Francis G. Spinale, Ph.D., M.D.
Professor of Cell Biology & Anatomy at the University of South Carolina School of Medicine
Staff Physician - Cardiology at Dorn VA Medical Center
Joint Appointment as Professor of Surgery, Cardiothoracic Surgery at MUSC
|Northeastern University – Bachelors of Science – Biology
||Medical University of South Carolina – Masters of Science – Biometry
||Medical University of South Carolina – Ph.D. – Pathology
||Medical University of South Carolina – M.D.
Over the past 2 decades I have directed a translational research effort in the thematic area of cardiovascular remodeling with a particular focus upon heart failure. While the etiologies which promulgate heart failure can be diverse, there are some common structural underpinnings which include alterations in the extracellular matrix (ECM). My original studies in the 1980s using electron microscopy revealed that a disrupted/disorganized ECM was a common feature in cardiovascular disease. These observations led to the discovery that a specific family of ECM degrading enzymes, the matrix metalloproteinases (MMPs), emerged in patients with myocardial remodeling and heart failure. Through NIH funding, we have now identified that a large portfolio of MMPs are expressed in the progression of heart failure and are not associated with a parallel increase in the endogenous inhibitors of the MMPs (TIMPs). Using murine constructs, large animal pre-clinical models, and patient based studies, we have identified that a dysregulation between MMPs/TIMPs occurs early in the development of heart failure. Through pharmacological and transgenic approaches, we have established a cause-effect relation between increased MMP proteoltyic activity and adverse myocardial remodeling- particularly following a myocardial infarction (MI). Moreover, our clinical studies have demonstrated that the magnitude of MMP induction is directly related to the degree of late post-MI remodeling and the risk of heart failure. To that end, my recent work as been to focus upon developing diagnostic/prognostic biomarker panels of MMP/TIMPs, identifying the upstream regulatory pathways of MMP/TIMP induction, as well as to develop methods for post-translational regulation- ie MMP inhibition.
McGarvey JR, Kondo N, Witschey WR, Takebe M, Aoki C, Burdick JA, Spinale FG, Gorman JH 3rd, Pilla JJ, Gorman RC (2014) Injectable microsphere gel progressively improves global ventricular function, regional contractile strain and mitral regurgitation after myocardial infarction. Ann Thorac Surg S0003-4975(14)01824-4.
- McGarvey JR, Pettaway S, Shuman JA, Novack CP, Zellars KN, Freels PD, Echols RL Jr, Burdick JA, Gorman JH 3rd, Gorman RC, Spinale FG (2014) Targeted injection of a biocomposite material alters macrophage and fibroblast phenotype and function following myocardial infarction: relation to left ventricular remodeling. J Pharmacol Exp Ther 350:701-709.
- Yarbrough WM, Baicu C, Mukherjee R, Van Laer A, Rivers WT, McKinney RA, Prescott CB, Stroud RE, Freels PD, Zellars KN, Zile MR, Spinale FG (2014) Cardiac-restricted overexpression or deletion of tissue inhibitor of matrix metalloproteinase-4: differential effects on left ventricular structure and function following pressure overload-induced hypertrophy. Am J Physiol Heart Circ Physiol 307:H752-761.
- Purcell BP, Lobb D, Charati MB, Dorsey SM, Wade RJ, Zellars KN, Doviak H, Pettaway S, Logdon CB, Shuman JA, Freels PD, Gorman JH 3rd, Gorman RC, Spinale FG, Burdick JA. Injectable and bioresponsive hydrogels for on-demand matrix metalloproteinase inhibition. Nat Mater 13:653-661.
- Zavadzkas JA, Stroud RE, Bouges S, Mukherjee R, Jones JR, Patel RK, McDermott PJ, Spinale FG (2014) Targeted overexpression of tissue inhibitor of matrix metalloproteinase-4 modifies post-myocardial infarction remodeling in mice. Circ Res. 2014 Apr 25;114(9):1435-1445.
- Eckhouse SR, Purcell BP, McGarvey JR, Lobb D, Logdon CB, Doviak H, O'Neill JW, Shuman JA, Novack CP, Zellars KN, Pettaway S, Black RA, Khakoo A, Lee T, Mukherjee R, Gorman JH, Gorman RC, Burdick JA, Spinale FG (2014) Local hydrogel release of recombinant TIMP-3 attenuates adverse left ventricular remodeling after experimental myocardial infarction. Sci Transl Med 6:223ra21.
- Zile MR, Baicu CF, Stroud RE, Van Laer AO, Jones JA, Patel R, Mukherjee R, Spinale FG (2014) Mechanistic relationship between membrane type-1 matrix metalloproteinase and the myocardial response to pressure overload. Circ Heart Fail 7:340-350.
- Graham EM, Atz AM, McHugh KE, Butts RJ, Baker NL, Stroud RE, Reeves ST, Bradley SM, McGowan FX Jr, Spinale FG (2014) Preoperative steroid treatment does not improve markers of inflammation after cardiac surgery in neonates: results from a randomized trial. J Thorac Cardiovasc Surg 147:902-908.
- Spinale FG (2013) Epilysin (matrix metalloproteinase-28) joins the matrix metalloproteinase team on the field of postmyocardial infarction remodeling. Circ Res 112(4):579-582
- Mukherjee R, Akar JG, Wharton JM, Adams DK, McClure CD, Stroud RE, Rice AD, Desantis SM, Spinale FG, Gold MR (2013) Plasma profiles of matrix metalloproteinases and tissue inhibitors of the metalloproteinases predict recurrence of atrial fibrillation following cardioversion. J Cardiovasc Transl Res 6:528-535.
- Eckhouse SR, Akerman AW, Logdon CB, Oelsen JM, O'Quinn EC, Nadeau EK, Stroud RE, Mukherjee R, Jones JA, Spinale FG (2013) Differential membrane type 1 matrix metalloproteinase substrate processing with ischemia-reperfusion: relationship to interstitial microRNA dynamics and myocardial function. J Thorac Cardiovasc Surg 145(1):267-275
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