Genetics and cell biology
Genome-Phenome Relationship Unit
The genome-phenome relationship is a complex interplay between the genetic makeup and its observable traits, where genetic information translates into functional or dysfunctional features. The study of such relationship, notably unidirectional from genome to phenome, enhances our understanding of fundamental biology but also holds the promise of personalized medicine.
Disease gene identification and characterization, as well as the elucidation of pathogenetic mechanisms leading to inherited diseases, represent the primary objectives of our group. Several projects have successfully identified genes responsible for disorders of the central nervous system, host susceptibility to viral infections, and male infertility.
Dissecting the molecular events that lead to inherited diseases and understanding their underlying mechanisms is crucial for tailoring new, specific therapeutic interventions. To achieve this goal, our group employs a range of complementary approaches, based on molecular genetics and genomics, as well as on biochemistry and cell biology, utilizing both cellular and animal models.
Research activity
Our research project focuses on:
- The protease paraplegin shapes the mitochondrial metabolism in hereditary spastic paraplegia
- The significant and unforeseen burden of Mendelian causes of male infertility
- The human genetic and immunological determinants of longCOVID
- Neonatal genomic screening: is it worth doing, at present?
Asano, T., Boisson, B., Onodi, F., Matuozzo, D., Moncada-Velez, M., Renkilaraj, M. R. L. M., Zhang, P., Meertens, L., Bolze, A., Materna, M., Korniotis, S., Gervais, A., Talouarn, E., Bigio, B., Seeleuthner, Y., Bilguvar, K., Zhang, Y., Neehus, A.-L. L., Ogishi, M., … Casanova, J.-L. L. (2021). X-linked recessive TLR7 deficiency in ~1% of men under 60 years old with life-threatening COVID-19. Science Immunology, 6(62). https://doi.org/10.1126/sciimmunol.abl4348
Bastard, P., Gervais, A., Le Voyer, T., Rosain, J., Philippot, Q., Manry, J., Michailidis, E., Hoffmann, H.-H., Eto, S., Garcia-Prat, M., Bizien, L., Parra-Martínez, A., Yang, R., Haljasmägi, L., Migaud, M., Särekannu, K., Maslovskaja, J., de Prost, N., Tandjaoui-Lambiotte, Y., … Casanova, J.-L. (2021). Autoantibodies neutralizing type I IFNs are present in ~4% of uninfected individuals over 70 years old and account for ~20% of COVID-19 deaths. Science Immunology, 6(62). https://doi.org/10.1126/sciimmunol.abl4340
Casari, G., De Fusco, M., Ciarmatori, S., Zeviani, M., Mora, M., Fernandez, P., De Michele, G., Filla, A., Cocozza, S., Marconi, R., Dürr, A., Fontaine, B., & Ballabio, A. (1998). Spastic paraplegia and OXPHOS impairment caused by mutations in paraplegin, a nuclear-encoded mitochondrial metalloprotease. Cell, 93(6), 973–983. https://doi.org/10.1016/S0092-8674(00)81203-9
Manry, J., Bastard, P., Gervais, A., Le Voyer, T., Rosain, J., Philippot, Q., Michailidis, E., Hoffmann, H.-H., Eto, S., Garcia-Prat, M., Bizien, L., Parra-Martínez, A., Yang, R., Haljasmägi, L., Migaud, M., Särekannu, K., Maslovskaja, J., de Prost, N., Tandjaoui-Lambiotte, Y., … Cobat, A. (2022). The risk of {COVID}-19 death is much greater and age dependent with type {I} {IFN} autoantibodies. Proceedings of the National Academy of Sciences of the United States of America, 119(21), e2200413119. https://doi.org/10.1073/pnas.2200413119
Manry, J., Bastard, P., Gervais, A., Voyer, T. Le, Rosain, J., Philippot, Q., Michailidis, E., Hoffmann, H.-H., Eto, S., Garcia-Prat, M., Bizien, L., Parra-Martínez, A., Yang, R., Haljasmägi, L., Migaud, M., Särekannu, K., Maslovskaja, J., de Prost, N., Tandjaoui-Lambiotte, Y., … Cobat, A. (2022). The risk of COVID-19 death is much greater and age-dependent with type I IFN autoantibodies. Research Square. https://doi.org/10.21203/rs.3.rs-1225906/v1
Quarantani, G., Sorgente, A., Alfano, M., Pipitone, G. B., Boeri, L., Pozzi, E., Belladelli, F., Pederzoli, F., Ferrara, A. M., Montorsi, F., Moles, A., Carrera, P., Salonia, A., & Casari, G. (2023). Whole exome data prioritization unveils the hidden weight of Mendelian causes of male infertility. A report from the first Italian cohort. PloS One, 18(8). https://doi.org/10.1371/JOURNAL.PONE.0288336
Sambri, I., Massa, F., Gullo, F., Meneghini, S., Cassina, L., Carraro, M., Dina, G., Quattrini, A., Patanella, L., Carissimo, A., Iuliano, A., Santorelli, F., Codazzi, F., Grohovaz, F., Bernardi, P., Becchetti, A., & Casari, G. (2020). Impaired flickering of the permeability transition pore causes SPG7 spastic paraplegia. EBioMedicine, 61, 103050. https://doi.org/10.1016/j.ebiom.2020.103050
Zhang, Q., Bastard, P., Karbuz, A., Gervais, A., Tayoun, A. A., Aiuti, A., Belot, A., Bolze, A., Gaudet, A., Bondarenko, A., Spaan, A. N., Guennoun, A., Arias, A. A., Planas, A. M., Sediva, A., Shcherbina, A., Neehus, A. L., Puel, A., Froidure, A., … Casanova, J. L. (2022). Human genetic and immunological determinants of critical COVID-19 pneumonia. Nature. https://doi.org/10.1038/s41586-022-04447-0
