Associate Professor, Departments of Oncology, Pharmacology & Therapeutics, McGill University
Lady Davis Institute for Medical Research
Sir Mortimer B. Davis-Jewish General Hospital
3755 Côte Ste-Catherine Road
Montreal, Quebec H3T 1E2
Tel.: 514-340-8222 ext. 5055
Uri.saragovi [at] mcgill.ca (Email)
Expertise: Receptor-Ligand Interactions; Protein Mimicry; Rational Drug Design; Receptor Pharmacology
Summary of Research Activities
Dr. Saragovi’s research focuses on understanding macromolecular structure function relationships, particularly in receptor-ligand interactions. His group applies this knowledge to experimental therapeutics and to translational research.
Dr. Saragovi’s group has contributed towards the development of protein mimicry technology. Using molecular design, biochemistry, and molecular biology techniques, large proteins may be dissected into their smallest functional units. These approaches can be adapted for rational drug design and the development of agonists and antagonists.
The group has developed mimics of antibodies, cellular receptors, and polypeptide growth factors (antagonists and agonists). Compared to mAbs, small molecule mimetic ligands are better in vivo at imaging and localizing tumours.
Structural studies of these small molecule artificial ligands demonstrated that they adopt the predicted configurations. Pharmacological studies demonstrated that these small molecule designed agents can be as useful as drugs or drug leads. Dr. Saragovi and his group have succeeded in using these agents in various in vivo models of neurodegeneration (cognitive impairment in ageing, glaucoma) and of cancer.
Small molecules can be used to identify the relevant sites on receptors that can induce a biological response. Using small molecule ligands, the group can carry out fine studies of receptor biology such as studies of cross-regulation by different receptor activation sites, and biophysical analyses of ligand-receptor interactions.
Lastly, Dr. Saragovi’s group has also developed a technology where therapeutic agents can be selectively delivered to the target cell. In vivo therapeutic studies have shown that this approach can improve the therapeutic index of useful (yet toxic) drugs by many fold. They are following therapeutic studies of cancer and neurodegenerative disorders.
Ivanisevic L, Zheng W, Woo SB, Neet KE, Saragovi HU. TrkA receptor "hot spots" for binding of NT-3 as a heterologous ligand. J Biol Chem. 2007 Apr 17; [Epub ahead of print]
Shi Z, Birman E, Saragovi HU. Neurotrophic rationale in glaucoma: A TrkA agonist, but not NGF or a p75 antagonist, protects retinal ganglion cells in vivo. Dev Neurobiol. 2007 Jun;67(7):884-94.
Esteban PF, Yoon HY, Becker J, Dorsey SG, Caprari P, Palko ME, Coppola V, Saragovi HU, Randazzo PA, Tessarollo L. A kinase-deficient TrkC receptor isoform activates Arf6-Rac1 signaling through the scaffold protein tamalin. J Cell Biol. 2006 Apr 24;173(2):291-299.