Bruno Reversade

Bruno Reversade (born 1978) is an American human geneticist and developmental biologist . He is a Director of the Institute of Molecular and Cellular Biology and the Genome Institute of Singapore at A*STAR (Singapore) and holds several faculty positions at other universities. Reversade is known for identifying mutated genes that cause Mendelian diseases, for his research on the genetics of identical twins and for the characterizations of novel hormones.

Early life and education Bruno Reversade was born in 1974 into a French-American family. He was raised in Grenoble (France) and Washington, D.C. (US). Bruno Reversade studied at the University Joseph Fourier, Pierre and Marie Curie University and UCLA.

Scientific career Reversade became interested in developmental biology in 1997 when studying at the University of Western Ontario (Canada) under the tutelage of Greg Kelly.

He earned his master's degree at the Pasteur Institute (Paris, France), where he studied head development in the mouse embryo. He then moved to the United States to work at the HHMI laboratory of Edward M. De Robertis at the University of California, Los Angeles. There he studied the specification of the dorsal-ventral axis during vertebrate development using Xenopus embryos. In 2005, Reversade and De Robertis detailed how multiple extracellular proteins allow embryos that are cut in two to self-regulate consistently.

In 2006, Reversade earned his PhD from the Pierre and Marie Curie University. In 2008, he received the A*STAR investigatorship (Singapore) award and set up his team in 2008 at the Institute of Medical Biology to carry out human embryology and genetic research. In 2015, he became a Director at A*STAR. Also in 2015, he received AAA Fellowship from the Vrije Universiteit Amsterdam and was appointed Professor of Human Genetics at the Centre for Reproductive Medicine at the university's Academic Medical Center. Since 2016, Reversade is a Distinguished Professor of Human Genetics at Koç University (Turkey). In 2023, Reversade became a bioscience Professor at KAUST in the Kingdom of Saudi Arabia.

Research areas Mendelian genetics Reversade's team works on the genetic characterization and clinical description of inherited conditions in humans.

They have identified mutations responsible for progeroid syndromes in humans, NLRP1 inflammasome-related diseases, self-healing cancers 614438 2010 CHSY1 Recessive Temtamy preaxial brachydactyly syndrome 605282 2011 TGFBR1 Dominant Multiple Self-healing Squamous Epithelioma (Fergurson-Smith disease) 132800 2012 IRX5 Recessive Hamamy syndrome 611174 2012 AAGAB Recessive Punctate palmoplantar keratoderma, type IA 148600 2014 KATNB1 Recessive Lissencephaly with Microcephaly 6 616212 2015 DCPS Recessive Al-Raqad syndrome 616459 2015 ALDH18A1 Dominant Dominant Cutis laxa type 3 616603 2016 NLRP1 Dominant Multiple self-healing palmoplantar carcinoma 615225 2016 NLRP1 Recessive familial keratosis lichenoides chronica (FKLC) 300968 2016 ELMO2 Recessive Primary intraosseous vascular malformation 606893 2017 ENPP1 Recessive Cole disease 615522 2017 CDK10 Recessive Al Kaissi syndrome 617694 2017 LGI4 Recessive Neurogenic Arthrogryposis multiplex congenita with myelin defect 617468 2017 KIAA1109 Recessive Alkuraya-Kucinskas syndrome 617822 2017 SMCHD1 Dominant Bosma arhinia microphthalmia syndrome 603457 2018 CAMK2A Recessive Intellectual disability, autosomal recessive 63 618095 2018 RSPO2 Recessive Tetraamelia syndrome with pulmonary agenesis 618021 2019 TBX4 Recessive PAPPA syndrome 601719 2019 NLRP1 Recessive Congenital juvenile recurrent respiratory papillomatosis (JRRP) 618803 2020 UGDH Recessive Jamuar Syndrome 603370 2020 MTX2 Recessive Mandibuloacral dysplasia progeroid syndrome 619452 2021 C2orf69 Recessive Elbracht-Işikay Syndrome 619423 2021 WLS Recessive Zaki Syndrome 619648 2021 CIROP Recessive Visceral heterotaxy-12 (HTX12) 619702 2022 DPP9 Recessive Hatipoğlu syndrome 608258 2022 FOCAD Recessive Severe Liver congenital disease 619991 2022 TMEM147 Recessive Neurodevelopmental disorder with facial dysmorphism & absent language 620075 2023 TAPT1 Recessive Lethal Osteochondrodysplasia 616897 2023 DRG1 Recessive Neurodevelopmental disorder 603952 2023 RAF1 Recessive Progeroid disease 164760

Developmental biology and Twinning Reversade's investigations in developmental biology have relied on various animal model organisms (C. elegans, Drosophila, zebrafish, Xenopus and transgenic mice) and covered such embryonic processes as neural induction, pertaining to the self-regulation of an embryonic morphogenetic field mediated by the extracellular Chordin/BMP/Sizzled pathway.

Reversade also researches the genetics of dizygotic and monozygotic twinning in humans.

In 2021, together with the VU Amsterdam, his group revealed that MZ twins harbor an epigenetic signature in their somatic tissue even decades after their birth. This stable DNA mark could be employed to retrospectively assess if a person is a MZ twin even if his/her co-twin vanished in utero.

Hormones and Micropeptides Reversade's research has also pioneered the annotation of novel micropeptides.

ELABELA In 2013, he discovered and patented a novel hormone named Elabela (ELA). This secreted circulating peptide works as an endogenous ligand for the Apelin receptor (a G protein-coupled receptor). The genetic inactivation of ELA leads to cardiovascular defects, predisposes to preeclampsia and is needed for the self-renewal of human embryonic stem cells. Analogues of Elabela have entered clinical trials by Amgen. BRAWNIN In 2020, he participated in the characterization of C12orf73, a protein-coding gene responsible for the making of a 71 amino-acid peptide called BRAWNIN. This small peptide is essential for respiratory chain complex III (CIII) assembly in human cells and zebrafish. C2orf69 In 2021, together with I. Kurth and colleagues, his team identified a fatal syndrome caused by the homozygous inactivation of C2orf69. This gene codes for a 385 amino-acid peptide which can be secreted or associated with mitochondria. C2ORF69 possesses homology to esterase/lipase enzymes. Inaugural A*STAR Investigatorship award (2008), Agency for Science, Technology and Research;