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Major Research Interest of the Lab
Cell-based therapy for cardiovascular diseases
Our main interest is to elaborate advanced therapeutic strategies for boosting ischemic tissue recovery by enforcing adult stem cells to activate the endogenous repair mechanisms.
Stem and progenitor cells are reported to importantly contribute to tissue repair in numerous ischemic diseases and are currently considered for therapeutic purposes. Our investigations make use of animal models of human ischemic diseases (e.g. myocardial infarction or hind limb ischemia mouse models) as well as in vivo imaging and advanced cell-based assays. All these research models are jointly used to identify actionable early cellular and molecular changes in order to develop next-generation cell therapies in cardiovascular medicine.
Fundamental mechanisms of cardiac function decline in natural ageing process
Aging is a progressive process of functional decline that develops at multiple levels and increases the risk for cardiovascular pathologies. Our lab is interested in the active role of cardiac fibroblasts (cFb) in the ventricular remodeling associated to the natural aging process, as well as in cell-specific signaling pathways upon interference with myocardial infarction. The population of cFb is composed of adventitial and interstitial fibroblasts, which are geometrically interspersed between cardiomyocytes and are of the appropriate molecular program to allow rapid responsiveness after injury.
Previous findings demonstrated that cFb is a unique cell type (as opposed to a generic body-wide cell) that retains its embryological cardiac identity and is engineered to make part of the cardiac microenvironment, with a critical role in the structural and mechanical maintenance of the cardiac tissue.
By analyzing the multi-OMICS signatures of various populations of cFb isolated from young and old individuals with and without myocardial infraction, we hope to identify the key drivers of cFb activation and their molecular alterations during the aging process. Besides, by deciphering the cross-talk between cFb and infiltrating immune cells within the aged heart, we attempt to identify molecular targets that short-circuit the feed-forward signaling pathways leading to adverse ventricular remodeling on old individuals with myocardial infarction in the hopes of better preserving tissue integrity long-term.
Oxygen sensing mechanisms in mesenchymal stromal cell biology
Oxygen is the basis for life on Earth and taking oxygen and transforming it into energy was a fundamental biological step in the evolution of multicellular life on our planet. Understanding the oxygen-sensing pathway or the ability of cells to sense and adapt to oxygen availability is of significant importance for human physiology and pathology, as hypoxia, or the pathological reduction in oxygen availability, is now considered as a hallmark of disease conditions.
Low oxygen concetration has been shown to enhance the effector properties of mesenchymal stromal cells (MSC), though the exact mechanisms remain to be elucidated. In the bone marrow, MSC are known to reside in a low oxygen environment (1-4% O2). Despite this, most preclinical and clinical studies use cells that are grown at atmospheric oxygen concentration as a common practice. However, growing MSCs in ambient air could lead to abnormal behavior and misunderstanding of their biology, which could eventually translate to their misuse in the clinical applications. Therefore, uncovering the “real” mechanisms in MSC biology would be critical in order to improve their therapeutic value for a wide range of diseases.
Welcome to the Laboratory of Stem Cell Biology
Cell culture expertise:
- derivation of cell lines: mesenchymal stromal cells (human and mouse), endothelial progenitor cells (human and mouse), rat neonatal cardiomyocytes, mouse embryonic stem cells (ESC), etc;
- in vitro hypoxia and ischemia models (H35 Hypoxystation, Don Whitley Scientific);
- cell-cell interactions;
- xCELLigence analysis;
- 3D culture systems (aggregates, co-cultures, hanging-drops; in vitro transplant systems);
- biocompatibility assays;
- mouse model of myocardial infarction (by permanent ligation of the left coronary artery);
- mouse model of cardiac ischemia-reperfusion, which is able to generate infarct with variable size, according to the length of ischemia period;
- mouse model of hind limb ischemia;
- Confocal microscopy (Leica TCS-SP5)
- Fluorescence microscopy (Leica DMi8)
- Ecocardiography (VEVO 2100, Visualsonics)
- In vivo imaging (IVIS Spectrum, Perkin Elmer)
- Flow cytometry (Cytoflex, Beckman Coulter)
- Fluorescence-activated cell sorting (MoFlo Astrios, Beckman Coulter)
Molecular biology assays: cloning, transfection, qRT-PCR, digital-PCR.