Dr. Paolo Giacobini, Ph.D.

[email protected]
Group Leader (tenured) “Development & Plasticity of the Neuroendocrine Brain” Team, INSERM U1172
Ph.D. in Neuroscience, University of Turin, Italy & NIH, Bethesda, USA. 2005
M.Sc. in Molecular Biology, University of Turin, Italy. 1998
Paolo Giacobini obtained his Master in Science in Molecular Biology (1998) at the University of Torino, Italy, where he started studying the development of the olfactory/vomeronasal system in rodents. In 2005, he obtained a Ph.D Degree in Neuroscience from the University of Torino, working on the development and function of specialized neurons controlling reproduction in all vertebrates, namely the Gonadotropin Releasing Hormone Neurons (GnRH). The Ph.D was a graduate partnership program between Prof. Fasolo’s laboratory (Lab. Neurobiology, Dept. Human and Animal Biology, University of Torino, Italy) and Dr. Susan Wray’s laboratory at the National Institute of Neurological Strokes and Disorders (NINDS), National Institute of Health (NIH), Bethesda, USA, where he spent several years during his Ph.D and Post-Doctoral formation. In 2009 he was appointed Research Scientist and group leader at French National Institute of Health and Medical Research (INSERM, tenured position), Jean-Pierre Aubert Research Center, Lille, France.Dr Giacobini is currently an elected member of the Administrative Council of the French Neuroscience Society (Société des Neurosciences), discipline: Neuroendocrinology as well as a member of the Administrative Council of the French Neuroendocrine Society (Société de Neuroendocrinologie).Dr. Giacobini’s research group is interested in dissecting the molecular mechanisms underlying the migration, survival and structural/functional plasticity of GnRH neurons. Alterations in the development and or function of the GnRH system are associated with several reproductive disorders such as hypogonadotropic hypogonadism and polycystic ovary syndrome (PCOS).During the last 12 years, combining mouse genetics with cutting-edge imaging and molecular biology techniques, in vivo physiological manipulations, and translational clinical research, he has made important contributions in understanding GnRH neuron ontogeny/migration/plasticity and the neuroendocrine and gonadal control of human reproduction. His team is interested in dissecting the molecular mechanisms underlying normal and pathological development of the neuroendocrine GnRH system and to identify new therapeutic strategies to treat infertility in humans. Among infertility disorders, Dr. Giacobini is interested in understanding the neuroendocrine basis of PCOS which is the most common female reproductive disorder and occurs in up to 10% of all women. Infertility treatments of PCOS have heterogeneous and limited success and alternative and more efficient therapies are needed. Dr. Giacobini has recently been awarded an ERC-Consolidator Grant (2016, REPRODAMH) that will be focused on the central neuroendocrine abnormalities of PCOS leading to infertility and development of new potential therapeutic strategies.More recently Dr. Giacobini became also interested in using tissue-clearing techniques to study the 3D-organization of human fetal development. This project is a joint effort from the team of Dr. Giacobini and the team directed by Dr. Alain Chedotal (“Role of Axon Guidance Molecules”, Vision Institute in Paris, affiliated to INSERM, CNRS & UPMC University). Combining whole-mount immunostaining, 3DISCO clearing, and light-sheet imaging these two teams have started building a 3D cellular map of the human development during the first trimester of gestation (https://transparent-human-embryo.com/). The aim of this open-access project is to build a cutting-edge research consortium that will allow scientists and clinicians to implement our knowledge of human development and ontogenetic processes.

Free access to view data and short movies on GnRH development in humans, such as those seen below can be found here

A cellular atlas of human development can be found here

Selected Publications

Tata BK, Mimouni NEH, Barbotin AL, Malone SA, Loyens A, Pigny P, Dewailly D, Catteau-Jonard S, Sundström-Poromaa I, Piltonen TT, Dal Bello F, Medana C, Prevot V, Classadonte J, Giacobini P (2018) Elevated prenatal anti-Müllerian hormone reprograms the fetus and induces polycystic ovary syndrome in adulthood. Nature Medicine. 2018. DOI:10.1038/s41591-018-0035-5

Belle M, Godefroy D, Couly G, Malone SA, Collier F, Giacobini P, Chedotal A (2017)  Tridimensional Visualization and Analysis of Early Human Development. Cell. DOI: http://dx.doi.org/10.1016/j.cell.2017.03.008

Casoni F, Malone SA, Belle M, Luzzati L, Collier F, Allet C, Hrabovszky E, Rasika S, Prevot V, Chédotal A, Giacobini P (2016) Development of the Neurons Controlling Fertility in Humans: New Insights from 3D Imaging and Transparent Fetal Brains. Development DOI: 10.1242/dev.139444

Cimino I., Casoni F., Liu X., Messina A., Parkash J., Jamin S.P., Catteau-Jonard S. Collier F., Baroncini M., Dewailly D., Pigny P., Prescott M, Campbell R., Herbison A.E., Prevot V., Giacobini P. (2016) Novel Role for Anti-Müllerian Hormone in the Regulation of GnRH Neuron Excitability and Hormone Secretion. Nature Communications DOI: 10.1038/ncomms10055.

Boehm U., Bouloux P.M., Dattani M.T., de Roux N., Dodé C., Dunkel L., Dwyer A.A., Giacobini P., Hardelin JP., Juul A., Maghnie M., Pitteloud N., Prevot V., Raivio T., Tena-Sempere M., Quinton R. and Young J. (2015). European Consensus Statement on congenital hypogonadotropic hypogonadism—pathogenesis, diagnosis and treatment. Nature Reviews Endocrinology (doi:10.1038/nrendo.2015.112). Review article.

Parkash J., Messina A., Langlet F., Cimino I., Loyens A., Mazur D., Gallet S., Balland E., Malone S.A., Pralong F., Cagnoni G., Schellino R., De Marchis S., Mazzone M., Pasterkamp R.J., Tamagnone L., Prevot V., Giacobini P. (2015). Semaphorin7A regulates neuroglial plasticity at the adult hypothalamic median eminence. Nature Communications. DOI:10.1038/ncomms7385.

Giacobini P., Parkash J., Campagne C., Messina A., Casoni F., Vanacker C., Langlet F., Hobo B., Cagnoni G., Gallet S., Hanchate N.K., Mazur D., Taniguchi M., Mazzone M., Verhaagen J., Ciofi P., Bouret S.G., Tamagnone L., Prevot V. (2014). Brain Endothelial Cells Control Fertility through Ovarian- Steroid–Dependent Release of Semaphorin 3A. PLoS Biology DOI: 10.1371/journal.pbio.1001808. Weekly Editors’ pick. BPoD – Biomedical Picture of the Day (MRC Clinical Science Center, UK)

Parkash J., Cimino C., Ferraris N., Casoni F., Wray S., Cappy H, Prevot V., Giacobini P. (2012). Suppression of β1-Integrin in Gonadotropin-Releasing Hormone (GnRH) Cells Disrupts Migration and Axonal Extension Resulting in Severe Reproductive Alterations. The Journal of Neuroscience 32(47):16992–17002.

Hanchate N. K. *, Giacobini P. *, Lhuillier P., Parkash J., Espy C., Fouveaut C., Leroy C., Baron S., Campagne C., Vanacker C., Collier F., Cruaud C., Meyer V., García-Piñero A., Dewailly D., Cortet-Rudelli C., Gersak K., Metz C., Chabrier G., Pugeat M., Young J., Hardelin J.P., Prevot V., Dodé C (2012). SEMA3A, a gene involved in axonal pathfinding, is mutated in patients with Kallmann syndrome. PLoS Genetics 8(8): e1002896. * Equal contribution

Messina A., Ferraris N., Wray S., Cagnoni G., Donohue D.E., Casoni F., Kramer P.R., Derijck A.A.H., Adolfs Y., Fasolo A., Pasterkamp R.J., Giacobini P.* (2011) Dysregulation of Semaphorin7A/β1-integrin signaling leads to defective GnRH-1 cell migration, abnormal gonadal development and altered fertility in mice. Human Molecular Genetics 20(24):4759-74.

Giacobini P., Messina A., Morello F., Ferraris N., Corso S., Penachioni J., Giordano S., Tamagnone L., Fasolo A. (2008). Semaphorin 4D regulates gonadotropin hormone–releasing hormone-1 neuronal migration through PlexinB1–Met complex. The Journal of Cell Biology 183 (3): 555-566.

Ongoing Research Support

Awarded an ERC-Consolidator Grant: « Extra-gonadal roles of Anti-Müllerian Hormone in the aetiology of polycystic ovary syndrome: the domino effect to reproductive neuroendocrine dysfunctions ».

Federation pour la recherche sur le cerveau (FRC), “Espoir en tête” 2016, France. Title: Optical clearing and light-sheet laser-scanning ultramicroscopy: a powerful tool to study brain connectivity in physiological and pathological conditions.

ANR (French National Research Agency): RoSes and GnRH, Role: PI-Coordinator. Title: The role of semaphorin-signalling in the neuroendocrine control of reproduction. 2014-2017.

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