TO THE LUYT LAB
Our research explores methods to target cancer with new chemical entities. We are a synthetic chemistry laboratory, where the compounds that we design and prepare are useful for the molecular imaging or therapy of cancer tumours.
Dr. Len Luyt
Office: Rm 219a ChB,
Lab: A4-817 LRCP
Phone (Office): 519-685-8600 ext 53302
Phone (Lab): 519-685-8600 ext 53299
I am a research scientist devoted to using chemical ingenuity to further the discovery of cancer imaging agents and therapeutics. I lead an amazing team of undergrads, graduate students, post-docs and scientists who have exceptional skills in bioorganic chemistry and medicinal chemistry. My educational background includes receiving my Ph.D. from the University of Western Ontario in Chemistry under the mentorship of Prof Duncan Hunter and a post-doctoral fellowship with Prof. John Katzenellenbogen at the University of Illinois, Urbana-Champaign. I then led a research team as a Senior Medicinal Chemist with the pharmaceutical company Bayer-Schering. In 2005 I joined Western as a faculty member with a joint appointment in the departments of Chemistry, Oncology, and Medical Imaging. My research program spans from basic chemistry activities, looking at novel methods of incorporating metal complexes into peptide structures, through to applied research, investigating new peptide therapeutics and molecular imaging agents for novel cancer targets.
Imaging Agents Targeting the Ghrelin Receptor
The ghrelin receptor, also referred to as the growth hormone secretagogue receptor (GHSR), is a GPCR that has been determined to have differential expression in a number of cancers. In particular, we have shown a significant difference in ghrelin receptor expression in prostate cancer as compared to benign prostatic hyperplasia, suggesting a potential role for imaging this receptor. Our lab has developed three classes of PET imaging agents that target the ghrelin receptor: peptide based imaging agents, peptidomimetics and small molecules containing the PET radioisotope fluorine-18. We continue to develop the medicinal chemistry of ligands that target the ghrelin receptor as we develop optimized PET imaging agents.
Metal-organic compounds as scaffolds for the exploration of biologically relevant chemical space
This research program seeks to explore metal-organic compounds as novel entities capable of targeting cell surface receptors. These compounds are uniquely created such that they exist as integrated metal-organic constructs, where the metal complex itself is critical for receptor binding and/or for unique functional properties. Some of the unique capabilities include creating metal-based turn mimics, where a radiometal coordinates and provides a conformational lock to a peptide structure. We have also developed fluorescent agents where the metal plays an important role in the fluorescent properties, while at the same time being able to exist as a radiolabelled version for non-invasive imaging.
Peptide Drugs Interfering with RHAMM:Hyaluronan Interactions
The interaction of the polysaccharide hyaluronan (HA) with RHAMM (receptor for hyaluronan mediated motility) is implicated in the promotion of inflammatory responses. RHAMM is an intracellular tubulin-binding protein that, in response to injury, is exported to the cell surface, associates with CD44 and, upon binding to HA, results in activation of growth factor signalling pathways, including ERK1,2. Interfering with RHAMM-HA interactions has therapeutic potential for inflammation-related diseases including cancer. We have discovered peptides that interfere with RHAMM-HA binding. In one approach, peptides that bind to RHAMM were developed based upon sequences of the carboxy-terminal tail region of tubulins that bind to the RHAMM HA binding region. These peptides act as mimics of HA and it has been shown that they have selectivity for RHAMM over other HA receptors such as CD44. In another approach, stapled peptides consisting solely of the HA binding domain of RHAMM were discovered to maintain the alpha-helical character of RHAMM and bind to HA. The ability to discover peptides that interfere in RHAMM-HA interactions sets a precedent for a new approach in the development of drugs that target protein-carbohydrate interactions.
Bahrami, SB; Tolg, C; Peart, T; Symonette, C; Veiseh, M; Umoh, JU; Holdsworth, DW; McCarthy, JB; Luyt, LG; Bissell, MJ; Yazdani, A; Turley, EA. Receptor for hyaluronan mediated motility (RHAMM/HMMR) is a novel target for promoting subcutaneous adipogenesis. Integrative Biology 9, 223-237, 2017.
Barbon, SM; Novoa, S; Bender, D; Groom, H; Luyt, LG; Gilroy, JB. Copper-assisted azide-alkyne cycloaddition chemistry as a tool for the production of emissive boron difluoride 3-cyanoformazanates. Org. Chem. Frontiers 4(2), 178-190, 2017.
Hou, J; Charron, CL; Fowkes, MM; Luyt, LG. Bridging Computational Modeling with Amino Acid Replacements to Investigate GHS-R1a-Peptidomimetic Recognition. Eur. J. Med. Chem., 822-833, 2016.
Cho, CF; Lee, K; Speranza, MC; Bononi, FC; Viapiano, MS; Luyt, LG; Weissleder, R; Chiocca, EA; Lee, H; Lawler, SE. Design of a Microfluidic Chip for Magnetic-Activated Sorting of One Bead-One-Compound Libraries. ACS Combi. Sci. 18(6), 271-278, 2016.
Charron, CL; Hickey, JL; Cruickshank, D; Nsiama, T; Turnbull, W; Luyt, LG. Molecular Imaging Probes Derived from Natural Peptides. Natural Product Reports 33, 761-800, 2016.
Our laboratory is located at the London Regional Cancer Program, and is part of the Cancer Research Laboratories. Graduate students in the Luyt group are candidates of the Department of Chemistry Graduate Program.
Please direct any questions regarding research opportunities or collaborations to Dr. Len Luyt.
Tel: 519.685.8600, ext. 53302
London Regional Cancer Program
Cancer Research Laboratory Program
790 Commissioners Rd. E.
Canada N6A 4L6
Copyright ©2017, Dr. Len Luyt. All Right Reserved