Waleed O. Twal, Ph.D.
Research Associate Professor
Room 642, Basic Science Building
Office: (843) 792-7054
Education:BS Animal Science University of Jordan 1977
MS Animal Science University of Tennessee 1988
PhD Physiology Pennsylvania State University 1993
My main area of research involves a bioengineering project to build replacement blood vessels. We have shown that toroids made from macroporous building blocks of gelatin microspheres (Cultispher) seeded with human endothelial and smooth muscle cells can form a short vessel-like structure. These structures express both collagen and elastin and posses a uniaxial mechanical response that is qualitatively similar to that of native vascular tissues and consistent with their elastin and collagen composition. The mechanical response of these tubular structures increased with static culture time. We have also made 30 mm-long constructs using the same Cultipher beads and are in the process of testing them in a bioreactor for maturation using different flow regimens.
One other aspect of my scientific interests is extracellular matrix (ECM) biology. I have found that fibulin-1 inhibits the adhesion, spreading and migration of certain types of cancer cells and also transformed cell lines. However, fibulin-1 has no effect on primary cultured cell line such as fibroblasts and endothelial cells. I have also discovered a fifth member of the fibulin-1 family of proteins that is similar to fibulin-1D that can bind to the cytoplasmic domain of integrin beta 1. This discovery have solved a controversy that have lasted for over two decades regarding the initial isolation of fibulin-1 as an integrin beta 1 cytoplasmic domain-binding protein and subsequent reports that fibulin-1 was an extracellular matrix protein binding to a myriad of molecules extracellularly. Currently we are working on defining the function of this interaction and elucidating its effect on integrin signaling.
Another interest of mine is the role played by fibulin-1 in FGF8 function/s. We have shown that fibulin-1 binds to FGF8 with high affinity and fibulin-1 protects FGF8 from enzymatic degradation by ADAM-17. Down regulation of fibulin-1 by siRNA reduces the expression levels of FGF8 while up-regulation of fibulin-1 C and D variants up-regulates FGF8 expression. Currently we are characterizing the role of this interaction in a double heterozygote mating of mice haplo-insufficient in both FGF8 and fibulin-1.
- Fresco VM, Kern CB, Mohammadi M, Twal WO. Fibulin-1 Binds to Fibroblast Growth Factor 8 with High Affinity: Effects on Embryo Survival. J Biol Chem. 2016, July 8.
- Ge Q, Chen L, Jaffar J, Argraves WS, Twal WO, Hansbro P, Black JL, Burgess JK, Oliver B. Fibulin1C peptide induces cell attachment and extracellular matrix deposition in lung fibroblasts. Sci Rep. 2015 Apr 2;5:9496-9501.
- Twal WO, Hammad SM, Guffy SL, Argraves WS. A novel intracellular fibulin-1D variant binds to the cytoplasmic domain of integrin beta 1 subunit. Matrix Biol. 2015 Apr;43:97-108.
- Mainous AG 3rd, Wright RU, Hulihan MM, Twal WO, McLaren CE, Diaz VA, McLaren GD, Argraves WS, Grant AM. Elevated transferrin saturation, health-related quality of life and telomere length. Biometals. 2014 Feb;27(1):135-141.
- Twal, W. O., S. C. Klatt, K. Harikrishnan, E. Gerges, M. A. Cooley, T. C. Trusk, B. Zhou, M. G. Gabr, T. Shazly, S. M. Lessner, R. R. Markwald and W. S. Argraves. "Cellularized Microcarriers as Adhesive Building Blocks for Fabrication of Tubular Tissue Constructs." Ann Biomed Eng, (2013) [PMID: 23943070]
- Mainous, A. G., 3rd, R. U. Wright, M. M. Hulihan, W. O. Twal, C. E. McLaren, V. A. Diaz, G. D. McLaren, W. S. Argraves and A. M. Grant. "Telomere Length and Elevated Iron: The Influence of Phenotype and Hfe Genotype." Am J Hematol 88, no. 6 (2013): 492-6 [PMID: 23512844]
- Hartwell, K. J., M. M. Moran-Santa Maria, W. O. Twal, S. Shaftman, S. M. DeSantis, A. L. McRae-Clark and K. T. Brady. "Association of Elevated Cytokines with Childhood Adversity in a Sample of Healthy Adults." J Psychiatr Res 47, no. 5 (2013): 604-10 [PMID: 23415658]
- Al Gadban, M. M., J. German, J. P. Truman, F. Soodavar, E. C. Riemer, W. O. Twal, K. J. Smith, D. Heller, A. F. Hofbauer, J. C. Oates and S. M. Hammad. "Lack of Nitric Oxide Synthases Increases Lipoprotein Immune Complex Deposition in the Aorta and Elevates Plasma Sphingolipid Levels in Lupus." Cell Immunol 276, no. 1-2 (2012): 42-51 [PMID: 22560558]
- Gooz, P., Y. Dang, S. Higashiyama, W. O. Twal, C. J. Haycraft and M. Gooz. "A Disintegrin and Metalloenzyme (Adam) 17 Activation Is Regulated by Alpha5beta1 Integrin in Kidney Mesangial Cells." PLoS One 7, no. 3 (2012): e33350 [PMID: 22413019]
- Cooley, M. A., V. M. Fresco, M. E. Dorlon, W. O. Twal, N. V. Lee, J. L. Barth, C. B. Kern, M. L. Iruela-Arispe and W. S. Argraves. "Fibulin-1 Is Required During Cardiac Ventricular Morphogenesis for Versican Cleavage, Suppression of Erbb2 and Erk1/2 Activation, and to Attenuate Trabecular Cardiomyocyte Proliferation." Dev Dyn 241, no. 2 (2012): 303-14 [PMID: 22183742]
- Cangemi, C., V. Skov, M. K. Poulsen, J. Funder, W. O. Twal, M. A. Gall, V. Hjortdal, M. L. Jespersen, T. A. Kruse, J. Aagard, H. H. Parving, S. Knudsen, P. F. Hoilund-Carlsen, P. Rossing, J. E. Henriksen, W. S. Argraves and L. M. Rasmussen. "Fibulin-1 Is a Marker for Arterial Extracellular Matrix Alterations in Type 2 Diabetes." Clin Chem 57, no. 11 (2011): 1556-65 [PMID: 21926180]
- Szabo, A., R. Unnep, E. Mehes, W. O. Twal, W. S. Argraves, Y. Cao and A. Czirok. "Collective Cell Motion in Endothelial Monolayers." Phys Biol 7, no. 4 (2010): 046007 [PMID: 21076204]
- Al Gadban, M. M., K. J. Smith, F. Soodavar, C. Piansay, C. Chassereau, W. O. Twal, R. L. Klein, G. Virella, M. F. Lopes-Virella and S. M. Hammad. "Differential Trafficking of Oxidized Ldl and Oxidized Ldl Immune Complexes in Macrophages: Impact on Oxidative Stress." PLoS One 5, no. 9 (2010) [PMID: 20824093]
- Smith, K. J., W. O. Twal, F. Soodavar, G. Virella, M. F. Lopes-Virella and S. M. Hammad. "Heat Shock Protein 70b' (Hsp70b') Expression and Release in Response to Human Oxidized Low Density Lipoprotein Immune Complexes in Macrophages." J Biol Chem 285, no. 21 (2010): 15985-93 [PMID: 20348092]
- Argraves, W. S., A. Tanaka, E. P. Smith, W. O. Twal, K. M. Argraves, D. Fan and C. C. Haudenschild. "Fibulin-1 and Fibrinogen in Human Atherosclerotic Lesions." Histochem Cell Biol 132, no. 5 (2009): 559-65 [PMID: 19693531]