School of Medicine Columbia
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 Columbia
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.
- Spinale FG, Meyer TE, Stolen CM, Van Eyk JE, Gold MR, Mittal S, DeSantis S, Wold N, Beshai JF, Stein KM, Ellenbogen KA. Development of a biomarker panel to predict cardiac resynchronization therapy response: results from the SMART-AV trial. Heart Rhythm. 2019 May; 16(5): 743-753.
- Oatmen K, Cull E, Spinale FG. Heart failure as interstitial cancer: emergence of a malignant fibroblast in cancer and cardiac failure. Nat Rev Cardiol. 2020 Aug; 17(8): 523-531.
- Torres WM, Jacobs J, Doviak H, Barlow SC, Zile MR, Shazly T, Spinale FG. Changes in myocardial microstructure and mechanics with progressive left ventricular pressure overload. JACC Basic Transl Sci. 2020 Apr 29; 5 (5): 463-480. Editorial Comment, Interstitial Fibrosis and Diastolic Dysfunction in Aortic Stenosis. JACC Basic Transl Sci. 2020 May 25; 5(5): 481-483.
- Matesic LE, Freeburg LA, Synder LB, Duncan LA, Moore A, Perreault PE, Zellars KN, Goldsmith EC, Spinale FG. The ubiquitin ligase Wwp1 contributes to shifts in matrix proteolytic profiles and a myocardial aging phenotype with diastolic heart failure. Am J Physiol Heart Circ Physiol. 2020 Oct 1; 319(4): H765-H774.
- Lobb DC, Doviak H, Brower GL, Romito E, O’Neill JW, Smith S, Shuman JA, Freels PD, Zellars KN, Pettaway S, Khakoo AY, Lee T, Spinale FG. Targeted injection of a truncated form of tissue inhibitor of metalloproteinase 3 alters post-MI remodeling. J Pharmacol Exp Ther. 2020 Nov; 375(2): 296-307.