Dr Joseph Cheriyan

My research focuses on vascular function and inflammation, NO bioavailability and vascular-ventricular interactions. I have a keen interest in identifying novel agents that may improve vascular health, as measured in vivo, in human models of health and disease. I am the only MHRA accredited Phase 1 first-in-human physician on the Cambridge Biomedical Campus working in the University/NHS domains since 2006.

Vascular function and inflammation

We use well-described models to characterise this in our Department as well as more experimental approaches to stratify patients. These include forearm plethysmography, flow mediated dilatation and arterial stiffness as well as a range of haemodynamic and circulatory measurements. These biomarkers enable us to understand the mechanisms underlying the improvement or deterioration in vascular health in vivo from an NO bioavailability viewpoint, provide proof of concept of human physiology and pathophysiology and also help interrogate the role of various peptides and hormones in the regulation of vascular tone. The strength of these unique types of clinical physiological studies lies in their direct relevance to human biology, occasionally confirming pre-clinical models, but simultaneously providing relevance to human pathophysiology.

We are also interested in developing more novel approaches to understanding vascular pathophysiology using non-invasive imaging and bespoke technologies to understand angiogenesis. These techniques may be applied to human physiological studies and clinical trials of investigational medicinal products. This enables the translation of pre-clinical models of novel therapeutic agents into niche products differentiating an investigational medicinal product from existing therapies, or providing proof of mechanism in order to progress such a product through the stages of clinical drug development. For example, building on some seminal work performed by local collaborators, we have used FDG PET-CT in a novel experimental medicine study to understand the effects of a new therapeutic agent in altering the biology of atherosclerosis. We have applied similar techniques to assess existing therapies for patients with chronic inflammatory conditions, to understand if they possess off-target pharmacology which may improve outcomes as an inadvertent benefit of therapy. Along similar lines, we are aiming to understand how new drugs may disrupt vascular networks in the microcirculatory environment by examining the effects of such therapies on conjunctival vessels.

Phase 1/2 and First in human clinical trials in cardiovascular disease

We have an active programme of work in early phase studies in the cardiovascular arena. This includes repurposing of currently licensed drugs for novel indications where they are currently contraindicated, or in the execution of first in human trials in conjunction with the GSK Clinical Unit based on the campus.

Most early phase studies now embed proof of mechanism and proof of concept pharmacodynamic markers in their trials to discharge risks and provide evidence of benefit.

We also work closely with other industrial partners on pre-competitive and early phase conceptual studies to provide evidence of target engagement.

Cardiovascular Trials Office

I direct the Cardiovascular Trials Office of the Cambridge Clinical Trials Unit which leads the design, implementation and delivery of clinical trials on campus. This includes experimental studies in the cardio-respiratory arena in keeping with the Biomedical Research Centre theme. ​

Teaching

I lead an active programme of educational programmes for junior doctors and medical students. This includes the Cambridge Medical Seminars (http://cambsems.org​) and the Experimental Medicine Training Initiative (http://www.emi-training.org) for doctoral clinical/non-clinical students. This programme of education is set to be expanded internationally in 2018 with courses in SE Asia.