Supervisor View Full Details 2nd

• infectious disease and the immune system
• cancer/oncology

• Medicine

• Haematology
• Oncology

As a HRB Clinician Scientist I am actively involved in clinical and translational research in blood cancers, with a specific emphasis on Multiple Myeloma (MM). In 2012 I established a translational program of research in MM at NUI Galway.

Three major areas of focus: (1) how aberrant glycosylation (especially sialylation) can influence cellular adhesion and trafficking in MM and be utilized as novel diagnostic and prognostic tools, (2) survival signalling in MM and (3) applications of genetically modified natural killer (NK) cells as cell therapy for cancer. Our work on glycosylation has implicated interactions between selectins, siglecs and their ligands in disease progression, drug resistance and immune evasion in MM. These findings have provided new insights into the role of glycosylation in the progression of MM which could lead to new strategies to overcome resistance to treatment.

Based on research conducted in my lab I am Chief Investigator on the first clinical trial evaluating an E-selectin inhibitor in MM. We published the preclinical rationale for this study in the high impact journal Leukemia earlier this year. I am Director of Blood Cancer Network Ireland and lead phase I trials of novel agents in MM, e.g. CyBorD-Dara (clinicaltrials.gov NCT02955810).

For more information see: http://www.bloodcancers.ie and https://www.linkedin.com/in/michael-o-dwyer-a2636241/

Selected recent publications:
Natoni A, Smith TAG, Keane N, McEllistrim C, Connolly C, Jha A, Andrulis M, Ellert E, Raab MS, Glavey SV, McCarthy-Kirkham L, Kumar SK, Locatelli-Hoops SC, Oliva I, Fogler WE, Magnani JL, O’Dwyer ME. E-selectin ligands recognized by Heca452 induce drug resistance in myeloma, which is overcome by the E-selectin antagonist, GMI-1271. Leukemia. 2017 Apr 25. doi: 10.1038/leu.2017.123. [Epub ahead of print] PMID:28439107

McEllistrim C, Krawczyk J, O’Dwyer ME. "New developments in the treatment of multiple myeloma - clinical utility of daratumumab". Biologics: Targets and Therapy 2017:11 31–43.

Natoni A, Macauley MS, O'Dwyer ME. Targeting Selectins and Their Ligands in Cancer. Front Oncol. 2016 Apr 18;6:93. doi: 10.3389/fonc.2016.00093. eCollection 2016. Review. PubMed PMID: 27148485; PubMed Central PMCID: PMC4834419.

Glavey, S.V., Huynh, D., Reagan, M.R., Manier, S., Moschetta, M., Kawano, Y., Roccaro, A.M., Ghobrial, I.M., Joshi, L., O'Dwyer, M.E. ‘The cancer glycome: carbohydrates as mediators of metastasis.’ Blood Reviews. 2015: 29(4), 269-79.

Keane, N.A., Reidy, M., Natoni, A., Raab, M.S., O'Dwyer, M. ‘Targeting the Pim kinases in multiple myeloma.’ Blood Cancer Journal. 2015: 5, 325.

Glavey, S.V., Manier, S., Natoni, A., Sacco, A., Moschetta, M., Reagan, M.R., Murillo, L.S., Sahin, I., Wu, P., Mishima, Y., Zhang, Y., Zhang, W., Zhang, Y., Morgan, G., Joshi, L., Roccaro, A.M., Ghobrial, I.M., O'Dwyer, M.E. ‘The sialyltransferase ST3GAL6 influences homing and survival in multiple myeloma.’ Blood. 2014: 124(11), 1765-76.

Keane, N.A., Glavey, S.V., Krawczyk, J., O'Dwyer, M. ‘AKT as a therapeutic target in multiple myeloma.’ Expert Opinion on Therapeutic Targets. 2014: 18(8), 897-915.

Potential research projects in my lab include: (1) studying how hypersialylation of MM cells leads to polarization of macrophages and affects other myeloid cells, e.g. myeloid derived suppressor cells to promote immune suppression within the tumour microenvironment; (2) exploration of means of modulating the tumour microenvironment (TME) to increase the cytotoxicity of NK cells, which can be negatively affected by factors elaborated within the TME, such as PGE2, lactate, hypoxia, adenosine etc.; (3) evaluating expression of death ligands on NK cells as a means of increasing their cytotoxic potential; (4) evaluating novel small molecule inhibitors in pre-clinical models of MM and AML.