Overview
The SIgN
Immune Dysfunctions program aims to characterize how immune homeostasis can be perturbed to result in immune
dysregulation and disease manifestation, and how homeostasis can be recovered. Here, our researchers are
investigating the basic principles underlying immune-cell ontogeny and differentiation, the environmental,
genetic and aging-related factors that can trigger immune system dysregulation, and the identity of specific
markers and signatures of dysregulation in order to develop new therapeutic interventions.
The program covers four main themes:
- Homeostasis: ontogeny, immune-regulation and inflammation
- Allergy: including airway, skin and drug-induced allergies
- Aging: involving immunosenescence and effects on metabolism and the microbiome
- Immunomonitoring: by deep immune-phenotyping, immunogenomics and studies of the immune-repertoire
Principal Investigators involved include:
- Subhra BISWAS
- Florent GINHOUX
- Kaibo DUAN
- Lai Guan NG
- Ee Chee REN
- Olaf ROTZSCHKE
Click here to
visit the Principal Investigators page.
Research Highlights
The data
produced by researchers in this program is of high scientific excellence, as indicated by numerous successful
publications in high impact journals including Immunity, Nature
Immunology and
the Journal
of Experimental Medicine (see
below). Furthermore, the studies conducted by our researchers have health, economic and industrial impact.
Examples of the translational research conducted, and novel discoveries and innovative technologies contributed
by the program include:
- ImmunoSCAPE, a multidimensional cell profiling (spin-off company)
- An advanced microscopy cluster for intravital organ imaging
- The dominance of a single allergen (dust mite) in tropical urban cities
- Identification of human dendritic cell precursors (patented)
- Development of a new platform for microbiome studies
Based on
such developments, long-standing collaborative partnerships with a number of industry partners have been
established, including Sanofi, Nestle, Servier, Merck, Galderma, L’Oreal, Danone, CIEA Japan, Becton Dickinson,
Kyowa Hakko Kirin, Abbott and immunoSCAPE (local spin-off biotech).
Finally, the
Immune Dysfunctions program has collaboratively established various cohorts for:
- Allergy — with the National University of Singapore
- Aging program & Sg90 cohort — with the Singapore Institute for Clinical Sciences and the National University of Singapore
- Skin program — with the Institute of Medical Biology, the Nanyang Technological University–Lee Kong Chian School of Medicine, and the Skin Research Institute of Singapore
The Immune
Dysfunctions program has international collaborations with researchers including at: the Peter Doherty
Institute, Australia; the University of Melbourne, Australia, the University of Sydney, Australia; the Shanghai
Institute of Immunology, China.
Key Publications
Evrard M et
al. Developmental Analysis of Bone Marrow Neutrophils Reveals Populations Specialized in Expansion, Trafficking,
and Effector Functions. Immunity. 2018.
McGovern N
et al. Human fetal dendritic cells promote prenatal T-cell immune suppression through
arginase-2. Nature. 2017.
See P et al.
Mapping the human DC lineage through the integration of high-dimensional techniques. Science. 2017.
Wong MT et
al. A High-Dimensional Atlas of Human T Cell Diversity Reveals Tissue-Specific Trafficking and Cytokine
Signatures. Immunity. 2016.
Chong SZ et
al. CXCR4 identifies transitional bone marrow premonocytes that replenish the mature monocyte pool for
peripheral responses. J
Exp Med. 2016.
Simoni Y et
al. Human Innate Lymphoid Cell Subsets Possess Tissue-Type Based Heterogeneity in Phenotype and
Frequency. Immunity. 2016.
Derny D et
al. Complete human CD1a deficiency on Langerhans cells due to a rare point mutation in the coding
sequence. J
Allergy Clin Immunol. 2016.
Chen J et
al. Mpath maps multi-branching single-cell trajectories revealing progenitor cell progression during
development. Nat
Commun. 2016.
Andiappan AK
et al. Functional variants of 17q12-21 are associated with allergic asthma but not allergic
rhinitis. J
Allergy Clin Immunol. 2016.
Schlitzer A
et al. Identification of cDC1- and cDC2-committed DC progenitors reveals early lineage priming at the common DC
progenitor stage in the bone marrow. Nat
Immunol. 2015.
Ginhoux F et
al. New insights into the multidimensional concept of macrophage ontogeny, activation and
function. Nat
Immunol. 2015.
Hoeffel G et
al. C-myb(+) erythro-myeloid progenitor-derived fetal monocytes give rise to adult tissue-resident
macrophages. Immunity. 2015.
Andiappan AK
at el. Genome-wide analysis of the genetic regulation of gene expression in human neutrophils. Nat
Commun. 2015.
Viganò E et
al. Human caspase-4 and caspase-5 regulate the one-step non-canonical inflammasome activation in
monocytes. Nat
Commun. 2015.
McGovern N
et al. Human Dermal CD14+ Cells Are a Transient Population of Monocyte-Derived Macrophages. Immunity. 2014.
Click here to
visit the full SIgN Publications page.