About

Jay Humphrey is the John C. Malone Professor of Biomedical Engineering at Yale University. His research focuses on vascular mechanics and mechanobiology, utilizing genetic, pharmacologic, and surgical models to elucidate mechanisms underlying diverse vascular diseases. He develops theoretical frameworks for understanding vascular disease progression and designing clinical interventions, alongside using computational models to design and evaluate tissue-engineered vascular grafts based on mechanobiology and immunobiology concepts. Humphrey has made significant contributions to understanding arterial aging, aortic aneurysms, and vascular remodeling, with over 400 archival papers published. His work has earned him numerous awards and honors, including fellowships in the American Society of Mechanical Engineers and the American Institute for Medical and Biological Engineering, as well as international recognition such as the Collen-Francqui Chair in Belgium and Doctorate Honoris Causa from École Nationale Supérieure des Mines in France.

Research topics

• Medicine
• Computer Science
• Artificial Intelligence
• Cardiology
• Pathology
• Internal medicine
• Mathematics
• Materials science
• Cell biology
• Anatomy
• Applied mathematics
• Algorithm
• Mathematical analysis
• Statistical physics
• Biology
• Physics

Selected publications

• Arterial Stiffness and Cardiovascular Risk in Hypertension

  Circulation Research · 2021 · 702 citations

  • Cardiology
  • Medicine
  • Internal medicine

  Arterial stiffness, a leading marker of risk in hypertension, can be measured at material or structural levels, with the latter combining effects of the geometry and composition of the wall, including intramural organization. Numerous studies have shown that structural stiffness predicts outcomes in models that adjust for conventional risk factors. Elastic arteries, nearer to the heart, are most sensitive to effects of blood pressure and age, major determinants of stiffness. Stiffness is usually considered as an index of vascular aging, wherein individuals excessively affected by risk factor exposure represent early vascular aging, whereas those resistant to risk factors represent supernormal vascular aging. Stiffness affects the function of the brain and kidneys by increasing pulsatile loads within their microvascular beds, and the heart by increasing left ventricular systolic load; excessive pressure pulsatility also decreases diastolic pressure, necessary for coronary perfusion. Stiffness promotes inward remodeling of small arteries, which increases resistance, blood pressure, and in turn, central artery stiffness, thus creating an insidious feedback loop. Chronic antihypertensive treatments can reduce stiffness beyond passive reductions due to decreased blood pressure. Preventive drugs, such as lipid-lowering drugs and antidiabetic drugs, have additional effects on stiffness, independent of pressure. Newer anti-inflammatory drugs also have blood pressure independent effects. Reduction of stiffness is expected to confer benefit beyond the lowering of pressure, although this hypothesis is not yet proven. We summarize different steps for making arterial stiffness measurement a keystone in hypertension management and cardiovascular prevention as a whole.

  DOI

• Spontaneous reversal of stenosis in tissue-engineered vascular grafts

  Science Translational Medicine · 2020 · 121 citations

  • Medicine
  • Cardiology
  • Pathology

  We developed a tissue-engineered vascular graft (TEVG) for use in children and present results of a U.S. Food and Drug Administration (FDA)-approved clinical trial evaluating this graft in patients with single-ventricle cardiac anomalies. The TEVG was used as a Fontan conduit to connect the inferior vena cava and pulmonary artery, but a high incidence of graft narrowing manifested within the first 6 months, which was treated successfully with angioplasty. To elucidate mechanisms underlying this early stenosis, we used a data-informed, computational model to perform in silico parametric studies of TEVG development. The simulations predicted early stenosis as observed in our clinical trial but suggested further that such narrowing could reverse spontaneously through an inflammation-driven, mechano-mediated mechanism. We tested this unexpected, model-generated hypothesis by implanting TEVGs in an ovine inferior vena cava interposition graft model, which confirmed the prediction that TEVG stenosis resolved spontaneously and was typically well tolerated. These findings have important implications for our translational research because they suggest that angioplasty may be safely avoided in patients with asymptomatic early stenosis, although there will remain a need for appropriate medical monitoring. The simulations further predicted that the degree of reversible narrowing can be mitigated by altering the scaffold design to attenuate early inflammation and increase mechano-sensing by the synthetic cells, thus suggesting a new paradigm for optimizing next-generation TEVGs. We submit that there is considerable translational advantage to combined computational-experimental studies when designing cutting-edge technologies and their clinical management.

  DOI

• Smooth Muscle Cell Reprogramming in Aortic Aneurysms

  Cell stem cell · 2020 · 205 citations

  • Biology
  • Internal medicine
  • Cell biology
  DOI

• Non-invasive inference of thrombus material properties with physics-informed neural networks

  Computer Methods in Applied Mechanics and Engineering · 2020 · 176 citations

  • Computer Science
  • Artificial Intelligence
  • Applied mathematics
  DOI

Recent grants

• Improving Tissue Engineered Vascular Graft Performance via Computational Modeling

  NIH · $6.4M · 2018–2027

• NIH Grant R01HL064372

  NIH · $3.0M · 2008

• NIH Grant R01HL068118

  NIH · $407k · 2005

• Mechanisms Underlying The Progression of Large Artery Stiffness in Hypertension

  NIH · $3.0M · 2010–2021

• NIH Grant R21NS062242

  NIH · $338k · 2012

Frequent coauthors

• George Tellides

  Yale University

  130 shared

• Matthew R. Bersi

  Washington University in St. Louis

  100 shared

• David G. Harrison

  Brunel University of London

  77 shared

• Alexander W. Caulk

  Yale University

  75 shared

• C. Alberto Figueroa

  University of Michigan–Ann Arbor

  71 shared

• Guangxin Li

  Yale University

  71 shared

• Lingfeng Qin

  Yale University

  70 shared

• Yang Jiao

  Nanjing Drum Tower Hospital

  68 shared

Education

• Ph.D., Engineering Science and Mechanics

  Georgia Institute of Technology

  1985

Awards & honors

• Fellow, International Academy of Medical and Biological Engi…
• Collen-Francqui Chair – Belgium (Ghent University and KU Leu…
• Doctorate Honoris Causa, École Nationale Supérieure des Mine…
• H.R. Lissner Medal, American Society of Mechanical Engineers
• Academy of Distinguished Engineering Alumni, Georgia Tech

Similar researchers at Yale University

• Mark Gersteinh-217
• Liangbing Huh-172
• Akiko Iwasakih-145
• Alan Kazdinh-142
• Douglas L. Rothmanh-125