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• cell and developmental biology/regenerative medicine
• bioengineering/medical devices

• Medicine
• Surgery
• Pathology
• Radiology
• Sports and Exercise Medicine

• Cardiac Surgery
• Endocrinology
• Orthopaedic surgery
• Rheumatology

Biomechanical interactions of self-expanding valves:
We have developed experimental and computational models to simulate implantation of Transcatheter Aortic Valve Implants (TAVI). In collaboration with Medtronic we investigated how non-concentric stent deployment influenced (1) the fluid mechanics and haemolytic potential of the device and (2) leaflet mechanics and deformation (Gunning et al., 2015, Gunning et al., 2014a, Gunning et al., 2014b). In collaboration with Boston Scientific we experimentally and computationally investigated stent-root interaction for calcified aortic valves (McGee et al., 2018a, McGee et al.b). These studies inform design of next-generation TAVI devices.

Biological consequences of thermal elevations during surgical cutting:
In collaboration with Stryker Instruments, experimental and computational methods were employed to predict thermal elevations to bone cells due to orthopaedic surgical cutting (Dolan et al., 2014). The effects of such thermal elevations on cell damage, regeneration and signalling responses by bone cells to initiate remodelling were uncovered in vivo and in vitro (Dolan et al., 2016, Dolan et al., 2015, Dolan et al., 2012).

The role of mechanobiology in the aetiology osteoporosis and metastatic bone disease:
Our research was the first to show that bone tissue composition is also altered at the microscopic level (McNamara et al., 2006, Brennan et al., 2011a, Brennan et al., 2011b, Brennan et al., 2012b), which is undetectable by conventional diagnostic techniques (DEXA) but may contribute to bone fracture. We have found that such changes likely arise due to (a) disrupted mechanosensory proteins (Voisin and McNamara, 2015), (b) altered biochemical responses (Brennan et al., 2014, Brennan et al., 2012 , Brennan et al., 2012a, Deepak et al., 2017) and (c) changes in mechanical stimuli (Verbruggen et al., 2015, Vaughan et al., 2015, Verbruggen et al., 2016) to bone cells following estrogen deficiency. These findings uncover fundamental changes in mechanobiology, a crucial process in healthy bone, not previously understood during osteoporosis. We are currently applying these methods and techniques to understand the role of mechanobiology in bone metastasis.

Mechanobiological investigations into tumour invasion and metastasis in Bone:

Metastatic bone disease arises when primary cancerous tumours, most commonly originating from the breast or prostate, spread and invade bone tissue and form secondary metastatic tumours [1]. Approximately 50-70% of patients with advanced breast cancer develop bone metastases [2], and although radiotherapy and bisphosphonates delay metastases progression, these are often ineffective and the disease is incurable once patients have overt metastases [1, 3]. While anti-hormonal therapies can be effective for preventing breast cancer recurrence [4], such treatments can lead to osteoporosis, whereas patients who receive estrogen hormone treatment for osteoporosis are at increased risk of developing breast cancer. Thus, therapeutics for breast cancer, metastatic bone disease and osteoporosis are at odds and comorbidity is common, due to the fact that estrogen is crucial for the survival and growth of both breast cancer cells and bone cells. Indeed, recent studies have demonstrated major differences in tumour growth and colonization by breast cancer cells seeded onto bone tissue from healthy and osteoporotic patients [5-7]. While this research is intriguing, the specific features of bone (i.e. tissue composition, mechanical properties, mechanobiology) that render the tissue susceptible to metastasis, particularly during osteoporosis, are unknown.

The global objective of this project is to provide a paradigm change for studies of bone metastasis. In particular we will (i) provide a fundamental understanding of the biomechanical properties of bone tissue that render it susceptible to metastasis, particularly during osteoporosis, and, using this information, we will (ii) investigate whether biomechanical changes arising during tumour invasion perpetuate the “vicious cycle”. All of the techniques and equipment are available in the College of Engineering and Informatics at NUI Galway and the candidate will be integrated to an established research group (www.mechanobiology.ie). Collaborators will provide interdisciplinary expertise in cancer cell biology, cells and tissue for experiments (Dr. Roisin Dwyer, Professor Michael Kerin).