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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.

About Len

Dr. Len Luyt

Associate Professor

Office: Rm 219a ChB,

Lab: A4-817 LRCP

Phone (Office): 519-685-8600 ext 53302

Phone (Lab): 519-685-8600 ext 53299

E-mail: lluyt@uwo.ca

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.

Research

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.

People

Graduate students

Neha Sharma

Axie Hauser-Kawaguchi

William Turnbull

Emily Macil Murrell

Tyler Lalonde

Emily Nicole Rodrigues

Jordan Cole LeSarge

Marina Lazarakos

Claire Browne

Undergraduate students

Michaela Fernandes

Natalie (Yuting) Liang

Scientist, Research associate, Postdoc

Lihai Yu

Zhanna.Potetinova

JQ (Jinqiang) Hou

Publications

2017

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.

DOI: 10.1039/c7ib00002b

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.

DOI: 10.1039/c6qo00640j

 

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.

DOI: 10.1016/j.ejmech.2016.07.078

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.

DOI: 10.1021/acscombsci.5b00180

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.

DOI: 10.1039/C5NP00083A

Pictures

Contacts

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

Fax: 519.685.8646

Email: lluyt@uwo.ca

Mailing Address

London Regional Cancer Program

Room A4-817A

Cancer Research Laboratory Program

790 Commissioners Rd. E.

London, Ontario

Canada N6A 4L6

 

Copyright ©2017, Dr. Len Luyt. All Right Reserved

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Pictures