Dr michele petruzzelli
Position: Clinical Lecturer
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Human cancer develops as a localized focus of uncontrolled cell growth and subsequently progresses into systemic disease. Cancer research primarily focuses on the agents, events, and genetic alterations underlying tumor initiation, progression and metastasis. However, many cancer patients die because of cachexia, a systemic wasting disease caused by the tumor, but manifested by alterations in distant organs resulting in weight loss, fatigue, anemia, progressive atrophy of the white adipose tissue (WAT) and skeletal muscle. Systemic inflammation and metabolic dysfunction have been proposed as the major culprits in cachexia patho-physiology, but their chronological appearance and regulation remain elusive. I have recently shown that brown fat is prevalent in cachectic cancer patients (Petruzzelli M et al. Cell Metabolism 2014) and I now plan to investigate the cellular players and molecular events that drive the inflammatory response during cachexia.
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A switch from white to brown fat increases energy expenditure in cancer-associated cachexia. Petruzzelli M, Schweiger M, Schreiber R, Campos-Olivas R, Tsoli M, Allen J, Swarbrick M, Rose-John S, Rincon M, Robertson G, Zechner R, Wagner EF. Cell Metab. 2014 Sep 2;20(3):433-47. Selective activation of nuclear bile acid receptor FXR in the intestine protects mice against cholestasis. Modica S, Petruzzelli M, Bellafante E, Murzilli S, Salvatore L, Celli N, Di Tullio G, Palasciano G, Moustafa T, Halilbasic E, Trauner M, Moschetta A. Gastroenterology. 2012 Feb;142(2):355-65 Intestinal specific LXR activation stimulates reverse cholesterol transport and protects from atherosclerosis. Lo Sasso G, Murzilli S, Salvatore L, D'Errico I, Petruzzelli M, Conca P, Jiang ZY, Calabresi L, Parini P, Moschetta A. Cell Metab. 2010 Aug 4;12(2):187-93. Micellar lipid composition profoundly affects LXR-dependent cholesterol transport across CaCo2 cells. Petruzzelli M, Groen AK, van Erpecum KJ, Vrins C, van der Velde AE, Portincasa P, Palasciano G, van Berge Henegouwen GP, Lo Sasso G, Morgano A, Moschetta A. FEBS Lett. 2009 Apr 17;583(8):1274-80. Expression and localisation of insulin receptor substrate 2 in normal intestine and colorectal tumours. Regulation by intestine-specific transcription factor CDX2. Modica S, Morgano A, Salvatore L, Petruzzelli M, Vanier MT, Valanzano R, Esposito DL, Palasciano G, Duluc I, Freund JN, Mariani-Costantini R, Moschetta A. Gut. 2009 Sep;58(9):1250-9.