Faculty and Staff
Frank Spinale, Ph.D., M.D.
|Title:||Associate Dean for Research and Graduate Education
|Department:||Research and Graduate Education
School of Medicine
Research and Graduate Education
1977-1979 Northeastern University - Bachelors of Science - Biology
1982-1984 Medical University of South Carolina - Masters of Science - Biometry
1990-1993 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
- Spinale FG (2013) Epilysin (matrix metalloproteinase-28) joins the matrix metalloproteinase team on the field of postmyocardial infarction remodeling. Circ Res. 2013 Feb 15;112(4):579-82
- Chen H, Zheng D, Abbott J, Liu L, Bartee MY, Long M, Davids J, Williams J, Feldmann H, Strong J, Grau KR, Tibbetts S, Macaulay C, McFadden G, Thoburn R, Lomas DA, Spinale FG, Virgin HW, Lucas A (2013) Myxomavirus-derived Serpin Prolongs Survival and Reduces Inflammation and Hemorrhage in an Unrelated Lethal Mouse Viral Infection. Antimicrob Agents Chemother (In Press)
- 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 In Press.
- Spinale FG, Stolen CM (2013) Biomarkers and heart disease: what is translational success. J Cardiovasc Transl Res (In Press)
- Spinale FG, Janicki JS, Zile MR (2013) Membrane-associated matrix proteolysis and heart failure. Circ Res 112(1):195-208.
- 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. 2013 Jan;145(1):267-275
- Zile MR, DeSantis SM, Baicu CF, Stroud RE, Thompson SB, McClure CD, Mehurg SM, Spinale FG. Plasma biomarkers that reflect determinants of matrix composition identify the presence of left ventricular hypertrophy and diastolic heart failure. Circulation Heart Failure, 2011 May 1; 4(3):246-56. PMID: 21350055.
- Spinale FG, Mukherjee R, Zavadzkas JA, Koval CN, Bouges S, Stroud RE, Dobrucki LW, Sinusas AJ. Cardiac restricted over-expression of membrane type-1 matrix metalloproteinase causes adverse myocardial remodeling following myocardial infarction. J Biol Chem. 2010 Sep 24;285(39):30316-27. PMCID: PMC2943310.
- Dixon JA, Gaillard WF, Rivers WT, Koval CN, Stroud RE, Mukherjee R, Spinale FG. Heterogeneity in MT1-MMP activity with ischemia-reperfusion and previous myocardial infarction: relation to regional myocardial function. Am J Physiol, 2010 Dec; 299(6):H1947-58. PMCID: PMC3006286.
- Ellenbogen KA, Gold MR, Meyer TE, Lozano IF, Mittal S, Waggoner AD, Lemke B, Singh JP, Spinale FG, Van Eyk JE, Whitehill J, Weiner S, Bedi M, Stein KM. Primary results from the SMART AV trial: a randomized trial comparing empiric, echocardiographic guided and algorithmic AV delay programming in cardiac resynchronization therapy (CRT). Circulation, 2010 Dec 21; 122(25):2660-8.
- Dixon JA, Spinale FG. Myocardial remodeling: cellular and extracellular events and targets. Annu Rev Physiol, 2011; 73:47-68. PMID: 21314431.
- McQuinn TC, Deardorff RL, Mukherjee R, Taylor AGB, Graham EM, Atz AM, Forbus GA, DeSantis SM, Young JB, Stroud RE, Hsia TY, Crawford FA, Bradley SM, Reeves ST, Spinale FG. Circulating matrix metalloproteinase levels following ventricular septal defect repair in infants. J Thorac Cardiovasc Surg, 2010 Dec; 140(6):1257-65. PMCID: PMC2972374
- Mukherjee R, Rivers WT, Ruddy JM, Matthews RG, Koval CN, Plyler RA, Chang EI, Patel RK, Kern CB, Stroud RE, Spinale FG. Long-term localized high frequency electrical stimulation within the myocardial infarct: effects on matrix metalloproteinases and regional remodeling. Circulation, 2010 July 6; 122(1):20-32. PMCID: PMC2946370.