My interest in biomedical research began through a clinical mentor in medical school in 1996. We were investigating the utility of electromagnetic imaging to ensure complete assessment of the colon during colonoscopy. The excitement of improving patient care, the process of data analysis, and the satisfaction of publication inspired me to pursue a scientific career within medicine.
During medical school, I developed an interest in cardiovascular disease. This took me in 1998 to the University of Cambridge where I worked with a clinical scientist and cardiac surgeon during my elective. I was inspired by my mentors enthusiasm and tireless energy for clinical science despite his clinical duties as a surgeon. From this original encounter came my first cardiovascular article investigating neuropsychological outcomes after cardiac surgery.
I graduated from Medical School as Valedictorian with Honors, Distinction and the Gold Medal, intent on becoming a cardiothoracic surgeon. To pursue my aspirations as a clinician and researcher, following internship, I applied for and successfully obtained a residency position in surgery at the University of Cambridge. There, parallel to clinical training, I was able to expand my research skillset further by learning how to create and manage a database, perform statistical analysis and write a scientific paper. Whilst a resident, I designed and executed a randomized controlled trial investigating the utility of remote ischemic preconditioning on myocardial and renal injury after major vascular surgery (cited ≈ 500). This project led to young investigator awards from the European Vascular Society and British Cardiovascular Society. The work was published in Circulation. The learning that came from designing and running a clinical trial at an early stage in my career was of great value and the skills that I developed allowed me to collaborate with other researchers allowing me to publish extensively during my clinical training, including in high impact journals such as the BMJ.
Training at the University of Cambridge introduced me to an entirely new area of science – the basic sciences. After finishing residency, and having developed a skill set in clinical research, I was convinced of the need to embrace molecular and cellular techniques to fully realize my ambitions of becoming a cardiovascular scientist. As I was clear that I wanted to pursue a career in academic medicine, I applied for and received a prestigious Physician-Scientist PhD award from the Wellcome Trust to train in the basic sciences. My thesis, entitled "Regulation of Endothelial Nitric Oxide Synthase by Tetrahydrobiopterin in Response to Vascular Injury," was aimed at understanding molecular mechanisms and biological pathways involved in disease induced vascular remodeling. As a Wellcome Fellow I studied the role of redox signaling, specifically the role of the essential eNOS cofactor tetrahydrobiopterin on the response to vascular injury. From this we learned the critical effect of tetrahydrobiopterin on superoxide signaling of chemokine mediated vascular inflammation. This project led to young investigator awards from the British Atherosclerosis Society and the American College of Cardiology. In addition this work led to a pair of publications in Circulation.
Using the technical skills that I had learned as a trainee surgeon, during my DPhil studies I also developed and validated the seminal mouse model of balloon angioplasty and stenting, providing the opportunity to explore molecular mechanisms of restenosis in greater detail. Characterization of the model was published in ATVB.
To broaden my scientific horizons, particularly in extending my knowledge of molecular pathways, I identified Stanford as one of the few centers capable of fulfilling my goal of becoming expert physician and scientist. Stanford was known for pioneering genomic and molecular approaches to cardiovascular disease. I moved from the UK and held a postdoctoral scholarship at Stanford. Using murine models of venous bypass surgery, abdominal aortic aneurysm formation and balloon angioplasty and stenting, we investigated the role of the endogenous vasculoprotective peptide, apelin, in the vascular remodeling response focusing on the interaction between apelin, angiotensin, eNOS and reactive oxygen species. This work was published in JCI. Together, these multiple distinct research opportunities provided me with a comprehensive understanding of vascular biology while providing me with a diverse training in biomedical research.
Following my post-doctoral training, I decided that the research environment, funding opportunities and potential to grow as a clinician-scientist would be best served in the United States. I thus forfeited my funded position for advanced clinical training at the University of Cambridge and re-trained entirely in internal medicine and cardiovascular medicine at Stanford University. Staying at Stanford allowed me to remain active in the basic science lab and secure external grant funding to help continue my research. Using human atherectomy tissue from patients with de novo atherosclerosis and in-stent restenosis, applying systems biology approaches, we identified genes that were differentially regulated in these two distinct processes and identified a receptor present in vascular smooth muscle cells but not endothelium that dramatically impacted cell fate after vascular injury. This latter work formed the basis for a Young Investigator Award from the American Heart Association, and an NIH/NHLBI K99/R00 Pathway to Independence Award which I successfully obtained during my second year of cardiovascular medicine fellowship. This work was eventually published in JCI.
Following the completion of my training as an interventional cardiologist, I joined the faculty at Columbia in late 2011 as a practicing clinician-scientist. My translational science laboratory utilized systems biology methodologies to investigate signaling events in the propagation of cardiovascular pathogenic conditions. Coupled with unique models of cardiovascular injury developed in my lab (including mouse models of balloon angioplasty and stenting, venous bypass grafting and rat models of cardio-pulmonary bypass and extra-corporeal membrane oxygenation), we made several novel insights publishing multiple basic and translational science manuscripts in journals such as JCI, EHJ and Circulation.
In the spirit of translational medicine, my clinical research progressed in parallel to my basic science work. I developed a unique interest and skillset in intravascular imaging and invasive physiology, establishing myself as a leader in this area on the national and international level. I was the global principal investigator of the multi-center randomized controlled trial, ILUMIEN III – OPTIMIZE PCI, which investigated whether intravascular imaging modalities offered advantages over conventional angiography for patients undergoing stenting for coronary artery disease. This study was published in the Lancet. I was also global principal investigator for the development of the Resting Full-Cycle Ratio (RFR). Traditionally invasive physiological assessment is performed by administrating patient’s adenosine, which may lead to patient discomfort and is known to add cost and procedural time, RFR eliminates this step, and is thus a major advancement in interventional cardiology, helping determine which patients may benefit from stenting compared to those who may be managed conservatively. I independently developed the algorithm for RFR which was approved by the FDA in March 2019 and is now used clinically around the world. This work was presented as late breaking research at EuroPCR and published as featured research in Eurointervention. In concert with these activities, I was heavily involved in the concept of bioresorbable vascular scaffolds. Current drug eluting stents are made of metal alloy and remain within the body forever. Bioresorbable scaffolds alternately, are made of absorbable polymers which provide temporary scaffolding with programmed disintegration over time. These devices held great promise as they would eliminate the permanence of metal and thus late strut fractures, abnormal caging of the vessel wall, and new atherosclerosis within the stent cage, known collectively to contribute to a 2% to 3% annual risk of stent-associated events. Unfortunately, these scaffolds failed to show superiority to metallic DES perhaps due to their bulky design and impact on local rheology. The 2- and 3-year clinical outcomes were published in the Lancet and Circulation respectively.
I have applied my expertise in intravascular imaging and physiology directly to patient care, pioneering strategies to minimize or eliminate the use of radiographic contrast during stenting procedures. Patients with advanced chronic kidney disease are at risk from contrast administration, with the injury from contrast potentially leading to permanent dialysis, and mortality. Using a protocolized approach of “ultra-low contrast angiography”, we have virtually eliminated the need for dialysis from angiography. Furthermore, using “ultra-low contrast angiography”, to create a blueprint of the coronary arteries we are now able to perform “zero-contrast-PCI” for the first time. This work was seminally published in the EHJ.
I have a passion for innovation. In addition to developing the seminal model of balloon angioplasty and stenting in mice and RFR, I developed the seminal model of extra-corporeal membrane oxygenation in rodents. Most recently, I have been involved in the development of a device used to treat severe coronary artery calcification. Intravascular lithotripsy (IVL) (Shockwave Medical, Fremont, CA) is a technique based on established technology used to treat kidney stones. IVL is now available commercially in many countries, and is being hailed as one of the major breakthroughs in interventional cardiology in recent years. The derivation and validation of this work has been published in Circulation and Circulation Intervention.
My current research continues to focus on intravascular imaging and physiology. I am currently the global principal investigator of the ILUMIEN IV – OPTIMAL PCI trial, the largest randomized controlled trial investigating whether intravascular imaging can improve clinical outcomes compared to angiography ever performed. This trial, which has randomized 1200 of up to 3600 patients in 125 sites across 30 countries will be the pivotal study impacting societal guidelines. I am also currently the Director of the Angiographic Core Laboratory at the Cardiovascular Research Foundation. In that capacity, I serve as co-chair for the angiography and optimal revascularization therapy publication committees for the NIH/NHLBI funded multicenter randomized controlled trial - International Study of Comparative Health Effectiveness With Medical and Invasive Approaches (ISCHEMIA). In addition to these large trials, I maintain an active original research program at Columbia University Medical Center currently investigating a) the long-term clinical outcomes of ultra-low contrast angiography and zero contrast PCI; b) alternatives to radiocontrast medium for intravascular imaging; c) the impact of atherectomy strategies on microcirculatory function; d) progression of atherosclerosis after stenting versus bypass surgery. While I have closed my basic science laboratory due to time constraints resultant from my clinical work and clinical research, I maintain an active presence in basic science, focusing currently on vascular regeneration. I have held continuous NIH funding either as PI or Co-I for over a decade.
I have a commitment to education and mentorship. Since completing my training, I have mentored 20 medical students, post-doctoral scientists, residents or fellows resulting in more than 70 publications for these trainees. Since 2015, I lead an externally funded advanced Intravascular Imaging and Physiology Fellowship. In the Angiographic Core Laboratory at the Cardiovascular Research Foundation, I mentor 14 technicians. In addition to training general and interventional fellows on the technical aspects of invasive cardiology, I make a concerted effort to teaching nursing staff and allied health professionals. I also run monthly courses teaching invasive imaging and physiology to physicians from around the world. St Francis Heart Center is the only training center for zero-contrast-PCI in the world, which I lead.
In summary, I have dedicated my career to being a cutting edge physician and scientist. I graduated with Honors and Distinction from medical school. I am a Member of both the Royal College of Physicians and Royal College of Surgeons in the United Kingdom. I have investigator awards from the European Vascular Society, British Cardiovascular Society, British Atherosclerosis Society, American College of Cardiology, American Heart Association, Cardiovascular Research Foundation and European Association of Percutaneous Coronary Intervention. I serve on the Editorial Board for two major cardiovascular journals and peer review regularly for over 20 journals. I write curriculum for the American College of Cardiology. I have mentored 16 medical students, residents and fellows since beginning at Columbia University. I was or am the Principal Investigator of multiple global multicenter randomized trials and inventor of novel technologies used in clinical practice. I have published more than 200 peer-reviewed manuscripts including major journals such as the New England Journal of Medicine, Lancet, European Heart Journal, Journal of the American College of Cardiology, Journal of the American Medical Association - Cardiology, and Circulation. I am hopeful you find my accomplishments worthy of your trust as a patient.