Host University: Université libre de Bruxelles, Belgium
Host research group or department:Laboratory of Pathophysiological and Nutritional Biochemistry - LPNB
Co-host University: BioMatter, Polytechnical School - Université Libre de Bruxelles, Belgium
Secondment institution: Marseille Medical Genetics at Aix-Marseille University
Advisor: Prof. Christine Delporte
Co-advisor: Prof. Amin Shavandi
Secondment mentor: Dr Frédérique MAGDINIER
Houman Alimoradi, with a master’s in medical toxicology and a PhD in pharmacology and toxicology, focuses on nitric oxide (NO) modulation in disease conditions. His research involves developing novel nitric oxide donors to enhance NO function in cardiovascular diseases and nitric oxide synthase inhibitors to reduce excessive NO levels in disorders like inflammation and cancer. Through this work, he aims to improve treatment strategies by targeting nitric oxide regulation in various pathophysiological conditions.
My research
SyNeRgIC - Synthesis of Novel Immune Regulating Ionic Complexes for the Treatment of Autoimmune Diseases and Inflammatory conditions
Primary Sjogren's syndrome (pSS) is a progressive autoimmune exocrinopathy that predominantly affects lachrymal and salivary glands (SG), leading to dry eyes (sicca) and mouth (xerostomia) and systemic manifestations. pSS is the second most prevalent autoimmune disease for which there are limited therapies available. Despite all the progresses have been made in understanding the mechanisms that underlie the pathogenesis of pSS during the past decades, the management of the disease has been negatively affected by a lack of effective medicines. Therefore, there is an unmet clinical need to develop novel therapeutic targets for the disease. Inducible nitric oxide synthase (iNOS) and inosine monophosphate dehydrogenase (IMPDH) are two key regulators of immunity and the pathophysiology of pSS. Inhibition of these enzymes has been shown to suppress inflammatory induced angiogenesis and disease progression. However, currently available NOS inhibitors have no clinical utility since they cannot selectively target a specific tissue of interest, and off-target inhibition of NOS results in serious side effects such as fatal hypertension. Besides, the applications of IMPDH inhibitors such as mycophenolic acid (MPA) rigorously stalled due to short circulation half-life, adverse effects and low water solubility. In addition, non-specific delivery of MPA inhibitors causes several side effects. Hence, the overall aim of the project is to develop synergistic anti-inflammatory and immunoregulatory formulations for the treatment of pSS via inhibition of the two complementary systems of iNOS and IMPDH. To this end, our specific objectives are: 1) To Synthesize novel polymeric iNOS inhibiting prodrugs and then develop potent NPs for pSS therapy, targeting iNOS and IMPDH; 2) To assess the anti-angiogenic, immune-stimulatory and cytotoxic effects of the NPs; 3) To evaluate the NPs on preclinical models of pSS, and 4) To ensure further professional development of the ER (WPs 4-6). We anticipate that results from this project will open new therapeutic avenues for the treatment of pSS and other auto-immune diseases. From an educational point of view (considering the multi-disciplinary, significance and novelty of the project) SyNeRgIC project will provide an excellent opportunity to foster the transition of the applicant (as an experienced researcher) to an independent scientist.
Date started – Date End
01.01.2024 - 31.07.2025
