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Cambridge Cardiovascular

 

Research

In a heart attack, a significant proportion of the heart muscle dies. The adult mammalian heart is the least replicative organ in the body. It cannot generate new heart muscle to restore its pumping action. 

Heart failure ensues which carries 1 in 2 chances of death within 5 years of diagnosis. A heart transplant is the only definitive cure for chronic heart failure but is a limited resource. Thus, chronic heart failure remains a clinically unmet need. 

Stem cells are cells that can turn into any cell type in the body, and so adding new heart muscle using a stem cell-based approach holds great promise to reinstate the pumping ability of the heart. During my PhD (supervised by Prof Sanjay Sinha in collaboration with Prof Charles E Murry), I discovered that cardiomyocyte-based cellular therapy has the potential to biologically repower the chronically failing heart. 

Ongoing research is focused on developing novel therapies (stem cell-based and/or gene therapy) to regenerate the chronically failing heart. I use a combinatorial approach of data-driven target discovery with downstream validation in complex human heart assays.  To translate this work into clinics, I collaborate with academics, clinicians, and industry scientists.

Publications

Key publications: 

Ong LP*, Bargehr J*, Knight-Shriver V* Lee J, Colzani M, Bayraktar S, Bernard WG, Marchiano S, Bertero A, Murry CE, Gambardella L, Sinha S. Epicardially secreted fibronectin drives cardiomyocyte maturation in 3D-engineered heart tissues. Stem Cell Reports, 2023 Apr 11;18(4):936-951

Arkley J*, Ong LP* Gunaratnam N, Butt T, Clark SC. 2023 A distractions capture tool for cardiac surgery and lung transplantation: impact on outcomes. Journal of Cardiothoracic Surgery, 2023 Jan 23;18(1):46.

Marchiano S, Hsiang TY, Khanna A, Higashi T, Whitmore LS, Bargehr J, Davaapil H, Chang J, Smith E, Ong LP, Colzani M, Reinecke H, Yang X, Pabon L, Sinha S, Najafian B, Sniadecki NJ, Bertero A, Gale M Jr, Murry CE. 2021. SARS-CoV-2 Infects Human Pluripotent Stem Cell-Derived Cardiomyocytes, Impairing Electrical and Mechanical Function. Stem Cell reports. 2021 Mar 9;16(3):478-492

Bargehr J, Ong LP, Colzani M, Davaapil H, Hofsteen P, Bhandari S, Gambardella L, Le Novère N, Iyer D, Sampaziotis F, Weinberger F, Bertero A, Leonard A, Bernard WG, Martinson A, Figg N, Regnier M, Bennett MR, Murry CE, Sinha S. Epicardial cells derived from human embryonic stem cells augment cardiomyocyte-driven heart regeneration. Nature Biotechnology. 2019 Aug;37(8):895-906.

Ong LP, Sachdeva A, Ramesh BC, Muse H, Wallace K, Parry G, Clark SC.  Lung Transplant With Cardiopulmonary Bypass: Impact of Blood Transfusion on Rejection, Function, and Late Mortality. Annals of Thoracic Surgery. 2016 Feb;101(2):512-9.

Ong LP, Thompson E, Sachdeva A, Ramesh BC, Muse H, Wallace K, Parry G, Clark SC. Allogeneic Blood Transfusion in Bilateral Lung Transplantation - Impact on Early Function and Survival. European Journal of Cardiothoracic Surgery. 2016 Feb;49(2):668-74

Mahesh B, Peddaayyavarla P, Ong LP, Gardiner S, Nashef SA. Cardiac Surgery Improves Survival in Advanced Left Ventricular Dysfunction: Multivariate Analysis of a Consecutive Series of 4491 Patients over an 18-year Period. European Journal of Cardiothoracic Surgery. 2016 Nov;50(5):857-866. 

Balakrishnan Mahesh, Ong LP, Ramesh Kutty and Yasir Abu-Omar Tamponade by an expanding left ventricular pseudoaneurysm: A unique presentation. Asian Cardiovascular Thoracic Annals. 2014 Apr 1. PMID: 24692597

Ma D, Williamson P, Januszewski A, Nogaro MC, Hossain M, Ong LP, Shu Y, Franks NP, Maze M. Xenon mitigates isoflurane-induced neuronal apoptosis in the developing rodent brain. Anesthesiology. 2007 Apr;106(4):746-53.