CBMR's cardiovascular research aims to identify novel genes or alterations in gene expression leading to congenital malformations or other heart conditions/pathologies by identifying candidate gene-variants in cohorts of patients. The contribution of identified gene alterations/mutations will be determined using animal- and cell models. Patient-specific somatic cells will be reprogrammed into induced pluripotent stem cells that retain the mutations of interest in the overall genetic context of the patient. The functionally validated genes may become useful as genetic markers for better predictions of susceptibility, time course, severity, and treatment outcomes, as well as the development of novel prophylactic approaches to limit disease severity and patient management prior to onset. CBMR will also investigate the role of gut microbiota in congenital heart, cardiovascular and metabolic disease (atherosclerosis, diabetes, and obesity).Portfolio Details
CBMR's oncobiology research covers tumor formation & progression, susceptibility to these processes, their diagnosis & therapeutic targeting. Human cell lines, drosophila mutants, mouse models and patient samples are used to elucidate the molecular mechanisms underlying the development of melanoma, leukemia, salivary gland & colorectal carcinomas and other cancer types. CBMR investigates genetic factors in the susceptibility to cancer, develops computational molecular modelling and structural bioinformatics to study the structure & function of therapeutic targets and perform screening campaigns to identify inhibitors. One focuses is on the role of PI3K/AKT/FOXO & ROS-dependent signaling. The aim is to develop TRIB2, an oncogenic FOXO repressor, to predict and overcome cancer drug resistance and identify inhibitors. Susceptibility variants in breast cancer and novel epigenetic signatures to improve cancer diagnostics & prognostics are investigated.Portfolio Details
CBMR's biomolecular research is focused on bio-medically relevant molecules, their structure & function & therapeutic delivery. The main objective is to extend CBMR's toolbox to address thestructure/function of newly identified molecules linked to neurodegenerative disorders & aging, cardiovascular & infectious disease and in the cell toxic effects in cancer therapy. A new facility to purify/analyze proteins, small molecules and target molecules is under development. The platform will consist of preparative/analytic chromatography, analytic electrophoresis & biophysical techniques with media throughput capabilities, including pre-existing fluorescence & circular dichroism instruments and the new bio-layer interferometry to measure binding. The platform is a key step in developing strategies for in-vitro study of new target molecules. A new device for cell delivery of dry powders is also under development and a Crisp/Cas high-throughput screening to identify molecules involved in cell-uptake of neurotoxic proteins, cell-cell spreading of protein misfolding and clearance of oxidative stress is planned.
CBMR's brain research aims to resolve fundamental questions related to: (1) learning & memory; (2) language, reading acquisition & developmental dyslexia; (3) molecular mechanisms underlying neurological conditions; (4) develop disease model for brain disorders; (5) neuromuscular changes related to aging, dementia & Parkinson's disease. For instance, ~5% of school children are affected by developmental dyslexia and CBMR has recently formulated a new research program to address the basic causes of developmental dyslexia, which are still poorly understood. Based on the research outcomes, CBMR will develop new strategies & remedial approaches to dyslexia. CBMR is investigating the role of nitric oxide in injury-induced neurogenesis. The identification of neurogenic targets modified by S-nitrosylation opens the possibility new therapeutic approaches to brain repair. CBMR has also contributed significantly to the molecular understanding of a specific group of incurable neurodegenerative disease and will develop advanced gene- and cell therapeutic strategies aiming to stop or delay disease progression.Portfolio Details