There are two main areas of research in Dr. Orynbayeva's laboratory: mitochondria pathophysiology and nanomedicine.

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Mitochondrial dysregulation is a common attribute of metabolic disorders. There is a gap in our understanding of pre- and post-translational regulation of metabolism, the control of metabolic enzymes and protein complexes by transcriptomic effectors. Dr. Orynbayeva’s lab seeks ways to exploit the bioenergetic properties of mitochondria and associated metabolic signaling for improved diagnostics and therapies in cancer, neurodegeneration, reproductive system pathologies and aging. Common to seemingly unrelated pathologies is two-compartmental energy metabolism. Bi-directional communication of a tumor with its stroma, neurons and astrocytes, oocyte and surrounding cumulus cells is based on control mechanisms that orchestrate hormonal and ionic signals, wiring of intermediate metabolites and energetic signaling. Yet, cancer cells having the highest metabolic rates possible seem to adapt the mechanisms of metabolically highly active tissues, such as brain, muscles, heart and developing embryos that enable elevated mitochondria performance.

Specifically, the lab focuses on:

• Mitochondria-associated metabolic adaptations of tumors
• Developing anti-cancer therapies by targeting energy metabolism 
• Energy metabolism prerequisites of oocyte competence
• Developing single cell-scale array nanotechnologies for energetic stress analysis of cell dynamic metabolic functions

The energy metabolism is studied on different levels: isolated mitochondria, intact and permeabilized cells, and tissue samples, utilizing optical spectroscopic/microscopic and amperometric methods. The Oxygraph-2K analytic technique available in the laboratory provides an integrated screening approach for studying structural and biochemical injuries of mitochondria that reflect not only rearrangement of membrane structure, but also defects in enzymatic systems resulting in the interrupted flux of metabolites, electron transport, calcium and ROS signaling, and ATP synthesis.

Patent

"A method and apparatus for measuring biological activity with single cell resolution"
Z. Orynbayeva, Y. Gao, Y. Gogotsi, G. Friedman
Patent #US10253289, April 17, 2015

Recent Publications

"Malate-aspartate shuttle promotes L-lactate oxidation in mitochondria"
Altinok O, Poggio JL, Stein DE, Bowne WB, Shieh AC, Snyder NW, Orynbayeva Z
J Cell Physiol. 2019. doi: 10.1002/jcp.29160. [Epub ahead of print]

"Mitochondrial respiratory states and rates"
Gnaiger E, ... Orynbayeva Z, et al.
MitoFit Preprint Arch. doi:10.26124/mitofit:190001.v2 (2019)

"Cardiolipin mediates curcumin interactions with mitochondrial membranes"
Ben-Zichri S, Kolusheva S, Danilenko M, Ossikbayeva S, Stabbert WJ, Poggio JL, Stein DE, Orynbayeva Z, Jelinek R
Biochim Biophys Acta Biomembr. 1861(1):75-82 (2019)

"Respirometric reserve capacity of cumulus cell mitochondria correlates with oocyte maturity"
Anderson SH, Glassner MJ, Melnikov A, Friedman G, Orynbayeva Z
J Assist Reprod Genet. 2018. 35(10):1821-1830

"Rapamycin increases oxidative metabolism and enhances metabolic flexibility in human cardiac fibroblasts"
Nacarelli T, Azar A, Altinok O, Orynbayeva Z, Sell C
Geroscience. doi: 10.1007/s11357-018-0030-2 (2018)

"Artefactual formation of pyruvate from in-source conversion of lactate"
Trefely S, Mesaros C, Xu P, Doan MT, Jiang H, Altinok O, Orynbayeva Z, Snyder NW
Rapid Commun Mass Spectrom. doi: 10.1002/rcm.8159 (2018)

"Perfusion double-channel micropipette probes for oxygen flux mapping with single-cell resolution"
Gao Y, Li B, Singhal R, Fontecchio A, Pelleg B, Orynbayeva Z, Gogotsi Y, Friedman G
Beilstein J Nanotech. 9:850-60 (2018)

"Determination of mitochondrial metabolic phenotype through investigation of the intrinsic inhibition of succinate dehydrogenase"
Panov A, Orynbayeva Z
Anal Biochem. 552: 30-37 (2018)

"Tumor microenvironment promotes dicarboxylic acid carrier-mediated transport of succinate to fuel prostate cancer mitochondria"
A Zhunussova, B Sen, L Friedman, S Tuleukhanov, AD Brooks, R Sensenig, Z Orynbayeva
American Journal of Cancer Research, 5(5), 1665-79 (2015)

"Knockout of cyclophilin D in Ppif-/- mice increases stability of brain mitochondria against Ca2+ stress"
T Gainutdinov, JD Molkentin, D Siemen, M Ziemer, G Debska-Vielhaber, S Vielhaber, Z Gizatullina, Z Orynbayeva, FN Gellerich
Archives of Biochemistry and Biophysics, 579, 40-6 (2015)

"Fatty acids in energy metabolism of the central nervous system"
AV Panov, Z Orynbayeva, V Vavilin, V Lyakhovich
Biomedical Research International, 2014, 472459 (2014)

"Bioenergetic and antiapoptotic properties of mitochondria from cultured human prostate cancer cell lines PC-3, DU145 and LNCaP"
AV Panov, Z Orynbayeva
PLoS One, 8(8), e72078 (2013)

"The control of brain mitochondrial energization by cytosolic calcium: the mitochondrial gas pedal"
FNGellerich, Z Gizatullina, T Gainutdinov, K Muth, E Seppet, Z Orynbayeva, S Vielhaber
IUBMB Life, 65(3),180-90 (2013)

"Multifunctional Carbon-Nanotube Cellular Endoscopes"
R Singhal, Z Orynbayeva, RVK Sundaram, M Schrlau, S Bhattacharyya, E Vitol, JJ Niu, E Papazoglou, G Friedman, Y Gogotsi
Nature Nanotechnology, 6, 57-64 (2011)

View Dr. Orynbayeva's publications in PubMed