Allan Ramirez, MD - Basic Science Research Faculty

Allan Ramirez

Assistant Professor of Medicine
Department of Surgery
Emory University School of Medicine

Dr. Ramirez conducts research that centers on chronic rejection after lung transplantation, which is the major limitation to long-term survival. Chronic rejection manifests as a progressive, fibrotic disorder of small airways called obliterative bronchiolitis (OB). The factors that initiate and maintain this process are poorly understood. However, strategies to further suppress immune responses in OB have been largely unsuccessful, suggesting that other processes belie OB.

Using an animal model of experimental OB, Dr. Ramirez’ research has shown that the molecule Transforming Growth Factor-beta (TGFbeta) and its second messenger Smad3 play a critical role in fibroproliferative process of this disease. In studies of fibroblasts in cell culture, Smad3 is required for these cells to transform into myofibroblasts which then produce the excess amounts of connective tissue matrices that eventually become deposited in the airways of transplanted lungs with OB. Thus, the focus of Dr. Ramirez’ research is in identifying other pathways and molecules that modulate the actions of Smad3 in the fibroblast.

The findings from these studies have demonstrated that:

  1. perturbations in the oxidation state of the cysteine/cystine redox couple can lead to activation of Smad3 in the absence of other stimuli and
  2. the connective tissue molecules that obliterate the airway serve to stimulate Smad3 activity in the fibroblasts that produced them, further amplifying and perpetuating the fibrotic process.

The search for mediators to counteract the activity of Smad3 has led Dr. Ramirez to the study of several members of the family of nuclear hormone receptors that, when activated, can prevent the elaboration of extracellular matrices in fibroblasts, all through the inhibition of Smad3. It is hoped that this research will lead to the identification of novel targets for the treatment of this otherwise incurable disease.

Recent Publications (2007 – 2008)

  • Naik P, Lyon GM, Lawrence EC, Neujahr DC, Ramirez AM, Force SD, Pelaez A. Dapsone-Induced Hemolytic Anemia in Lung Allograft Recipients.  J Heart Lung Transpl [in press].  
  • Force SD, Kogon B, Pelaez A, Neujahr DC, Ramirez AM, Miller DL, Lawrence EC Bilateral lung transplant with pulmonary thromboendarterectomy for Eisenmenger's syndrome. Ann Thorac Surg 2008; 85(3):1097-99.  
  • Ramirez AM, Nunley DR, Rojas M, Roman J. Activation of Tissue Remodeling Precedes Obliterative Bronchiolitis in Lung Transplant Recipients. Biomarker Insights 2008; 3:351-9.  
  • Ramirez A, Ramadan B, Ritzenthaler JD, Rivera HN, Jones DP, Roman J.  Extracellular cysteine/cystine redox potential controls lung fibroblast proliferation and matrix expression through upregulation of transforming growth factor-beta. Am J Physiol Lung Cell Mol Physiol. 2007 Oct;293(4):L972-81.  
  • Force SD, Pelaez A, Neujahr DC, Ramirez AM, Whitley W, Miller DL, Lawrence EC.  Technique of right single-lung transplantation for idiopathic pulmonary fibrosis using cross-field ventilation. J Thorac Cardiovasc Surg. 2007 Jan;133(1):272-3.  
  • Messler J and Ramirez A (2007): Pulmonary Hypertension.  In  M.V. Williams (Ed.), Comprehensive Hospital Medicine (1st ed, 383-8). Philadelphia, PA: Elsevier.