The research interest of my group is focused on the understanding of the contributions of genetic and genomic variation to rare genetic disorders.  In the last years, our activity was best known for the work on X-linked genes and recently we focused on NEMO/IKBKG gene that cause the incontinentia pigmenti (IP) disease, a rare multi-organ disorder. We conducted studies on the largest cohort of patients with Incontinentia Pigmenti establishing the extreme variability of disease presentation, the absence of genotype-phenotype correlation, and the role of cell death in the pathogenesis of the disease. The articles of my group have been influential works in the field of IP and other X-linked diseases.

We studied IP with a classical genetic approach coupled to the study of the multifaceted role of the NEMO protein that controls the activation of the NF-kB pathway and more in general cellular homeostasis. We use cutting-edge, synthetic biology and chemical biology to understand the role IP-associated NEMO mutations in the cell upon inflammatory cytokines triggering. This has led to the discovery of the novel components or novel role for known components of the cell death machinery, in particular related to the engagement of the TNF receptor1. We studied the effect of post-translation modifications of NEMO and of their interactors /regulators that can lead to different cellular and pathological outcomes in the cells of patients with IP.

Moreover, the genetic studies on IP through a personalized medicine approach have led my group to collaborate with hundreds of patients and their families. They were an invaluable source of extensive information that were collected, analyzed and used to improve and promote tailored cures. In this regard, during the COVID pandemic, we participated in a large consortium of scientists who demonstrated that the presence of self-neutralizing type I IFN antibody predisposes to severe COVID. We found that 40% of patients with IP had neutralizing self-abs versus the 0.3% in the control population.

1: Pescatore A, Spinosa E, Casale C, Lioi MB, Ursini MV and Fusco F Human genetic diseases linked to the absence of NEMO: an obligatory Somatic Mosaic Disorder in male Int. J. Mol. Sci. 2022 Feb.1, 23 (3):1179 doi.org/10.3390/ijms23031179

2: Asano T, Boisson B, Onodi F, Matuozzo D, Moncada-Velez M, Maglorius Renkilaraj MRL, Zhang P, Meertens L, Bolze A, Materna M, Korniotis S, Gervais A, Talouarn E, Bigio B, Seeleuthner Y, Bilguvar K, Zhang Y, Neehus AL, Ogishi M, Pelham SJ, Le Voyer T, Rosain J, Philippot Q, Soler-Palacín P, Colobran R, Martin-Nalda A, Rivière JG, Tandjaoui-Lambiotte Y, Chaïbi K, Shahrooei M, Darazam IA, Olyaei NA, Mansouri D, Hatipoğlu N, Palabiyik F, Ozcelik T, Novelli G, Novelli A, Casari G, Aiuti A, Carrera P, Bondesan S, Barzaghi F, Rovere- Querini P, Tresoldi C, Franco JL, Rojas J, Reyes LF, Bustos IG, Arias AA, Morelle G, Christèle K, Troya J, Planas-Serra L, Schlüter A, Gut M, Pujol A, Allende LM, Rodriguez-Gallego C, Flores C, Cabrera-Marante O, Pleguezuelo DE, de Diego RP, Keles S, Aytekin G, Akcan OM, Bryceson YT, Bergman P, Brodin P, Smole D, Smith CIE, Norlin AC, Campbell TM, Covill LE, Hammarström L, Pan-Hammarström Q, Abolhassani H, Mane S, Marr N, Ata M, Al Ali F, Khan T, Spaan AN, Dalgard CL, Bonfanti P, Biondi A, Tubiana S, Burdet C, Nussbaum R, Kahn-Kirby A, Snow AL; COVID Human Genetic Effort; COVID-STORM Clinicians; COVID Clinicians; Imagine COVID Group; French COVID Cohort Study Group; CoV-Contact Cohort; Amsterdam UMC Covid-; Biobank; NIAID-USUHS COVID Study Group, Bustamante J, Puel A, Boisson-Dupuis S, Zhang SY, Béziat V, Lifton RP, Bastard P, Notarangelo LD, Abel L, Su HC, Jouanguy E, Amara A, Soumelis V, Cobat A, Zhang Q, Casanova JL. X-linked recessive TLR7 deficiency in ~1% of men under 60 years old with life-threatening COVID-19. Sci Immunol. 2021 Aug 19;6(62):eabl4348. doi: 10.1126/sciimmunol.abl4348. PMID: 34413140; PMCID: PMC8532080.

3: Bastard P, Gervais A, Le Voyer T, Rosain J, Philippot Q, Manry J, Michailidis E, Hoffmann HH, 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, Luyt CE, Amador-Borrero B, Gaudet A, Poissy J, Morel P, Richard P, Cognasse F, Troya J, Trouillet-Assant S, Belot A, Saker K, Garçon P, Rivière JG, Lagier JC, Gentile S, Rosen LB, Shaw E, Morio T, Tanaka J, Dalmau D, Tharaux PL, Sene D, Stepanian A, Megarbane B, Triantafyllia V, Fekkar A, Heath JR, Franco JL, Anaya JM, Solé-Violán J, Imberti L, Biondi A, Bonfanti P, Castagnoli R, Delmonte OM, Zhang Y, Snow AL, Holland SM, Biggs C, Moncada-Vélez M, Arias AA, Lorenzo L, Boucherit S, Coulibaly B, Anglicheau D, Planas AM, Haerynck F, Duvlis S, Nussbaum RL, Ozcelik T, Keles S, Bousfiha AA, El Bakkouri J, Ramirez-SantanaC, Paul S, Pan-Hammarström Q, Hammarström L, Dupont A, Kurolap A, Metz CN, Aiuti A, Casari G, Lampasona V, Ciceri F, Barreiros LA, Dominguez-Garrido E, Vidigal M, Zatz M, van de Beek D, Sahanic S, Tancevski I, Stepanovskyy Y, Boyarchuk O, Nukui Y, Tsumura M, Vidaur L, Tangye SG, Burrel S, Duffy D, Quintana-Murci L, Klocperk A, Kann NY, Shcherbina A, Lau YL, Leung D, Coulongeat M, Marlet J, Koning R, Reyes LF, Chauvineau-Grenier A, Venet F, Monneret G, Nussenzweig MC, Arrestier R, Boudhabhay I, Baris-Feldman H, Hagin D, Wauters J, Meyts I, Dyer AH, Kennelly SP, Bourke NM, Halwani R, Sharif-Askari NS, Dorgham K, Sallette J, Sedkaoui SM, AlKhater S, Rigo-Bonnin R, Morandeira F, Roussel L, Vinh DC, Ostrowski SR, Condino-Neto A, Prando C, Bonradenko A, Spaan AN, Gilardin L, Fellay J, Lyonnet S, Bilguvar K, Lifton RP, Mane S; HGID Lab; COVID Clinicians; COVID-STORM Clinicians; NIAID Immune Response to COVID Group; NH-COVAIR Study Group; Danish CHGE; Danish Blood Donor Study; St. James's Hospital; SARS CoV2 Interest group; French COVID Cohort Study Group; Imagine COVID-Group; Milieu Intérieur Consortium; CoV-Contact Cohort; Amsterdam UMC Covid-19; Biobank Investigators; COVID Human Genetic Effort; CONSTANCES cohort; 3C-Dijon Study; Cerba Health-Care; Etablissement du Sang study group, Anderson MS, Boisson B, Béziat V, Zhang SY, Vandreakos E, Hermine O, Pujol A, Peterson P, Mogensen TH, Rowen L, Mond J, Debette S, de Lamballerie X, Duval X, Mentré F, Zins M, Soler- Palacin P, Colobran R, Gorochov G, Solanich X, Susen S, Martinez-Picado J, Raoult D, Vasse M, Gregersen PK, Piemonti L, Rodríguez-Gallego C, Notarangelo LD, Su HC, Kisand K, Okada S, Puel A, Jouanguy E, Rice CM, Tiberghien P, Zhang Q, Cobat A, Abel L, Casanova JL. Autoantibodies neutralizing type I IFNs are present in 4% of uninfected individuals over 70 years old and account for 20% of COVID-19 deaths. Sci Immunol. 2021 Aug 19;6(62):eabl4340. doi: 10.1126/sciimmunol.abl4340. PMID: 34413139; PMCID: PMC8521484.

4: Pescatore A, Casale C, Fusco F, Ursini MV. Methods to Study the Effect of IKK Inhibition on TNF-Inducing Apoptosis and Necroptosis in Cultured Cells. Methods Mol Biol. 2021;2366:243-254. doi: 10.1007/978-1-0716-1669-7_14. PMID: 34236642.

5: Bastard P, Rosen LB, Zhang Q, Michailidis E, Hoffmann HH, Zhang Y, Dorgham K, Philippot Q, Rosain J, Béziat V, Manry J, Shaw E, Haljasmägi L, Peterson P, Lorenzo L, Bizien L, Trouillet-Assant S, Dobbs K, de Jesus AA, Belot A, Kallaste A, Catherinot E, Tandjaoui-Lambiotte Y, Le Pen J, Kerner G, Bigio B, Seeleuthner Y, Yang R, Bolze A, Spaan AN, Delmonte OM, Abers MS, Aiuti A, Casari G, Lampasona V, Piemonti L, Ciceri F, Bilguvar K, Lifton RP, Vasse M, Smadja DM, Migaud M, Hadjadj J, Terrier B, Duffy D, Quintana-Murci L, van de Beek D, Roussel L, Vinh DC, Tangye SG, Haerynck F, Dalmau D, Martinez-Picado J, Brodin P, Nussenzweig MC, Boisson-Dupuis S, Rodríguez-Gallego C, Vogt G, Mogensen TH, Oler AJ, Gu J, Burbelo PD, Cohen JI, Biondi A, Bettini LR, D'Angio M, Bonfanti P, Rossignol P, Mayaux J, Rieux-Laucat F, Husebye ES, Fusco F, Ursini MV,

Imberti L, Sottini A, Paghera S, Quiros-Roldan E, Rossi C, Castagnoli R, Montagna D, Licari A, Marseglia GL, Duval X, Ghosn J; HGID Lab; NIAID-USUHS Immune Response to COVID Group; COVID Clinicians; COVID-STORM Clinicians; Imagine COVID Group; French COVID Cohort Study Group; Milieu Intérieur Consortium; CoV-Contact Cohort; Amsterdam UMC Covid-19 Biobank; COVID Human Genetic Effort, Tsang JS, Goldbach-Mansky R, Kisand K, Lionakis MS, Puel A, Zhang SY, Holland SM, Gorochov G, Jouanguy E, Rice CM, Cobat A, Notarangelo LD, Abel L, Su HC, Casanova JL. Autoantibodies against type I IFNs in patients with life-threatening COVID-19. Science. 2020 Oct 23;370(6515):eabd4585. doi: 10.1126/science.abd4585. Epub 2020 Sep 24. PMID: 32972996; PMCID: PMC7857397.

6: Zhang Q, Bastard P, Liu Z, Le Pen J, Moncada-Velez M, Chen J, Ogishi M, Sabli IKD, Hodeib S, Korol C, Rosain J, Bilguvar K, Ye J, Bolze A, Bigio B, Yang R, Arias AA, Zhou Q, Zhang Y, Onodi F, Korniotis S, Karpf L, Philippot Q, Chbihi M, Bonnet-Madin L, Dorgham K, Smith N, Schneider WM, Razooky BS, Hoffmann HH, Michailidis E, Moens L, Han JE, Lorenzo L, Bizien L, Meade P, Neehus AL, Ugurbil AC, Corneau A, Kerner G, Zhang P, Rapaport F, Seeleuthner Y, Manry J, Masson C, Schmitt Y, Schlüter A, Le Voyer T, Khan T, Li J, Fellay J, Roussel L, Shahrooei M, Alosaimi MF, Mansouri D, Al-Saud H, Al-Mulla F, Almourfi F, Al-Muhsen SZ, Alsohime F, Al Turki S, Hasanato R, van de Beek D, Biondi A, Bettini LR, D'Angio' M, Bonfanti P, Imberti L, Sottini A, Paghera S, Quiros-Roldan E, Rossi C, Oler AJ, Tompkins MF, Alba C, Vandernoot I, Goffard JC, Smits G, Migeotte I, Haerynck F, Soler-Palacin P, Martin-Nalda A, Colobran R, Morange PE, Keles S, Çölkesen F, Ozcelik T, Yasar KK, Senoglu S, Karabela ŞN, Rodríguez-Gallego C, Novelli G, Hraiech S, Tandjaoui-Lambiotte Y, Duval X, Laouénan C; COVID-STORM Clinicians; COVID Clinicians; Imagine COVID Group; French COVID Cohort Study Group; CoV-Contact Cohort; Amsterdam UMC Covid-19 Biobank; COVID Human Genetic Effort; NIAID-USUHS/TAGC COVID Immunity Group, Snow AL, Dalgard CL, Milner JD, Vinh DC, Mogensen TH, Marr N, Spaan AN, Boisson B, Boisson-Dupuis S, Bustamante J, Puel A, Ciancanelli MJ, Meyts I, Maniatis T, Soumelis V, Amara A, Nussenzweig M, García-Sastre A, Krammer F, Pujol A, Duffy D, Lifton RP, Zhang SY, Gorochov G, Béziat V, Jouanguy E, Sancho-Shimizu V, Rice CM, Abel L, Notarangelo LD, Cobat A, Su HC, Casanova JL. Inborn errors of type I IFN immunity in patients with life-threatening COVID-19. Science. 2020 Oct 23;370(6515):eabd4570. doi: 10.1126/science.abd4570. Epub 2020 Sep 24. PMID: 32972995; PMCID: PMC7857407.

7: Bodemer C, Diociaiuti A, Hadj-Rabia S, Robert MP, Desguerre I, Manière MC, de la Dure-Molla M, De Liso P, Federici M, Galeotti A, Fusco F, Fraitag S, Demily C, Taieb C, Ursini MV, El Hachem M, Steffann J. Multidisciplinary consensus recommendations from a European network for the diagnosis and practical management of patients with incontinentia pigmenti. J Eur Acad Dermatol Venereol. 2020 Jul;34(7):1415-1424. doi: 10.1111/jdv.16403. PMID:32678511

8: Verzella D, Pescatore A, Capece D, Vecchiotti D, Ursini MV, Franzoso G, Alesse E, Zazzeroni F. Life, death, and autophagy in cancer: NF-κB turns up everywhere. Cell Death Dis. 2020 Mar 30;11(3):210. doi: 10.1038/s41419-020-2399-y. PMID: 32231206; PMCID: PMC7105474.

9: Fusco F, Pescatore A, Steffann J, Bonnefont JP, De Oliveira J, Lioi MB, Ursini MV. Clinical utility gene card: for incontinentia pigmenti. Eur J Hum Genet. 2019 Dec;27(12):1894-1900. doi: 10.1038/s41431-019-0463-9. Epub 2019 Jul 9. PMID: 31289372; PMCID: PMC6871521.

10: Fusco F, Valente V, Fergola D, Pescatore A, Lioi MB, Ursini MV. The Incontinentia Pigmenti Genetic Biobank: study design and cohort profile to facilitate research into a rare disease worldwide. Eur J Hum Genet. 2019 Oct;27(10):1509-1518. doi: 10.1038/s41431-019-0451-0. Epub 2019 Jun 23. PMID: 31231133; PMCID: PMC6777495.

11: Cammarata-Scalisi F, Fusco F, Ursini MV. Incontinentia Pigmenti. Actas Dermosifiliogr (Engl Ed). 2019 May;110(4):273-278. English, Spanish. doi: 10.1016/j.ad.2018.10.004. Epub 2019 Jan 17. PMID: 30660327.

12: Scheuerle AE, Ursini MV. Incontinentia Pigmenti. 1999 Jun 8 [updated 2017 Dec 21]. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Mirzaa GM, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2022. PMID: 20301645.

13: Santoro A, Ciaglia E, Nicolin V, Pescatore A, Prota L, Capunzo M, Ursini MV, Nori SL, Bifulco M. The isoprenoid end product N6-isopentenyladenosine reduces inflammatory response through the inhibition of the NF-κB and STAT3 pathways in cystic fibrosis cells. Inflamm Res. 2018 Apr;67(4):315-326. doi: 10.1007/s00011-017-1123-6. Epub 2017 Dec 11. PMID: 29230506; PMCID: PMC5843674.

14: Romano R, Grasso F, Gallo V, Cirillo E, Prencipe R, Mamone G, Mollica C, Ursini MV, De Ville De Goyet J, Pignata C, Giardino G. A case of incontinentia pigmenti associated with congenital absence of portal vein system and nodular regenerative hyperplasia. Br J Dermatol. 2019 Mar;180(3):674-675. doi: 10.1111/bjd.17319. Epub 2018 Dec 2. PMID: 30328117.

15: Bal E, Laplantine E, Hamel Y, Dubosclard V, Boisson B, Pescatore A, Picard C, Hadj-Rabia S, Royer G, Steffann J, Bonnefont JP, Ursini VM, Vabres P, Munnich A, Casanova JL, Bodemer C, Weil R, Agou F, Smahi A. Lack of interaction between NEMO and SHARPIN impairs linear ubiquitination and NF-κB activation and leads to incontinentia pigmenti. J Allergy Clin Immunol. 2017 Dec;140(6):1671-1682.e2. doi: 10.1016/j.jaci.2016.11.056. Epub 2017 Feb 27. PMID: 28249776.

16: Fusco F, Conte MI, Diociaiuti A, Bigoni S, Branda MF, Ferlini A, El Hachem M, Ursini MV. Unusual Father-to-Daughter Transmission of Incontinentia Pigmenti Due to Mosaicism in IP Males. Pediatrics. 2017 Sep;140(3):e20162950. doi: 10.1542/peds.2016-2950. Epub 2017 Aug 9. PMID: 28794079.

17: Müller K, Courtois G, Ursini MV, Schwaninger M. New Insight Into the Pathogenesis of Cerebral Small-Vessel Diseases. Stroke. 2017 Feb;48(2):520-527. doi: 10.1161/STROKEAHA.116.012888. Epub 2017 Jan 12. PMID: 28082670.

18: Cuomo F, Coppola A, Botti C, Maione C, Forte A, Scisciola L, Liguori G, Caiafa I, Ursini MV, Galderisi U, Cipollaro M, Altucci L, Cobellis G. Pro- inflammatory cytokines activate hypoxia-inducible factor 3α via epigenetic changes in mesenchymal stromal/stem cells. Sci Rep. 2018 Apr 11;8(1):5842. doi: 10.1038/s41598-018-24221-5.

Bioskech

I am a biologist and have been working in the field of genetics for 30 years since my post-doc at the University of Lyon I in France and subsequently at the Federico II University of Naples, as research fellow at the NIH Lab. Biochemistry and then when in 1990 I joined the IGB-CNR as researcher. I am currently Research Director of the CNR and group leader of the Human Molecular Genetics laboratory and Contract professor of Human Genetics at the University of Basilicata. Most of my scientific activity has been devoted to the discovery of the genetic basis of rare human diseases and in recent years I have focused on studying the molecular basis of Incontinentia pigmenti (IP) a rare inflammatory disease caused by mutation in the NEMO/IKBKG gene.

My writing experience includes authoring or co-authoring more than 90 academic articles and books on human genetic diseases. Based on the research activity of my group I have patented a one-step kit for the molecular diagnosis of IP. This activity has made me a reference partner in a vast network of scientific and personal interactions with clinicians, scientists and patient’s families belonging to the international "Incontinentia Pigmenti community". I have established a long-standing partnership with patient associations from different countries (from Italy, France, the United States and recently Spain) and those foundations have awarded me with research grant over the past 15 years. Through ongoing interaction with patient organizations, my group and I have built a biobank of related samples and data that includes IP cases from 50 countries and is an invaluable means for future applications. I have received funding from national and international agencies and charities mostly for research on rare disease, including two coordinated grants from TELETHON, grants from Regione Campania and from non-profit foundations such as Banco Napoli, Banco Roma etc.

I have been Expert Reviewer among others for the European Union Commission for the Framework Projects 6 (FP6), the Institut Universitaire de France (IUF), the French National Research Agency (ARN), the Case Western Reserve University (US), the Agency for Health Quality and Assessment of Catalonia (AQuAS) and for MIUR.

I am member of the American Society of Human Genetics where I serve in the Digital Learning Committee. I have received numerous awards, including the most recent Paolo Limongelli award for the work done on COVID and fragile IP patients.