Английская Википедия:Bruno Reversade

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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 Smart-Health Initiative Director and 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 and numerous diseases causing birth defects

Reversade's group has identified the following genes to be responsible for novel Mendelian diseases:

Year	Gene	Inheritance	Mendelian disease	Phenotype MIM number
2009	PYCR1	Recessive	Cutis laxa, autosomal recessive, type IIB (wrinkly skin syndrome)	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)	615225
2016	USP9X	Heterozygous	X-linked syndromic mental retardation 99	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	Mental retardation, 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	619127
2020	NUAK2	Recessive	Anencephaly 2	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, limb development, and various human diseases causing birth defects.

In 2005, during his Ph.D. thesis in the laboratory of Edward De Robertis, the scientists published two discoveries, pertaining to the self-regulation of an embryonic morphogenetic field mediated by the extracellular Chordin/BMP/Sizzled pathway. This helped provide a molecular framework for how embryos split in two halves can develop into perfect, albeit smaller, identical twinned embryos.

Reversade also researches the genetics of dizygotic and monozygotic twinning in humans. He has been searching for genes responsible for monozygotic (MZ) twinning from rare population isolates.

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.

Awards and recognition

• Society-in-Science Branco Weiss Fellowship (2007), ETH Zurich;
• Inaugural A*STAR Investigatorship award (2008), Agency for Science, Technology and Research;
• EMBO Young Investigator award (2012), European Molecular Biology Organization;
• AAA Fellow (2015), Vrije Universiteit Amsterdam;
• Senior NRF Investigator (2018), National Research Foundation, Government of Singapore.

External links

• Official web site