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  • Prof.  Michal Horowitz
Born 1939, Afula, Israel
Ph.D. 1971, Hebrew Univ.
Lect. 1976
Sen. Lect. 1978
Assoc. Prof. 1985
Prof. 1990
External Academic Positions:

Lecturer, Orange Free St. Univ., 1975
Visiting Assoc. Fellow, John B. Pierce Foundation, Conn. 1979-80.
Visiting Assoc. Prof., Prefectural Univ. of Medicine , Kyoto

Memberships and Fellowships:

Isr. Soc. for Physiology and Pharmacology, Secretary, 1987- 93;
Isr. Soc. of Zoology; Eur. Soc. of Comparative Physiolo- gy;
Eur. Soc. for Heart Research; Int'l Committee for Therm-al Physiology;
Int'l Committee for Envionmental Physiology) Am Physiol Soc, Cell stress and Chaperon

Research Interest

Heat stress, thermal dehydration and heat acclimation, in particular, in cardiac muscle, ischemia/reperfusion insult, and the cardiovascular system. Heat acclimation and cross-tolerance with: oxygen deprivation stress (hypoxia, ischemia), traumatic brain injury, ionized irradiation.

Research Projects

  • Mechanisms underlying cross-tolerance between heat acclimation and oxygen deprivation stress in C. elegans (with M. Treinin).
  • Gene transfer - an approach for the induction of protection against ionized irradiation (with Y. Marmary).
  • Heat acclimation - O2 deprivation/reoxygenation cross-tolerance: integrated genomic/proteomic approaches (with Prof. Gary Gerstenblith, John s Hopkins University ; and Dr. Michael Stern, NIH). Funding: BSF (2004-2008).
  • Does acclimation have a memory: an epigenetic phenomenon? Funding: ISF (2005-2009) .
  • The mitochondrial contribution to heat-acclimation O2 deprivation/reoxygenation cross-tolerance.
  • Heat intolerance (with Dani Moran) Funding: Ministry of Health.

Abstracts of Current Research

Mechanisms underlying cross-tolerance between heat acclimation and oxygen deprivation stress: (with M. Treinin)
We study mechanisms leading to cardioprotection against ischemia, at molecular cellular and integrative levels in mammalian (small rodents) and avian (pigeon) species. Acclimation to an environmental stressor is a “within life time” phenotypic adaptation, involving selective reprogrammed gene expression. The acclimated steady state enhances coping with the selected stressor. It may also reinforce or interfere with the ability to combat other environmental stressors. Upon reinforcement, “cross-tolerance” is acquired. The mechanisms underlying such cross-tolerance require study. We have substantiated the induction of heat acclimation evoked cross-tolerance against oxygen deprivation, and ionized irradiation in rodents, and more recently in the nematode C. elegans , against heavy metals, chemical anoxia and heat stress. Our work suggests that heat acclimation per se elevates the constitutive level of HSP 72kDa, and predisposes this molecular signaling pathway to respond faster to acute heat stress. We hypothesize that following acclimation, evocation of cross-tolerance stems from activation of the enhanced “reprogrammed molecular signaling pathways” by the superimposed stressor. Heat acclimation induced cross-tolerance against oxygen deprivation in two different taxa (rats/mice and C. elegans ) will be studied. The introduction of the C. elegans genetic model could provide a novel, low-cost approach to environmental studies.
Gene transfer - an approach for the induction of protection against ionized irradiation : (with Y. Marmary)
Toxicity to non-tumor derived tissues is a significant obstacle in the use of ionizing radiation for the treatment of cancer. Treatment of head and neck malignancies often includes the salivary glands: radiation causes an irreversible loss of salivary gland function leading to dryness of the mouth and resulting oral malfunctions, speech and other difficulties. This project focuses on a new technique using gene therapy to prevent the development of irradiation injuries. We plan to elevate HSP70, one of the protective gene products essential in the natural response to stress, by gene transfer.


Recent Publications

  • Treinin M, Shliar J, Jiang H, Powell-Coffman JA, Bromberg Z, Horowitz M (2003) HIF-1 is required for heat acclimation in the nematode Caenorhabditis elegans. Physiol. Genomics , 14(1): 17-24.
  • Paz Z, Freeman S, Horowitz M, Sohmer H (2004) Prior heat acclimation confers protection against noise-induced hearing loss. Audiol. Neurootol. , 9(6): 363-369.
  • Schwimmer, H, Gerstberger, R, Horowitz, M. (2004) NO and AngII: Neuromodulation of thermoregulation during combined heat and hypohydration stress. Brain Res. , 1006(2): 177-189.
  • Horowitz, M, Eli-Berchoer, L, Wapinski, I, Friedman, N, Kodesh, E (2004) Stress-related genomic responses during the course of heat acclimation and its association with ischemic/reperfusion cross-tolerance. J. Appl. Physiol. , 97(4): 1496-1507.
  • Schwimmer, H, Gerstberger R, and Horowitz M. (2004) Heat acclimation affects the neuromodulatory role of AngII and nitric oxide during combined heat and hypohydration stress. Brain Res. Mol. Brain Res. , 130(1-2): 95-108.
  • Maloyan, A, Eli-Berchoer, E, Semenza, GL, Gerstenblith, G, Stern, M, and Horowitz, M. (2005) HIF-1?-targeted pathways are activated by heat acclimation and contribute to acclimation-ischemic cross-tolerance in the heart. Physiol. Genomics , 23: 79-88.
  • Shein NA, Horowitz M, Alexandrovich AG, Tsenter J, Shohami E (2005) Heat acclimation increases hypoxia-inducible factor 1alpha and erythropoietin receptor expression: Implication for neuroprotection after closed head injury in mice. J. Cereb. Blood Flow Metab. , 25 (11): 1456-1465.
  • Milman G, Maor Y, Abu-Lafi S, Horowitz M, Gallily R, Batkai S, Mo FM, Offertaler L, Pacher P, Kunos G, Mechoulam R (2006) N-arachidonoyl L-serine, an endocannabinoid-like brain constituent with vasodilatory properties. Proc. Natl. Acad. Sci. USA, 103(7): 2428-2433.
  • Schwimmer H, Eli-Berchoer L, Horowitz M. (2006) Heat-Acclimation phase specificity of gene expression during the course of heat acclimation and superimposed hypohydration in the rat hypothalamus. J. Appl. Physiol., 100: 1992-2003.
  • Moran D S, Eli-Berchoer L, Heled, Y, Mendel L, Schochina M, Horowitz, M (2006) Heat intolerance: Does gene transcription contribute? J. Appl. Physiol. , 100(4): 1370-1376.
  • Horowitz M (2007) Heat acclimation and cross tolerance against novel stressors: Genomic-physiological linkage. Progress in Brain Research ( The Neurobiology of Hyperthermia , ed. H.S. Sharma), 162 (Chapt 18): 373-392. Review.
  • Horowitz M, and Robinson S. (2007) Heat shock proteins and the heat shock response during hyperthermia and its modulation by altered physiological conditions. In: Progress in Brain Res. (The Neurobiology of Hyperthermia, ed. H.S. Sharma), 162 (Chapter 21): 433-446. Review
  • Shein NA, Horowitz M, Shohami E. (2007) Heat acclimation: A unique model of physiologically mediated global preconditioning against traumatic brain injury. Prog. Brain Res., 161: 353-363. Review.
  • Cohen O, Kanana H, Zoizner R, Gross C, Meiri U, Stern MD, Gerstenblith G, Horowitz M (2007) Altered Ca2+ handling and myofilaments desensitization underlie cardiomyocyte performance in normothermic and hyperthermic heat acclimated rat hearts. J. Appl. Physiol. , 103(1): 266-275.
  • Shein NA, Tsenter J, Alexandrovich AG, Horowitz M, Shohami E. (2007) Akt phosphorylation is required for heat acclimation- induced neuroprotection. Journal of Neurochemistry , 103(4): 1523-1529.
  • Shein N A, Doron H, Horowitz M, Trembovler V, Alexandrovich AG, Shohami E (2007) Altered cytokine expression and sustained hypothermia following traumatic brain injury in heat acclimation. Brain Res., 1185: 313-320.
  • Shein NA, Grigoriadis N, Alexandrovich AG, Simeonidou C, Spandou E, Tsenter J, Yatsiv I, Horowitz M, Shohami E (2008) Differential neuroprotective properties of endogenous and exogenous erythropoietin in a mouse model of traumatic brain injury. J. Neurotrauma , 25(2): 112-123.
  • Tetievsky A, Cohen O, Eli-Berchoer L, Gerstenblith G, Stern MD, Wapinski I, Friedman N, Horowitz M. (2008) Physiological and molecular evidence of heat acclimation memory: A lesson from thermal responses and ischemic cross-tolerance in the heart. Physiol. Genomics , 34(1): 78-87.
  • Shein NA, Grigoriadis N, Horowitz M, Umscheief G, Alexandrovich AG, Simeonidou C, Grigoriadis S , Touloumi O, Shohami E (2008) BDNF positive ramified microglia are enhanced adter TBI in heat acclimated mice. Brain Res. , 1244: 132-141.
  • Umschwief, G, Shein, NA, Alexandrovich AG, Trembovler V, Horowitz M, Shohami E. (2009) Heat acclimation provides sustained improvement in functional recovery and attenuates apoptosis following traumatic brain injury. J. Cereb. Blood Flow Metab . , 2009 Nov 11. [Epub ahead of print ].
  • Horowitz M, Assadi H. (2010) Heat-Acclimation Mediated Cross-Tolerance in Cardioprotection: Do HSP70 and Play a Role?" New York Academy of Sciences vol 1187 - "Analysis of a HIF-1 Cardiac Development, from Embryo to Old Age", Eds: Rafael Beyar and Amir Landesberg (in Press).
  • Kodesh E, Horowitz M. (2009) Soleus adaptation to combined exercise and heat acclimation: physio-genomic aspects. Medicine & Science in Sports & Exercise (in Press)
  • Horowitz M, Shohami E (2009) Environmental Stress is not Always Vicious: A Lesson From Heat Acclimation-Induced Neuroprotection after Traumatic Brain Injury, in: 'STRESS: from molecules to behaviour', edited by Hermona Soreq, Alon Friedman and Daniela Kaufer Wiley-Blackwell
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