Imad Shams lab:
Environmental Stress Tolerance in Mammals

RESEARCH INTERESTS

A tremendous biodiversity evolved on Earth allows species to face the challenges in their diverse habitats. The subterranean blind mole-rat of the genus Nannospalax (hereafter, Spalax) is a remarkably long-lived, solitary, wild, obligatory fossorial rodent of the Eastern Mediterranean region. Spalax inhabits sealed underground burrows, relatively protected from extreme climatic changes, pathogens, and predators; however, it faces extreme hypoxic and hypercapnic conditions that can reach ~7% O2, and ~6%CO2 in the natural habitat, which appears to be lethal to many mammalian species. Hypoxia stimulates reactive oxygen species excessive generation that compromises genome integrity, proteostasis, and homeostasis in general. Spalax is an extremely long-living mammal relatively to its body mass (~20 years in captivity; 120-200 g); moreover, it tolerates chemical carcinogens. I am interested in studying the physiological, cellular and genetic strategies; and the evolutionary changes the fine-tuning of the molecular mechanisms that underlies longevity, resistance to environmental stress and cancer.

Specific research interests: 

  1. Oxidative and genotoxic stress response, DNA repair capacity, and homeostasis in Spalax cells and tissues challenged by hypoxic stress.

  2. Longevity-related epigenetic changes, transposable elements activity, and gene transcription regulation.

  3. Evolutionary molecular changes that determine cell-to-cell transmission of senescence, inflammatory signaling, migration and differentiation patterns in Spalax as requisites for stress and cancer resistance.

 
 

THE TEAM

IMAD SHAMS, PhD

Principal Investigator

Email: imadshams@gmail.com

            imad.shams@univ.haifa.ac.il

Phone:  +972-4-8249972

Fax: +972-4-8288235

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IRINA MANOV, MD PhD

Associate Professor

LITAL SHARVIT, PhD

Lab Manager

Email: lsharvit@univ.haifa.ac.il

Phone:  +972-4-6647963

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ANASTASIA

CHABAN

PhD Student

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NADINE MOZALBAT

MSc Student

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LUJAIN SHAWASHA

MSc Student

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MIKHAIL GORDEEV

PhD Student

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AMANI ODEH

Post Doc

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MARK MAZIN

PhD student

ALUMNI

  • Maria Dronin - Research Associate

  • Vered Domankevich-Bachar - PhDCurrent position: Basic and Translational Research Laboratory Manager, Alpha Tau Medical. 

  • Salah-Hussiesy - MScCurrent position: Product Manager, Teva Pharmaceutical Industries.

  • Robert Altwasser - Post Doc

  • Amani Odeh - PhD; Current position: Post Doc Karolinska Institutet

  • Dmitry Miskevich - PhD 

  • Hossam Eddini - PhD

  • Huda Adwan - Research Associate

 

PUBLICATIONS

IMAD SHAMS - full publications list - 

  1. Miskevich D, Chaban A, Dronina M, Abramovich I, Gottlieb E, Shams I. (2021) Glutamine Homeostasis and Its Role in the Adaptive Strategies of the Blind Mole Rat, Spalax. Metabolites. 2021 Oct 31;11(11):755. doi: 10.3390/metabo11110755.PMID: 34822413.

  2. Miskevich D, Chaban A, Dronina M, Abramovich I, Gottlieb E, Shams I. (2021) Comprehensive Analysis of 13 C 6 Glucose Fate in the Hypoxia-Tolerant Blind Mole Rat Skin Fibroblasts. Metabolites. 2021 Oct 27;11(11):734. doi: 10.3390/metabo11110734. PMID: 34822392.

  3. Manov I, Odeh A, Shams I. (2020) Aging without inflammaging: lesson from Spalax. Aging (Albany NY) 2020 Aug 27;12(16):15875-15877. doi: 10.18632/aging.103953. Epub 2020 Aug 27. PMID: 32855359; PMCID: PMC7485727.

  4. Adwan Shekhidem H, Sharvit L, Leman E, Manov I, Roichman A, Holtze S, M Huffman D, Y Cohen H, Bernd Hildebrandt T, Shams I, Atzmon G. (2020) Telomeres and Longevity: A Cause or an Effect? Int J Mol Sci. 2019 Jul 1;20(13):3233. doi: 10.3390/ijms20133233. PMID: 31266154; PMCID: PMC6651551.

  5. Shams I, Raskina O. (2020) Supernumerary B Chromosomes and Plant Genome Changes: A Snapshot of Wild Populations of Aegilops speltoides Tausch (Poaceae, Triticeae). Int J Mol Sci. 2020 May 26;21(11):3768. doi: 10.3390/ijms21113768. PMID: 32466617; PMCID: PMC7312783.

  6. Odeh A, Dronina M, Domankevich V, Shams I, Manov I. (2019) Downregulation of the inflammatory network in senescent fibroblasts and aging tissues of the long-lived and cancer-resistant subterranean wild rodent, Spalax. Aging Cell. 2020 Jan;19(1):e13045. doi: 10.1111/acel.13045. Epub 2019 Oct 11. PMID: 31605433; PMCID: PMC6974727.

  7. Adwan Shekhidem H, Sharvit L, Leman E, Manov I, Roichman A, Holtze S, M Huffman D, Y Cohen H, Bernd Hildebrandt T, Shams I, Atzmon G. (2019) Telomeres and Longevity: A Cause or an Effect? Int J Mol Sci. 2019 Jul 1;20(13). pii: E3233. doi: 10.3390/ijms20133233.

  8. Altwasser R, Paz A, Korol A, Manov I, Avivi A, Shams I. (2019) The transcriptome landscape of the carcinogenic treatment response in the blind mole rat: insights into cancer resistance mechanisms. BMC Genomics. 2019 Jan 8;20(1):17. doi: 10.1186/s12864-018-5417-z.

  9. Salah-Hussiesy S., Mamchur A., Odeh A., Domankevich V., Shams I. (2018) Reduced calcium influx in the hypoxia-tolerant Spalax: The role of the erythropoietin receptor. Cell Calcium. 2018 Sep;74:123-130

  10. Shams, I., and Raskina, O. (2018) Intraspecific and intraorganismal copy number dynamics of retrotransposons and tandem repeat in Aegilops speltoides Tausch (Poaceae, Triticeae). Protoplasma 255, 1023-1038

  11. Michaeli, S., Dakwar, V., Weidenfeld, K., Granski, O., Gilon, O., Schif-Zuck, S., Mamchur, A., Shams, I., and Barkan, D. (2018) Soluble Mediators Produced by Pro-Resolving Macrophages Inhibit Angiogenesis. Front Immunol 9, 768

  12. Domankevich, V., Eddini, H., Odeh, A., and Shams, I. (2018) Resistance to DNA damage and enhanced DNA repair capacity in the hypoxia-tolerant blind mole rat Spalax carmeli. J Exp Biol 221

  13. Anzi, S., Stolovich-Rain, M., Klochendler, A., Fridlich, O., Helman, A., Paz-Sonnenfeld, A., Avni-Magen, N., Kaufman, E., Ginzberg, M. B., Snider, D., Ray, S., Brecht, M., Holmes, M. M., Meir, K., Avivi, A., Shams, I., Berkowitz, A., Shapiro, A. M. J., Glaser, B., Ben-Sasson, S., Kafri, R., and Dor, Y. (2018) Postnatal Exocrine Pancreas Growth by Cellular Hypertrophy Correlates with a Shorter Lifespan in Mammals. Dev Cell 45, 726-737 e723

  14. Schmidt, H., Malik, A., Bicker, A., Poetzsch, G., Avivi, A., Shams, I., and Hankeln, T. (2017) Hypoxia tolerance, longevity and cancer-resistance in the mole rat Spalax - a liver transcriptomics approach. Sci Rep 7, 14348

  15. Schmidt, H., Hangmann, J., Shams, I., Avivi, A., and Hankeln, T. (2016) Molecular evolution of antioxidant and hypoxia response in long-lived, cancer-resistant blind mole rats: The Nrf2-Keap1 pathway. Gene 577, 293-298

  16.  Malik, A., Domankevich, V., Lijuan, H., Xiaodong, F., Korol, A., Avivi, A., and Shams, I. (2016) Genome maintenance and bioenergetics of the long-lived hypoxia-tolerant and cancer-resistant blind mole rat, Spalax: a cross-species analysis of brain transcriptome. Sci Rep 6, 38624

  17. Domankevich, V., Opatowsky, Y., Malik, A., Korol, A. B., Frenkel, Z., Manov, I., Avivi, A., and Shams, I. (2016) Adaptive patterns in the p53 protein sequence of the hypoxia- and cancer-tolerant blind mole rat Spalax. BMC Evol Biol 16, 177

  18. Iancu, T. C., Arad, T., Shams, I., and Manov, I. (2014) Iron-rich ferritin in the hypoxia-tolerant rodent Spalax ehrenbergi: a naturally-occurring biomarker confirms the internalization and pathways of intracellular macromolecules. J Struct Biol 187, 254-265

  19. Fang, X., Nevo, E., Han, L., Levanon, E. Y., Zhao, J., Avivi, A., Larkin, D., Jiang, X., Feranchuk, S., Zhu, Y., Fishman, A., Feng, Y., Sher, N., Xiong, Z., Hankeln, T., Huang, Z., Gorbunova, V., Zhang, L., Zhao, W., Wildman, D. E., Xiong, Y., Gudkov, A., Zheng, Q., Rechavi, G., Liu, S., Bazak, L., Chen, J., Knisbacher, B. A., Lu, Y., Shams, I., Gajda, K., Farre, M., Kim, J., Lewin, H. A., Ma, J., Band, M., Bicker, A., Kranz, A., Mattheus, T., Schmidt, H., Seluanov, A., Azpurua, J., McGowen, M. R., Ben Jacob, E., Li, K., Peng, S., Zhu, X., Liao, X., Li, S., Krogh, A., Zhou, X., Brodsky, L., and Wang, J. (2014) Genome-wide adaptive complexes to underground stresses in blind mole rats Spalax. Nat Commun 5, 3966

  20. Shams, I., Malik, A., Manov, I., Joel, A., Band, M., and Avivi, A. (2013) Transcription pattern of p53-targeted DNA repair genes in the hypoxia-tolerant subterranean mole rat Spalax. J Mol Biol 425, 1111-1118

  21. Manov, I., Hirsh, M., Iancu, T. C., Malik, A., Sotnichenko, N., Band, M., Avivi, A., and Shams, I. (2013) Pronounced cancer resistance in a subterranean rodent, the blind mole-rat, Spalax: in vivo and in vitro evidence. BMC Biol 11, 91

  22. Hussein, O., Zidan, J., Abu Jabal, K., Shams, I., Szvalb, S., Grozovski, M., Bersudsky, I., Karry, R., and Aviram, M. (2012) Paraoxonase activity and expression is modulated by therapeutics in experimental rat nonalcoholic Fatty liver disease. Int J Hepatol 2012, 265305

  23. Band, M., Shams, I., Joel, A., and Avivi, A. (2008) Cloning and in vivo expression of vascular endothelial growth factor receptor 2 (Flk1) in the naturally hypoxia-tolerant subterranean mole rat. FASEB J 22, 105-112

  24. Shams, I., Rohmann, E., Eswarakumar, V. P., Lew, E. D., Yuzawa, S., Wollnik, B., Schlessinger, J., and Lax, I. (2007) Lacrimo-auriculo-dento-digital syndrome is caused by reduced activity of the fibroblast growth factor 10 (FGF10)-FGF receptor 2 signaling pathway. Mol Cell Biol 27, 6903-6912

  25. Ravid, O., Shams, I., Ben Califa, N., Nevo, E., Avivi, A., and Neumann, D. (2007) An extracellular region of the erythropoietin receptor of the subterranean blind mole rat Spalax enhances receptor maturation. Proc Natl Acad Sci U S A 104, 14360-14365

  26. Shams, I., Nevo, E., and Avivi, A. (2005) Ontogenetic expression of erythropoietin and hypoxia-inducible factor-1 alpha genes in subterranean blind mole rats. FASEB J 19, 307-309

  27. Shams, I., Nevo, E., and Avivi, A. (2005) Erythropoietin receptor spliced forms differentially expressed in blind subterranean mole rats. FASEB J 19, 1749-1751

  28. Shams, I., Avivi, A., Nevo, E., and Ivanitskaya, E. (2005) Assignment of erythropoietin (EPO) to blind subterranean mole rat chromosome 1q by in situ hybridization. Cytogenet Genome Res 108, 362

  29. Shams, I., Avivi, A., and Nevo, E. (2005) Oxygen and carbon dioxide fluctuations in burrows of subterranean blind mole rats indicate tolerance to hypoxic-hypercapnic stresses. Comp Biochem Physiol A Mol Integr Physiol 142, 376-382

  30. Avivi, A., Shams, I., Joel, A., Lache, O., Levy, A. P., and Nevo, E. (2005) Increased blood vessel density provides the mole rat physiological tolerance to its hypoxic subterranean habitat. FASEB J 19, 1314-1316

  31. Shams, I., Avivi, A., and Nevo, E. (2004) Hypoxic stress tolerance of the blind subterranean mole rat: expression of erythropoietin and hypoxia-inducible factor 1 alpha. Proc Natl Acad Sci U S A 101, 9698-9703

 

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