Espen E. Spangenburg, Ph.D.
My research program is focused on understanding the endocrine-based regulation of physiological and metabolic function of skeletal muscle. My lab employs an integrative experimental approach, in which we use cell culture and animal models to define mechanisms that we then work to translate to the human. Specifically, we have developed skeletal muscle specific-inducible BRCA1 and ER-alpha knock out mice and the ability to ablate BRCA1 or ER-alpha expression in cultured human myotubes through shRNA delivered via AV virus approach. This integrative approach allows us to examine the same loss-of function approach using in vivo animal models and cultured myotubes from humans. My lab has developed a number of techniques that allow us to measure or image metabolic and physiological changes in whole muscle or cultured adult single muscle fibers. The ability to integrate these approaches gives us a significant experimental advantage because it allows us to make reductionist based measures in a whole muscle or a single muscle cell that retains a true adult functional phenotype. For example, we have recently developed and/or optimized approaches to measure force, mitochondrial function, deliver cDNA, image lipid droplets or other organelles, and employ co-culture approaches in these single muscle fibers.
- 2021-present Professor (with tenure) East Carolina Diabetes and Obesity Institute, Department of Physiology, School of Medicine, East Carolina University, Greenville, NC
- 2015-2021 Associate Professor (with tenure) East Carolina Diabetes and Obesity Institute, Department of Physiology, School of Medicine, East Carolina University, Greenville, NC
- 2012-2015 Associate Professor School of Public Health University of Maryland, College Park, MD
- 2006-2012 Assistant Professor School of Public Health University of Maryland, College Park, MD
- 2003-2006 Assistant Professor, Dual appointments in the Neurobiology, Physiology and Behavior and Department of Physiology and Membrane Biology, University of California-Davis, Davis, CA
- 2000-2003 Postdoctoral Fellow, Dept. of Biomedical Sciences. University of Missouri, Columbia, MO
(Selected from over 100 peer-reviewed publications; h-index = 43; 6307 times referenced, 10+ publications referenced over 100 times.)
- Schmidt, C. A., T. Ryan , C. T. Lin, MMR. Inigo*, T. D. Green, J. J. Brault E. E. Spangenburg, J. McClung Diminished force production and mitochondrial respiratory deficits are strain-dependent myopathies of subacute limb ischemia. J Vasc Sur. (2017) 65(5) 1504-1514.
- Ryan, T. E., C. A. Schmidt, T. D. Green, E. E. Spangenburg, P. D. Neufer, J. M. McClung. Targeted expression of Catalase to Mitochondria Protects Against Ischemic Myopathy in High Fat Fed Mice. Diabetes. (2016) 65(9) 2553-2568.
- McClung, J. M., T. J. McCord, T. E. Ryan, C. A. Schmidt, T. D. Green, K. W. Southerland, J. L. Reinardy, S. B. Mueller, T. Venkatrama, C. D. Lascola, D. A. Marchuk, E. E. Spangenburg, A. Dokun, B. H. Annex, C. D. Kontos. A BAG3 coding variant in mice determines susceptibility to ischemic limb muscle myopathy by directing autophagy. Circulation. (2017) 136(3): 281-296. link
- Torres, MJ, KA Kew, TE Ryan TE, Pennington ER, Lin CT, Buddo KA, Fix AM, Smith CA, Gilliam LA, Karvinen S, Lowe DA, Spangenburg EE, Zeczycki TN, Shaikh SR, Neufer PD. 17beta-Estradiol directly lowers mitochondrial membrane microviscosity and improves bioenergetic function in skeletal muscle. Cell Metabolism. (2018) 27(1): 167-179.
- Collins, BC., TL Mader, CA Cabelka, MR Inigo*, EE Spangenburg, DA Lowe. Deletion of estrogen receptor alpha in skeletal muscle results in impaired contractility in female mice. J Appl Physiol. (2018) 124 (4): 980-992.
- O’Rourke, AR, A. Lindsay, MD Tarpey*, S Yuen, P McCourt, DM Nelson, BJ Perrin, DD Thomas, E. E Spangenburg, DA Lowe, JM Ervasti. Impaired muscle relaxation and mitochondrial fission associated with genetic ablation of cytoplasmic actin isoforms. FEBS Journal. (2018) 285 (3): 481-500.
- Jackson, K. C.*, M. D. Tarpey*, A. P. Valencia*, M. R. Inigo*, S. J. Pratt, D. J. Patteson*, J. M. McClung, R. M. Lovering, D. M. Thomson, E. E. Spangenburg†. Induced Cre-mediated knockdown of Brca1 in skeletal muscle reduces mitochondrial respiration and prevents glucose intolerance in adult mice on a high fat diet. FASEB Journal. (2018) 32(6): 3070-304. **Chosen for Cover.
- Schmidt, CA, AJ Amorese*, TE Ryan, EJ Goldberg, MD Tarpey*, TD Green, RR Karnekar, DJ Yamaguchi, EE Spangenburg, JM McClung. Strain-Dependent Variation in Acute Ischemic Muscle Injury. Amer. J. Pathology (2018) 188(5): 1246-1262.
- Tarpey, MD*, AJ Amorese*, NB Balestrieri, TE Ryan, CA Schmidt, JM McClung, EE Spangenburg†. Characterization and utilization of the flexor digitorium brevis for assessing skeletal muscle function. Skeletal Muscle. (2018) 8(1): 14.
- Ryan TE, Yamaguchi DJ, Schmidt CA, Zeczycki TN, Shaikh SR, Brophy P, Green TD, Tarpey MD*, Karnekar R, Goldberg EJ, Sparagna GC, Torres MJ, Annex BH, Neufer PD, Spangenburg EE, McClung JM. Extensive skeletal muscle cell mitochondriopathy distinguishes critical limb ischemia patients from claudicants. JCI Insight. 2018 Nov 2;3(21) pii: 123235.
- Cabelka CA, Baumann CW, Collins BC, Nash N, Le G, Lindsay A, Spangenburg EE, Lowe DA. Effects of ovarian hormones and estrogen receptor α on physical activity and skeletal muscle fatigue in female mice. Exp Gerontol. 2019 Jan;115:155-164.
- Tarpey MD*, Valencia AP*, Jackson KC*, Amorese AJ*, Balestrieri NP, Renegar RH, Pratt SJP, Ryan TE, McClung JM, Lovering RM, Spangenburg EE†. Induced in vivo knockdown of the Brca1 gene in skeletal muscle results in skeletal muscle weakness. J Physiol. 2019 Feb;597(3):869-887.
- Iyer SR, Shah SB, Ward CW, Stains JP, Spangenburg EE, Folker ES, Lovering RM. Differential YAP nuclear signaling in healthy and dystrophic skeletal muscle. Am J Physiology. 2019. 317(1): C48-C57.
- Collins BC, Arpke RW, Larson AA, Baumann CW, Xie N, Cbelka CA, Nash NL, Juppi HK, Laakkoen EK, Sipilä S, Kovanen V, Spangenburg EE, Kyba M, Lowe DA. Estrogen regulates the satellite cell compartment in females. Cell Rep. 2019. 28(2): 368-381.
- Verkerke, A. R. P., Ferrara P. J. C. T. Lin, J. M. Johnson, T. E. Ryan, J. A. Maschek, H. Eshima, C. W. Paran, B. T. Laing, P. Siripoksup, T. S. Tippetts, E. J. Wentzler, H. Huang, E. E. Spangenburg, J. J. Brault, C. J. Villanueva, S. A. Summers, W. L. Holland, J. E. Cox, D. E. Vance, P. D. Neufer, K. Funai. Phospholipid methylation regulates muscle metabolic rate through Ca2+ transport efficiency. Nature Metabolism. 2019. 1; 876-885.
- Tarpey MD*, Amorese AJ*, Balestrieri NP, Fisher-Wellman KH, Spangenburg EE†. Doxorubicin causes lesions in the electron transport system of skeletal muscle mitochondria that are associated with a loss of contractile function. J Biol Chem. 2019 294 (51): 19709-19722.
- Iñigo MR*, Amorese AJ*, Tarpey MD*, Balestrieri NP*, Jones KG*, Patteson DJ*, Jackson KC*, Torres MJ, Lin CT, Smith CD, Heden TD, McMillin SL, Weyrauch LA, Stanley EC, Schmidt CA, Kilburg-Basnyat BB, Reece SW, Psaltis CE, Leinwand LA, Funai K, McClung JM, Gowdy KM, Witczak CA, Lowe DA, Neufer PD, Spangenburg EE†. Estrogen receptor-alpha in female skeletal muscle is not required for regulation of muscle insulin sensitivity and mitochondrial regulation. Molecular Metabolism. 2020. 34: 1-15.
- Schmidt CA, Goldberg EJ, Green TD, Karnekar RR, Brault JJ, Miller SG, Amorese AJ, Yamaguchi DJ, Spangenburg EE, McClung JM. Effects of fasting on isolated murine skeletal muscle contractile function during acute hypoxia. PLoS One. 2020. 15(4):e0225922.
- Pal A, Al-Shaer AE, Guesdon W, Torres MJ, Armstrong M, Quinn K, Davis T, Reisdorph N, Neufer PD, Spangenburg EE, Carroll I, Bazinet RP, Halade GV, Clària J, Shaikh SR. Resolvin E1 derived from eicosapentaenoic acid prevents hyperinsulinemia and hyperglycemia in a host genetic manner. FASEB Journal. In press.
Other Experience and Professional Memberships
- Editorial Board: American Journal of Physiology: Cell Physiology, Journal of Applied Physiology, Frontiers in Skeletal Muscle Physiology, Faculty of 1000 member
- American Diabetes Study Section Member: 2015-present
- NIH Grant Review (Ad Hoc): Skeletal Muscle and Exercise Physiology (SMEP) 2011, 2013 (2X), 2014; 2015, 2016 Special Emphasis Panel EMNR-S (2) 2014, MOSS 2013, 2014, 2015; NHBLI-Women’s Health Initiative 2012; SCORE Grants Ad Hoc 2010; RO3 Special Emphasis Study Section, 2005-2010
- NASA Study Section, Ad Hoc Member, 2004, 2009, 2012; Mail in reviewer 2010, 2011.
- Medical Research Council (England), Mail-In Reviewer, Fall 2004, 2012
- Regular Member: American Diabetes Association, American Physiological Society
- 2014 Leda Amick Wilson UMD Mentor of the Year Award
- 2011 Best Paper Award UMD School of Public Health Research Interaction Day
- 2010 Virginia Tech HNFE Outstanding Alumnus Award
- 2008-2014 NIH Loan Repayment Grant Recipient
- 2007 New Investigator Award-American Physiological Society-EEP Section
- 2002 NIH F32 Individual Post-doctoral fellow Award
Ongoing Research Support
- R01 AR0666601-01A1 (PI: Spangenburg)
07/01/2015 – 06/30/2020
BRCA1 is necessary for optimal skeletal muscle function
The major goals of this project are define the role BRCA1 plays in the regulation of skeletal muscle function and mitochondrial function.
- #7-14-BS170 (PI: Spangenburg)
American Diabetes Association
Estrogens protect skeletal muscle from metabolic insults.
The major goal of this proposal is mechanistically define how the estrogen receptor alpha protects skeletal muscle from lipid-based insults.
Completed Research Support
- 5 R21 AR059913 (PI: Spangenburg)
The role of BRCA1 in regulation of lipid metabolism in skeletal muscle.
The major goals of this project are define the role BRCA1 plays in the regulation of lipid metabolism in skeletal muscle.
- P-F Maryland Diabetes Research Training Center (DRTC). (PI: Spangenburg)
Estrogens regulate endocrine influences of visceral adipose tissue on skeletal muscle.
The major goal of this project is develop a co-culture system that allows for the ability to mechanistically define the influence of estrogens on visceral adipocytes and skeletal muscle.
- 5 R21 HL098810 (Co-Investigator)
Potential role of endothelial progenitor cells in cardiovascular risk.
The major goal of this project is define EPC function as it relates to in vivo endothelial function in sedentary and trained older adults.
- ARRA R21 HD062868 (Co-Investigator)
Role of maternal exercise environment on transgenerational offspring health.
The major goal of this project was to determine the potential role of “exercise ancestry” on mouse offspring body composition, metabolism, gene expression, and other health outcomes by examining multiple generations of mice with and without exercise training exposures in parental generations.