Directory

National Research Foundation (NRF) fellowship

NRF Singapore,2016

Best Ph.D award

Hannover Medical School,2006

Junior Research Fellowship (JRF)

CSIR-UGC, Government of India,2002

Department of Biotechnology Fellowship

DBT India,2000

Congenital and adult heart diseases are the leading cause of death globally, contributing 32% of global deaths. In Singapore, Cardiovascular disease accounted for 31.4% of all deaths in 2022. Our laboratory studies the molecular mechanisms that regulate cardiovascular development, homeostasis, and disease. Our goal is to understand how signaling pathways and transcriptional networks regulate cardiovascular cell lineage differentiation and their interaction (epicardium-myocardium and myocardium-endocardium) during heart morphogenesis. Defects in these processes during embryonic development underlie congenital heart disease (e.g. LVNC) and may contribute to the development of diseases in adulthood. Our work aims for a better understanding of congenital human diseases of the heart by establishing mouse models for these disorders and delineating the molecular changes associated with them. Our long-term goal is to apply lessons learned from our developmental studies to better understand and treat cardiovascular diseases.

There is increasing evidence that molecules and signaling pathways required during embryonic development also play an important role in cardiac homeostasis and disease in adults. For example, in the adult heart, epicardial cells are generally quiescent. However, ischemic injury results in the reactivation of a fetal gene program in the adult epicardium leading to increased epicardial cell proliferation and differentiation into cardiac fibroblasts. Additional evidence suggests that epicardial activation also amplifies the inflammatory response after ischemic injury. In the ischemic heart, fibrosis-inflammation axis is a key pathological driver of cardiac dysfunction in heart failure. So, the identification of intrinsic factors in the epicardial cells and extrinsic factors from immune cells (e.g. macrophages) that activate the epicardium will stimulate new discoveries in biology and potential therapeutic strategies for ischemic injury-induced heart failure.

Loss of Yap/Taz in cardiac fibroblasts attenuates adverse remodeling and improves cardiac function

Cardiovascular Research – Mia MM, Cibi DM, Abdul Ghani SAB, Singh A, Tee N, Sivakumar V, Cook SA, Mao J, Singh MK. (2022)

Jun 16:cvab205 (N/A); N/A-N/A

Critical role of the BAF chromatin remodeling complex during murine neural crest development.

PLoS Genetics – Bi-Lin KW, Seshachalam PV, Tuoc T, Stoykova A, Ghosh S, Singh MK. (2021)

Mar 22;17(3):e1009446.

YAP/TAZ deficiency reprograms macrophage phenotype and improves infarct healing and cardiac function after myocardial infarction

PLOS Biology – Mia MM, Cibi DM, Binte Abdul Ghani SA, Ramesh S, Song W, Tee N, Ghosh S, Mao J, Olson EN, Singh MK. (2020)

Dec 2;18(12):e3000941. (N/A); N/A-N/A

Prdm16 deficiency leads to age-dependent cardiac hypertrophy, adverse remodeling, mitochondrial dysfunction, and heart failure. (Cover Story)

Cell Reports – Cibi DM, Wung Bi-Lin K, Guna Shekeran S, Sandireddy R, Tee N, Singh A, Wu Y, Srinivasan DK, Kovalik JP, Ghosh S, Seale P, Singh MK. (2020)

Oct 20;33(3):108288.

Semaphorin 3E/PlexinD1 signaling is required for cardiac ventricular compaction.

JCI Insight – Sandireddy R, Cibi DM, Gupta P, Singh A, Tee N, Uemura A, Epstein JA, Singh MK (2019)

22;4(16).

Neural crest-specific deletion of Rbfox2 in mice leads to craniofacial abnormalities including cleft palate.

eLife – Cibi DM, Mia MM, Guna Shekeran S, Yun LS, Sandireddy R, Gupta P, Hota M, Sun L, Ghosh S, Singh MK. (2019)

26;8. pii: e45418.

The Hippo Signaling Pathway in Cardiac Development and Diseases.

Frontiers in Cell and Developmental Biology – Mia MM, Singh MK. (2019)

Oct 1;7:211.

Epicardial YAP/TAZ orchestrate an immunosuppressive response following myocardial infarction.

The Journal of Clinical Investigation – Ramjee V, Li D, Manderfield LJ, Liu F, Engleka KA, Aghajanian H, Rodell CB, Lu W, Ho V, Wang T, Li L, Singh A, Cibi DM, Burdick JA, Singh MK*, Jain R*, Epstein JA*. (*Corresponding author) (2017)

127 (3); 899-911

Hippo Signaling Mediators Yap and Taz Are Required in the Epicardium for Coronary Vasculature Development.

Cell Reports – Singh A, Ramesh S, Cibi DM, Yun LS, Li J, Li L, Manderfield LJ, Olson EN, Epstein JA, Singh MK. (2016)

15 (7); 1384-1393

Semaphorin signaling in cardiovascular development. (Cover Story)

Cell metabolism – Epstein JA, Aghajanian H, Singh MK. (2015)

21 (2); 163-173

Semaphorin 3d signaling defects are associated with anomalous pulmonary venous connections.

Nature Medicine – Degenhardt K*, Singh MK*, Aghajanian H*, Massera D, Wang Q, Li J, Li L, Choi C, Yzaguirre AD, Francey LJ, Gallant E, Krantz ID, Gruber PJ, Epstein JA. (*equal contribution) (2013)

19 (6); 760-5

Distinct compartments of the proepicardial organ give rise to coronary vascular endothelial cells.

Developmental cell – Katz TC*, Singh MK*, Degenhardt K*, Rivera-Feliciano J, Johnson RL, Epstein JA, Tabin CJ. (*equal contribution) (2012)

22 (3); 639-50

Cardiac Tissue Factor Regulates Inflammation, Hypertrophy, and Heart Failure in Mouse Model of Type 1 Diabetes. (Cover Story)

Diabetes – Cibi DM, Sandireddy R, Bogireddi H, Tee N, Ghani SABA, Singh BK, Mackman N, Singh MK, Singh A. (2021)

70 (9); 2131-2146

Gata4 and Gata5 cooperatively regulate cardiac myocyte proliferation in mice.

The Journal of biological chemistry – Singh MK, Li Y, Li S, Cobb RM, Zhou D, Lu MM, Epstein JA, Morrisey EE, Gruber PJ. (2010)

285 (3); 1765-72

MicroRNA-processing enzyme Dicer is required in epicardium for coronary vasculature development.

The Journal of biological chemistry – Singh MK*, Lu MM, Massera D, Epstein JA. (*Corresponding author) (2011)

286 (47); 41036-45

Emerging role of the Hippo Signaling pathway in modulating immune response and inflammation-driven tissue repair and remodeling.

FEBS Journal – Mia MM and Singh MK (2022)

New approaches under development: cardiovascular embryology applied to heart disease.

The Journal of clinical investigation – Degenhardt K, Singh MK, Epstein JA. (2013)

123 (1); 71-4

Epicardium-derived cardiac mesenchymal stem cells: expanding the outer limit of heart repair.

Circulation research – Singh MK, Epstein JA. (2012)

110 (7); 904-6

Tbx20 is essential for cardiac chamber differentiation and repression of Tbx2.

Development (Cambridge, England) – Singh MK, Christoffels VM, Dias JM, Trowe MO, Petry M, Schuster-Gossler K, Bürger A, Ericson J, Kispert A. (2005)

132 (12); 2697-707

The T-box transcription factor Tbx15 is required for skeletal development. (Cover Story)

Mechanisms of Development – Singh MK, Petry M, Haenig B, Lescher B, Leitges M, Kispert A. (2005)

122 (2); 131-44