Department of Physiology
28 Medical Drive, Centre for Life Sciences, Level 3, Singapore 117456
Tel: 6516 7773
Major Research Interests
CD137L is expressed by hematopoietic progenitor cells (HPC) and dendritic cells (DC), and CD137L transmits activating signals into HPC and DC. A main effect of CD137L signalling is inducing myeloid differentiation. We are exploring this activity of CD137L for treatment of Acute Myeloid Leukaemia (AML). AML is due to HPC failing to complete the myeloid differentiation pathway. CD137 protein, which engages CD137L on AML cells, induces their differentiation. This is expected to reduce the aggressiveness of AML.
Dendritic cells are key regulators of immune responses. In monocytes CD137L signalling generates a novel, more potent kind of dendritic cells (CD137L-DC). We are evaluating CD137L-DC for inducing immune responses against tumors, starting with nasopharyngeal carcinoma. Further, we are investigating the ectopic expression of CD137 in Hodgkin Lymphoma, and how CD137 facilitates escape of Hodgkin Lymphoma from immune surveillance.
CD137L signalling is activating the myeloid cells in the brain, the microglia. CD137L-induced microglia activation enhances the pathogenesis of neuroinflammatory diseases, such as Multiple Sclerosis. We are also investigating the contribution of CD137L-induced microglia activation to neurodegenerative diseases, such as Alzheimer’s and Parkinson’s Disease.
The interaction of CD137 and CD137L during DC-T cell contact leads to a strong enhancement of immune responses, which often worsens autoimmune diseases. Indeed, inhibiting CD137-CD137L interactions stops autoimmune diseases in experimental animals. We are assessing anti-CD137 antibodies as treatments for Rheumatoid Arthritis (RA) and Systemic Lupus Erythematous (SLE), and potentially other autoimmune diseases.
Mak A, Nien YK, Schwarz H, Gong L, Tay SH, Ling LH (2017) Endothelial dysfunction in lupus erythematosus – a case-control study and an updated meta-analysis and meta-regression. Scientific Reports (in press)
Wu M, Moh MC, Schwarz H (2016) hepaCAM associates with connexin 43 and enhances its localization in cellular junctions. Scientific Reports 6: 36218
Harfuddin Z, Dharmadhikari B, Wong SC, Duan K, Poidinger M, Shaqireen K, Schwarz H (2016) Transcriptional and functional characterization of CD137L-dendritic cells identifies a novel dendritic cell phenotype. Scientific Reports 6: 29712
Rajendran S, Ho WT, Schwarz H (2016) CD137 signaling in Hodgkin and Reed-Sternberg cell lines induces IL-13 secretion, immune deviation and enhanced growth. OncoImmunology 5(6): e1160188
Zhe S, Harfuddin Z, Pang WL, Nickles E, Koh LK, Schwarz H (2015) Trogocytic CD137 transfer causes an internalization of CD137 ligand on murine APC leading to reduced T cell costimulation. J. Leukocyte Biology 97(5): 909-19
Raghunath M, Blocki A, Wang Y, Koch M, Goralczyk A, Beyer S, Agarwal N, Lee M, Moonshi S, Dewavrin J-Y, Peh P, Schwarz H, Bhakoo K (2015) Sourcing of an alternative pericyte-like cell type from peripheral blood in clinically relevant numbers for therapeutic angiogenic applications. Molecular Therapy 23(3): 510-22
Cheng CK, Wong SC, Linn YC, Ho LP, Chng WJ, Schwarz H (2014) CD137 Ligand Signalling Induces Differentiation of Primary Acute Myeloid Leukemia Cells. British Journal of Haematology, 165(1): 134-44
Martínez Gómez JM, Koh VHQ, Yan B, Lin WW, Zainul Rahim SZ, Ang MLT, Schwarz H, Alonso S. (2014) The CD137 signaling pathway contributes to the adaptive immune responses to M. tuberculosis infection. Immunobiology 219(1):78-86
Harfuddin Z, Kwajah S, Sim ACN, MacAry PA, Schwarz H (2013) CD137L-stimulated dendritic cells are more potent than conventional dendritic cells at eliciting cytotoxic T-cell responses. OncoImmunology 2(12): e26770
Tang Q, Koh LK, Jiang D, Schwarz H (2013) CD137 ligand reverse signaling skews hematopoiesis towards myelopoiesis during aging. Aging 5(9): 643-52