The ongoing worldwide obesity epidemic is creating enormous heath consequences, including increased type-2 diabetes, cancer, and heart disease. Metabolic syndrome is a pernicious complication that affects many, but not all, obese individuals and greatly increases the likelihood of such diseases. Although drug treatments exist, the cost to treat all obese individuals would be prohibitive. Therefore, a critical public health need exists for instruments that provide early diagnosis of metabolic syndrome and enable cost-effective treatment. The long-term goal is to develop technologies that detect metabolic activity in humans for research and clinical applications. The chemical currency of energy and metabolism is adenosine triphosphate (ATP), produced by enzyme complexes within mitochondria. Preliminary work suggests that such complexes generate harmonics in response to oscillatory electric fields. The focus of this proposal is to develop sensors, based on harmonic generation spectroscopy, which detect metabolic activity in mitochondria.
The specific aims are to: (1) develop sensors that detect activity of mitochondrial complexes in cells in vitro; (2) determine which features of the harmonic spectra correlate with activity of specific enzyme complexes;and (3) assess the viability of detecting metabolic syndrome in obese patients. This approach will enable eventual development of clinical devices that can detect metabolic syndrome early or monitor resting and active metabolism.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Exploratory/Developmental Grants (R21)
Project #
3R21CA133153-03S1
Application #
7908145
Study Section
Special Emphasis Panel (ZHL1-CSR-J (S1))
Program Officer
Ross, Sharon A
Project Start
2009-08-01
Project End
2011-07-31
Budget Start
2009-08-01
Budget End
2011-07-31
Support Year
3
Fiscal Year
2009
Total Cost
$181,800
Indirect Cost
Name
University of Houston
Department
Physics
Type
Schools of Arts and Sciences
DUNS #
036837920
City
Houston
State
TX
Country
United States
Zip Code
77204
Cordero-Reyes, Andrea M; Gupte, Anisha A; Youker, Keith A et al. (2014) Freshly isolated mitochondria from failing human hearts exhibit preserved respiratory function. J Mol Cell Cardiol 68:98-105
Padmaraj, Divya; Pande, Rohit; Miller Jr, John H et al. (2014) Mitochondrial membrane studies using impedance spectroscopy with parallel pH monitoring. PLoS One 9:e101793
Gupte, Anisha A; Hamilton, Dale J; Cordero-Reyes, Andrea M et al. (2014) Mechanical unloading promotes myocardial energy recovery in human heart failure. Circ Cardiovasc Genet 7:266-76
Miller Jr, John H; Rajapakshe, Kimal I; Infante, Hans L et al. (2013) Electric field driven torque in ATP synthase. PLoS One 8:e74978
Hamilton, Dale J (2013) Mechanisms of disease: is mitochondrial function altered in heart failure? Methodist Debakey Cardiovasc J 9:44-8
Miller Jr, J H; Wijesinghe, A I; Tang, Z et al. (2012) Correlated quantum transport of density wave electrons. Phys Rev Lett 108:036404
Miller Jr, John H; Wijesinghe, Asanga I (2012) Quantum mechanisms of density wave transport. Physica B Condens Matter 407:1734-1736
Palanisami, Akilan; Fang, Jie; Lowder, Thomas W et al. (2012) Rapid morphological characterization of isolated mitochondria using Brownian motion. Anal Methods 4:513-521
Padmaraj, Divya; Miller Jr, John H; Wosik, Jarek et al. (2011) Reduction of electrode polarization capacitance in low-frequency impedance spectroscopy by using mesh electrodes. Biosens Bioelectron 29:13-7
Palanisami, Akilan; Miller Jr, John H (2010) Simultaneous sizing and electrophoretic mobility measurement of sub-micron particles using Brownian motion. Electrophoresis 31:3613-8

Showing the most recent 10 out of 12 publications