- Knowles Group | Hypoxia in Musculoskeletal Disease Research Group
University Research Lecturer and Arthritis Research UK Career Development Fellow
From a scientific background studying hypoxia in cancer and tumour-associated macrophages, I joined the department in 2006 as a post-doc in the group of Professor Nick Athanasou. It was then that I started studying osteoclasts; the cells responsible for causing pathological bone loss in conditions such as rheumatoid arthritis, bone metastasis and primary bone cancer. Working as part of an EU Network of Excellence (EuroBoNeT), I started investigating the role of hypoxia and the hypoxia-inducible transcription factor, HIF, in regulation of osteoclast formation and function within the context of primary bone tumours.
In 2010, I was awarded an Arthritis Research UK Career Development Fellowship to continue this work in the context of rheumatoid arthritis. My work now focusses on studying the HIF-driven pathways that regulate osteoclast activity; for example, investigation of a modified HIF-driven pathway that actually increases hypoxic flux through the mitochondrial electron transport chain. I am also investigating the HIF-induced, osteoclast-activating adipokine angiopoietin-like 4 (ANGPTL4) as both a causative factor for, and a marker of, pathological bone resorption in rheumatoid arthritis.
Swales C. et al, (2014), PloS one, 9
Morten KJ. et al, (2013), The Journal of pathology, 229, 755 - 764
Knowles HJ. et al, (2012), Virchows Archiv : an international journal of pathology, 461, 205 - 210
Knowles HJ. et al, (2010), FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 24, 4648 - 4659
Knowles HJ. and Athanasou NA., (2009), The Journal of pathology, 218, 256 - 264
Hulley PA. et al, (2017), The Journal of pathology, 242, 322 - 333
Knowles HJ., (2017), Calcified tissue international, 100, 382 - 391
Knowles HJ., (2017), Frontiers in endocrinology, 8
How does hypoxia-inducible factor (HIF) regulate osteoclastogenesis and bone erosion?
Knowles HJ. et al, (2016), Frontiers in Endocrinology: Bone Research
Hypoxia, hypoxia-inducible factor (HIF) and bone homeostasis: focus on osteoclast-mediated bone resorption
Knowles HJ., (2015), Trends in Cell & Molecular Biology