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Benedetto Grimaldi

Senior Researcher Tenure Track - Principal Investigator
Senior Researcher

Research Line

Molecular Medicine

Center

IIT Central Research Labs Genova

Contacts

Via Morego 30
+39 010 2896 299
Contact Me

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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