Professor Emeritus
Department of Physiology,
University of South Alabama
College of Medicine
MSB 3074
Mobile, AL 36688
Mailing Address:
Department of Physiology
Room 3074 Medical Sciences Building
University of South Alabama
College of Medicine
Mobile, Alabama 36688

Phone: 251-460-6826
FAX: 251-460-6464                 

Ph.D., University of Mississippi Medical Center
Postdoctoral Studies: University of Mississippi

Research Interests:

A recent large scale clinical study demonstrated a 22% reduction in mortality of patients on mechanical ventilation for Acute Respiratory Distress Syndrome (ARDS) when tidal volume was reduced from the conventional 12 ml/kg to 6 ml/kg. This clinical study was based on previous animal experiments from our laboratory and others showing that alveolar overdistention produces microvascular injury and increased vascular permeability.  While previous hypotheses have proposed a "stretched pore" effect forcing open intracellular junctions or a "stress failure" limited by the tensile strength of the basement membrane, recently studies from our laboratory suggest that an active endothelial cell response to mechanical stress contributes significantly to the fluid and protein leak observed at high vascular and airway pressures. We have proposed that calcium entry through non-selective stretch activated cation channels (SACC) produces a necessary increase in cell calcium that triggers a permeability response utilizing many of the signal pathways involved in ligand mediated permeability increases. The Ca++ /calmodulin/myosin light chain kinase (MLCK) pathway has been implicated by studies showing that increased permeability in rat lungs due to lung overdistention was blocked by inhibition of either SACC,  Ca++ /calmodulin, or MLCK. Calcium transients in cultured pulmonary endothelial cells were also prevented by inhibition of SACC or MLCK. A possible role for tyrosine phosphorylation involved in focal adhesions has been suggested by isolated rat lung studies that demonstrate an enhanced susceptibility to mechanical injury after inhibition of protein tyrosine phosphatase and a reduced injury with inhibition of tyrosine kinase. Separation of epithelium and endothelium from basement membranes is a prominent feature of ventilator induced lung injury (VILI) in experimental animals suggesting a role of cell adhesion in this injury. During the tenure of  a recently awarded 5 year grant, we will explore the role of SACC using cultured endothelial cells from each vascular segment in the rat lung; artery, vein and microcirculation, with new methods for evaluating monolayer permeability under strain and pressure. A state-of-the art confocal microscope with multiple fluorochrome capability will be used. In addition, we have obtained the plasmid containing the MID1 gene from yeast which codes for the only SACC gene product cloned to date. The responses of native and transfected endothelial cells will be studied using fluorescent analysis of intracellular Ca++  and electrophysiologic response using single channel patch clamp methods. With these studies we hope to characterize the events which initiate and propagate increased vascular permeability secondary to mechanical stress and identify potential targets for pharmacological intervention in patients.
An additional recent direction in my laboratory has been the development of a perfluorocarbon liquid  ventilator in cojunction with Mallard Medical Co. of Redding, CA. This project is funded through the SBIR/STTR program of NIH and utilizes a patented method of liquid delivery through a bias flow mode that improves both gas exchange and fluid clearance from the lung compared to conventional tidal liquid ventilation. We are currently applying for Phase II funding and will finalize prototype designs for production. Controller algorithms are being developed for optimal control of tidal wave forms and automatic control of residual liquid volumes in the lung for efficient long term ventilation with minimal peak alveolar pressures.

Recent Publications:

Click here for a list of recent publications.
Click here for a full CV

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