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Zadeh Lab

Zadeh Lab

Research Focus

The Zadeh lab has a primary research focus in studying primary brain tumours including Glioblastoma, Meningiomas and Schwannomas. The lab focuses on several aspect of brain tumour biology including:

  • Angiogenesis
  • Tumour Metabolism
  • miRNA and Tumour Microenvironment
  • Response to Radiotherapy

Angiogenesis

Tumour neo-vascularisation occurs as a result of an imbalance of factos in the tumour microenvironment in favor of pro-angiogenesis. There are many mechanisms by which tumour neo-vascularization can occur including

  1. Cooption - the invasion and use of pre-existent vessels
  2. Angiogenesis - develops form cooption, signals cause the existing vessels to branch generating larger vessel networks
  3. Vasculogenesis - the recruitment of precursor cells to the site of tumour growth which in turn
        give rise to vascular components and new vessels
  4. Vascular Mimicry - Direct differentiation of tumour cells to endothelial cells of the new vasculature

There is a large level of redundancy of signal pathways revolving around neo-vascularisation, which results in heterogeneity of tumour development. Mechanisms of neo-vascularisation are, as such, determined by the tumour type, stage of progression, microenvironment.

Metabolism Tumour/Proliferating Cells

A key difference between tumour cells and normal differentiated cells is altered metabolism. These alterations both genetic and epigenetic allow tumour cells to proliferate and survive under unfavorable micro environments. A classic biochemical adaptation is the metabolic shift to aerobic glycolysis rather than mitochondrial oxidative phosphorylation, regardless of oxygen availability, a phenomenon termed the "Warburg Effect". Aerobic glycolysis, characterized by high glucose uptake, low oxygen consumption and elevated production of lactate, is associated with a survival advantage as well as the generation of substrates such as fatty acids, amino acids and nucleotides necessary in rapidly proliferating cells. The Zadeh lab is interested in identifying key regulators of the Warburg effect and to identify novel therapeutic targets of the Warburg effect.

miRNA and Tumour Microenvironment

MicroRNAs are mostly negative regulators of gene expression. In a number of cancers global levels of miRNAs have been shown to be lower and in many cases this decrease is due to decreased expression of biogenesis genes e.g Drosha and DICER. However, complete loss of DICER/miRNA expression has not been reported, suggesting that miRNAs, albeit at a reduced levels, play a critical role in tumour growth. The Zadeh lab is interested in identifying the vital nodes of miRNA-mRNA network in context of specific cellular compartments of brain tumours and their role in maintenance and establishment of tumour heterogeneity.