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Full NameDr Michael Conall Dennedy
Department:Discipline of Pharmacology & Therapeutics
Organisation:National University of Ireland Galway
- cell and developmental biology/regenerative medicine
- bioengineering/medical devices
- Vascular Medicine
The focus of our laboratory group is on imaging and therapeutics of functioning adrenocortical tumours. Our research is translational cell biology which is linked to the adrenal and hypertension clinical services. More broadly, we currently look at two therapeutic areas:
1. Thermal therapy of Functioning Adrenocortical Tumours - (Associated Clinical Services: Hypertension and Adrenal Clinics)
We lead a cross-institutional group (Kansas State University, University of Cambridge, Mayo Clinic Rochester) and take a multi-disciplinary approach across medicine, physics, engineering and radiology, to explore thermal therapeutics of benign and malignant adrenocortical tumours looking at (i) microwave ablation, (ii) nanotechnology, (iii) thermally-sensitive liposomes and (iv) extra-cellular vesicles.
2. Lipotoxicity in Adrenocortical Cancer - (Associated Clinical Services: Adrenal Clinic)
This work investigates the role of nuclear receptors in adrencortical cancer and how modulation of LXR can induce lipotoxicity in these cancer cells by affecting lipid-droplet integrity and steroidogenesis.
An ICAT PhD joining the lab will bring with them their own specialty interest and ideas. We will work with them to finesse these ideas into a project and proposal that will align with the interests of the laboratory. The following principals will be followed when designing a project:
1. The project will be translational and interventional. While observational studies can be used to support out approach, the ICAT fellow will be expected to follow a more involved mechanistic pathway of developing new therapeutic approaches through understanding mechanism of disease.
2. The fellow will be expected to design the project with methodological rigor.
3. Core principles of project design such as the generation of a logical research question and hypothesis will be followed.
4. The project will be impact focused.
Project 1: The use of 3D culture and microfluidics to understand the effects of sub-lethal thermal therapy on steroidogenesis in functioning adrenocortical tumours.
Adrenocortical cell lines and primary adrenocortical cells grown in 3D culture will be exposed to heat, in the presence and absence of heat-sensitizing agents. The steroidogenic response (measured by Mass spectrometry) and cell cycle will be evaluated. Cell work will proceed to a mouse model.
The study is expected to expand into nanotechnology or heat sensitive liposomes. One year of the project will be spent in another laboratory (outside of NUIG)
This study will be carried out in association with the SFP CURAM Centre at NUI Galway and the following co-investigators will provide fellow supervision: Dr Ronan T Fleming (University of Leiden), Dr Irina Bancos (Mayo Clinic, Rochester), Prof Punit Prakash (Kansas State University), Dr Martin O’Halloran (NUIG).
Project 2: The role of lipid droplets and lipid droplet associated proteins in the survival of adrenocortical cancer.
This project focuses on cancer and rare disease. Adrenocortical cancer cells - derived from primary tumours and metastases will be grown in 2D and 3D culture and exposed to a range of traditional and novel cytotoxic agents. The specific effects of these agents on cell survival and steroidogenesis will be investigated by evaluating their effects at the level of the lipid droplet, their associated proteins and their effects on cellular cholesterol flux. A systematic approach to pathway stimulation and blockade will be followed and findings will be validated using genetic knockdowns and mouse models.
This study will be carried out in association with the following co-supervisors: (i) Dr Roisin Dwyer (NUI Galway), (ii) Dr Irina Bancos (Mayo Clinic Rochester), (iii) Prof Mark Gurnell (University of Cambridge).