Accueil
MS

Majid Sheykhzade

122
4
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À Propos du Membre

Biographie

Primary fields of research Throughout my academic career, I have been focusing on the regulation of vascular tone in health and disease (diabetes, hypertension, stroke, congestive heart failure, age-related changes and migraine). Coronary arteries are densely innervated by sensory nerve endings containing calcitonin gene-related peptide (CGRP). CGRP is a potent naturally occurring 37 amino acid vasodilatory neuropeptide, which is released from the perivascular sensory nerve endings in the wall of flow regulating intramural coronary arteries during hypoxia and by low pH levels in the myocardium, thus suggesting a vasodilatory role under ischemic conditions. Receptor subtypes for CGRP, the intracellular signaling pathways and the mechanism behind CGRP-induced desensitization and neuronal reuptake are still under investigation in both resistance and conductance arteries of different species including human. So far, our studies indicate a higher CGRP receptor density in resistance arteries (internal lumen diameter < 200 µm) compared to larger conductance arteries (internal lumen diameter > 200 µm), suggesting that receptor distribution, calcium handling, ion channels, and second messengers may be finely adjusted within the circulatory system, probably reflecting the physiological demands on the vascular segments. CGRP receptor consists of three components, calcitonin receptor-like receptor (CLR), a specific chaperone called receptor activity modifying protein 1 (RAMP1) and receptor component protein (RCP). A novel family of chaperone proteins, called RAMPs (RAMP1, RAMP2 and RAMP3) were identified as proteins escorting CLR to the plasma membrane to generate either CGRP (when associated with RAMP1) or adrenomedullin receptors (when associated with RAMP2 or RAMP3). CLR belongs to class B of the G protein-coupled receptor (GPCR) family and is linked to Gs protein. It was recently reported that the small non-peptide CGRP receptor antagonists (olcegepant and telcagepant) act by blocking access of CGRP to the peptide-binding cleft at the interface of CLR and RAMP1. Our recent studies on isolated human subcutaneous arteries clearly show that key components of the CGRP receptor (CLR and RAMP1) are located on both smooth muscle and endothelial cells. Despite the presence of functional endothelium in these human vessels (verified by functional studies using carbachol, substance P and bradykinin), the contribution of the endothelium to CGRP-induced vasodilation seems to be insignificant. Perhaps, the CGRP receptors located on the endothelium have different biological effects than being directly involved in the vasomotor control or the density of CGRP receptors is significantly higher on smooth muscle cells compared with the endothelium. Recent studies have shown that CGRP acts as a pro-angiogenic growth factor by increasing the secretion of vascular endothelial growth factor and expression of focal adhesion kinase, thereby contributing to vascular remodeling. In addition, our recent studies on this topic show synergism or possible interplay between smooth muscle Kv7.4/7.5 channels and CGRP receptor signaling in isolated human subcutaneous arteries so that CGRP-induced vasodilation becomes more potent and prolonged. However, XE-991 dihydrochloride (a non-selective blocker of KCNQ channels) was not able to block the CGRP-induced vasodilation in these vessels. These studies will shed light on the complexity of CGRP receptor pharmacology as well as its complex signaling pathway, thereby helping us understand its physiology as well as its role under different circulatory complications such as stroke, ischemia, hypertension, and migraine. Furthermore, our most recent studies in human subcutaneous arteries using 10 microM Gallein indicate involvement of Beta-gamma subunit of G-protein in intracellular signaling pathway leading to vasodilation perhaps via activation of potassium channels. Teaching experience: Over 20 years of teaching experience in the field of Pharmacology covering a wide range of areas: Cardiovascular Pharmacology, Endocrinology (diabetes and obesity), Receptor Pharmacology and Intracellular Signaling Pathways, and Pharmacokinetics and –dynamics (PK-PD). Supervision of students: Supervised over 60 Master Thesis students and 15 PhD-students. Administrative responsibilities: Member of didactic committee at the Faculty of Pharmaceutical Sciences and Chairman of the teaching committee at the Department of Pharmacology and Pharmacotherapy, Faculty of Pharmaceutical Sciences, University of Copenhagen: from January 2008 - March 2012 Aug. 2012 - May 2019 : Member of the committee for Research and Innovation (FIU) at the Dept. of Drug Design and Pharmacology, University of Copenhagen. Jan. 2017 - Jan. 2020: Course director for "Organ pharmacology", Bachelor course for Pharmacy students at the 4th semester. Dec. 2023 - Feb. 2025: Course director for "Basic pharmacology", Bachelor course at the 3rd semester.

Formation

  • University of Copenhagen, Faculty of Health and Medical Sciences, PharmaSchool
    Diplôme PhD / Characterization of Calcitonin Gene-Related Peptide (CGRP) receptor subtype and function in ra
    Domaine d'études Dept. of Drug Design and Pharmacology
    Date de début 01/1996
    Date de fin 01/2000
    Description PhD / Characterization of Calcitonin Gene-Related Peptide (CGRP) receptor subtype and function in rat coronary arteries
  • University of Copenhagen, Faculty of Health and Medical Sciences, PharmaSchool
    Diplôme Master of Science in Pharmacy / Pharmacist
    Domaine d'études Dept. of Drug Design and Pharmacology
    Date de début 01/1987
    Date de fin 01/1993

Expérience

UO

Assistant Professor

University of Copenhagen, Faculty of Health and Medical Sciences, PharmaSchool

01/200101/2004

Dept. of Drug Design and Pharmacology

IS

Regulatory Affairs Associate

IPSEN Scandinavia A/S

01/199401/1995

Department of Regulatory Affairs

IS

Clinical data management and monitoring

IPSEN Scandinavia A/S

01/199501/1995

Medical Department

BH

Pharmacien

Bispebjerg Hospital Pharmacy

01/199401/1994

Aseptic and sterile production