Mission Statement
| Mr. Wafic Said, a prominent international businessman and philanthropist, provided substantial funding for the establishment of this laboratory. Please visit http://www.waficsaid.com/ for a biography. |
Our mission is to improve the treatments available for patients suffering from cardiovascular disease by combining basic research aimed at understanding the molecular mechanisms of heart disease with the discovery of innovative small molecule and cell-based therapeutics.
Projects
- Enhance the applicability of stem cells in regenerative medicine.
- Investigate the stem cell niche and the role it plays in tissue regeneration.
- Define the role integrins and chemokine receptors play in normal heart physiology as well as cardiovascular disease.
- Develop small molecule therapeutics for the treatment of heart disease.
Definitions
What is a stem cell?
A stem cell is a unique cell that can proliferate and differentiate into other cell types with specialized functions such as those of muscle, brain, blood or skin. In adults, they contribute to the repair of damaged tissue by regenerating those cell types necessary for proper organ function.
What is the stem cell niche?
The stem cell niche is the microenvironment in which the stem cells reside. The niche supports the maintenance of stem cell identity and regulates the function of stem cells.
What is an integrin?
The integrins are a family of proteins present on the surface of all cells that are critical for cell movement, growth, and adherence. During an immune response, integrins mediate white blood cell trafficking to sites of inflammation. In a similar fashion, integrins are required for stem cell localization in bone marrow and the subsequent trafficking of these cells to sites of tissue damage.
What is a cell-based versus a small molecule therapeutic?
Cell-based therapies involve the injection of cells into a patient to replace those damaged by disease. Typically, these cells are isolated from a donor (in some cases, the patient) and manipulated in some fashion prior to injection. In contrast, small molecules are low molecular weight drugs chemically synthesized in the laboratory. They are typically administered orally, intravenously, or locally and act on the patient’s own cells. Such drugs are typically optimized for potency, selectivity, bioavailability and side-effect profile.
Principal Investigators and staff
- Richard A. F. Dixon, PhD, Director
- Peter Vanderslice, PhD, Associate Director, Biology
- Ron Biediger, PhD, Associate Director, Chemistry
- Darren Woodside, PhD, Assistant Director, Biology
- Qi Liu, PhD, Research Associate
- Amy R. Caivano, BS, Research Associate
- C. William Gundlach, MS, Research Associate
- Toya Terry, BS, Senior Research Assistant
Contact Information
Richard A. F. Dixon, PhD
For More Information
Texas Heart Institute at St. Luke's Episcopal Hospital Appoints New Research Director . (PDF)
Texas Heart Institute Update. 2008; Issue 2:17.
Researchers Study the Roles of Integrins and Chemokines in Stem Cell Mobilization, Homing, and Engraftment. (PDF)
Heart Watch. 2009; Winter: 4.
Selected Publications
Woodside, D.G. and Vanderslice P. Cell Adhesion Antagonists: Therapeutic Potential in Asthma and COPD. BioDrugs. 2008;22(2):85-100.
Vanderslice, P. andWoodside D.G. Integrin antagonists as therapeutics for inflammatory diseases. Expert Opin Investig Drugs. 2006;15(10):1235-55.
D. Woodside, R.M. Kram, J.S. Mitchell, T. Belsom, M.J. Billiard, B.W. McIntyre, and P. Vanderslice. Contrasting Roles for Domain 4 of VCAM-1: A negative regulator of soluble binding, but a mediator of firm adhesion as an immobilized substrate. J Immunol. 2006; 176(8):5041-9.
Liu Q, Chen ZQ, Bobustuc GC, McNatt JM, Segall H, Pan S, Willerson JT, Zoldhelyi P. Local gene transduction of cyclooxygenase-1 increases blood flow in injured atherosclerotic rabbit arteries. Circulation. 2005;111:1833-40.
Biediger, R. J.; Chen, Q.; Decker, E. R.; Holland, G. W.; Kassir, J. M.; Li, W.; Market, R. V.; Scott, I. L.; Wu, C.; Li, J. “Carboxylic Acid Derivatives that Inhibit the Binding of Integrins to Their Receptors” U. S. Patent No. 6,972,296. December 6, 2005.
Biediger, R. J.; Dupre, B.; Hamaker, L. K.; Holland, G. W.; Kassir, J. M.; Li, W.; Market, R. V.; Nguyen, N.; Scott, I. L.; Wu, C.; Decker, E. R. “Propanoic Acid Derivatives that Inhibit the Binding of Integrins to Their Receptors” U. S. Patent No. 6,723,711. April 20, 2004
Vanderslice P, Biediger RJ, Woodside DG, Berens KL, Holland GW, Dixon RA. Development of cell adhesion molecule antagonists as therapeutics for asthma and COPD. Pulm Pharmacol Ther. 2004;17(1):1-10.
Langer R, Wang M, Stepkowski SM, Hancock WW, Han R, Li P, Feng L, Kirken RA, Berens KL, Dupre B, Podder H, Dixon RA, Kahan BD. Selectin inhibitor bimosiamose prolongs survival of kidney allografts by reduction in intragraft production of cytokines and chemokines. J Am Soc Nephrol. 2004 Nov;15(11):2893-901
Barst RJ, Langleben D, Frost A, Horn EM, Oudiz R, Shapiro S, McLaughlin V, Hill N, Tapson VF, Robbins IM, Zwicke D, Duncan B, Dixon RA, Frumkin LR; STRIDE-1 Study Group. Sitaxsentan therapy for pulmonary arterial hypertension. Am J Respir Crit Care Med. 2004 Feb 15;169(4):441-7
Wu C, Decker ER, Blok N, Bui H, You TJ, Wang J, Bourgoyne AR, Knowles V, Berens KL, Holland GW, Brock TA, Dixon RA. Discovery, modeling, and human pharmaco-kinetics of N-(2-acetyl-4,6-dimethylphenyl)-3-(3,4-dimethylisoxazol-5-ylsulfamoyl)thiophene-2-carboxamide (TBC3711), a second generation, ETA selective, and orally bioavailable endothelin antagonist. J Med Chem. 2004;47(8):1969-86.
Wu C, Holland GW, Brock TA, Dixon RA. Recently discovered sulfonamide-, acyl sulfonamide- and carboxylic acid-based endothelin antagonists. IDrugs. 2003 Mar;6(3):232-9
You TJ, Maxwell DS, Kogan TP, Chen Q, Li J, Kassir J, Holland GW, Dixon RA. A 3D structure model of integrin alpha 4 beta 1 complex: I. Construction of a homology model of beta 1 and ligand binding analysis. Biophys J. 2002 Jan;82(1 Pt 1):447-57
Holland, G. W.; Biediger, R. J.; Vanderslice, P. Antagonists of VLA-4. Annual Reports In Medicinal Chemistry., 2002, 37, 65.
Woodside DG, Obergfell A, Talapatra A, Calderwood DA, Shattil SJ, Ginsberg MH. The N-terminal SH2 domains of Syk and ZAP-70 mediate phosphotyrosine-independent binding to integrin beta cytoplasmic domains. J Biol Chem. 2002 Oct 18;277(42):39401-8.
Chen M, Capps C, Willerson JT, Zoldhelyi P. E2F-1 regulates nuclear factor-kappaB activity and cell adhesion: potential antiinflammatory activity of the transcription factor E2F-1. Circulation. 2002;106:2707-13.
Woodside DG, Obergfell A, Leng L, Wilsbacher JL, Miranti CK, Brugge JS, Shattil SJ, Ginsberg MH. Activation of Syk protein tyrosine kinase through interaction with integrin beta cytoplasmic domains. Curr Biol. 2001; 11(22):1799-804
Woodside DG, Shattil SJ, Ginsberg MH. The T cell receptor SLAPs integrins together. Nat Immunol. 2001 Oct;2(10):904-5.
Tilton RG, Brock TA, Dixon RA. Therapeutic potential of endothelin receptor antagonists and nitric oxide donors in pulmonary hypertension. Expert Opin Investig Drugs. 2001 Jul;10(7):1291-308.
Zoldhelyi, P., Beck, P.J., Robert, J., Bjercke, R.J., Ober, J.C., Hu, X., McNatt, J.M., Akhtar, S., Ahmed, M., Clubb, F.J. Jr., Chen, Z-Q, Dixon, R.A.F., Yeh, E.T.H., Willerson, J.T. Inhibition of coronary thrombosis and local inflammation by a noncarbohydrate selectin inhibitor. Am J Physiol Heart Circ Physiol. 2000;279:H3065-H3075.
Tilton RG, Munsch CL, Sherwood SJ, Chen SJ, Chen YF, Wu C, Block N, Dixon RA, Brock TA. Attenuation of pulmonary vascular hypertension and cardiac hypertrophy with sitaxsentan sodium, an orally active ET(A) receptor antagonist. Pulm Pharmacol Ther. 2000;13(2):87-97.
Wu, C.; Decker, E. R.; Blok, N.; Bui, H.; Chen, Q.; Raju, B.; Bourgoyne, A. R.; Knowles, V.; Biediger, R. J.; Market, R. V.; Lin, S.; Dupre, B.; Kogan, T. P.; Holland, G. W.; Brock, T. A.; Dixon, R. A. F. Endothelin Antagonists: Substituted Mesitylcarboxamides with High Potency and Selectivity for ETA Receptors. J. Med. Chem., 1999, 42, 4485.
Kogan TP, Dupré B, Bui H, McAbee KL, Kassir JM, Scott IL, Hu X, Vanderslice P, Beck PJ, Dixon RA. Novel synthetic inhibitors of selectin-mediated cell adhesion: synthesis of 1,6-bis[3-(3-carboxymethylphenyl)-4-(2-alpha-D- mannopyranosyloxy)phenyl]hexane (TBC1269). J Med Chem. 1998 Mar 26;41(7):1099-111.
Wu C, Chan MF, Stavros F, Raju B, Okun I, Mong S, Keller KM, Brock T, Kogan TP, Dixon RA. Discovery of TBC11251, a potent, long acting, orally active endothelin receptor-A selective antagonist. J Med Chem. 1997 May 23;40(11):1690-7.
McIntyre, B. W., D. G. Woodside, D. A. Caruso, D. K. Wooten, S. I. Simon, S. Neelamegham, J. K. Revelle, and Vanderslice, P. "Regulation of Human Lymphocyte Coactivation with an a4 Integrin Antagonist Peptide. J. Immunol. (1997) 158, 4180-4186.
Vanderslice, P., Ren, K., Revelle, J.K., Kim, D.C., Scott, D., Bjercke, R.J., Yeh, E.T.H., Beck, P.J. and Kogan, T.P. A Cyclic Hexapeptide is a Potent Antagonist of a4 Integrins J. Immunol (1997) 158, 1710-1718.
Updated: January 2009
