Bruno REVERSADE

Bruno REVERSADE

Senior Group Leader,
Laboratory of Human Genetics and Therapeutics

bruno_reversade@gis.a-star.edu.sg

 

 

RESEARCH

Over the last 10 years, a revolution in the speed and accessibility of high volume sequencing has introduced a paradigm shift in human genetics and regenerative medicine. Monogenic diseases – the human experiment – remains one of the most powerful tool for assigning function to our genes.

As such, our team has combined the power of Mendelian genetics, patient-derived iPSCs/organoids and animal modeling to decipher the aetiology of inherited disorders affecting development, metabolism, immunity, ageing, and familial cancers.

By identifying the genes responsible for transmitted diseases, the Reversade laboratory is best positioned to pinpoint the subverted biological pathways which not only underlie the pathology of a rare condition but which will, in many cases, reveal biological nodes whose perturbation contributes to more common pathologies – i.e. rare begets common.

A number of discoveries made by our team are being developed for diagnostic/ therapeutic purposes or have been licensed to pharmaceutical partners for clinical indications with unmet medical needs.

For more details you may visit the Laboratory's personal website: www.reversade.com

Selected Publications

  • Robinson KS, Teo DET, Tan KS, Toh GA, Ong HH, Lim CK, Lay K, Au BV, Lew TS, Chu JJH, Chow VTK, Wang Y, Zhong FL, Reversade B. "Enteroviral 3C protease activates the human NLRP1 inflammasome in airway epithelia." Science. 2020 Oct 22:eaay2002. doi: 10.1126/science.aay2002. Online ahead of print. Abstract
  • Elouej S, Harhouri K, Le Mao M, Baujat G, Nampoothiri S, Kayserili H, Menabawy NA, Selim L, Paneque AL, Kubisch C, Lessel D, Rubinsztajn R, Charar C, Bartoli C, Airault C, Deleuze JF, Rötig A, Bauer P, Pereira C, Loh A, Escande-Beillard N, Muchir A, Martino L, Gruenbaum Y, Lee SH, Manivet P, Lenaers G, Reversade B, Lévy N, De Sandre-Giovannoli A. "Loss of MTX2 causes mandibuloacral dysplasia and links mitochondrial dysfunction to altered nuclear morphology." Nat Commun. 2020 Sep 11;11(1):4589. doi: 10.1038/s41467-020-18146-9. Abstract
  • Bonnard C, Navaratnam N, Ghosh K, Chan PW, Tan TT, Pomp O, Ng AYJ, Tohari S, Changede R, Carling D, Venkatesh B, Altunoglu U, Kayserili H, Reversade B. "A loss-of-function NUAK2 mutation in humans causes anencephaly due to impaired Hippo-YAP signaling." J Exp Med. 2020 Dec 7;217(12):e20191561. doi: 10.1084/jem.20191561. Abstract
  • Escande-Beillard N, Loh A, Saleem SN, Kanata K, Hashimoto Y, Altunoglu U, Metoska A, Grandjean J, Ng FM, Pomp O, Baburajendran N, Wong J, Hill J, Beillard E, Cozzone P, Zaki M, Kayserili H, Hamada H, Shiratori H, Reversade B. "Loss of PYCR2 Causes Neurodegeneration by Increasing Cerebral Glycine Levels via SHMT2." Neuron. 2020 Jul 8;107(1):82-94.e6. doi: 10.1016/j.neuron.2020.03.028. Epub 2020 Apr 23. Abstract
  • Hengel H, Bosso-Lefèvre C, Grady G, Szenker-Ravi E, Li H, Pierce S, Lebigot É, Tan TT, Eio MY, Narayanan G, Utami KH, Yau M, Handal N, Deigendesch W, Keimer R, Marzouqa HM, Gunay-Aygun M, Muriello MJ, Verhelst H, Weckhuysen S, Mahida S, Naidu S, Thomas TG, Lim JY, Tan ES, Haye D, Willemsen MAAP, Oegema R, Mitchell WG, Pierson TM, Andrews MV, Willing MC, Rodan LH, Barakat TS, van Slegtenhorst M, Gavrilova RH, Martinelli D, Gilboa T, Tamim AM, Hashem MO, AlSayed MD, Abdulrahim MM, Al-Owain M, Awaji A, Mahmoud AAH, Faqeih EA, Asmari AA, Algain SM, Jad LA, Aldhalaan HM, Helbig I, Koolen DA, Riess A, Kraegeloh-Mann I, Bauer P, Gulsuner S, Stamberger H, Ng AYJ, Tang S, Tohari S, Keren B, Schultz-Rogers LE, Klee EW, Barresi S, Tartaglia M, Mor-Shaked H, Maddirevula S, Begtrup A, Telegrafi A, Pfundt R, Schüle R, Ciruna B, Bonnard C, Pouladi MA, Stewart JC, Claridge-Chang A, Lefeber DJ, Alkuraya FS, Mathuru AS, Venkatesh B, Barycki JJ, Simpson MA, Jamuar SS, Schöls L, Reversade B. "Loss-of-function mutations in UDP-Glucose 6-Dehydrogenase cause recessive developmental epileptic encephalopathy." Nat Commun. 2020 Jan 30;11(1):595. doi: 10.1038/s41467-020-14360-7. Abstract
  • Ding Z, Ericksen RE, Escande-Beillard N, Lee QY, Loh A, Denil S, Steckel M, Haegebarth A, Wai Ho TS, Chow P, Toh HC, Reversade B, Gruenewald S, Han W. "Metabolic pathway analyses identify proline biosynthesis pathway as a promoter of liver tumorigenesis." J Hepatol. 2020 Apr;72(4):725-735. doi: 10.1016/j.jhep.2019.10.026. Epub 2019 Nov 11. Abstract
  • Szenker-Ravi E, Altunoglu U, Leushacke M, Bosso-Lefèvre C, Khatoo M, Thi Tran H, Naert T, Noelanders R, Hajamohideen A, Beneteau C, de Sousa SB, Karaman B, Latypova X, Başaran S, Yücel EB, Tan TT, Vlaminck L, Nayak SS, Shukla A, Girisha KM, Le Caignec C, Soshnikova N, Uyguner ZO, Vleminckx K, 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. doi: 10.1038/s41586-018-0118-y. Epub 2018 May 16. Abstract
  • Yamauchi T, Masuda T, Canver MC, Seiler M, Semba Y, Shboul M, Al-Raqad M, Maeda M, Schoonenberg VAC, Cole MA, Macias-Trevino C, Ishikawa Y, Yao Q, Nakano M, Arai F, Orkin SH, Reversade B, Buonamici S, Pinello L, Akashi K, Bauer DE, Maeda T. "Genome-wide CRISPR-Cas9 Screen Identifies Leukemia-Specific Dependence on a Pre-mRNA Metabolic Pathway Regulated by DCPS." Cancer Cell. 2018 Mar 12;33(3):386-400.e5. doi: 10.1016/j.ccell.2018.01.012. Epub 2018 Feb 22. Abstract
  • Ho L, van Dijk M, Chye STJ, Messerschmidt DM, Chng SC, Ong S, Yi LK, Boussata S, Goh GH, Afink GB, Lim CY, Dunn NR, Solter D, Knowles BB, Reversade B. "ELABELA deficiency promotes preeclampsia and cardiovascular malformations in mice." Science. 2017 Aug 18;357(6352):707-713. doi: 10.1126/science.aam6607. Epub 2017 Jun 29. Abstract
  • Gordon CT, Xue S, Yigit G, Filali H, Chen K, Rosin N, Yoshiura KI, Oufadem M, Beck TJ, McGowan R, Magee AC, Altmüller J, Dion C, Thiele H, Gurzau AD, Nürnberg P, Meschede D, Mühlbauer W, Okamoto N, Varghese V, Irving R, Sigaudy S, Williams D, Ahmed SF, Bonnard C, Kong MK, Ratbi I, Fejjal N, Fikri M, Elalaoui SC, Reigstad H, Bole-Feysot C, Nitschké P, Ragge N, Lévy N, Tunçbilek G, Teo AS, Cunningham ML, Sefiani A, Kayserili H, Murphy JM, Chatdokmaiprai C, Hillmer AM, Wattanasirichaigoon D, Lyonnet S, Magdinier F, Javed A, Blewitt ME, Amiel J, Wollnik B, Reversade B. "De novo mutations in SMCHD1 cause Bosma arhinia microphthalmia syndrome and abrogate nasal development." Nat Genet. 2017 Feb;49(2):249-255. doi: 10.1038/ng.3765. Epub 2017 Jan 9. Abstract