- Dr. Fawaz Awad
Dr. Fawaz Awad
Dr. Fawaz Awad
Department: Department of Biochemistry and Molecular Biology
Faculty: Faculty of Medicine
Specialization: Human Genetics
Host French partner: Sorbonne University
Host Department: Maladies génétiques d'expression pédiatrique (UMR_S933)
French Partner: Pr. Sonia Karabina
Research Domain: Human Genetics, Molecular Biology
Research Project Title: Elucidation of the molecular and cellular basis of familial Mediterranean fever-like disease
Research Project Purpose: Familial Mediterranean fever (FMF) is the prototype of hereditary systemic auto-inflammatory disorders characterized by excessive clinical and biological self-directed inflammation. Clinical features of FMF include recurrent episodes of fever accompanied by severe abdominal pain, arthritis, and skin manifestation. Left untreated, most FMF patients will suffer from amyloidosis, a major life-threatening complication that can lead to end-stage renal failure.
Due to the absence of any specific biochemical marker, FMF diagnosis is based on clinical exclusion criteria and usually confirmed by the identification of biallelic mutations in MEFV, the only gene that has so far been related to FMF. However, a causal mutation can be found in less than 50% of patients.
In the present proposal, we aim to identify new genes involved in FMF. We intend to exome sequence 20 informative probands who are negative for the known mutations in the MEFV gene and reveal possible gene mutations. The best candidate genes will be subsequently screened in additional 700 patients of our cohort. We will study the biological implication of these mutations and their frequencies in the Palestinian population. Affected families will be counselled accordingly.
- We are confident that this work will allow the identification of new genes involved in the FMF-like disease and that a genetic diagnosis will be achieved in a substantial number of patients (Translational study).
- The scientific outcomes also include academic training for at least 2 master students from Al-Quds University (Biochemistry and Molecular Biology Master Program) \
Expected future impact:
- The translation of new gene discovery to clinical practice (molecular diagnosis) will provide an objective diagnostic test for the FMF-like patients leading to a fast and accurate diagnosis.
- The patients will benefit by getting better genetic counseling, prognosis, and accelerating the administration of proper therapy (e.g., colchicine).
- Discovery of new genes involved in autoinflammatory disorders may reveal a novel mechanism underlying the inflammatory cascade driven by the innate immune response, which will ultimately lead to personalized treatments with existing biotherapies and improve patient care.
Future Plan: In the future, the molecular and cellular basis for other autoinflammatory diseases will be investigated, thanks to the large cohort of autoinflammatory patients we have. We will also establish a cell culture lab at Al-Quds University, which is essential to perform functional studies to assess the consequences of the identified variations in candidate genes. Our objectives, which are beyond the scope of the present proposal, will extend over a long-term period. We are planning to set up a research and training center for researchers in Palestine.
Main Impact: Obtaining Al-Maqdisi fund is essential for the Palestinian coordinator to reach independency; the data we will generate with the present proposal will be a pre-requisite to apply for other international and collaborative grants.