Dr. Khaled A. Alhosaini
Department of Pharmacology & Toxicology
College of Pharmacy, King Saud University
Ph.D. in Cell Physiology and Pharmacology (2011)
University of Leicester, United Kingdom
GPCRs signalling, Cell signalling events, Calcium imaging and measurement, Confocal Microscopy, cAMP measurement, Medical Neurosciences
Brief description of on-going research
The G protein-coupled receptor (GPCR) superfamily is one of the largest human gene families comprising approximately 800 genes (2% of the human genome). These receptors regulate a wide diversity of patho-physiological processes. As such, they provide excellent drug targets and this is reflected in the fact that approximately 40-50% of currently prescribed drugs target GPCRs. Despite this, a relatively small number (~30) of the approximately 400 non-olfactory receptors are therapeutic targets, highlighting the great potential for the development of novel therapeutics.
My PhD project focused on understanding aspects of desensitization, resensitization and trafficking of two GPCRs, both of which are receptors for the neuropeptides, Neuromedin U and Neuromedin S. Through the two Neuromedin U receptors, these peptides regulate a variety of patho-physiological processes including blood pressure, stress response, pain, cancer, feeding behavior and energy expenditure.
Currently, I’m further investigating these aspects using different endogenous agonists (hNmU-25 and hNmS-33) for these receptors (NMU1/2) to explore the possibility of biased signaling.
As future interest, the isolation of cortical astrocytes and investigation of signalling by GPCRs including glutamate receptors (mGluR5 and mGluR3) and their involvement in central nervous system patho-physiological events such as CNS cancer (e.g. gliobastoma), and brain ischemic disease. Furthermore, following the evolution of GPCRs crystallization and generation of nanobodies towards a specific confirmation of GPCRs, I’m very interested to apply these tools in CNS Pharmacology and cancer field.
Figure 1: Binding of fluorescently-tagged pNmU-8 (Cy3B-pNmU-8) to either HEK-NMU1-eGFP or HEK-NMU2-eGFP visualized by confocal microscopy.
- Alhosaini, K., Challiss, R. A. J., & Willars, G. B. (2013). A role for Endothelin Converting Enzyme-1 activity in the regulation of neuromedin U receptor re-sensitization and ERK signaling. The FASEB Journal, 27 (Meeting Abstracts), 1173-9.
- Abuohashish, H.M., Al-Rejaie, S.S., Al-Hosaini, K.A., et al. (2013). Alleviating effects of morin against experimentally-induced diabetic osteopenia. Diabetology & metabolic syndrome, 5(1), 1.
- Mansour, M.A., Aljoufi M.A., Al-Hosaini, K., et al. (2014). A possible antineoplastic potential of selective, irreversible proteasome inhibitor, carfilzomib on chemically induced hepatocarcinogenesis in rats. J Biochem Mol Toxicol. PMID: 24861196
- Fatani, A.J., Al-Hosaini K.A., et al. (2015). Carvedilol Attenuates Inflammatory Biomarkers and Oxidative Stress in a Rat Model of Ulcerative Colitis. Drug Development Research. 76(4) 204-215.