Dan Kelly

Dr Daniel Kelly BSc, PhD, PGCertHE

Senior Lecturer


Summary

Daniel obtained a BSc with honours in Human Biology and Psychology from Aston University, including a year placement at Unilever R&D where he investigated biomarkers of stress and heart health/lifestyle interventions in a clinical study. Following his degree he undertook a PhD at Sheffield Hallam University investigating the effects of testosterone on atherosclerosis before moving to the University of Sheffield to continue this research as a postdoc. Focus shifted towards testosterone’s tissue-specific metabolic actions and how these relate to cardiovascular risk and type-2 diabetes in males using cell culture systems, pre-clinical models and medical trials of testosterone replacement. Daniel moved to Sheffield Hallam in 2016 as a lecturer in Biochemistry.


About

Daniel is a lecturer in Biochemistry with research interests in cardiovascular disease, type-2 diabetes, obesity and the role of testosterone in these diseases. Daniel's current research focuses on testosterone’s tissue-specific metabolic actions and how these relate to cardiovascular risk and type-2 diabetes in males using cell culture systems, pre-clinical models and medical trials of testosterone replacement. This research extends through ongoing collaborations with partners at the University of Sheffield, University of Chile, Barnsley NHS Foundation Trust and Bayer Healthcare. His research is published in top endocrine peer-reviewed journals as critical reviews and he presented at international conferences. His research has featured on BBC News Health and he further won the Kroto Research Inspiration 2016 award at the University of Sheffield.

Daniel is a Fellow of the Higher Education Academy. His teaching areas relate to his research interests and include metabolism, immunology, cell biology and biological basis of disease.


Teaching

School of Biosciences and Chemistry

College of Health, Wellbeing and Life Sciences

Daniel is a Fellow of the Higher Education Academy. He teaches in the general area of Biochemistry with a particular focus on metabolism. This expands into other key areas related to physiology, nutrition and human biology. He is deputy course leader for the Biomedical Sciences undergraduate degree.


Research

Testosterone in health and disease

Testosterone is no longer a hormone limited to reproductive/sexual medicine but is rather a multi-system player with much wider range of actions. Epidemiological studies draw clear associations between low testosterone in men and metabolic disorders such as, type-2 diabetes, obesity and cardiovascular risk to the extent that low testosterone is now considered an independent risk factor for heart disease. The majority of testosterone replacement trials do indeed demonstrate beneficial effects on men’s health, however, the detailed mechanisms of how testosterone may offer this protection is not fully known. Daniel's research continues to investigate the tissue-specific actions of testosterone related to the pathogenesis of type-2 diabetes and cardiovascular disease to try and harness the therapeutic potential of this hormone.

Developing an in vitro artery model for investigating diabetic atherosclerosis.

In vitro human cell models are valuable research tools for exploration of novel mechanisms in atherogenesis, but are most commonly limited to 2D single-cell culture. While endothelial dysfunction is recognised as an initial step in the atherosclerotic process that is well advanced in diabetes, the pathogenesis of atherosclerosis involves multiple vascular and immune cell interactions; primarily endothelial cells (EC) and smooth muscle cells (SMC) as well as blood borne inflammatory cells such as monocyte-derived macrophages. 2D single cell cultures do not account for the complexity of the native artery environment with physiological pulsatile flow conditions and don’t allow study of interactions between various cell types and/or the extracellular matrix. Daniel's research interests are involved in providing an applicable 3D in vitro co-culture vascular model that could accelerate advances in the field allowing for novel mechanisms to be investigated. This research is supported by the Society for Endocrinology.


Publications

Journal articles

Yassin, A., Kelly, D., Nettleship, J., Talib, R., Al-Zoubi, R.M., Aboumarzouk, O.M., & Albaba, B. (2023). Testosterone treatment and change of categories of the International prostate symptom score (IPSS) in hypogonadal patients: 12 years prospective controlled registry study. The Aging Male, 26 (1). http://doi.org/10.1080/13685538.2023.2220567

Yassin, A., Alwani, M., Al-Zoubi, R.M., Aboumarzouk, O.M., Talib, R., Nettleship, J., ... Albaba, B. (2023). Voiding function improves under long-term testosterone treatment (TTh) in hypogonadal men, independent of prostate size. International Urology and Nephrology, 55, 1649-1658. http://doi.org/10.1007/s11255-023-03602-4

Yassin, A., Sabsigh, R., Al‐Zoubi, R.M., Aboumarzouk, O.M., Alwani, M., Nettleship, J., & Kelly, D. (2022). Testosterone and Covid‐19: An update. Reviews in Medical Virology. http://doi.org/10.1002/rmv.2395

Yassin, A., Saad, F., Alwani, M., Aboumarzouk, O.M., Al-Zoubi, R.M., Nettleship, J., ... Al-Ansari, A. (2022). The effects of long-term testosterone treatment on endocrine parameters in hypogonadal men: 12-year data from a prospective controlled registry study. The Aging Male, 25 (1), 185-191. http://doi.org/10.1080/13685538.2022.2099828

Alwani, M., Yassin, A., Al-Zoubi, R.M., Aboumarzouk, O.M., Nettleship, J., Kelly, D., ... Shabsigh, R. (2021). Sex-based differences in severity and mortality in COVID-19. Rev Med Virol, 31 (6). http://doi.org/10.1002/rmv.2223

Kilby, E.L., Kelly, D.M., & Jones, T.H. (2021). Testosterone stimulates cholesterol clearance from human macrophages by activating LXRα. Life Sciences, 269. http://doi.org/10.1016/j.lfs.2021.119040

Yassin, A.A., Alwani, M., Talib, R., Almehmadi, Y., Nettleship, J.E., Alrumaihi, K., ... Saad, F. (2021). Long-term testosterone therapy improves liver parameters and steatosis in hypogonadal men: a prospective controlled registry study. The Aging Male. http://doi.org/10.1080/13685538.2020.1867094

Jones, T.H., & Kelly, D. (2018). Randomized controlled trials - mechanistic studies of testosterone and the cardiovascular system. Asian journal of andrology, 20 (2), 120-130. http://doi.org/10.4103/aja.aja_6_18

Jones, T.H., & Kelly, D. (2018). Randomized controlled trials-mechanistic studies of testosterone and the cardiovascular system. Asian Journal of Andrology, 20 (2), 120-130. http://doi.org/10.4103/aja.aja-6-18

Kelly, D., Akhtar, S., Sellers, D., Muraleedharan, V., Channer, K.S., & Jones, T.H. (2016). Testosterone differentially regulates targets of lipid and glucose metabolism in liver, muscle and adipose tissues of the testicular feminised mouse. Endocrine, 54 (2), 504-515. http://doi.org/10.1007/s12020-016-1019-1

Kelly, D., & Jones, T.H. (2015). Testosterone and obesity. Obesity Reviews, 16 (7), 581-606. http://doi.org/10.1111/obr.12282

Kelly, D.M., Nettleship, J.E., Akhtar, S., Muraleedharan, V., Sellers, D., Brooke, J.C., ... Jones, T.H. (2014). Testosterone suppresses the expression of regulatory enzymes of fatty acid synthesis and protects against hepatic steatosis in cholesterol-fed androgen deficient mice. Life sciences, 109 (2), 95-103. http://doi.org/10.1016/j.lfs.2014.06.007

Kelly, D.M., Sellers, D.J., Woodroofe, M.N., Jones, T.H., & Channer, K.S. (2013). Effect of testosterone on inflammatory markers in the development of early atherogenesis in the testicular-feminized mouse model. Endocrine Research, 38 (3), 125-138. http://doi.org/10.3109/07435800.2012.735307

Rao, P.M., Kelly, D., & Jones, T.H. (2013). Testosterone and insulin resistance in the metabolic syndrome and T2DM in men. Nature Reviews Endocrinology, 9 (8), 479-493. http://doi.org/10.1038/nrendo.2013.122

Kelly, D.M., & Jones, T.H. (2013). Testosterone: a metabolic hormone in health and disease. Journal of Endocrinology, 217 (3), R25-R45. http://doi.org/10.1530/joe-12-0455

Kelly, D.M., & Jones, T.H. (2013). Testosterone: a vascular hormone in health and disease. Journal of Endocrinology, 217 (3), R47-R71. http://doi.org/10.1530/joe-12-0582

Conference papers

Rao, P.M., Jones, T.H., & Kelly, D. (2023). Testosterone improves symptom severity, quality of life (QOL), triglycerides and strength: A randomised placebo-controlled study in men with uncontrolled type-2 diabetes and hypogonadism: Stride study. DIABETIC MEDICINE, 40.

Smith, C.L., Kelly, D.M., Le Maitre, C.L., & Stafford, P. (2023). Developing a microfluidic model to investigate the crosstalk between Porphyromonas gingivalis and vascular endothelial cells. TISSUE ENGINEERING PART A, 29 (13-14).

Kelly, D.M., Akhtar, S., Sellers, D.J., Muraleedharan, V., Channer, K.S., & Jones, T.H. (2016). Testosterone protects against early atherogenesis by beneficially modulating tissue-specific metabolic function in liver, muscle and adipose of male mice. Atherosclerosis, 244, e7. http://doi.org/10.1016/j.atherosclerosis.2015.10.072

Kelly, D.M., Harrison, P.S., Akhtar, S., & Jones, T.H. (2014). Testosterone Increases Glucose Uptake and Glycolysis in HepG2 Human Liver Cells. ENDOCRINE REVIEWS, 35 (3).

Kelly, D.M., Sellers, D.J., Woodroofe, M.N., Jones, T.H., & Channer, K.S. (2010). Effect of Testosterone on Inflammatory Markers in Development of Early Atherogenesis in the Testicular Feminised Mouse (Tfm) Model. ENDOCRINE REVIEWS, 31 (3).

Kelly, D., Sellers, D., Woodroofe, M., & Channer, K. (2009). INVESTIGATING ANTI-INFLAMMATORY EFFECTS OF TESTOSTERONE IN ATHEROSCLEROSIS. ATHEROSCLEROSIS SUPPLEMENTS, 10 (2).

Woodroofe, N.W., Sellers, D., Channer, K.S., & Kelly, D.M. (2008). Investigating the role of testosterone and inflammation in atherosclerosis. Immunology, 125 (1), 116-117. http://doi.org/10.1111/j.1365-2567.2008.02826.x

Kelly, D., Channer, K., Woodroofe, N., & Sellers, D. (2008). Investigating the immunomodulatory effects of testosterone on cell type-specific expression of CX3CL1 in human aortic vascular cells. FUNDAMENTAL & CLINICAL PHARMACOLOGY, 22, 73-74.

Book chapters

Shabsigh, R., & Kelly, D. (2022). COVID-19 Crisis Timeline: The Warning and the Surge. In Shabsigh, R. (Ed.) Health Crisis Management in Acute Care Hospitals, Lessons Learned from COVID19 and Beyond. Springer: http://doi.org/10.1007/978-3-030-95806-0_2

Theses / Dissertations

Bateman, L.E.R. (2020). The anti-inflammatory effects of testosterone on atherosclerosis. (Doctoral thesis). Supervised by Kelly, D. http://doi.org/10.7190/shu-thesis-00351

Other activities

Invited reviewer of original manuscripts for several journals in the endocrine and life sciences field.

External examiner (MPhil), University of Sheffield, 2017.

Honorary Lectureship, University of Sheffield, awarded in 2016.


Postgraduate supervision

Lauren Bateman - "The anti-inflammatory effects of testosterone on atherosclerosis" (Sep 2016 - Sep 2020)

Robert Tempest - "Colon-derived extracellular vesicles and their impact on adipose cells" (Sep 2017 - Sep 2021)


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