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Marco Eugenio Cabrera, Ph.D.

Education
  • 1978 BS Physics - Mathematics
    Universidad del Valle de Guatemala, Guatemala
  • 1989 MS Biomedical Engineering
    Case Western Reserve University, Cleveland, USA
  • 1995 Ph.D. Biomedical Engineering
    Case Western Reserve University, Cleveland, USA

Current Appointments at Case Western and University Hospitals of Cleveland

  • Associate Professor, Department of Pediatric, School of Medicine
  • Assistant Professor of Biomedical Engineering and Physiology and Biophysics.
  • Associate Director, "Center for Modeling Integrated Metabolic Systems (MIMS)".
  • Director, Computational Physiology Laboratory (Case Western Reserve University).
  • Director, Exercise Physiology Laboratories (Rainbow Babies and Children's Hospital).
Research Interests

My current research focuses on gaining quantitative understanding of the regulation of cellular energy transfer and metabolism in skeletal and cardiac muscle as tissue/organ, as well as in the context of the whole body. My approach to research is multidisciplinary in nature and combines computational modeling and physiological experiments. The mathematical models are based on dynamic mass balances and reaction kinetics that describe metabolic and transport processes within and between compartments in a whole tissue/organ. In silico (model simulations) and in vivo/in situ experiments are then performed by subjecting the system under investigation to acute perturbations, such as hypoxia, ischemia, and exercise with some of the system components or elements inhibited/enhanced. Simulations and experimental results are interactively used in the design of critical experiments and in model development and validation, respectively. The resulting validated models can then be used to predict dynamic changes in fluxes and concentrations that are not easily obtained from experiments alone or to test hypotheses with respect to potential mechanisms of regulation. Experiments to investigate skeletal muscle metabolism are conducted in dogs whose gastrocnemius muscle is perfused via a controlled pump and stimulated electrically. Experiments to investigate cardiac metabolism are conducted in swine hearts perfused with a controlled pump and stimulated with dobutamine. Experiments to investigate metabolism in the context of the whole body are conducted in humans or rodents, with measurements of oxygen transport and cellular metabolism obtained during exercise on a cycle ergometer or a treadmill, respectively.

In addition, we are investigating how the regulation of skeletal muscle energetics and whole body metabolism is affected by chronic adaptations induced by continuous unloading (e.g., limb suspension, or physical inactivity) or loading (exercise training). Over the next years, we are also planning to investigate the effects of diabetes and heart failure on the regulation of cardiac and skeletal muscle energetics during increased energy expenditure, with emphasis on fuel selection, oxygen transport and utilization, and muscle efficiency.

Publications
  • Lai N, Nasca MM, Silva MA, Silva FT, Whipp BJ, and Cabrera ME. Appl. Physiol. Nutr. Metab. In Press. 2008.
  • Kim J, Saidel GM, and Cabrera ME. Multi-scale computational model of fuel homeostasis during exercise: effect of hormonal control. Ann Biomed Eng. 35:69-90, 2007.
  • Zhou L, Cabrera ME, Huang H, Yuan CL, Monika DK, Sharma N, Bian F. and Stanley WC. Parallel activation of mitochondrial oxidative metabolism with increased cardiac energy expenditure is not dependent on fatty acid oxidation in pigs. J Physiol 579:811-821, 2007.
  • Zhou H, Saidel GM, and Cabrera ME. Multi-organ system model of O2 and CO2 transport during isocapnic and poikilocapnic hypoxia. Respir Physiol Neurobiol. 156:320-30, 2007.
  • Dash RK, Somersalo E, Cabrera ME, Calvetti D. An efficient deconvolution algorithm for estimating oxygen consumption during muscle activities. Comput Methods Programs Biomed. 85:247-256, 2007.
  • Lai N, Camesasca M, Saidel GM, Dash RK, Cabrera ME. Linking pulmonary oxygen uptake, muscle oxygen utilization and cellular metabolism during exercise. Ann Biomed Eng. 35(6): 956-968, 2007.
  • Dash RK, DiBella JA, Cabrera ME. A computational model of skeletal muscle metabolism linking cellular adaptations induced by altered loading states to metabolic responses during exercise. Biomed Eng Online Apr 20; 6(1):14, 2007.
  • Lai N, Saidel GM, Grassi B, Gladden LB, and Cabrera ME Model of O2 transport and metabolism predicts effect of hyperoxia on canine muscle oxygen uptake dynamics. J. Appl. Physiol. 103:1366-78, 2007.
  • Hakimi P, Yang J, Casadesus G, Massillon D, Tolentino-Silva F, Nye CK, Cabrera ME, Hagen DR, Utter CB, Baghdy Y, Johnson DH, Wilson DL, Kirwan JP, Kalhan SC, Hanson RW. Over-expression of the cytosolic form of phosphoenolpyruvate carboxykinase (GTP) in skeletal muscle repatterns energy metabolism in the mouse. J. Biol. Chem. 282:32844-55, 2007.
  • Dash RK, Li Y, Kim J, Saidel GM, and Cabrera ME. Modeling cellular metabolism and energetics in skeletal muscle: Large-scale parameter estimation and sensitivity analysis. IEEE Trans. Biomed. Eng. In Press. 2007
  • Calvetti D, Dash RK, Somersalo E, and Cabrera ME. Local regularization method applied to estimating oxygen consumption during muscle activities. Inverse Problems, 22:229-243, 2006.
  • Lai N, Dash RK, Nasca MM, Saidel GM, and Cabrera ME. Relating pulmonary oxygen uptake to muscle oxygen consumption at exercise onset: in vivo and in silico studies. Eur J Appl Physiol. 97:380-94, 2006.
  • Zhou L, Cabrera ME, Okere IC, Sharma N, Stanley WC. Regulation of myocardial substrate metabolism during increased energy expenditure: Insights from computational studies. Am J Physiol 291:H1036-46, 2006.
  • Zhou L, Yu X, Cabrera ME, and Stanley WC. Role of cellular compartmentation in the metabolic response to stress: mechanistic insights from computational models. Ann N Y Acad Sci. 1080:120-139, 2006.
  • Landesberg A, Shenhav A, Shofty R, Konyukhov E, Levy C, Lichtenstein O, Beyar R, ter Keurs HE, Landesberg G, Cabrera ME, Stanley WC, Saidel GM. Effects of synchronized cardiac assist device on cardiac energetics. Ann N Y Acad Sci. 1080:466-478, 2006.
  • Grossner CM, Johnson EM, and Cabrera ME. Efficiency and economy in female adolescents and adults matched for height and weight. Ped. Exer. Sci., 17:301-310, 2005.
  • Zhou L, Salem JE, Saidel GM, Stanley WC, and Cabrera ME. Mechanistic model of cardiac energy metabolism predicts localization of glycolysis to cytosolic sub-domain during ischemia. Am. J. Physiology, Heart & Circ. 288:H2400-11, 2005.
  • Cabrera ME, Zhou L, Stanley WC, and Saidel GM. Regulation of cardiac energetics: Role of redox state and cellular compartmentation during ischemia. Ann. N.Y. Acad. Sci., 1047:259-270, 2005.
  • Zhou L, Stanley WC, Saidel GM, Yu X, and Cabrera ME. Regulation of lactate production at the onset of ischemia is independent of mitochondrial NADH/NAD+: Insights from in silico studies. J. Physiol., 569(Pt 3):925-37, 2005.
  • Salem JE, Cabrera ME, Chandler M, McElfresh T, Huang H, Sterk J, and Stanley WC. Step and ramp induction of myocardial ischemia: comparison of in vivo and in silico results. J Physiol Pharmacol, 55:519-536, 2004.
  • Salem JE, Stanley WC, and Cabrera ME. Computational studies of the effects of myocardial blood flow reduction on cardiac metabolism. Biomed. Eng. Online. 3(1):15, 2004.
  • Saidel GM, DiBella JA, and Cabrera ME. Metabolic system dynamics: lumped and distributed models. In: Simulations in Biomedicine V. Eds.: ZM Arnez et al. Southampton, Boston, WIT Press, pp. 101-110. 2003.
  • Grossner CM, Johnson EM, Cabrera ME. Effects of high-intensity training on exercise performance of pre-adolescent female soccer players. Revista Portuguesa de Ciencias do Desporto 3(2):79-82, 2003.
  • Radhakrishnan K, LaManna JC, Cabrera ME. A quantitative study of oxygen as a metabolic regulator. Adv Exp Med Biol. 530:547-54, 2003.
  • Salem JE, Saidel GM, Stanley WC, and Cabrera ME. Mechanistic model of myocardial energy metabolism under normal and ischemic conditions. Ann. Biomed. Eng. 30:202-216, 2002.
  • Cabrera ME, Portzline G, Aach S, Condie C, Dorostkar P, Mianulli M. Can current minute ventilation rate adaptive pacemakers provide appropriate chronotropic response in pediatric patients? PACE 25:907-914, 2002.
  • Soller BR, Cabrera ME, Smith SM, and Sutton JP. Smart medical systems with application to nutrition and fitness in space. Nutrition 18:930-936, 2002.
  • DiBella II JA, Johnson EM, and Cabrera ME. Ramped vs. Standard Bruce protocol in children. A comparison of exercise responses. Ped. Exerc. Sci. 14(4):391-400, 2002.
  • Radhakrishnan K, LaManna JC, Cabrera ME. A quantitative study of oxygen as a metabolic regulator. Appl. Cardiopulmonary Pathophys. 9:363-367, 2000.
  • Cabrera ME, Saidel GM, and Kalhan SC. Lactate metabolism during exercise. Analysis by an integrative systems model. Am. J. Physiol. 277:R1522-R1536, 1999.
  • Cabrera ME, Saidel GM, and Kalhan SC. A model analysis of lactate accumulation during muscle ischemia. J. Crit. Care. 14:151-163, 1999.
  • Cabrera ME, Saidel GM, and Kalhan SC. Role of oxygen in regulation of lactate dynamics during hypoxia: mathematical model and analysis. Ann. Biomed. Eng. 26:1-27, 1998.
  • Cabrera ME, Saidel GM, and Kalhan SC. Modeling metabolic dynamics. From cellular processes to organ and whole body responses. Progress in Biophysics and Molecular Biology, 69:539-557, 1998.
  • Mateescu, GD, Cabrera, ME, and Fercu D. 17O/31P Magnetic Resonance Imaging and Localized Spectroscopy: In vivo Investigations of Cell Bioenergetics. In: Spatially Resolved Magnetic Resonance. Eds.: Bluemler P. et al. Weinheim, Wiley -VCH Publishers, pp. 421-429, 1998.
  • Mateescu GD and Cabrera ME. In vivo 17O magnetic resonance spectroscopy: determination of temperature effects on metabolic rates (Q10 factor). Adv. Exp. Med. Biol. 411:585-590. 1997.
  • Cabrera ME and Chizeck HJ. On the existence of a lactate threshold during incremental exercise; A systems engineering approach. J. Appl. Physiol. 80:1819-1828, 1996.
  • Cabrera ME, Lough MD, Doershuk CF, and Salvator A. An expanded scoring system including an index of nutritional status for patients with cystic fibrosis. Pediatr. Pulmonol. 18:199-205, 1994.
  • Cabrera ME, Hanisch DG, Cohen MH, Spector ML and Liebman J. Cardiopulmonary responses to exercise in children with activity-sensing rate-responsive ventricular pacemakers. PACE 16:1386-93, 1993.
  • Cabrera ME, Lough MD, Doershuk CF, DeRivera GA. Anaerobic performance -assessed by the Wingate Test- in patients with cystic fibrosis. Pediatric Exercise Science 5:78-87, 1993.
  • Cabrera ME, Saidel GM, and Cohen MH. Noninvasive estimation of cardiac output with nonprescribed breathing. Ann. Biomed. Eng., 19:723-742, 1991.
See Proceedings
See Presentations & Abstracts
Memberships
  • American College of Sports Medicine, 1989. Fellow (FACSM) 2003.
  • "Colegio de Ingenieros de Guatemala" (Guatemalan College of Engineering), 1979.
  • Founding Member of "Asociación Guatemalteca de Física", 1980.
  • North American Society of Pediatric Exercise Medicine, 1987.
  • Biomedical Engineering Society, 1992.
  • Institute of Electric & Electronic Engineers, Engineers in Biology and Medicine, 1992.
  • American Physiology Society, 1992.
  • American Heart Association, 1998.
  • International Society of Oxygen Transport to Tissue, 1999.

Advisory Groups:

  • Member of the International Academy of Astronautics Study Group on Mathematical Modeling and Physiological Simulation: The Digital Astronaut/Cosmonaut (Oct 2004 - present)
  • Member of the Council on Cardiovascular Disease in the Young of the American Heart Association Committee on Atherosclerosis, Hypertension, and Obesity in Youth of the Council on Cardiovascular Disease in the Young Working Group to update the "Guidelines for Exercise Testing in the Pediatric Age Group" (Nov 2002 - May 2006)
  • Member, NASA/National Space Biomedical Research Institute Working Group on Standardized Flight Data Collection (2001).
  • Scientific Consultant for teaching/training indirect calorimetry to hospitals and clinics. SensorMedics. Yorba Linda, CA (1996-98).
  • Scientific Consultant for the Integrated Human Function Research Group of the National Space Biomedical Research Institute, Houston TX (1999). cientific Consultant, Bradycardia Research Group, Medtronic Inc., Minneapolis MN. (99-00)