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Jaffe Laboratory

The Jaffe laboratory is focused on understanding the molecular mechanisms by which blood vessels become dysfunctional to lead to common cardiovascular conditions, including heart attack, stroke, high blood pressure, in-stent restenosis, vein graft failure and heart failure. We are interested in understanding how traditional risk factors like aging, obesity, high blood pressure or high cholesterol, or new risk factors like novel cancer treatments, cause blood vessels to become diseased. We are also focused on understanding sex differences in how these cardiovascular diseases develop, in order to identify sex-specific precision medicine strategies.
jaffe lab iris sitting at desk

A major area of interest is the role of the hormone aldosterone and the receptor by which it functions, the mineralocorticoid receptor (MR), in the molecular mechanisms of cardiovascular disease. The steroid hormone aldosterone is the final step in the renin-angiotensin-aldosterone pathway that regulates blood pressure and electrolyte homeostasis by activating MR in the kidney to regulate genes involved in renal sodium handling. We and others have demonstrated that MR is expressed in cells of the human blood vessel, supporting the possibility that direct effects of aldosterone on the vasculature could play a role in vascular function and disease. This is clinically significant because, in human clinical trials, pharmacologic inhibition of the MR prevents heart attacks, strokes and cardiovascular deaths with minimal effects on systemic blood pressure.

A second major area fits in the field of cardio-oncology. The Jaffe lab is exploring the impact of cancer treatment on blood vessels and how this might contribute to side effects in cancer survivors. We are exploring the molecular mechanisms for these clinical findings in order to gain a better understanding of the mechanisms of cardiovascular disease and to identify novel therapeutic drug targets for common vascular diseases or to protect cancer patients from adverse side effects.

The Jaffe laboratory routinely uses in vitro molecular and cellular biology methods, primary human vascular cell culture models, state-of-the-art transgenic mouse models with in vivo capabilities to study rodent models of cardiovascular physiology and disease, unbiased transcriptomics, proteomics, and epi-genomics methods, and translational studies utilizing human samples from our patients across Tufts Medicine.

Current projects include:

The sex-specific role of vascular MR in endothelial dysfunction, atherosclerosis and vascular remodeling in response to obesity, hypertension and aging

We have demonstrated that MR is expressed in human vascular cells where it acts as a ligand-activated transcription factor to regulate gene expression in response to the hormone aldosterone. In human vascular smooth muscle cells, we have found that MR regulates genes involved in vasoconstriction and stiffness to contribute to rising blood pressure. In endothelial cells, MR contributes to blood vessel inflammation and atherosclerosis. It does this by sexually dimorphic mechanisms that are under investigation.

jaffe lab figure 1
Figure 1. Animal models of aldosterone-induced vascular injury and atherosclerosis were used in the Jaffe lab to study the in vivo role of MR in vascular function and disease.
Mechanisms of vascular aging and hypertension

Learn more about this work in Dupont et al, 2016 and Ibarrola et al, 2022 and by reviewing the figure below.

Jaffe Lab Figure 2
Figure 2. Model of the Role of Smooth Muscle Cell Mineralocorticoid Receptor in Vascular Aging.
Vascular complications of targeted cancer therapy

Learn more about this work in Gopal, et al 2016 and by reviewing the figure below.

Jaffe Lab Figure 3
Figure 3: The Jaffe lab is exploring the endothelial cell as a central mediator of vascular toxicities of targeted anti-cancer agents. Detailed mechanisms and mitigating strategies are being studied in the Jaffe lab using proteomics, in vitro and in vivo approaches.
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Lab members

  • Qing Lu, Research Associate
  • Jaime Ibarrola, PhD, Postdoctoral Research Fellow
  • Richard Travers, MD, PhD, Postdoctoral Research Fellow
  • Nicholas Camarda, Graduate Student (MD/PhD program), Tufts Graduate School of Biomedical Sciences
  • Alec Stepanian, Graduate Student (MD/PhD program), Tufts Graduate School of Biomedical Sciences
  • Nicole Wolter, Graduate Student (MD/PhD program), Tufts Graduate School of Biomedical Sciences
Contact info
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Iris Jaffe, MD, PhD
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