Education & Training:
Cornell University, B.A.
University of Michigan Ph.D. in Human Genetics
University of Oxford, Postdoctoral Fellow

Research Interests:

The overall goal of my laboratory is to identify novel treatment strategies for Duchenne muscular dystrophy (DMD), a disease that affects both skeletal muscles and the heart. We use mouse models to unravel the molecular pathogenesis of DMD, identify novel molecular treatment targets, and test potential therapeutic approaches.

We have identified that prophylactic treatment with standard-of-care heart failure drugs can prevent both cardiac and skeletal muscle damage in dystrophic mice. We have shown mineralocorticoid receptors, known to be important therapeutic targets for heart failure, to also be present and functional in skeletal muscles. Our collaborations have led to the first two published clinical trials in DMD patients with mineralocorticoid receptor antagonists, which were found to be efficacious in slowing the progression of cardiomyopathy in DMD patients. Current research on this project is focused on unraveling the mechanisms of action of these heart failure drugs on skeletal muscles with the ultimate goal of designing novel therapeutic approaches for muscular dystrophy and other causes of muscle weakness.

We have also shown that dystrophin/utrophin-deficient double-knockout mice are a useful model of cardiomyopathy onset that parallels DMD patients and display all of the physiological, histological, and biochemical indicators common to the majority of the human heart failure population. We recently developed an improved model with skeletal muscle rescue that allows cardiomyopathy to progress into heart failure and for the first time demonstrated efficacy of clinically applied gene therapy approaches on dystrophic heart failure.

Selected Publications:

• Rafael-Fortney, J.A. *, Chimanji, N.S., Schill, K.E., Martin, C.D., Murray. J.D., Ganguly, R., Stangland, J.E., Tran, T., Xu, Y., Canan, B.D., Mays, T.A., Delfín, D.A., Janssen, P.M.L. *, Raman, S.V. (*Equal Contributions) (2011) ” Early treatment with lisinopril and spironolactone preserves cardiac and skeletal muscle in Duchenne Muscular Dystrophy mice.”, Circulation, 124:582-588. Epub 2011 July 18. PMID: 21768542.
• Chadwick JA, Hauck JS, Lowe J, Shaw JJ, Guttridge DC, Gomez-Sanchez CE, Gomez-Sanchez EP, Rafael-Fortney JA. (2015) Mineralocorticoid Receptors are Present in Skeletal Muscle and Represent a Potential Therapeutic Target. FASEB J. 2015 Nov;29(11):4544-54. PMID: 26178166.
• Chadwick, JA, Swager, SA, Welc, S, Lowe, JA, Gomez-Sanchez, EP, Gomez-Sanchez, CE, Tidball, JA, and Rafael-Fortney, JA.  (2016) Myeloid cells are capable of synthesizing aldosterone to exacerbate damage in muscular dystrophy. Hum Mol Genet., 2016 Dec 1;25(23):5167-5177. doi: 10.1093/hmg/ddw331. PMID: 27798095.
• Hauck, JS, Lowe, J, Rastogi, N, McElhanon, K, Petrosino, J, Peczkowski, KK, Chadwick, AN, Zins, JG, Accornero, F, Janssen, PM, Weisleder, N, and Rafael-Fortney, JA (2019) Mineralocorticoid Receptor Antagonists Improve Membrane Integrity Independent of Muscle Force in Muscular Dystrophy, Hum Mol Genet. 2019 Jun 15;28(12):2030-2045. doi: 10.1093/hmg/ddz039 PMID:30759207.
• Hauck, JS, Howard, ZM, Lowe, J, Rastogi, N, Pico, M, Swager, S, Petrosino, JM, Gomez-Sanchez-, CE, Gomez-Sanchez, EP, Accornero, F, and Rafael-Fortney, JA (2019) Mineralocorticoid Receptor Signaling Contributes to Normal Muscle Repair After Acute Injury, Front Physiol. 2019 Oct 25;10:1324. doi: 10.3389/fphys.2019.01324. eCollection 2019. PMID: 31736768.
• Lowe, J, Kolkhof, P, Haupt, MJ, Peczkowski, KK, Rastogi, N, Hauck, JS, Kadakia, FK, Zins, JG, Ciccone, PC, Smart, S, Sandner, P, Raman, SV, Janssen, PML, and Rafael-Fortney, JA. (2020) Mineralocorticoid receptor antagonism by finerenone is sufficient to improve function in preclinical muscular dystrophy. ESC Heart Fail. 2020 Sep 18;7(6):3983-95. doi: 10.1002/ehf2.12996. PMID: 32945624.
• Howard, ZM*, Dorn, LE*, Lowe, J*, Gertzen, MD, Ciccone, PC, Rastogi, N, Odom, GL, Accornero, F, Chamberlain, JS and Rafael-Fortney, JA.  (*equal contribution) (2021).  A new mouse model for evaluating micro-dystrophin gene therapy prevention of heart failure in Duchenne muscular dystrophy cardiomyopathy, JCI Insight, 2021 Apr 8;6(7):146511. doi: 10.1172/jci.insight.146511.PMID:33651713.
• Howard, ZM, Gomatam, CK, Rabolli, CP, Lowe, J, Bansal, SS, Accornero, F and Rafael-Fortney, JA, (2022) Mineralocorticoid Receptor Antagonists and Glucocorticoids Differentially Affect Skeletal Muscle Inflammation and Pathology in Muscular Dystrophy.  JCI Insight. 2022;7(19):e159875. https://doi.org/10.1172/jci.insight.159875. PMID: 36040807

My NCBI Link: http://www.ncbi.nlm.nih.gov/sites/myncbi/jill.rafael- fortney.1/bibliography/45600091/public/?sort=date&direction=ascending