Translating genetic susceptibility to clinical application: SYNGR1--an Asian-specific biomarker and drug target for systemic lupus erythematosus (SLE)

Professor Yang, Wanling   (Principal Investigator (PI))

Dr Wang Yongfei   (Co-Investigator)

Dr Yang Jing   (Co-Investigator)

Professor Lau Wallace Chak Sing   (Co-Investigator)

Dr Li Philip Hei   (Co-Investigator)

Dr Mok Chi Chiu   (Co-Investigator)

Dr Chan Sau Fong   (Co-Investigator)

36

2022-01-01

1482597

Translating genetic susceptibility to clinical application: SYNGR1--an Asian-specific biomarker and drug target for systemic lupus erythematosus (SLE)

Biomarkers, Genetics, Precision treatment, SYNGR1, systemic lupus erythematosus

Others - Medicine, Dentistry and Health

08192456

Health and Medical Research Fund - Full Grant

2020

On-going

Background: Systemic lupus erythematosus (SLE) is a prototype autoimmune disease affecting women of child-bearing age. East Asians have higher prevalence and severity than Europeans and genetic factors play important roles in SLE. We are among the first in Asia to conduct genetic studies on SLE and have identified more than 40 susceptibility genes in Chinese populations. SYNGR1 is a gene associated with several autoimmune diseases, including SLE, RA, IBD and PBC, and its association with SLE seems to be Asian-specific according to our data. It is a gene with unclear function, but studies suggest its involvement in cytokine production and cellular responses to infection. Objectives: To elucidate the immune functions of SYNGR1 and the mechanisms of its association with autoimmune diseases. By understanding its function and signal transduction pathways in which it is involved, we may identify biomarkers and novel drug targets for diagnosis and stratified treatment of SLE. Methods: We will use a combination of animal models and clinical studies to elucidate the function and association mechanisms of SYNGR1 in SLE. Animals with SYNGR1 knockout and overexpression will be examined in both C57 and spontaneous lupus mouse models, with and without chemical induction, to study the role of Syngr1 on lupus-like phenotypes and immune functions. Potential correlations between genetic variants in this locus and clinical subphenotypes, cytokine productions and immune cell profiles will be examined in SLE patients. Expected results: We will have a much better understanding of the functions of SYNGR1 and its mechanisms impacting autoimmunity.