Luca Proietti De Santis

PRESENTATIONBorn in Viterbo, December 10th 1967. He got his master degree in 1994 and his PhD degree in Biological and Biochemical Evolution in 1999 at the University of Viterbo “Tuscia”. During his training he has worked as a Visiting Fellow at the National Institute on Aging-NIH at the Johns Hopkins University, Baltimore (USA), under the supervision of Dr. Vilhelm Bhor, where he started out some studies on the understanding of mechanisms of DNA repair and transcription, and the consequences of these defects in the patients. In 2002 he joined the group of Dr. Egly, in Strasbourg, a pioneeristic laboratory in the transcription field. Here, he has published a number of milestone papers that lead to a better understanding of the molecular basis of human syndromes such as xeroderma pigmentosum, trichothiodystrophy and Cockayne syndrome. Of note, he contributed to provide new insights into the understanding of the molecular basis associated to the action of CSB gene in either RNA polymerase I and RNA polymerase II basal and activated transcription (Bradsher et al., 2002; Proietti De Santis et al., 2006). Although these years in France have been successful and scientifically stimulating, encouraged by Prof. Egly, he decided to return to Italy to establish his own research group. Therefore, he applied for the governmental program “Brain Gain” (Rientro dei Cervelli), which sponsors reintegration of young scientists, after a prolonged period abroad, into the Italian research infrastructures. Eventually, he has obtained a contract which supports his salary for 3+1 years and in 2005 he has came back to Italy with the aim to start an independent unit at the University of Viterbo, where, a few years before, he spent part of his PhD program. There, He has continued his studies on Cockayne syndrome with the aim to deeply investigate the molecular mechanisms responsible of this disease. He has been awarded with several fellowships (EMBO, Poste Vert INSERM, FRM (Fondation de Recherche Medicale). At present, he is Associate Professor of Genetics of Aging and Longevity and Human genetic diseases courses at the Department of Ecology and Biology Sciences of the University of Viterbo – Italy. He is coordinating or has coordinated projects sponsored by Associazione Italiana per la Ricerca sul cancro (AIRC), Ministero per lo Sviluppo Economico (MISE), Telethon, and Fondazione per l’Avanzamento della Medicina Molecolare (FARMM). He is referee for several international journals. Expert of European Commission - 2009 and 2014.Research Area Main scientific interest is focussed on investigating the molecular mechanisms involved in DNA repair, transcription and genomic instability. In particular focus is placed on the study of three human diseases which are Xeroderma pigmentosum, Trichothiodistrophy and Cockayne syndrome and more generally on the role of DNA repair and transcription systems on aging and carcinogenesis. Employment and research experience1997/1998: Visiting Scientist in Molecular Biology (DNA repair) at the laboratory of Molecular Gerontology of NIH, Baltimore−USA. 1999/2001: Post−Doctoral Scientist in Genetics and Molecular Biology (Transcription and DNA repair) at the laboratory of Molecular Cytogenetics of the University of Viterbo−Italy. 2001−2005: Research Scientist at the IGBMC (Institut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch, France). Position funded by Institut National de la Santé et de la Recherche Médicale – (INSERM−France). 2005- 2009: lecturer in charge of Genetics of Aging and Longevity course at the Faculty of Mathematical, Physical and Natural Sciences of the University of Viterbo-Italy and coordinating the project linked to the “Brain Gain” governmental program, which sponsors reintegration of young scientists, after a prolonged period abroad, into the Italian research infrastructures. 2010-2015: he has been assistant professor at the the Faculty of Mathematical, Physical and Natural Sciences of the University of Viterbo-Italy 2015- at present: he is associate professor in Genetics at the Department od Ecological and Biological Sciences of the University of Viterbo-Italy 2017- at present: habilitation for full professor in Genetics. 2018 - at present: Director of Large Equipment Center at the University of Viterbo-Italy.PUBLICATIONSProietti De Santis L, Balzerano A, Prantera G (2018). CSB: An Emerging Actionable Target for Cancer Therapy. Trends Cancer vol. 4, p. 172-175.Epanchintsev A, Costanzo F, Rauschendorf MA, Caputo M, Ye T, Donnio LM, Proietti De Santis L, Coin F, Laugel V, Egly JM. (2017). Cockayne's Syndrome A and B Proteins Regulate Transcription Arrest after Genotoxic Stress by Promoting ATF3 Degradation. Mol. Cell 68(6):1054-1066.Caputo M, Balzerano A, Arisi I, D'Onofrio M, Brandi R, Bongiorni S, Brancorsini S, Frontini M, Proietti-De-Santis L. (2017) CSB ablation induced apoptosis is mediated by increased endoplasmic reticulum stress response. PLoS One 12(3):e0172399.Fabbretti F, Iannetti I, Guglielmi L, Perconti S, Evangelistella C, Proietti De Santis L, Bongiorni S, Prantera G. (2016) Confocal Analysis of Nuclear Lamina Behavior during Male Meiosis and Spermatogenesis in Drosophila melanogaster. PLoS One 11(3):e0151231.Nicolai S, Filippi S, Caputo M, Cipak L, Gregan J, Ammerer G, Frontini M, Willems D, Prantera G, Balajee AS, Proietti-De-Santis L. (2015) Identification of Novel Proteins Co- Purifying with Cockayne Syndrome Group B (CSB) Reveals Potential Roles for CSB in RNA Metabolism and Chromatin Dynamics. PLoS One 10(6):e0128558. Ciaffardini F, Nicolai S, Caputo M, Canu G, Paccosi E, Costantino M, Frontini M, Balajee AS, Proietti-De-Santis L. (2014) The cockayne syndrome B protein is essential for neuronal differentiation and neuritogenesis. Cell Death Dis. 2014 May 29;5:e1268. Caputo M, Frontini M, Velez-Cruz R, Nicolai S, Prantera G, Proietti-De-Santis L (2013). The CSB repair factor is overexpressed in cancer cells, increases apoptotic resistance, and promotes tumor growth. DNA Repair 12(4): 293-9. Botta G, Proietti-De-Santis L, Saladino R. (2012) Current advances in the synthesis and antitumoral activity of SIRT1-2 inhibitors by modulation of p53 and pro-apoptotic proteins. Curr. Med. Chem. 19(34):5871-84.Frontini M, and Proietti-De-Santis L. (2012) Interaction between the Cockayne syndrome group B and p53 proteins: implications for aging. Aging 4(2):89-97.Latini P, Frontini M, Caputo M, Gregan J, Cipak L, Filippi S, Kumar V, Vélez-Cruz R, Stefanini M, Proietti-De-Santis L. (2011) CSA and CSB proteins interact with p53 and regulate its Mdm2-dependent ubiquitination. Cell Cycle 10(21): 3719-30Ropolo M, Cappelli E, Foresta M, Poggi A, Proietti-De-Santis L, Frosina G. (2011) Defective resolution of pH2AX foci and enhanced DNA breakage in ionizing radiation-treated cockayne syndrome B cells. IUBMB Life 63(4) 272-6.Yanrong Su, Jarah A. Meador, Gloria M Calaf, Luca Proietti-De-Santis, Yongliang Zhao, Vilhelm A Bohr and Adayabalam S. Balajee. (2010) Human RecQL4 helicase plays critical roles in prostate carcinogenesis. Cancer Research 70(22): 9207-17.Frontini M and Proietti De Santis L. (2009) Cockayne syndrome B protein (CSB): linking p53, HIF-1 and p300 o robustness, lifespan, cancer and cell fate decisions. Cell Cycle 8 (5): 693-96.Lorenti Garcia C, Mechilli M, Proietti De Santis L, Schinoppi A, Kobos K, Palitti F. (2009). Mutat. Res. 662 (1-2): 3-9.Filippi S, Latini P, Frontini M, Palitti F, Egly JM and Proietti De Santis L. (2008). CSB protein is (a direct target of HIF-1 and) a critical mediator of the hypoxic response. EMBO J. 27 (19): 2545-56;D’Errico M, Lemma T, Calcagnile A, Proietti De Santis L and Dogliotti E. (2007) Cell type and DNA damage specific response of human skin cells to environmental agents. Mutat. Res. 614: 37-47.Proietti De Santis L, Drané P and Egly JM. (2006) Cockayne syndrome B protein regulates the transcriptional program of a specific subset of genes. EMBO J. 25(9):1915-23;Coin F, Proietti De Santis L, Zlobinskaya O, Nardo T, Stefanini M and Egly JM (2006) p8/TTD-A a TFIIH repair subunit. Mol. Cell 21(2):215-26.Le May N1, Dubaele S1, Proietti De Santis L1, Billecocq A, Bouloy M and Egly JM (2004). TFIIH transcription factor, a target for the Rift Valley hemorrhagic fever virus. Cell 116(4):541-50 1Have to be considered as first authors with equal contribution.Dubaele S, Proietti De Santis L, Bienstock RJ, Keriel A, Stefanini M, Van Houten B, and Egly JM (2003) Basal transcription defect discriminates between Xeroderma Pigmentosum and Trichothiodystrophy in XPD patients. Mol. Cell 11(6):1635-46.Proietti De Santis L, Balajee AS, Lorenti Garcia C, Pepe G, Worboys AM, and Palitti F (2003). Inhibition of p53, p21 and Bax by pifithrin-α does not affect UV induced apoptotic response in CS-B cells. DNA repair 2 (8) 891-900.D’Errico M, Teson M, Calcagnile A, Proietti De Santis L, Nikaido O, Botta E, Zambruno G, Stefanini M, and Dogliotti E (2003) Apoptotis and efficient repair of DNA damage protect human keratinocytes against UVB. Cell Death and Differentiation 10(6):754-6.Bradsher J, Auriol J, Proietti De Santis L, Iben S, Vonesch JL, Grummt I, and Egly JM (2002). CSB is a component of RNA Pol I Transcription. Mol. Cell 10, 819-829.Proietti De Santis L, Lorenti Garcia C, Balajee AS, Latini P, Pichierri P, Nikaido O, Stefanini M and Palitti F. (2002) Transcription Coupled Repair efficiency determines the cell cycle progression and apoptosis after UV exposure in Hamster cells. DNA repair 1(3) 209-23.Proietti De Santis L, Garcia CL, Balajee AS, Brea Calvo GT, Bassi L, Palitti F. (2001).Transcription coupled repair deficiency results in increased chromosomal aberrations and apoptotic death in the UV61 cell line, the Chinese hamster homologue of Cockayne's syndrome B. Mutat. Res. 485(2):121-32;Balajee AS, Proietti De Santis L, Brosh RM Jr, Selzer R, Bohr VA. (2000) Role of the ATPase domain of the Cockayne syndrome group B protein in UV induced apoptosis. Oncogene 19(4):477-89;Pichierri P, Franchitto A, Mosesso P, Proietti de Santis L, Balajee AS, Palitti F. (2000) Werner's syndrome lymphoblastoid cells are hypersensitive to topoisomerase II inhibitors in the G2 phase of the cell cycle. Mutat. Res. 459(2):123-33;Brosh RM Jr, Balajee AS, Selzer RR, Sunesen M, Proietti De Santis L, Bohr VA. (1999) The ATPase domain but not the acidic region of Cockayne syndrome group B gene product is essential for DNA repair. Mol. Biol. Cell. 10(11):3583-94;Franchitto A, Proietti De Santis L, Pichierri P, Mosesso P, Palitti F. (1999). Lack of effect of caffeine post-treatment on X-ray-induced chromosomal aberrations in Werner's syndrome lymphoblastoid cell lines: a preliminary report. Int. J. Radiat. Biol. 75(11):1349-55;Palitti F, Pichierri P, Franchitto A, Proietti De Santis L, Mosesso P. (1999). Chromosome radiosensitivity in human G2 lymphocytes and cell-cycle progression. Int. J. Radiat. Biol. 75(5):621-7;

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