Research Projects
Molecular mechanisms of cellular senescence and kidney fibrosis in chronic kidney disease

Chronic kidney disease (CKD) is an escalating global health problem leading to considerable morbidity, mortality, and treatment costs. There is currently no effective treatment for CKD. 

CKD is characterized by the progressive accumulation of matrix proteins in the kidney parenchyma, which replaces normal kidney tissue with fibrous matter leading to a loss of kidney function. Irrespective of the primary etiology, tubulointerstitial fibrosis is considered the final common pathways that drives CKD to end-stage kidney disease. The mechanisms that mediate tubulointerstitial fibrosis are complex and incompletely understood. Emerging evidence suggests that cellular senescence promotes and exacerbates kidney fibrosis. Our research studies aim to investigate the molecular mechanisms that induces cellular senescence and kidney fibrosis in CKD using animal and in vitro studies, with particular focus on cellular mechanisms and phenotypic manifestations in resident renal tubulointerstitial cells. A greater understanding of disease pathogenesis and the identification of key pathways and molecules that contribute to CKD may allow for the development of novel therapeutic agents for CKD.

Professor TM Chan, Department of Medicine

Professor Tak Mao Daniel Chan is Chair Professor, Yu Chiu Kwong Professor in Medicine, and Chief of Nephrology Division in the Department of Medicine, School of Clinical Medicine at The University of Hong Kong (HKU) and Hong Kong West Cluster Hospitals of the Hospital Authority. He received his MBBS, MD, and DSc degrees from HKU, and trained in Nephrology and Internal Medicine in Hong Kong and at Guy’s Hospital, London, U.K.

His team’s translational and basic research focuses on immuno-pathogenesis of lupus nephritis and mechanisms leading to kidney fibrosis in chronic kidney disease due to lupus nephritis or other glomerular diseases. Their findings include the discovery that human anti-dsDNA antibodies could bind to glomerular mesangial cell membrane annexin II and get transported into the cytoplasmic and nuclear compartments leading to downstream cellular responses that contribute towards a pro-inflammatory and pro-fibrotic cellular phenotype. Their work using animal models examined the effects of novel treatments for lupus nephritis and mechanisms leading to kidney fibrosis and chronic kidney disease. The results have been published in J Am Soc Nephrol, Arthritis Rheum, Kidney Int, and other leading nephrology, rheumatology, or translational medicine journals.

Prof Chan is also recognised for his original contributions in advancing the management of lupus nephritis. He was the first to champion the use of mycophenolate in lupus nephritis [Chan TM, et al. N Engl J Med 2000; 343: 1156], which has since become standard-of-care internationally.

Biography
HKU Scholars Hub
ORCID
dtmchan@hku.hk

For more information or to express interest for this project, please email the supervisor or the specified contact point in the project description.  Interested candidates are advised to enclose with your email:

1. your CV,
2. a brief description of your research interest and experience, and
3. two reference letters (not required for HKUMed UG students seeking MRes[Med]/URIS projects).

Information on the research programme, funding support and admission documentations could be referenced online at the Research Postgraduate Admissions website. General admission enquiries should be directed to rpgmed@hku.hk.

HKUMed MBBS students interested in the Master of Research in Medicine (MRes[Med]) programme may visit the programme website for more information.  

HKUMed UG students interested in the Undergraduate Research Internship Scheme (URIS) may visit the scheme’s website for more information.