Riccardo Pofi

My career started in 2009 as a young MD student visiting the Department of Experimental Medicine in the Sapienza University of Rome. I initially showed an interest towards the pathophysiology of Diabetes micro/macrovascular complications. I designed a prospective longitudinal study which aimed to describe the "natural" history of Diabetic Cardiomyopathy measuring the changes in the viscoelastic properties of the left ventricular wall, demonstrating the involvement of the ECM and identifying potential disease marker and a molecular player for DCM progression. Meanwhile, I also investigated the pathways involved in diabetic end-organ damage, focusing on the role of the phosphodiesterase type 5 and its inhibitors (PDE5i). I tested the effects of PDE5i on the onset and progression of Diabetic Nephropathy. By designing an experimental study using an animal model of DN I demonstrated the beneficial effects of PDE5i on renal hemodynamic and function, also defining the underlying molecular mechanisms involved. Pushed from the inconsistencies of the published data about the protective role of PDE5i for diabetic complications, I performed the first non-sponsored, randomized, double-blind controlled trial to investigate the sex differences of PDE5 inhibition in patients with DCM demonstrating that the daily administration tadalafil improves cardiac contraction and the low-grade inflammation triggered by diabetes, in men, but not in postmenopausal women. Tadalafil also improved renal function in both sexes, showing, for the first time in humans, that the effects of PDE5i are sex and tissue-specific. I also provided a molecular pathway for the observed clinical findings.

In 2018 I joined Professor Jeremy Tomlinson’s research group at Oxford University and focused my interest on metabolism and steroid hormone biology. The research project was the topic of my PhD program titled: “Defining and predicting the adverse effects of prescribed steroids”, shared between Oxford University and Sapienza University of Rome. During the time spent in OCDEM, my interest on steroid hormones pushed me to deepen knowledge on adrenal insufficiency. I performed a retrospective analysis on patients with reversible causes of AI aiming to assess the potentially of HPA axis recovery. I found that Cortisol levels across an SST can be used to predict future recovery of Adrenal Insufficiency and may guide the frequency of repeat testing. Following these works, I studied the recovery of the HPA axis after TSA for non-ACTH secreting macro adenomas. I demonstrated that pre- and postoperative SST values can guide which patients are likely to recover function and potentially avoid unnecessary lifelong glucocorticoid replacement. Finally, a thrive collaboration with worldwide experts on adrenal diseases allowed me to evaluate possible relations between plasma renin measurements (PRC) and mineralocorticoid (MC) replacement dose in patients with primary AI. The analysis showed a wide variability in both PRC and MC dose, demonstrating that their relationship is complex and MC titration should not primarily be based only on renin normalization, but also on clinical parameters. As well as being involved in laboratory based research, I have contributed to, and lead, many other clinical research activities, generating a relevant scientific production, mostly translational, covering clinical and basic endocrine research.

After my PhD, I won a Clinical Research Fellow in OCDEM and I am involved in the DC-MACS study, a randomised controlled trial on the use of a 11β-HSD1 inhibitor in patients with mild autonomous cortisol secretion.