Ph.D. (Chemical Engineering)
Rice University, 1989
Xavier University of LA, 1978
Research in our laboratory has focused on the influence of hydrodynamics on blood cell interactions in the circulatory system and on mammalian cell and tissue culture in bioreactors. Our current primary interests are in two major areas: 1) molecular mechanisms of adhesion in sickle cell disease and 2) cartilage tissue engineering.
Sickle cell disease is a complex genetic blood disorder characterized by aberrant sickle hemoglobin resulting from a single amino acid substitution. The abnormal adhesion of sickle red blood cells to white blood cells and to the vessel wall is of central importance to the pathogenesis of vaso-occlusive events in patients with sickle cell disease. We have developed and employed in vitro microscopy-based flow adhesion assays to characterize sickle cell adhesion mechanisms under physiological conditions approximating those found in postcapillary venules, the primary site of sickle cell adhesion in vivo. Results from our studies will enhance our understanding of the molecular determinants of sickle cell adhesion and provide the basis for the development of anti-adhesion therapeutic agents. Some of our findings suggest that certain peptides and other small molecules may constitute novel therapeutic strategies to ameliorate sickle cell adhesion and painful vaso-occlusive crises. Complementary studies with collaborators using animal models provide further understanding of sickle cell disease pathophysiology.
Once injured, cartilage has limited ability for regeneration and self-repair due to its avascular nature. The use of bioreactors for the in vitro generation of clinically relevant cartilage tissues using chondrocyte seeded scaffolds represents a promising approach to address the increasing need for improved alternatives for cartilage repair. Studies have shown that cartilage tissue growth and function is greatly influenced by the hydrodynamic environment in the bioreactor, however, these effects are not fully understood. In order to better understand the role of the hydrodynamic environment and to optimize the development of tissue-engineered cartilage, it is necessary to understand both the local environment experienced by cartilage tissue constructs and the cause and effect relationship between the environment characteristics and the growing tissue. We have developed and employed a novel wavy-walled bioreactor to address both of these needs. The wavy-walled bioreactor was designed to enhance mixing while minimizing shear stress by the introduction of waves that mimic baffles. Some of our findings suggest that improved cell and tissue growth and development can be achieved in the wavy-walled bioreactor over that achieved in a conventional spinner flask bioreactor. The hydrodynamic environment within the wavy-walled bioreactor provides a unique model for fundamental studies aimed at elucidating the relationship between the culture environment and engineered tissue properties. These studies are critical for the development of optimally designed and clinically relevant engineered tissues.
- Adhesion Mechanisms in Sickle Cell Disease
- Cellular Engineering
- Tissue Engineering
- Cell and Tissue Bioreactors
“Increased rate of chondrocyte aggregation in a wavy-walled bioreactor.” E.M. Bueno, B. Bilgen, R.L. Carrier, and G.A. Barabino, Biotechnology and Bioengineering, 88(6),767 (2004).
“Adherence of phosphatidylserine exposing erythrocytes to endothelial matrix thrombospondin.” A.B. Manodri, G.A. Barabino, B.H. Lubin, and F.A. Kuypers, Blood, 95, 1293 (2000).
“Ex vivo evaluation of a Taylor-Couette flow, immobilized heparinase I device for clinical application.” G.A.Ameer, G.A.Barabino, R. Sasisekharan, W. Harmon, C.L. Cooney, and R. Langer,”Proceedings of the National Academy of Science, USA, 96, 2350, (1999).
“Anionic polysaccharides inhibit adhesion of sickle erythrocytes to the vascular endothelium and result in improved hemodynamic behavior.” G.A. Barabino, X.C. Liu, B.M. Ewenstein, and D.K. Kaul, Blood, 93, 1422, (1999).
“Inhibition of sickle erythrocyte adhesion to immobilized thrombospondin by von Willebrand factor under dynamic flow conditions.” G.A. Barabino, R.J.Wise, V.A.Woodbury, B. Zhang , K.R.Bridges, R.P. Hebbel, J. Lawler, B.M. Ewenstein, Blood, 89, 2560, (1997).