Disease Models Core

Background

The Disease Models​ core provides guidance, training, and service to support animal studies within NHCS. The core is a one-stop hub to provide state of art cardiovascular research equipment and technique for:

1. Developing experimental animal models for cardiac diseases, such as myocardial infarction and transverse aortic constriction;
2. Establishing animal models for metabolic diseases with cardiovascular complications;
3. Creating ischemic limb model for peripheral artery diseases;
4. Assessing cardiac function, such as Echo, MRI, and Pressure-Volume loop;
5. Measuring peripheral blood flow by Periscan; and
6. Isolating primary animal cardiomyocytes, cardiac fibroblasts, and endothelial cells using Langendorff apparatus or tissue dissociation.

The core is also equipped with microtome and cryostat machine to handle tissue sectioning of paraffin and cryopreserved tissues and Light, fluorescence, and confocal microscopies for imaging. The core has all necessary facilities needed for   tissue processing, embedding, sectioning, staining and Immunocytochemistry.

Research Area

1. Integrated multi-phenotype and systems-level analysis of human heart failure

Titin (TTN, the biggest gene in the genome) is the commonest cause of inherited heart failure. The mechanism by which this gene causes the heart to fail is unknown but it may be affected by the heart muscle responds to stress. This study will use rat models of human TTN heart disease to study the mechanism of TTN mutation as cause of heart failure.

2. Cell therapy for cardiac repair

This study investigates the biological mechanisms and bioenergetics underlying the cardiac repair using cell therapy and develops strategies to enhance the efficacy of the cell therapy for cardiac repair.

3. Myocardial regeneration of neonatal pig

The objective of the study is to investigate the regenerative potent of neonatal pig heart after injury.

4. Synergy between Thymosin β4 and cardiomyocytes for cardiac protection, regeneration and metabolism

Poor engraftment and diminished survival of stem cells or their CM derivatives is a barrier in harnessing the full benefits of cardiac regenerative medicine. In this study, the PI proposes to use hiPSC-CMs in combination with sustained-release of thymosin β4 (Tβ4) from gelatin microspheres for cardiac repair and regeneration. The main hypothesis is that synergy between Tβ4 and hiPSC-CMs transplantation is a safe therapeutic approach which will enhance hiPSC-CMs engraftment, inhibit myocardial apoptosis, promote cardiogenesis, and improve metabolism after myocardial infarction (MI) in an established clinically relevant large animal model

5. The role and mechanism of titin truncation variation following myocardial injury 

The aim of this study is to investigate the role and mechanism of TTN mutation following myocardial injury, such as MI or pressure overload. We hypothesize that TTN mutation modify the severity of ventricular dysfunction after myocardial injury, possibly through perturbation of metabolic remodeling processes as opposed to sarcomeric mechanical mechanisms.

Achievements

Grants

1. NMRC Clinician Scientist Individual Research Grant (PI: Dr Ye Lei) “Synergy between Thymosin B4 and Cardiomyocytes for Cardiac protection, regeneration and metabolism”
2. Singhealth Foundation Research grant (PI: Dr. Ye Lei) “The role and mechanism of titin truncation variation following myocardial injury”
3. NMRC Open-Fund Individual Research Grant (PI: Dr Ye Lei) "Myocardial regeneration of neonatal pig"​​​​​​​​​​​​​