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Joey V. Barnett, Ph.D.

  • Acting Chair, Department of Pharmacology
  • Professor of Medicine (Clinical Pharmacology),
  • Professor of Pharmacology, Professor of Pediatrics,
  • Professor of Pathology, Microbiology & Immunology

Phone

615-936-1722

Email

joey.barnett@vanderbilt.edu
Vanderbilt University Medical Center
460B Preston Building
Nashville, TN 37232

Joey V. Barnett, Ph.D.

  • Acting Chair, Department of Pharmacology
  • Professor of Medicine (Clinical Pharmacology),
  • Professor of Pharmacology, Professor of Pediatrics,
  • Professor of Pathology, Microbiology & Immunology

615-936-1722

joey.barnett@vanderbilt.edu

Vanderbilt University Medical Center
460B Preston Building
Nashville, TN 37232

Research Program

  • Non-Programmatically Aligned

Profile

Education

Research Emphasis

Cardiac function, Developmental biology, Heart, Kinase,
Knockout, Molecular medicine, Pharmacology,
Phosphorylation, Physiology, Receptor,
Signal transduction, Vascular Biology, Pulmonary hypertension

Research Description

The Barnett lab has worked for a number of years on Transforming Growth Factor Beta (TGFß) biology and in the context of cardiac development. The Type III TGFß Receptor (TGFßR3), also known as betaglycan, is a ubiquitously expressed TGFß & BMP receptor that plays an essential role in regulating diverse cellular responses in cardiac development, cancer and angiogenesis. TGFßR3 functions as a rheostat balancing opposing signals downstream of TGFß & BMP receptors, and is down regulated in the lungs of patients with pulmonary arterial hypertension (PAH). PAH is a fatal disease for which no disease modifying therapies have been developed. Clues to the pathogenesis and disease modifying therapeutics for PAH may be gained from the analysis of patients with heritable (HPAH). About 80% of patients with HPAH have mutations in bone morphogenetic protein receptor type 2 (BMPR2), and patients with non-hereditary forms of PAH have decreased BMPR2 expression and signaling. BMPR2 is a member of the BMP and Transforming Growth Factor ß (TGFß) superfamily. It is expressed at high levels in pulmonary endothelial cells (PECs) and conditional deletion of Bmpr2 from PECs results in pulmonary hypertension (PH) in mice. Mutations in other BMP signaling genes that are restricted to the endothelium are also associated with HPAH. This suggests that endothelial cells may be one of the primary sites of cellular dysfunction in patients with HPAH and other forms of PAH. As seen in mice with Bmpr2 mutations, we have shown that Tgfbr3+/- mice develop PH on Western diets. In addition, Tgfbr3+/- cells have the same changes in metabolic reprogramming seen in Bmpr2+/- PECs. We also provide evidence that TGFßR3 over-expression rescues metabolic reprogramming in Bmpr2+/- PECs and that this is associated with increased expression of the master regulator of mitochondrial biogenesis, PGC1a. These findings pose fundamental questions about the role of BMPR2 & TGFßR3 cross talk in PAH pathogenesis, answers to which may lead to better understanding of the mechanisms underlying PAH and identification of novel therapeutic targets.

Publications

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