Research Interests

A respected physician-scientist, Victor J. Dzau, MD, specializes in cardiovascular translational research -- that is, turning basic science discoveries into practical applications that benefit patients with heart and vascular disease.

His laboratory research focuses on the molecular and genetic mechanisms of cardiovascular disease and the development of new gene-based therapies for heart disease.

The Dzau research team’s current projects include:

• Developing a gene therapy to prevent tissue damage from heart attack and heart disease
  
  Heart attack and coronary artery disease can result in ischemia -- a lack of blood flow to the heart that can kill heart muscle tissue and eventually cause the organ to fail.
  
  The Dzau lab is developing a new type of “smart” gene therapy to prevent such damage.
  
  The therapy combines a therapeutic gene -- heme-oxygenase 1, which has been shown to protect cells -- with a genetic "sensor" that recognizes and responds to the oxygen deprivation that follows the reduced blood flow. As soon as the oxygen declines, the sensor turns on the therapeutic gene, thereby preventing heart damage.
  
  In addition to its potential for patients with heart disease, the strategy might also prove useful for any condition in which tissues are susceptible to loss of blood supply, including stroke, shock, trauma and sepsis.
  
  Read more:
  
  Press Release: “Smart” Gene Therapy Protects Against Damage from Heart Attack
  
  Melo LG et al. Gene therapy strategy for long-term myocardial protection using adeno-associated virus-mediated delivery of heme oxygenase gene. Circulation. 2002 Feb 5;105(5):602-7.
  
  Pachori AS et al. Hypoxia-regulated therapeutic gene as a preemptive treatment strategy against ischemia/reperfusion tissue injury. Proc Natl Acad Sci U S A. 2004 Aug 17;101(33):12282-7.
  
  
• Improving stem-cell therapy for coronary artery disease
  
  Damaged heart tissue can be treated with bone-marrow-derived stem cells, which migrate to the injured tissue and then differentiate into endothelial cells (which line blood vessels) and myocardial cells (which make up heart muscle). These new cells replace the damaged cells, partially restoring heart function.
  
  The Dzau lab seeks to improve this therapy by identifying ways to help the stem cells home in on and adhere to the damaged heart tissue. The researchers are also working to determine the most effective method for delivering the stem cells to the patient’s heart.
  
  

• Genetically engineering stem cells to better treat damaged heart tissue
  
  Several research groups have shown that injecting mesenchymal stem cells (MSC) after a heart attack can limit tissue damage and in some cases improve heart function. However, improvement is only marginal, due to poor viability of the transplanted cells.
  
  The Dzau lab showed that engineering MSCs to overexpress the Akt1 gene can improve the treatment’s effectiveness.
  
  More recently, the team showed that Akt-MSC therapy reduced the extent of tissue death and restored heart ventricle function as early as 72 hours after injection -- too early to attribute the results to differentiation of the stem cells. Based on analyses of the media in which the Akt-MSCs were cultured, the team hypothesizes that Akt-MSCs secrete some paracrine factor(s), which can protect the cells, reduce cell death, and salvage heart muscle tissue.
  
  The team is now working to learn more about these factor(s) and their therapeutic potential, as well as looking for additional genes that might secrete heart-protective proteins.
  
  Read more:
  
  Mangi AA et al. Mesenchymal stem cells modified with Akt prevent remodeling and restore performance of infarcted hearts. Nat Med. 2003 Sep;9(9):1195-201.
  
  Gnecchi M et al. Paracrine action accounts for marked protection of ischemic heart by Akt-modified mesenchymal stem cells. Nat Med. 2005 Apr;11(4):367-8.
  
  [Abstract] Mirotsou M et al. Discovery of Novel Paracrine Factors Secreted from Akt Genetically Modified Mesenchymal Stem Cells for Cardiac Repair. Circulation. 112 (17): 660 Suppl. S Nov 17 2005.
  
  Gnecchi M et al. Evidence supporting paracrine hypothesis for Akt-modified mesenchymal stem cell-mediated cardiac protection and functional improvement. FASEB Vol. 20 April 2006, (In Press)
  
  
• Identifying a new factor that may protect heart tissue
  
  The Dzau research team is working to define the role of a certain hormone receptor, LXR alpha, in regulating renin -- an enzyme released by the kidney that can contribute to the development of high blood pressure and heart failure.
  
  Better understanding of renin regulation could lead to new therapies to treat and prevent these conditions.