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Characterization of IL11-deficiency in humans

Project

Project Details

Program
BioScience
Field of Study
human genetics
Division
Biological and Environmental Sciences and Engineering
Faculty Lab Link
https://www.kaust.edu.sa/en/study/faculty/bruno-reversade

Project Description

The student will investigate patients with germline homozygous variants in the cyokine IL11. He/she will make use of patient-derived fibroblasts and serum to confirm the pathogenicity of identified mutations and examine its downstream effects on cellular activity. Additionally, an animal model may be envisaged in collaboration with European group and new clinical assays may required to better define syndrome. This falls under the Smart Health Initiative towards the understanding of monogenic diseases. This may become a part of a PhD project.

About the Researcher

Bruno Reversade
Professor Bioscience
Biological and Environmental Science and Engineering Division

Affiliations

Education Profile

  • 2006 PhD in Molecular & Cellular Biology of Development, UniversitA© Pierre & Marie Curie (France) & UCLA (USA)
  • 2000 Master's degree, Institut Pasteur, (Paris, France)

Research Interests

Prof. Bruno REVERSADE is a human geneticist. By identifying mutations responsible for monogenic traits (that may be deleterious or beneficial), his teams have pioneered a paradigm shift in the field of Mendelian genetics. By pinpointing the subverted biological pathways which not only underlie the etiology of unique inherited conditions, Bruno's work has revealed biological nodes whose perturbation contributes to common maladies. This concept of ""rare begets common"" highlights how the study of humans with extreme phenotypes can foster innovation in therapies for common unmet medical needs. This ""bedside to bench and back"" paradigm has been realized for a wide array of conditions affecting metabolism, immunity, birth defects, infectious diseases or oncology indications. Bruno's work is characterized by its unusual breadth and depth whose foundations rely on mechanism-based investigations. The team employs patient-derived organoids, animal models and biochemical/structural assays to derive meaningful insights into the origin of each condition studied. Several of these discoveries have been licensed or are being developed for diagnostics and therapeutics purposes. Prof. Bruno REVERSADE was the inaugural A*STAR Investigator (Singapore), a fellow of the Branco Weiss Foundation (Switzerland), the first EMBO YIP established outside Europe, a senior Investigator of the National Research Foundation (Singapore), the inaugural AAA fellow and Professor at the University of Amsterdam (Netherlands), a distinguished visiting Professor at KoA§ University (TA¼rkiye) and adjunct Professor at NUS (Singapore). For more information please visit: www.reversade.com

Selected Publications

  • Harapas CR, Robinson KS, (...), Zhong FL, Masters SL, Reversade B. DPP9 deficiency: An inflammasomopathy that can be rescued by lowering NLRP1/IL-1 signaling. Science Immunology. 2022 Sep 16;7(75).
  • Moreno Traspas R, Teoh TS, (...), Vincent M, Girisha KM, Reversade B. Loss of FOCAD, operating via the SKI messenger RNA surveillance pathway, causes a pediatric syndrome with liver cirrhosis. Nature Genetics. 2022 Aug;54(8):1214-1226.
  • Szenker-Ravi E, Ott T, Khatoo M, (...), Attie-Bitach T, Blum M, Bouvagnet P, Reversade B. Discovery of a genetic module essential for assigning left-right asymmetry in humans and ancestral vertebrates. Nature Genetics. 2022 Jan;54(1):62-72.
  • Chai G, Szenker-Ravi E, (...), Willert K, Reversade B, Gleeson JG. A Human Pleiotropic Multiorgan Condition Caused by Deficient Wnt Secretion. New England Journal of Medicine. 2021 Sep 30;385(14):1292-1301.
  • Robinson KS, Teo DET, (...),Wang Y, Zhong FL, Reversade B. Enteroviral 3C protease activates the human NLRP1 inflammasome in airway epithelia. Science. 2020 Dec 4;370(6521).
  • Hengel H, Bosso-LefA¨vre C, (...), Jamuar SS, SchA¶ls L, Reversade B. Loss-of-function mutations in UDP- Glucose 6-Dehydrogenase cause recessive developmental epileptic encephalopathy. Nature Communications. 2020 Jan 30;11(1):595.
  • Szenker-Ravi E, Altunoglu U,(...), Barker N, Kayserili H, Reversade B. RSPO2 inhibition of RNF43 and ZNRF3 governs limb development independently of LGR4/5/6. Nature. 2018 May;557(7706):564-569.
  • Ho L, van Dijk M, (...), Solter D, Knowles BB, Reversade B. ELABELA deficiency promotes preeclampsia and cardiovascular malformations in mice. Science. 2017 Aug 18;357(6352):707-713.
  • Gordon CT, Xue S, (...), Javed A, Blewitt ME, Amiel J, Wollnik B, Reversade B. De novo mutations in SMCHD1 cause Bosma arhinia microphthalmia syndrome and abrogate nasal development. Nature Genetics. 2017 Feb;49(2):249-255.
  • Zhong FL, MamaA¯ O, (...), Hiller S, Reversade B. Germline NLRP1 Mutations Cause Skin Inflammatory and Cancer Susceptibility Syndromes via Inflammasome Activation. Cell. 2016 Sep 22;167(1):187-202.

Desired Project Deliverables

literature review and knowledge of IL11 pathway cell culture with patient and established cell lines signalling assays including Elisa, western blots, QPCR, immnuoflorescence, metabolomics biomarker analysis in serum and supernatants animal modeling clinical analysis and comparison clear communication at lab meetings and project report

Recommended Student Background

Experience in molecular lab
Knowledge of cell culture
Desire to learn
Interest in Mendelian diseases and Medicine
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3-6 months
Internship period
100+
Research Projects
3.5/4
Cumulative GPA
310
Interns a Year