Background
M.S. Biochemistry, University of Santiago, Chile (1995); Ph.D., Hebrew University of Jerusalem, Israel (2002); Postdoctoral Research, Cornell University (2013-2016).
Cancer Research
My research has continuously involved membrane proteins. As an independent researcher, I have aligned my work with the field of Barriology, the study of structures that form barriers in tissues and control the paracellular space and thus permeability. Tight Junctions are responsible for apical barriers in endothelial and epithelial cells, key for drug delivery in solid tumors.
1. Controlling permeability of the blood-brain barrier (BBB) to enable commercially available therapeutics to target glioblastoma. Our laboratory developed a bacterial high throughput system to discover small molecules that can transiently permeate the BBB. Controlling its permeability will enable current therapeutics that because of size cannot cross it and target Glioblastoma. We have identified small molecules and are currently validating their value in vitro models of the BBB.
2. Constitutively active death receptor to apoptosis in mammalian cells. Apoptosis is triggered during pathological events as a means to renew affected tissues and eliminate cancer cells. The immune system regulates the extrinsic pathway of apoptosis, where death receptors signal Apoptosis. Our lab has engineered a constitutively active death receptor (CADRE) based on a single mutation within the transmembrane domain of Fas (CD95, Apo-1, TNFRSF6). Overexpression of CADRE results in decreased proliferation. Upon closer inspection, CADRE overexpression caused apoptosis. Using 10 different cancer cell lines, we report that CADRE induced apoptosis in all of them. CADRE is a new tool in the search for a single solution to fight cancer.
Publications
https://pubmed.ncbi.nlm.nih.gov/?term=mizrachi%2C+d.&sort=pubdate