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.
- 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.
- Characterize lipoproteins that are linked to metabolic syndrome and heart disease.
- Develop small molecule therapeutics for the treatment of heart disease.
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 Key Personnel
- Richard A. F. Dixon, PhD* – Director MCRL
- Chu-Huang (Mendel ) Chen, MD, PhD* – Director Vascular & Medicinal Research
- Ronald J. Biediger, PhD* – Associate Director Chemistry MCRL
- Peter Vanderslice, PhD* – Associate Director Biology MCRL
- Darren G. Woodside, PhD* – Assistant Director MCRL
- Mehran Haidari, PhD – Sr Research Scientist MCRL
- Qi Liu, PhD – Research Scientist MCRL
- Xuhai (Jonathan) Lu, PhD – Research Scientist Vascular & Medicinal Research
- Shaolie S. Hossain, PhD – Research Scientist MCRL
- Lei Zhou, MD, PhD – Research Scientist MCRL
- Deenadayalan Bakthavatsalam, PhD – Research Associate MCRL
- Matthew Robertson, PhD – Research Associate MCRL
- Jianwen (Jane) Dong, PhD – Research Fellow Vascular & Medicinal Research
- Amy R. Caivano – Research Associate MCRL
- C. William Gundlach* – Research Associate MCRL
- Anna Kazansky – Research Associate MCRL
- Sayadeth Khounlo - Research Associate MCRL
- Robert V. Market – Research Associate MCRL
- Su Pan, MD – Research Associate MCRL
- Michael M. Savage – Research Associate MCRL
- Sidney J. Sherwood, III – Research Associate MCRL
- Navin D. Warier – Research Associate MCRL
- Zhenping Chen – Sr Research Assistant MCRL
- Toya J. Terry – Sr Research Assistant MCRL
* For THI professional staff member profiles, see Research.
Richard A. F. Dixon, PhD
Gundlach CW, Caivano A, Cabreira-Hansen MD, Gahremanpour A, Brown WS, Zheng Y, McIntyre B, Willerson JT, Dixon RA, Perin EC, Woodside D. Synthesis and Evaluation of an Anti-MLC1 x Anti-CD90 Bispecific Antibody for Targeting and Retaining Bone-Marrow Derived Multipotent Stromal Cells in Infarcted Myocardium. Bioconjug Chem.2011;in press.
Terry T, Chen Z, Dixon RA, Vanderslice P, Zoldhelyi P, Willerson JT, Liu Q. CD34/M-cadherin Bone Marrow Progenitor Cells Promote Arteriogenesis in Ischemic Hindlimbs of ApoE Mice. PLoS ONE.2011;6(6):e20673.
Haidari M, Zhang W, Ganjehei L, Ali M, Chen Z. Inhibition of MLC Phosphorylation Restricts Replication of Influenza Virus-A Mechanism of Action for Anti-Influenza Agents. PLoS ONE.2011;6(6):e21444.
Ruan CH, Dixon RA, Willerson JT, Ruan KH. Prostacyclin therapy for pulmonary arterial hypertension. Tex Heart Inst J.2010;37(4):391-399.
Vanderslice P, Woodside DG, Caivano AR, Decker ER, Munsch CL, Sherwood SJ, Lejeune WS, Miyamoto YJ, McIntyre BW, Tilton RG, Dixon RA. Potent in vivo suppression of inflammation by selectively targeting the high affinity conformation of integrin alpha4beta1. Biochem Biophys Res Commun. 2010;400(4):619-624.
Haidari M, Wyde PR, Litovsky S, Vela D, Ali M, Casscells SW, Madjid M. Influenza virus directly infects, inflames, and resides in the arteries of atherosclerotic and normal mice. Atherosclerosis.2010;208(1):90-96.
Chen CH, Dixon RAF, Ke LY, Willerson JT. Vascular progenitor cells in diabetes mellitus: roles of Wnt signaling and negatively charged LDL. Circ Res 2009;104:1038-40.
Liu Q, Chen Z, Terry T, McNatt JM, Willerson JT, Zoldhelyi P. Intra-arterial transplantation of adult bone marrow cells restores blood flow and regenerates skeletal muscle in ischemic limbs. Vasc Endovascular Surg. 2009;43(5):433-443.
Lu J, Jiang W, Yang JH, Chang PY, Walterscheid JP, Chen HH, Marcelli M, Tang D, Lee YT, Liao WS, Yang CY, Chen CH. Electronegative LDL impairs vascular endothelial cell integrity in diabetes by disrupting fibroblast growth factor 2 (FGF2) autoregulation. Diabetes. 2008;57(1):158-166.
Tang D, Lu J, Walterscheid JP, Chen HH, Engler DA, Sawamura T, Chang PY, Safi HJ, Yang CY, Chen CH. Electronegative LDL circulating in smokers impairs endothelial progenitor cell differentiation by inhibiting Akt phosphorylation via LOX-1. J Lipid Res. 2008;49(1):33-47.
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
Updated: July 2014