CARDIOVASCULAR
SINGLE CELL RESEARCH LAB
RESEARCH
CARDIOVASCULAR DISEASES
Cardiovascular diseases (CVDs) refer to the disorders of the heart and blood vessel including coronary heart disease and they are generally associated with atherosclerosis, which is the build-up of fatty deposits in the arteries. Moreover, the risk of CVDs is increased with pre-existing conditions such as obesity, diabetes and high blood pressure. These could affect the disease progression and prognosis of each patient.
Thus, there is a need to further understand the Cellular and Molecular Mechanisms, and Genetics behind the disease to allow better prevention, prognosis, prediction and CVD therapeutic. Moreover, as each individual patient differ in their genetic and environmental factors, the introduction of personalized disease modelling could also improve patient care and management.
Elucidating cellular architecture & cellular content of cardiovascular tissue - aorta, atherosclerotic plaques, aortic aneurysm, heart valves.
Histopathological and biochemical analysis of tissue provide limited understanding of biological processes. Tissue dissociation and single cell analytics provide broader opportunity to understand functionality and cells interactive physiology. Ex vivo culture of intact human cells from cardiovascular tissue (patient specific cells) provide unique opportunity for functional analysis and understanding patient specific pathology.
ONGOING PROJECTS
Currently, the key projects that our lab are involved in includes:
Development of 3D vessel modelling using patient`s specific cells as a platform to evaluate and treat cardiovascular diseases
In order to improve the evaluation and treatment cardiovascular disease (CV) patients, whom have different disease and genetic background, we will explore the potential of disease modelling that is specific to each individual patient to enable more accurate disease management (e.g., disease prognosis and treatment regimen efficacy). Patient-derived cells would be obtained from tissue samples and utilized to generate 3D vessel model incorporated in microfluidic device. Different CV diseases (e.g., inflammation in atherosclerosis, DM, aortic dissection and aneurysm) can then be modelled with upon different stimulation to enable for the study of disease progression and prediction of prognosis. In addition, the efficacy of drug treatment could also be studied for each individual patient and allow for better disease management.
Modulation of MBNL1 expression in aortic smooth muscle cells
We found that Muscleblind Like Splicing Regulator 1 (MBNL1) was differentially expressed in patient-derived aortic smooth muscle cells and depend on patient specific CVD. Elevated levels of MBNL1 mRNA and protein were observed in patients with CVD. Furthermore, we have identified miR-30b-5p as negative regulator of MBNL1 expression. In this present study, we aim to understand the clinical relevance of MBNL1/miR-30b-5p interaction in the development of atherosclerosis. We are in the process of assessing the of MBNL1 and miR-30b-5p-associated proteins and their biological implications in atherosclerosis.
IL1B is a major cytokine involved in various diseases, including cardiovascular diseases. From RNAseq analysis of patients aortic biopsy taken during Coronary Artery Bypass Graft (CABG) procedure, we found that IL1B was differentially expressed in varies clinical conditions. In this study, we aim to understand in depth the role of IL1B in cardiovascular diseases and looking for potential clinical application.
Examining the role of IL-1-Beta in Cardiovascular disease
Single cell Next Generation Sequencing of Smooth Muscle Cells in Diabetes Mellitus & Aneurysm
The advancement of research into single cell next generation sequencing has allowed us to extensively study and understand the genetic information and the function of the cells in its microenvironment in a high-throughput manner, unlike in the past. In the development of cardiovascular disease, examining the behaviour of vascular smooth muscle cells could be critical in understanding the disease progression. Furthermore, existing research has shown that vascular smooth muscle cells behaves differently in individuals with diabetes compared to non-diabetics. Thus, through the understanding of the genetic information and performing functional validation, we hope to identify significant players that could be useful in the prediction, prognosis and understanding of underline mechanism for therapeutic development.
Currently, we are exploring how type 2 diabetes mellitus (T2DM) modulates vascular smooth muscle cells (VSMCs) phenotype alteration and the underlying molecular signaling pathways using single-cell RNA sequencing and spatial transcriptomics, which would potentially help in the management of T2DM-associated cardiovascular patients and to prevent cardiovascular-related complications.
Development of 2D Materials as Coatings for Cardiovascular Disease (CVD) Devices
There is a rising trend of developing 2D materials (e.g., graphene and graphene oxide) for applications in regenerative medicine and tissue engineering. 2D materials have emerged as potential candidates for biomedical applications due to unique properties such as large surface area and biocompatibility. Despite extensive studies of 2D materials in biomedical applications such as stem cell engineering, application of 2D materials as medical device coating, especially blood-contacting devices have been underexplored and underutilized. Herein, we seek to innovate using 2D materials for the development of coating for blood-contacting devices, such as stent and vena cava filter.
Aortic Tissue Gene Expression and Expression Quantitative Trait Loci Identification in Coronary Artery Disease Patients
Genome-wide association studies (GWAS) data has been merged with gene expression data in expression quantitative trait loci (eQTL) study to identify the dysfunctional genes for coronary artery disease (CAD). A large proportion of likely functional variants are believed to be regulated and expressed in the coronary arteries. In this study, we aim to identify the gene expression and eQTL of arterial wall tissue in Asian patients with CAD.
COLLABORATION PROJECTS
"SINGLE CELL NGC IN ARTERIAL CALCIFICATION"
"ORGAN-ON-CHIP (ARTHEROSCLEROTIC PLAQUE)"
"SINGLE CELL ANALYSIS IN VASCULAR BIOLOGY"
"LIPIDOMIC ANALYSIS USING AORTIC WALL TISSUE"
