When Maria Luisa S. Sequeira-Lopez, MD, first began her research at UVA School of Medicine's Child Health Research Center, neuroendocrine-immunology didn't yet exist formally.
But her curiosity for the unknown and interest in renin cells led her to the perfect home for her research. Her research explores how renin cells differentiate themselves and define their roles.
By deepening the knowledge base of how the body develops and works, Sequeira-Lopez's work creates a foundation for future research into practical applications. At UVA's Child Health Research Center, the goal is to bridge the gap between cutting-edge research and bedside applications. All with the mission to improve the lives of children.
Watch the video below and read more about her research.
What are you working on right now?
I study how renin-producing juxtaglomerular (JG) cells acquire their identity. Renin cells regulate blood pressure and fluid-electrolyte homeostasis. They possess additional defensive roles in innate immunity and glomerular regeneration.
Interestingly, renin cells are crucial for the morphogenesis of the renal arterioles. As the arterioles mature, the renin cells differentiate into smooth muscle cells, mesangial cells, interstitial pericytes, and JG cells. However, the cells retain the memory of the renin phenotype and under physiological stress such as hypotension, dehydration, hemorrhage, or heart failure, smooth muscle cells along the arterioles and glomerular mesangial cells regain the ability to produce renin and thus reestablish homeostasis.
What are the most intriguing potential clinical applications of your work?
There are several important questions: how did these cells that existed in nature for over 400 million years evolve the structures or mechanisms to detect a fall in blood pressure or changes in body fluid volume and composition? We recently discovered the structure of the pressure-sensing mechanism, the renin baroreceptor. It's a mechanism whereby a fall in pressure elicits renin release whereas an increase in pressure diminishes it. This question of is, of course, of evolutionary biological relevance but it has implications for our understanding and management of our patients with hypertension, orthostatic hypotension, or those unable to conserve sodium as happens in salt-losing nephropathies.
Further, over a billion people in the world are hypertensive which carries the risks of cardiovascular disease and/or stroke. Many of the medications used today inhibit the renin pathway. Because we know that renin cells are crucial for the vasculature, the aggressive use of inhibitors of the renin-angiotensin system carries the risk of inducing arteriolar disease as shown in practically every animal studied today: frogs, mice, rats, monkeys, and humans.
What made you choose UVA Health Children's as the place to do your research?
Basically, the world’s experts on kidney development and renin cells were at UVA Health Children's. Before I joined, I had a strong interest in a field that didn’t yet exist formally: the field of neuroendocrine-immunology.
Interestingly, as I was referring to the arteriolar disease caused by renin-angiotensin inhibitors it turns out that the hypertrophic arterioles in the kidneys are hyper-innervated and are surrounded by numerous immune cells.
Each arteriole becomes in essence an independent mini neuro-immune-endocrine organ devoted to the production of renin at the expense of renal function. The kidney is transformed in a conglomerate of thousands of these interconnected organs whose sole — and detrimental — purpose is to produce renin to maintain organismal blood pressure and fluid volume.
So, in retrospect, it was a good choice, and as it happens often, given my curiosity for the unknown, I worked more than 20 years to find myself working on the discipline that didn’t formally exist. My perfect choice.
What do you wish more people knew about your area of research?
I wish people knew that translational medicine requires first and foremost fundamental discoveries. We need to understand how things work before they can be applied. Applications follow solid knowledge, otherwise they'll often fall apart.