation, our research group and others have shown that
kindlins promote integrin clustering, which strengthens cell-ECM and cell-cell
adhesion. There is also gaining evidence that kindlins are involved in cellular
signaling conduits that are independent of integrins. We are investigating the
roles of kindlins in these pathways in the context of cancer progression. Our
recent work suggests an important role of kindlin3 in chronic myeloid leukemia
cell proliferation. Some images for our research work and in collaboration with
others are shown below.
An illustration of intergrin signalling in antigen presentation
Silencing of kindlin3 slows the growth of chronic
myelogenous leukemia cells in soft agar and mouse xenograft.
Integrin LFA-1-mediated T cell migration on ICAM-1.
Immunofluorescence imaging of cytosolic molecules RACK1 (A), kindlin3 (B), and
MyH9 (C) (red). Actin (green) and nucleus (Blue).
SEM images of melanoma cells with kindlin overexpression and
mouse lung metastasis assay.
Wound healing assay to assess the effect of kindlin
overexpression in cancer cells.
Analyses of force contractions of HUVECs on micro-posts
coated with ECM. FN: fibronectin, COL: collagen
analyses of integrin cytoplasmic tails interactions.
Immunofluorescence analyses of HUVECs spreading on
fibronectin. Stainings of kindlins, RACK1 and hnRNPK are shown.
MD simulations of integrin transmembrane packing.