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Benedetto Grimaldi Write a Message

Senior Researcher TT (TT2)
Senior Researcher

Research Line

Molecular Medicine

Contacts

Via Morego 30
+39 010 71781 299

About

Dr. Benedetto Grimaldi obtained in 2001 the degree in Biological Science with a summa cum laude from the University of Rome “La Sapienza”.

After obtained a PhD in Genetics and Molecular Biology under the supervision of Dr. Paola Ballario (University of Rome, La Sapienza, Italy), an expert in the study of epigenetics and signal transduction, Dr. Grimaldi transitioned into a postdoctoral fellowship under the mentorship of Prof. Sassone-Corsi (University of California, Irvine, USA), a leader in the field of circadian clock, metabolism and epigenetics.

In 2011 Dr. Grimaldi joined the Drug Discovery and Development (D3) department at the Istituto Italiano di Tecnologia (IIT), where he began pursuing his own line of research focused on the study of “clock-related pathologies”, and on the identification and evaluation of novel molecules with “clock modulator” activity for therapeutic applications.

Some of his key findings are highlighted in a recent publication in the journal Oncogene (doi: 10.1038/onc.2014.203), and an invited author’s view in the journal Molecular and Cellular Oncology (doi: 10.4161/23723548.2014.965626). These works reported the first evidence that the pharmacological targeting of a circadian regulator may be a suitable anticancer strategy.

Projects

My current project is focused on the study of the links between clock factors and human pathologies, and on the identification and evaluation of novel molecules with “clock modulator” activity for therapeutic applications.
As an example, my group recently discovered that the circadian regulator REV-ERBβ is over-expressed in several tumor cells and it operates as a cytoprotective factors upon genetic and pharmacological autophagy inhibition. As a consequence, REV-ERBβ inhibition induces apoptosis in cancer cells exposed to autophagy suppressor molecules, such as the clinically relevant drug, chloroquine.

In addition, we identified a novel class of dual REV-ERB/autophagy inhibitor compounds that have a single-agent antitumor activity. This study is the first evidence that the pharmacological targeting of circadian regulators may be a suitable anticancer strategy.

My research activity is now focused on the identification of the molecular mechanism behind REV-ERBβ regulation in tumors and its cytoprotective action. Considering the increasing number of epidemiological evidences indicating an intimate link between circadian disruption and tumor development and progression, these studies will provide useful molecular and genetic insights on the circadian/cancer connection.

Selected Publications

Ercolani L, Ferrari A, De Mei C, Parodi C, Wade M, Grimaldi B (2015). Circadian clock: Time for novel anticancer strategies? Pharmacological Research 100 (2015) 288–295

http://authors.elsevier.com/a/1Rewi3jJHplxAW

 

Torrente E, Parodi C, Ercolani L, De Mei C, Ferrari A, Scarpelli R, Grimaldi B (2015). Synthesis and in Vitro Anticancer Activity of the First Class of Dual Inhibitors of REV-ERBβ and Autophagy. J Med Chem. 2015 Jul 2. [Epub ahead of print]

 

Grimaldi B (2014). Lysosomotropic REV-ERB antagonism: a metabolic connectionbetween circadian rhythm and autophagy may tell cancer cells “it’s time to die”. Molecular and Cellular Oncology. doi: 10.4161/23723548.2014.965626

 

De Mei C, Ercolani L, Parodi C, Veronesi M, Lo Vecchio C, Bottegoni G, Torrente E, Scarpelli R, Marotta R, Ruffili R, Wade M, Mattioli M, Reggiani A, Grimaldi B (2014). Dual inhibition of REV-ERBb and autophagy as a novel pharmacological approach to induce cytotoxicity in cancer cells. Oncogene (doi: 10.1038/onc.2014.203).
http://www.nature.com/onc/journal/vaop/ncurrent/full/onc2014203a.html

 

Hardman JA, Tobin DJ, Haslam IS, Farjo N, Farjo B, Al-Nuaimi Y, Grimaldi B, Paus R (2014). The Peripheral Clock Regulates Human Pigmentation. J Invest Dermatol. doi: 10.1038/jid.2014.442.



Al-Nuaimi Y, Hardman JA, Bíró T, Haslam IS, Philpott MP, Tóth BI, Farjo N, Farjo B, Baier G, Watson RE, Grimaldi B, Kloepper JE, Paus R. (2014) A Meeting of Two Chronobiological Systems: Circadian Proteins Period1 and BMAL1 Modulate the Human Hair Cycle Clock. J Invest Dermatol. 134:610-619.


Sahar S, Masubuchi S, Eckel-Mahan K, Vollmer S, Galla L, Ceglia N, Masri S, Barth TK, Grimaldi B, Oluyemi O, Astarita G, Hallows WC, Piomelli D, Imhof A, Baldi P, Denu JM, Sassone-Corsi P. (2014) Circadian Control of Fatty Acid Elongation by SIRT1 Protein-mediated Deacetylation of Acetyl-coenzyme A Synthetase 1.J Biol Chem. 289:6091-6097.


Bellet M.M., Deriu E. , Liu J.Z., Grimaldi B., Blaschitz C., Zeller M., Edwards R.A., Sahar S., Dandekar S., Baldi P., George M.D., Raffatellu M., Sassone-Corsi P. (2013) The circadian clock regulates the host response to Salmonella. Proc Natl Acad Sci USA110: 9897-9902.

Brenna A., Grimaldi B., Filetici P., Ballario P. (2012). Physical association of the WC-1 photoreceptor and the histone acetyltransferase NGF-1 is required for blue light signal transduction in Neurospora crassa. Mol Biol Cell. 23:3863-3872.

Grimaldi B, Bellet M.M., Katada S., Astarita G., Hirayama J., Amin R.H., Granneman J.G., Piomelli D., Leff T., Sassone-Corsi P. (2010) PER2 controls lipid metabolism by direct regulation of PPARγ. Cell Metab. 12: 509-520.

Grimaldi B., Nakahata Y., Kaluzova M., Masubuchi S., Sassone-Corsi P. (2009) Chromatin Remodeling, Metabolism and Circadian Clocks: The Interplay of CLOCK and SIRT1. Int J Biochem Cell Biol 41: 81-86.

Nakahata Y., Kaluzova M., Grimaldi B., Sahar S., Hirayama J., Chen D., Guarente G.P., Sassone-Corsi P. (2008) The NAD+- Dependent Deacetylase SIRT1 Modulates CLOCK-Mediated Chromatin Remodeling and Circadian Control. Cell 134: 329-340.

Grimaldi B., Nakahata Y., Sahar S., Kaluzova M., Gauthier D., Pham K., Patel N., Hirayama J., Sassone-Corsi P. (2007) Chromatin remodeling and circadian control: master regulator CLOCK is an enzyme. Cold Spring Harb Symp Quant Biol. 72: 105-112.

Hirayama J, Sahar S, Grimaldi B, Tamaru T, Takamatsu K, Nakahata Y, Sassone-Corsi P. (2007) CLOCK-mediated acetylation of BMAL1 controls circadian function. Nature 450: 1086-1090.

Grimaldi B, Sassone-Corsi P. (2007) Circadian rhythms: metabolic clockwork. Nature 447: 386-387.


Awards

PhD fellowship in Genetics and Molecular Biology from the Italian Centro Nazionale Ricerca (CNR), 2001-2005.

Mobility fellowship from the Italian Centro Nazionale Ricerca (CNR), 2004.

Post-doctoral fellowship from the Department of Cell and Developmental Biology, University of Rome (Italy), 2005.

Post-doctoral fellowships from the health care company Allergan Inc. (USA), 2009-2010.

Interdepartmental grant from the Istituto Italiano di Tecnologia, Genoa, Italy, 2012-2014.

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I numeri di IIT

L’Istituto Italiano di Tecnologia (IIT) è una fondazione di diritto privato - cfr. determinazione Corte dei Conti 23/2015 “IIT è una fondazione da inquadrare fra gli organismi di diritto pubblico con la scelta di un modello di organizzazione di diritto privato per rispondere all’esigenza di assicurare procedure più snelle nella selezione non solo nell’ambito nazionale dei collaboratori, scienziati e ricercatori ”.

IIT è sotto la vigilanza del Ministero dell'Istruzione, dell'Università e della Ricerca e del Ministero dell'Economia e delle Finanze ed è stato istituito con la Legge 326/2003. La Fondazione ha l'obiettivo di promuovere l'eccellenza nella ricerca di base e in quella applicata e di favorire lo sviluppo del sistema economico nazionale. La costruzione dei laboratori iniziata nel 2006 si è conclusa nel 2009.

Lo staff complessivo di IIT conta circa 1440 persone. L’area scientifica è rappresentata da circa l’85% del personale. Il 45% dei ricercatori proviene dall’estero: di questi, il 29% è costituito da stranieri provenienti da oltre 50 Paesi e il 16% da italiani rientrati. Oggi il personale scientifico è composto da circa 60 principal investigators, circa 110 ricercatori e tecnologi di staff, circa 350 post doc, circa 500 studenti di dottorato e borsisti, circa 130 tecnici. Oltre 330 posti su 1400 creati su fondi esterni. Età media 34 anni. 41% donne / 59 % uomini.

Nel 2015 IIT ha ricevuto finanziamenti pubblici per circa 96 milioni di euro (80% del budget), conseguendo fondi esterni per 22 milioni di euro (20% budget) provenienti da 18 progetti europei17 finanziamenti da istituzioni nazionali e internazionali, circa 60 progetti industriali

La produzione di IIT ad oggi vanta circa 6990 pubblicazioni, oltre 130 finanziamenti Europei e 11 ERC, più di 350 domande di brevetto attive, oltre 12 start up costituite e altrettante in fase di lancio. Dal 2009 l’attività scientifica è stata ulteriormente rafforzata con la creazione di dieci centri di ricerca nel territorio nazionale (a Torino, Milano, Trento, Parma, Roma, Pisa, Napoli, Lecce, Ferrara) e internazionale (MIT ed Harvard negli USA) che, unitamente al Laboratorio Centrale di Genova, sviluppano i programmi di ricerca del piano scientifico 2015-2017.

IIT: the numbers

Istituto Italiano di Tecnologia (IIT) is a public research institute that adopts the organizational model of a private law foundation. IIT is overseen by Ministero dell'Istruzione, dell'Università e della Ricerca and Ministero dell'Economia e delle Finanze (the Italian Ministries of Education, Economy and Finance).  The Institute was set up according to Italian law 326/2003 with the objective of promoting excellence in basic and applied research andfostering Italy’s economic development. Construction of the Laboratories started in 2006 and finished in 2009.

IIT has an overall staff of about 1,440 people. The scientific staff covers about 85% of the total. Out of 45% of researchers coming from abroad 29% are foreigners coming from more than 50 countries and 16% are returned Italians. The scientific staff currently consists of approximately 60 Principal Investigators110 researchers and technologists350 post-docs and 500 PhD students and grant holders and 130 technicians. External funding has allowed the creation of more than 330 positions . The average age is 34 and the gender balance proportion  is 41% female against 59% male.

In 2015 IIT received 96 million euros in public funding (accounting for 80% of its budget) and obtained 22 million euros in external funding (accounting for 20% of its budget). External funding comes from 18 European Projects, other 17 national and international competitive projects and approximately 60 industrial projects.

So far IIT accounts for: about 6990 publications, more than 130 European grants and 11 ERC grants, more than 350 patents or patent applications12 up start-ups and as many  which are about to be launched. The Institute’s scientific activity has been further strengthened since 2009 with the establishment of 11 research nodes throughout Italy (Torino, Milano, Trento, Parma, Roma, Pisa, Napoli, Lecce, Ferrara) and abroad (MIT and Harvard University, USA), which, along with the Genoa-based Central Lab, implement the research programs included in the 2015-2017 Strategic Plan.