Steven Goldman

Steven Goldman

Professor, Medicine - (Research Scholar Track)
Research Scientist
Professor, BIO5 Institute
Primary Department
Department Affiliations
Contact
(520) 626-2939

Work Summary

Our lab has a new treatment for heart failure. We have a biodegradable graft seeded with adult human cells that we put on the surface of the heart. The potential is to regenerate new heart muscle

Research Interest

Research in my laboratory over the last 30 years has focused on chronic heart failure (CHF), its pathophysiology and the development of new treatments for CHF. We have developed clinically relevant animal models of heart failure that allow us to explore the translational potential of new treatments. Our work initially examined the role of afterload reduction and neurohormal blockade. More recently we have been working with cell-based therapy for CHF using bioengineered scaffolds to prevent left ventricular (LV) remodeling and restore function in the damaged heart. Our most effective scaffold is a biodegradable vicryl mesh with embedded viable neonatal fibroblasts that secrete angiogenic growth factors. This patch increases myocardial blood flow, improves LV systolic function, and reverses LV remodeling if implanted at the time of an acute myocardial infarction. In CHF, this patch still improves myocardial blood flow but does not improve LV function or reverse LV remodeling. Thus, we have an effective delivery system for cell based therapy for CHF that increases myocardial blood flow and provides structural support for new cell growth. We are now focusing on seeding this patch with human inducible pluripotent stem cells in the cardiac lineage, the seeded cardiomyocytes align, communicate, contract in a spontaneous and rhythmic fashion. When implanted in rats with CHF, they improve LV function. We are exploring this patch seeded with human inducible cardiac pluripotent stem cells to treat patients with CHF. Keywords: induced pluripotent stem cells

Publications

Desai, A., Choi, B., Dudley, S. C., Kittles, R., Machado, R. F., Garcia, J. G., Hillery, C., Indik, J. H., Goldman, S., Juneman, E. B., Groth, J., Nair, N., Rutledge, C., Kanady, J., Fleming, I., Batai, K., Weigand, K., Shi, G., Kim, T. Y., , Gupta, G., et al. (2018). IL-18 is a novel mediator of prolonged QTc and ventricular arrhythmias associated with Sickle Cell Disease. Proceedings of the National Academy of Sciences.
BIO5 Collaborators
Joe GN Garcia, Steven Goldman
Gaudino, M., Alexander, J. H., Bakaeen, F. G., Ballman, K., Barili, F., Calafiore, A. M., Davierwala, P., Kappetein, P., Lorusso, R., Mylotte, D., Pagano, D., Ruel, M., Schwann, T., Suma, H., Taggart, D. P., Tranbaugh, R. F., Fremes, S., & Goldman, S. (2017). Randomized comparison of the clinical outcome of single versus multiple arterial grafts: the ROMA trial-rationale and study protocol. European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery, 52(6), 1031-1040.

The primary hypothesis of the ROMA trial is that in patients undergoing primary isolated non-emergent coronary artery bypass grafting, the use of 2 or more arterial grafts compared with a single arterial graft (SAG) is associated with a reduction in the composite outcome of death from any cause, any stroke, post-discharge myocardial infarction and/or repeat revascularization.

Shanmugasundaram, M., Ram, V., Jayasuria, S., Dewar, J., Nguyen, J., Boyella, R., & Goldman, S. (2011). The Effect of IVUS Guidance on Clinical Outcomes in Percutaneous Revascularization compared to Coronary Artery Bypass Grafting among High Risk Patients with Left Main Coronary Artery Disease. Journal of Investigative Medicine, 59(1), 888-217.
Hayward, R. A., Reaven, P. D., Wiitala, W. L., Bahn, G. D., Reda, D. J., Ge, L., McCarren, M., Duckworth, W. C., Emanuele, N. V., & , V. I. (2015). Follow-up of glycemic control and cardiovascular outcomes in type 2 diabetes. The New England journal of medicine, 372(23), 2197-206.

The Veterans Affairs Diabetes Trial previously showed that intensive glucose lowering, as compared with standard therapy, did not significantly reduce the rate of major cardiovascular events among 1791 military veterans (median follow-up, 5.6 years). We report the extended follow-up of the study participants.

O'Donoghue, M. L., Braunwald, E., White, H. D., Steen, D. P., Lukas, M. A., Tarka, E., Steg, P. G., Hochman, J. S., Bode, C., Maggioni, A. P., Im, K., Shannon, J. B., Davies, R. Y., Murphy, S. A., Crugnale, S. E., Wiviott, S. D., Bonaca, M. P., Watson, D. F., Weaver, W. D., , Serruys, P. W., et al. (2014). Effect of darapladib on major coronary events after an acute coronary syndrome: the SOLID-TIMI 52 randomized clinical trial. JAMA, 312(10), 1006-15.

Lipoprotein-associated phospholipase A2 (Lp-PLA2) has been hypothesized to be involved in atherogenesis through pathways related to inflammation. Darapladib is an oral, selective inhibitor of the Lp-PLA2 enzyme.