Team 3: Molecular Biology

Principal Investigator

Joseph Stephan, PhD
Associate Professor of Biochemistry
Gilbert and Rose-Marie Chagoury School of Medicine
Lebanese American University, Byblos Campus
Office: 4721
Telephone: +961 9 547254, ext. 2845
Email: joseph.stephan@lau.edu.lb

Research Expertise and Interests

My research team is interested in the molecular basis of memory and learning, as well as the impact of physiological activities such as exercise and its metabolites on these cognitive processes. This has led us to focus on individual exercise metabolites to assess their cognitive impact, as well as on a special class of prion-like proteins. Identified initially in the context of diseases such as Creutzfeld Jacob and Kuru, these shape-shifting proteins appear to play a wide variety of roles in different physiological contexts such as long-term memory storage, autophagy and cancer. Using mouse models, neuronal cultures, and the powerful biochemical and molecular arsenal of the budding yeast S. cerevisiae, we attempt to elucidate the role of exercise metabolites prions in learning and memory. In addition, we mentor medical student groups tackling several problems of clinical relevance.

Team Members and Collaborators

• Dr. Sama Sleiman, SoAS Neuroscience collaborator.
• Dr. Wissam Faour, SOM collaborator.
• Dr. Elias Akoury, SoAS Chemistry collaborator.
• Students:  Yara Zoghbi, Joanna Fadel, Yasmin Sahloul, Mahmoud Lakkis, Christopher Sahyoun, Lea Abi Gerges (SoAS); Medical student year and and year II YLP groups (SOM).

The laboratory also benefits from additional collaborations with LAU students, researchers and investigators at outside universities.

Selected Publications

Saab C, Stephan J, Akoury E. Structural insights into the binding mechanism of Clr4 methyltransferase to H3K9 methylated nucleosome. StrSci Rep. 2024 Mar 5;14(1):5438. doi: 10.1038/s41598-024-56248-2. PMID: 38443490.

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

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.

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.

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.

Khalifeh M, Hobeika R, El Hayek L, Saad J, Eid F, El-Khoury R, Ghayyad L-M, 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., Epub Jan 21. https://doi.org/10.1016/j.bbr.2020.112499

Stephan JS and Sleiman SF (2019). Exercise factors as potential mediators of cognitive rehabilitation following traumatic brain injury. Curr Opin Neurol. 2019 Dec; 32(6):808-814.

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.

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. Impact Factor: 7.2

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 Memory and its Reconsolidation Require CPEB3-Mediated Protein Synthesis in the Hippocampus Neuron. 2015 Jun 17;86(6):1433-48. Impact Factor: 16.2

Grants

Intramural LAU President’s Intramural Research Fund (PIRF) Grants as main PI and Co-PI; additional pending applications.