J.Edwin Blalock, PhD

blalockProfessor of Medicine

Department of Medicine
Division of Pulmonary, Allergy and Critical Care


Address: McCallumBldg, room896
UAB
Birmingham, AL 35294
Telephone: (205) 934-6439
FAX: (205) 934-1446
Email: This email address is being protected from spambots. You need JavaScript enabled to view it.

 

Publications

 

__________________________________________________________

Education


B.S., University of Florida, 1971
Ph.D., University of Florida, 1976
Post-doctoral Fellow, University of Texas Medical Branch, Galveston, TX


Research Interests


The overall objective of our current research is to delineate certain genetic rules that govern the shape and function of proteins and peptides. Specifically, nucleic acids encode amino acid sequences in a binary fashion with regard to hydropathy. We and others have provided compelling evidence that the exact pattern of polar and nonpolar amino acids, rather than the precise identity of particular R groups, is an important driving for protein shape. These design principles are being used:

  1. to make synthetic peptides specifically targeted to act as agonists and antagonists of Ca++ channels involved in apoptosis and respiratory burst in polymorphonuclear leukocytes (PMN) and
  2. to make synthetic peptide vaccines as immunotherapeutic agents against autoimmune diseases of the nervous system such as myasthenia gravis (MG) and multiple sclerosis (MS).
  3. to make antagonists of the PMN chemoattractant peptide, Pro-Gly-Pro (PGP) described below.

We are studying the tripeptide neutrophil chemoattractant N-acetyl PGP, derived from the breakdown of extracellular matrix (ECM), which shares sequence and structural homology with an important domain on alpha chemokines. PGP caused chemotaxis and production of superoxide through CXC receptors, and administration of peptide caused recruitment of neutrophils (PMNs) into lungs of control, but not CXCR2-deficient mice. PGP was generated in mouse lung after exposure to lipopolysaccharide, and in vivo and in vitro blockade of PGP with monoclonal antibody suppressed PMN responses as much as chemokine-specific monoclonal antibody. Extended PGP treatment caused alveolar enlargement and right ventricular hypertrophy in mice. PGP was detectable in substantial concentrations in a majority of bronchoalveolar lavage samples from individuals with chronic obstructive pulmonary disease, but not control individuals. Thus, PGP's activity links degradation of ECM with neutrophil recruitment in airway inflammation, and PGP may be a biomarker and therapeutic target for neutrophilic inflammatory diseases.

In addition, together with Dr. Frans Nijkamp and colleagues at the University of Utrecht, we are evaluating the aforementioned peptide regulators of Ca++ channels for utility in models of asthma. We are also studying the role of PGP in emphysema with colleagues at the University of Utrecht and have begun studies to determine whether PGP is a marker for human chronic lung diseases.