About

Joseph Stephan, PhD

Associate Professor
Biochemistry Discipline Coordinator
Chair of LAU Institutional Review Board

After completing my post-doctoral studies in the laboratory of Eric Kandel at Columbia University, I have recently relocated to Lebanon where I have established an independent research program at the LAU Gilbert and Rose-Marie School of Medicine. The main focus of my laboratory is the biological basis of memory and learning. In that context, we are interested in (1) the effects of exercise on memory and learning, and specifically the role that exercise factors such as lactate might play in improving cognitive abilities and (2) the biological roles of physiological prions: these proteins, identified initially in the context of diseases such as Creutzfeldt–Jakob and Kuru, appear to play a wide variety of roles in different physiological contexts such as long-term memory storage (and cancer). Using mouse models, neuronal cultures and the powerful biochemical and molecular arsenal of the budding yeast, S. cerevisiae, we attempt to investigate these two main questions.

Selected Publications

  1. Saab C, Stephan J, Akoury E. Structural insights into the binding mechanism of Clr4 methyltransferase to H3K9 methylated nucleosome. Sci Rep. 2024 Mar 5;14(1):5438. doi: 10.1038/s41598-024-56248-2. PMID: 38443490; PMCID: PMC10914790.
  2. Rodriguez-Morales AJ, Lopez-Echeverri MC, Perez-Raga MF, Quintero-Romero V, Valencia-Gallego V, Galindo-Herrera N, López-Alzate S, Sánchez-Vinasco JD, Gutiérrez-Vargas JJ, Mayta-Tristan P, Husni R, Moghnieh R, Stephan J, Faour W, Tawil S, Barakat H, Chaaban T, Megarbane A, Rizk Y, Sakr R, Escalera-Antezana JP, Alvarado-Arnez LE, Bonilla-Aldana DK, Camacho-Moreno G, Mendoza H, Rodriguez-Sabogal IA, Millán-Oñate J, Lopardo G, Barbosa AN, Cimerman S, Chaves TDSS, Orduna T, Lloveras S, Rodriguez-Morales AG, Thormann M, Zambrano PG, Perez C, Sandoval N, Zambrano L, Alvarez-Moreno CA, Chacon-Cruz E, Villamil-Gomez WE, Benites-Zapata V, Savio-Larriera E, Cardona-Ospina JA, Risquez A, Forero-Peña DA, Henao-Martínez AF, Sah R, Barboza JJ, León-Figueroa DA, Acosta-España JD, Carrero-Gonzalez CM, Al-Tawfiq JA, Rabaan AA, Leblebicioglu H, Gonzales-Zamora JA, Ulloa-Gutiérrez R. The global challenges of the long COVID-19 in adults and children. Travel Med Infect Dis. 2023 Jul-Aug;54:102606. doi: 10.1016/j.tmaid.2023.102606. Epub 2023 Jun 8. PMID: 37295581; PMCID: PMC10247301.
  3. Reine Khoury, Joelle Saad, Vanessa Jabre, Litsa Maria Ghayad, Mohamad Khalifeh, Rouba Houbeika, Perla El Ahmad, Amar Mezher, Diala El Masri, Zena Haddad, Fady Eid, Nour Barmo, Sama F. Sleiman and Joseph S. Stephan*. Autophagy mediates the positive effects of exercise on spatial learning and memory by promoting the release of exercise factors into the circulation and by modulating BDNF signaling in the hippocampus in young adult mice. Heliyon.  Volume 9, ISSUE 4, e14705, April 2023. March 24, 2023. DOI:https://doi.org/10.1016/j.heliyon.2023
  4. Marc Fakhoury, Fady Eid, Perla El Ahmad, Reine Khoury, Amar Mezher, Diala El Masri, Zena Haddad, Yara Zoghbi, Litsa Maria Ghayad, Sama F. Sleiman and Joseph S. Stephan*. Exercise and dietary factors mediate neural plasticity through modulation of BDNF signaling. Brain Plasticity. 2022 Oct 21;8(1):121-128. doi: 10.3233/BPL-220140. eCollection 2022.
  5. Stephan JS, Sleiman SF (2021) Exercise Factors Released by the Liver, Muscle, and Bones Have Promising Therapeutic Potential for Stroke. Front Neurol. 2021 May 24;12:600365. doi: 10.3389/fneur.2021.600365. eCollection 2021. PMID: 34108925.
  6. Bilen M, Ibrahim P, Barmo N, Abou Haidar E, Karnib N, El Hayek L, Khalifeh M, Jabre V, Houbeika R, Stephan JS, Sleiman SF (2020). Methionine mediates resilience to chronic social defeat stress by epigenetic regulation of NMDA receptor subunit expression. Psychopharmacology (Berl). 2020 Oct;237(10):3007-3020. doi: 10.1007/s00213-020-05588-8. Epub 2020 Jun 20.
  7. Khalifeh M, Hobeika R, El Hayek L, Saad J, Eid F, El-Khoury R, Ghayad LM, Jabre V, Nasrallah P, Barmo N, Stephan JS, Khnayzer R, Khalil C, Sleiman SF (2020). Nicotine induces resilience to chronic social defeat stress in a mouse model of water pipe tobacco exposure by activating BDNF signaling. Behav Brain Res. 2020 Mar 16;382:112499. doi: 10.1016/j.bbr.2020.112499. Epub 2020 Jan 21.
  8. Stephan JS, Sleiman SF (2019). Exercise factors as potential mediators of cognitive rehabilitation following traumatic brain injury. Curr Opin Neurol. 2019 Dec;32(6):808-814.
  9. Nasrallah P, Haidar EA, Stephan JS, El Hayek L, Karnib N, Khalifeh M, Barmo N, Jabre V, Houbeika R, Ghanem A, Nasser J, Zeeni N, Bassil M, Sleiman SF (2019). Branched-chain amino acids mediate resilience to chronic social defeat stress by activating BDNF/TRKB signaling. Neurobiol Stress. May 14;11:100170. doi: 10.1016/j.ynstr.2019.100170. eCollection 2019 Nov.
  10. El Hayek L, Khalifeh M, Zibara V, Abi Assaad R, Emmanuel N, Karnib N, El-Ghandour R, Nasrallah P, Bilen M, Ibrahim P, Younes J, Abou Haidar E, Barmo N, Jabre V, Stephan JS, Sleiman SF. (2019) Lactate mediates the effects of exercise on learning and memory through SIRT1-dependent activation of hippocampal Brain-Derived Neurotrophic Factor (BDNF). J Neurosci. 2019 Mar 27;39(13):2369-2382. Epub Jan 28.
  11. Stephan J.S., Fioriti L., Lamba N., Colnaghi L., Karl K., Derkatch I.L. and Kandel E.R. (2015) The CPEB3 protein is a functional prion that interacts with the actin cytoskeleton. Cell Reports. 2015 Jun 23;11(11):1772-85.
  12. Fioriti L., Myers C., Huang Y.Y., Li X., Stephan J.S., Trifilieff P., Kosmidis S., Drisaldi B., Pavlopoulos E., Kandel E.R. (2015) The Persistence of nemory and its reconsolidation require CPEB3-mediated protein synthesis in the hippocampus. Neuron. Jun 17;86(6):1433-48.)
  13. Stephan, J. S., Yeh, Y.Y., Ramachandran, V., Deminoff, S. J., Herman, P. K. (2010) The Tor and cAMP-dependent protein kinase signaling pathways coordinately control autophagy in Saccharomyces cerevisiae. Autophagy 6(2): 294-295.
  14. Stephan, J. S., Yeh, Y.Y., Ramachandran, V., Deminoff, S. J., Herman, P. K. (2009) The Tor and PKA signaling pathways independently target the Atg1/Atg13 protein kinase complex to control autophagy. Proceedings of the National Academy of Science, 106(40), 17049-54.
  15. Stephan, J. S. and Herman, P. K. (2006) The regulation of autophagy in eukaryotic cells: Do all roads pass through Atg1? Autophagy, 2:2, 146-148.
  16. Budovskaya, Y. V., Stephan, J. S., Deminoff, S. J., Herman, P. K. (2005) An evolutionary proteomics approach identifies novel substrates of the cAMP-dependent protein kinase. Proceedings of the National Academy of Science 102: 13933-13938.

Professional and Research Interests

Education and Training

Professional Memberships and Organizations

Keywords

Exercise, memory, learning, prions, cancer, neurodegeneration, kinases, yeast biology