Juan M. Jiménez
Our laboratory studies the interaction between fluid flow and biology, by integrating fluid dynamic engineering, cellular and molecular biology. Body fluids or biofluids, such as blood, lymph, and cerebrospinal fluid continuously interact with cells in the body eliciting biochemical and physical responses. Our research seeks to elucidate the fluid flow characteristics and fluid flow-dependent biomolecular pathways relevant in medicine.
Cardiovascular stents, fluid flow and endothelial cell phenotype.
Coronary heart disease is a major cause of death worldwide, and stenting has become one of the preferred therapies for treatment. In the USA alone about 650,000 stents are implanted yearly with 75% of these being drug eluting stents (DES). Unfortunately 1/3 of patients with bare metal stents (BMS) suffer from restenosis of the coronary artery, and about 1-2% of patients with DES suffer from in-stent thrombosis, leading to significant morbidity and mortality. My research explores how blood flow perturbations caused by the stent design contribute to in-stent restenosis and thrombosis, studying the impact of the fluid forces on blood components and endothelial cells. I have introduced aerodynamic and fluid dynamic engineering principles into stent design, creating streamlined stent struts that differ from commercially available BMS and DES non-streamlined stent struts. Using stented coronary artery models exposed to coronary-like arterial fluid flows we examine: 1) the phenotype change of endothelial cells transcriptionally and/or translationally in the vicinity of nonstreamlined and streamlined stent struts, 2) endothelial cell migration (motility) under the influence of fluid flows created by the different stents struts, with implications to wound healing after coronary artery stenting, a marker of clinical success, 3) in the absence of endothelial cells, the role that stent geometries effect on coagulation and thrombus formation using freshly isolated blood. Initial results have demonstrated that by introducing this novel engineering approach to stent design, the local blood flow field is changed yielding an anti-thrombotic endothelial cell phenotype, accelerated cell motility (wound healing), and decreased thrombus formation. Future research planned includes determining the molecular basis for fluid flow-induced differences in endothelial cell migration, optimization of streamlined stent design, and pre-clinical studies of streamlined stents in coronary heart disease animal models.
Cerebral aneurysm formation, fluid flow and vascular phenotype.
Five percent of adults are affected by brain aneurysms; one ruptures every 18 minutes. Forty percent of ruptures are fatal, while 2/3 of survivors suffer permanent neurologic injury. Little is known about the initiation of aneurysms, with therapies aimed at treatment instead of prevention. We study in vitro how blood flow characteristics present in the cerebral vasculature play a role in the initiation and progression of cerebral aneurysms to identify early factors that may prevent aneurysm formation or identify susceptible individuals before aneurysms are formed.
The role of lymphatic fluid flow in development and disease.
The role of fluid flow in development and disease is poorly understood in the lymphatic system. Our work has recently elucidated the pivotal role of fluid flow in the development of lymphatic valves. We have demonstrated that fluid flow serves as a physical stimulus inducing expression of genes required for lymphatic valve development and identified a novel role for GATA2, an upstream transcriptional regulator of FOXC2. Future research planned includes characterizing the interplay between lymphatic flow and transport diseases that affect the lymphatic system.
Interstitial fluid flow and bone growth
We are studying the effects of mechanotransduction via fluid flow on bone cells. Body movements drive interstitial fluid flow potentially stimulating bone cells. Bone cells respond to mechanical forces that regulate pathways involved in new bone deposition. Our in vivo and in vitro studies are elucidating biomolecular pathways involved in new bone deposition.
Learn more at https://JimenezLab.org
- BS, Michigan State University
- MS, Princeton University
- PhD, Princeton University
- Postdoctoral Fellowship, University of Pennsylvania