School of Medicine

Wayne State University School of Medicine

Maik H�ttemann

 

 

 

 

 

 

Maik Hüttemann, Ph.D.
Associate Professor
Wayne State University School of Medicine
Center for Molecular Medicine and Genetics
Department of Biochemistry and Molecular Biology
Karmanos Cancer Institute
3214 Scott Hall
540 East Canfield
Detroit, MI 48201
Voice: 313-577-9150
FAX: 313-577-5218
mhuttema@med.wayne.edu


Research Interests:

  • Role of mitochondria in cancer and cancer test development based on mitochondrial biomarkers.
  • Effect of cell signaling on mitochondrial metabolism, cytochrome c, and cytochrome c oxidase.
  • Development of mitochondria-targeted therapies for ischemia/reperfusion injury as seen in stroke and myocardial infarction.

Research Description:
Dr. Hüttemann’s team studies mitochondrial function using genetic, biochemical, and functional approaches. The group focuses on two key components of the mitochondrial oxidative phosphorylation machinery, cytochrome c oxidase (COX) and the small electron carrier cytochrome c (Cytc). COX is the terminal enzyme of the mitochondrial respiratory chain, “burns” the oxygen we breathe to water, and pumps protons across the inner mitochondrial membrane generating the mitochondrial membrane potential, which is utilized by ATP synthase to produce energy in the form of ATP. Cytc has two distinct functions: it delivers electrons to COX, but it also participates in programmed cell death (apoptosis). Together the two proteins play a key role in life and death decisions of the cell via energy production under healthy conditions and free radical generation and apoptosis under conditions of cellular stress. The overall goal is to understand the regulation of COX and Cytc in normal and disease conditions including cancer, and to apply this knowledge for diagnosis and treatment. 

Selected Publications:

Mahapatra, G., Varughese, A., Ji, Q., Lee, I., Liu, J., Vaishnav, A., Sinkler, C., Kapralov, A.A., Moraes, C.T., Sanderson, T.H., Stemmler, T.L., Grossman, L.I., Kagan, V.E., Brunzelle, J.S., Salomon, A.R., Edwards, B.F.P., Hüttemann, M. Phosphorylation of Cytochrome c Threonine 28 Regulates Electron Transport Chain Activity in Kidney: Implications for AMP Kinase. J Biol Chem, 2017;292:64-79.

Aras, S., Arrabi, H., Purandare, N., Hüttemann, M., Kamholz, J., Züchner, S., Grossman, L.I. Abl2 Kinase Phosphorylates Bi-organellar Regulator MNRR1 in Mitochondria, Stimulating Respiration. BBA – Mol Cell Res, 2017;1864:440-8.

Tyurina, Y.Y, Lou, W., Qu, F., Tyurin, V.A., Mohammadyani, D., Liu, J., Hüttemann, M., Frasso, M.A., Wipf, P., Bayir, H., Greenberg, M.L., Kagan, V.E. Lipidomics Characterization of Biosynthetic and Remodeling Pathways of Cardiolipins in Genetically and Nutritionally Manipulated Yeast Cells. ACS Chem Biol, 2017;12:265-81.

Diedrich, J.D., Rajagurubandara, E., Herroon, M.K., Mahapatra, G., Hüttemann, M., Podgorski, I. Bone marrow adipocytes promote the Warburg phenotype in metastatic prostate tumors via HIF-1α activation. Oncotarget, 2016;7:64854-77.  

Zhang, K., Wang, G., Zhang, X., Hüttemann, P.P., Qiu, Y., Liu, J., Mitchell, I., Lee, I., Zhang, C., Lee, J.S., Pecina, P., Wu., G., Yang, Z.Q., Hüttemann, M., Grossman, L.I. COX7AR is a stress-inducible mitochondrial COX subunit that promotes breast cancer malignancy. Scientific Reports, 2016;6:31742.

Lee I., Hüttemann M., Malek M.H. (-)-Epicatechin attenuates degradation of mouse oxidative muscle following hindlimb suspension. J Strength Cond Res, 2016;30:1-10.    

Maurer S.F., Fromme T., Grossman L.I., Hüttemann M., Klingenspor M. The brown and brite adipocyte marker Cox7a1 is not required for non-shivering thermogenesis in mice. Scientific Reports 2015;5:17704, 1-14.    

Horsch, M., Aguilar-Pimente, J.A., Bönisch, C., Côme, C., Kolster-Fog, C., Jensen, K.T., Lund, A.H., Lee, I., Grossman, L.I., Sinkler, C., Hüttemann, M., Bohn, E., Fuchs, H., Ollert, M., Gailus-Durner, V., Hrabê de Angelis, M., Beckers, J. Cox4i2, Ifit2, and Prdm11 Mutant Mice: Effective Selection of Genes Predisposing to an Altered Airway Inflammatory Response from a Large Compendium of Mutant Mouse Lines. PLoS One, 2015;10:e0134503.     

Marshall, J., Wong, K.Y., Rupasinghe, C.N., Tiwari, R., Zhao, X., Berberoglu, E.D., Sinkler, C., Liu, J., Lee, I., Parang, K., Spaller, M.R., Hüttemann, M., Goebel, D.J. Inhibition of N-methyl-D-aspartate-induced retinal neuronal death by polyarginine peptides is linked to the attenuation of stress-induced hyperpolarization of the inner mitochondrial membrane potential. J Bio Chem, 2015;290:22030-48.      

Lee, I., Hüttemann, M., Kruger, A., Bollig-Fischer, A., Malek, M.H. (‑)‑Epicatechin combined with 8 weeks of treadmill exercise is associated with increased angiogenesis and mitochondrial signaling in mice. Front Pharmacol, 2015;6:1-10.    

Aras, S., Bai, M., Lee, I., Springett, R., Hüttemann, M., Grossman, L.I. MNRR1 (formerly CHCHD2) is a bi-organellar regulator of mitochondrial metabolism. Mitochondrion, 2015;20:43-51.         

Kadenbach B., Hüttemann M. The subunit composition and function of mammalian cytochrome c oxidase. Mitochondrion 2015;24:64-76.

Shay, J. Elbaz, H.A., Lee, I., Zielske, S.P., Malek, M.H., Hüttemann, M. Molecular mechanisms and therapeutic effects of (-)-epicatechin and other polyphenols in cancer, inflammation, diabetes, and neurodegeneration. Oxid Med Cell Longev, 2015, 1-13      

Xie, Y., Zhou, S., Jiang, Z., Dai, J., Puscheck, E.E., Lee, I., Hüttemann, M., Rappolee, D.A.) Hypoxic stress induces, but cannot sustain trophoblast stem cell differentiation to labyrinthine placenta due to mitochondrial insufficiency. Stem Cell Res, 2014;13:478-91.      

Fasih, A., Elbaz, H.A., Hüttemann, M., Konski, A.A., Zielske, S.P. Radiosensitization of pancreatic cancer cells by metformin through the AMPK pathway. Radiation Res., 2014;182:50-9.     

Dingley, S.D., Polyak, E., OstrovskyJ., Srinivasan, S., Lee, I., Rosenfeld, A.B., Tsukikawa, M., Xiao, R., Selak, M.A., Coon, J.J., Hebert, A.S., Grimsrud, P.A., Pagliarini, D.J., Gai, X., Schurr, T.G., Hüttemann, M., Nakamaru-Ogiso, E., Falk, M.J. Mitochondrial DNA variant in COX1 subunit significantly alters energy metabolism of geographically divergent wild isolates in Caenorhabditis elegans. J Mol Biol, 2014;426:2199-216.   

Elbaz, H.A., Lee, I., Antwih, D.A., Liu, J., Hüttemann, M., Zielske, S.P. Epicatechin Stimulates Mitochondrial Activity and Selectively Sensitizes Cancer Cells to Radiation. PLoS One, 2014;9:e88322.   

Ye, C., Lou, W., Li, Y., Chatzispyrou, I.A., Hüttemann, M., Lee, I., Houtkooper, R.H., Vaz, F.M., Chen, S., Greenberg, M.L. Deletion of the cardiolipin-specific phospholipase Cld1 rescues growth and lifespan defects in the tafazzin mutant: Implications for Barth syndrome. J Biol Chem, 2014;289:3114-25.   

Appikatla, S., Bessert, D., Lee, I., Hüttemann, M., Mullins, C., Yao, F., Skoff, R.P. Insertion of proteolipid protein into oligodendrocyte mitochondria regulates extracellular pH and ATP. Glia, 2014;62:356-73.  

Przyklenk, K., Sanderson, T.H., Hüttemann, M. Clinical benefits of remote ischemic preconditioning: new insights . . . and new questions. Circ Res, 2014;114:748-50

Lee, I., Hüttemann, M. Energy crisis: The role of oxidative phosphorylation in acute inflammation and sepsis. Biochim Biophys Acta – Molecular Basis of Disease, 2014;1842;1579–86.     

Hüttemann, M., Doan, J.W., Goustin, A.S., Sinkler, C., Mahapatra, G., Shay, J., Liu, J., Elbaz, H., Aras, S., Grossman, L.I., Ding, Y, Zielske, S.P., Malek, M.H., Sanderson, T.H., Lee, I. (2014) Regulation of cytochrome c in respiration, apoptosis, neurodegeneration and cancer – the good, the bad and the ugly; in ‘Cytochromes b and c: Biochemical Properties, Biological Functions and Electrochemical Analysis’ Editor: Rurik Thom; Nova Science Publishers, 1-38, ISBN: 978-1-63117-467-4.   

Sanderson, T.H., Mahapatra, G., Pecina, P., Ji, Q., Yu, K., Sinkler, K., Varughese, A., Kumar, R., Tousignant, R.N., Salomon, A.R., Lee, I., Hüttemann, M. Cytochrome c is tyrosine 97 phosphorylated by neuroprotective insulin treatment. PLoS One, 2013;8:e78627.  

Lee, H., Abe, Y., Lee, I., Shrivastav, S., Crusan, A.P., Hüttemann, M., Hopfer, U., Felder, R.A., Asico, L.D., Armando, I., Jose, P.A., Kopp,. J.B.  Increased mitochondrial activity in renal proximal tubule cells from young spontaneously hypertensive rats. Kidney Int, 2013;85:561-9.   

Geng, X., Fu, P., Ji, X., Peng, C., Fredrickson, V., Sy, C., Meng, R., Ling, F., Du, H., Tan, X., Hüttemann, M., Guthikonda, M., Ding, Y. Synergetic neuroprotection of normobaric oxygenation and ethanol in ischemic stroke through improved oxidative mechanism. Stroke, 2013;44:1418-25.   

Kochanski R., Peng C., Higashida T., Geng X., Hüttemann M., Guthikonda M., Ding Y. Neuroprotection conferred by post-ischemia ethanol therapy in experimental stroke: an inhibitory effect on hyperglycolysis and NADPH oxidase activation. J. Neurochem., 2013;126:113-21.     

Malek, M.H., Hüttemann, M., Lee, I., Coburn, J.W. Similar skeletal muscle angiogenesis and mitochondrial signaling following 8-weeks of endurance exercise in mice: discontinuous versus continuous training. Exp. Physiol., 2013;98:807-18.   

Aras, S., Pak, O., Sommer, N., Finley Jr, R., Hüttemann, M., Weissmann, N., Grossman, L.I. Oxygen-dependent expression of cytochrome c oxidase subunit 4-2 gene expression is mediated by transcription factors RBPJ, CXXC5, and CHCHD2. Nucleic Acids Res., 2013;41:2255-66.    

Hüttemann, M., Lee, I., Perkins, G.A., Britton, S.T., Koch, L.G., Malek, M.H.  (‑)-Epicatechin is associated with increased angiogenic and mitochondrial signalling in the hindlimb of rats selectively bred for innate low running capacity. Clin Sci (Lond) 2013;124:663-74.   

Zheng, Z., Xu, X., Zhang, X., Wang, A., Zhang, C., Hüttemann, M., Grossman, L.I., Chen, L.C., Rajagopalan, S., Sun, Q., Zhang, K. Exposure to ambient particulate matter induces a NASH-like phenotype and impairs hepatic glucose metabolism in an animal model. J. Hepatol., 2013;58:148-54.    

Reynolds, C.A., Hüttemann, M., Przyklenk, K., Sanderson T.S. Hypoxia-induced damage to the adult and immature brain: molecular mechanism of oxidative damage and the need for targeted therapeutic intervention (Nova Publishers), Hypoxia: Causes, Types and Management, 2013;3-20.    

Sanderson, T.H., Reynolds, C.A., Kumar, R., Przyklenk, K., Hüttemann, M. Molecular Mechanisms of Ischemia-Reperfusion Injury in Brain:  Pivotal Role of the Mitochondrial Membrane Potential in Reactive Oxygen Species Generation. Mol. Neurobiol., 2013;47:9-23.    

Education and Training:
BS in Chemistry (1992): Philipps-University Marburg, Germany
MS in Chemistry and Biochemistry (1995): Philipps-University Marburg, Germany
PhD in Biochemistry and Molecular Biology (1999): Philipps-University Marburg, Germany

Cancer Biology Courses Taught:
CB7220 Molecular Biology of Cancer Development
CB7700 Recent Developments in Cancer Biology

http://genetics.wayne.edu/edunew/faculty/huttemann/index.php

http://genetics.wayne.edu/mitomed/faculty.php