Dr Gloria Bonuccelli

Research Associate Fellow

  • Cockcroft Building 203a
  • T: None
  • E: G.Bonuccelli@salford.ac.uk

Office Times

9:00am - 5:00pm

Biography

I am currently a Research Associate Fellow at the University of Salford in the School of Environment and Life Sciences. I earned my degree in Biology in Italy at the University of Genoa, discussing a thesis in pharmacology (1992). I also hold a PhD in Applied Genetics from the University of Pavia, Italy (1996-1999).  In this first stage of my career, I developed an extensive background and qualifications in pharmacology, molecular biology and genetics.

I worked for several years with Prof. Rosanna Gatti and Dr. Mirella Filocamo focused on the genetic and biochemical diagnosis of metabolic diseases, at the Gaslini Hospital in Genoa, Italy. During my time at the Gaslini Hospital, I also worked with Prof. Carlo Minetti, Director of the Department of Paediatric Neurology and Muscular Dystrophy. 

In the next stage of my career, I went abroad to study in the United States. From 2001 to 2006, I worked as a Post-doctoral Fellow in New York City at The Albert Einstein College of Medicine, within the Department of Molecular Pharmacology. I used experimental and pre-clinical models of muscular dystrophy to evaluate the pharmacological and therapeutics efficacy of proteasome inhibitors. During this time, I also worked on the role of caveolin proteins in human breast cancer. 

In 2006, I moved to Thomas Jefferson University (TJU), Philadelphia, USA, where I worked, until 2011. While at TJU and the Kimmel Cancer Center (KCC), I was first appointed as an Instructor and shortly thereafter promoted to the rank Assistant Professor. During this period, continued to work in the field of Oncology research, focusing on the metabolic features of cancer cells and cancer stem cells (CSCs) and the cross-talk between mesenchymal cells and tumor cells.

Ultimately, I decided to move back to Europe in 2011. I was recruited to the University of Bologna, where I worked with Prof. Baldini, in the field of Osteo-sarcoma research and therapy. Then, in 2014, I accepted a new position in the United Kingdom, joining the University of Manchester, as an Experimental Officer.

Finally, in February 2017, I started my current position, working in Greater Manchester at the University of Salford, with Prof. Michael P. Lisanti, Chair of Translational Medicine. In the Lisanti laboratory, my work will be focused on the identification and validation of new potential therapies for targeting the metabolic vulnerabilities of CSCs. 

Research Interests

My specific research interests are related to studying the key metabolic features of cancer cells and cancer stem cells, with a focus on drug discovery (natural products and the re-purposing of existing FDA-approved therapies, such as antibiotics).

My overall goal is to target the metabolic differences between cancer cells and normal cells, elucidating novel anticancer therapeutic approaches.

Qualifications and Memberships

PhD in Applied Genetics

2008 - Present   Member of Editorial Board, American Journal of Pathology

Publications

Publications, peer reviewed:

I have over 50 publications in peer-reviewed journals. My H-index is 29, with more than 2,732 citations, of which 1792 have occurred since 2012 (Scopus).

B Ozsvari, M Fiorillo, G Bonuccelli, AR Cappello, L Frattaruolo, F Sotgia, R Trowbridge, foster R, MP Lisanti. Mitoriboscins: Mitochondrial-based therapeutics targeting cancer stem cells (CSCs), bacteria and pathogenic yeast. Oncotarget 2017. In Press.

EM De Francesco, G Bonuccelli, M Maggiolini, F Sotgia, MP Lisanti. Vitamin C and Doxycycline: A synthetic lethal combination therapy targeting metabolic flexibility in cancer stem cells (CSCs). Oncotarget 2017. In Press.

Bonuccelli G, De Francesco EM, de Boer R, Tanowitz HB, Lisanti MP. NADH autofluorescence, a new metabolic biomarker for cancer stem cells: Identification of Vitamin C and CAPE as natural products targeting "stemness". Oncotarget. 2017 Mar 28;8(13):20667-20678.

Bonuccelli G, Peiris-Pages M, Ozsvari B, Martinez-Outschoorn UE, Sotgia F, Lisanti MP. Targeting cancer stem cell propagation with palbociclib, a CDK4/6 inhibitor: Telomerase drives tumor cell heterogeneity. Oncotarget. 2017 Feb 7;8(6):9868-9884.

Cortini M, Massa A, Avnet S, Bonuccelli G, Baldini N. Tumor-Activated Mesenchymal Stromal Cells Promote Osteosarcoma Stemness and Migratory Potential via IL-6 Secretion. PLoS One. 2016 Nov 16;11(11).

Chano T, Avnet S, Kusuzaki K, Bonuccelli G, Sonveaux P, Rotili D, Mai A, Baldini N. Tumour-specific metabolic adaptation to acidosis is coupled to epigenetic stability in    osteosarcoma cells. Am J Cancer Res. 2016 Mar 15;6(4):859-75.

Lamb R, Bonuccelli G, Ozsvári B, Peiris-Pagès M, Fiorillo M, Smith DL, Bevilacqua G, Mazzanti CM, McDonnell LA, Naccarato AG, Chiu M, Wynne L, Martinez-Outschoorn UE, Sotgia F, Lisanti MP. Mitochondrial mass, a new metabolic biomarker for stem-like cancer cells: Understanding WNT/FGF-driven anabolic signaling. Oncotarget. 2015 Oct 13;6(31):30453-71. doi: 10.18632/oncotarget.5852.

Perut F, Carta F, Bonuccelli G, Grisendi G, Di Pompo G, Avnet S, Sbrana FV, Hosogi S, Dominici M, Kusuzaki K, Supuran CT, Baldini N. Carbonic anhydrase IX inhibition is an effective strategy for osteosarcoma treatment. Expert Opin Ther Targets. 2015;19(12):1593-605. doi: 10.1517/14728222.2016.1086339. Epub 2015 Sep 10.

Lamb R, Ozsvari B, Bonuccelli G, Smith DL, Pestell RG, Martinez-Outschoorn UE, Clarke RB, Sotgia F, Lisanti MP. Dissecting tumor metabolic heterogeneity: Telomerase and large cell size metabolically define a sub-population of stem-like, mitochondrial-rich, cancer cells. Oncotarget. 2015 Sep 8;6(26):21892-905.

Salerno M, Avnet S, Bonuccelli G, Hosogi S, Granchi D, Baldini N. Impairment of lysosomal activity as a therapeutic modality targeting cancer stem cells of embryonal rhabdomyosarcoma cell line RD. PLoS One. 2014 Oct 20;9(10):e110340. doi: 10.1371/journal.pone.0110340.

Bonuccelli G, Avnet S, Grisendi G, Salerno M, Granchi D, Dominici M, Kusuzaki K, Baldini N. Role of mesenchymal stem cells in osteosarcoma and metaboli reprogramming of tumor cells. Oncotarget. 2014 Sep 15;5(17):7575-88.

Salerno M, Avnet S, Bonuccelli G, Eramo A, De Maria R, Gambarotti M, Gamberi G, Baldini N. Sphere-forming cell subsets with cancer stem cell properties in human musculoskeletal sarcomas. Int J Oncol. 2013 Jul;43(1):95-102.

Araujo KP, Bonuccelli G, Duarte CN, Gaiad TP, Moreira DF, Feder D, Belizario JE, Miglino MA, Lisanti MP, Ambrosio CE. Bortezomib (PS-341) treatment decreases inflammation and partially rescues the expression of the dystrophin glycoprotein complex in GRMD dogs. PLoS One. 2013 Apr 8;8(4):e61367.

Avnet S, Di Pompo G, Lemma S, Salerno M, Perut F, Bonuccelli G, Granchi D, Zini N, Baldini N. V-ATPase is a candidate therapeutic target for Ewing sarcoma.Biochim Biophys Acta. 2013 Aug;1832(8):1105-16.

Trimmer C, Bonuccelli G, Katiyar S, Sotgia F, Pestell RG, Lisanti MP, Capozza F. Cav1 suppresses tumor growth and metastasis in a murine model of cutaneous SCC through modulation of MAPK/AP-1 activation. Am J Pathol. 2013 Mar;182(3):992-1004.

Bonuccelli G, Castello-Cros R, Capozza F, Martinez-Outschoorn UE, Lin Z, Tsirigos A, Xuanmao J, Whitaker-Menezes D, Howell A, Lisanti MP, Sotgia F. The milk protein α-casein functions as a tumor suppressor via activation of STAT1 signaling, effectively preventing breast cancer tumor growth and metastasis. Cell Cycle. 2012 Nov 1;11(21):3972-82.

Carito V, Bonuccelli G, Martinez-Outschoorn UE, Whitaker-Menezes D, Caroleo MC, Cione E, Howell A, Pestell RG, Lisanti MP, Sotgia F. Metabolic remodeling of the tumor microenvironment: migration stimulating factor (MSF) reprograms myofibroblasts toward lactate production, fueling anabolic tumor growth. Cell Cycle. 2012 Sep 15;11(18):3403-14.

Capparelli C, Guido C, Whitaker-Menezes D, Bonuccelli G, Balliet R, Pestell TG, Goldberg AF, Pestell RG, Howell A, Sneddon S, Birbe R, Tsirigos A, Martinez-Outschoorn U, Sotgia F, Lisanti MP. Autophagy and senescence in cancer-associated fibroblasts metabolically supports tumor growth and metastasis via glycolysis and ketone production. Cell Cycle. 2012 Jun 15;11(12):2285-302.

Salem AF, Bonuccelli G, Bevilacqua G, Arafat H, Pestell RG, Sotgia F, Lisanti MP. Caveolin-1 promotes pancreatic cancer cell differentiation and restores membranous E-cadherin via suppression of the epithelial-mesenchymal transition. Cell Cycle. 2011 Nov 1;10(21):3692-700.

Remedios Castello-Cros, Gloria Bonuccelli, Alex Molchansky, Franco Capozza, Agnieszka K. Witkiewicz, Ruth C. Birbe, Anthony Howell, Richard G. Pestell, Diana Whitaker-Menezes, Federica Sotgia and Michael P. Lisanti. Matrix remodeling stimulates stromal autophagy, “fueling” cancer cell mitochondrial metabolism and metastasis. Cell Cycle. Jun 15 ;10(12):2021-34.

Martinez-Outschoorn UE, Whitaker-Menezes D, Pavlides S, Chiavarina B, Bonuccelli G, Casey T, Tsirigos A, Migneco G, Witkiewicz A, Balliet R, Mercier I, Wang C, Flomenberg N, Howell A, Lin Z, Caro J, Pestell RG, Sotgia F, Lisanti MP. The autophagic tumor stroma model of cancer or "battery-operated tumor growth": A simple solution to the autophagy paradox. Cell Cycle. 2010 Nov;9(21):4297-306.

Trimmer C, Whitaker-Menezes D, Bonuccelli G, Milliman JN, Daumer KM, Aplin AE, Pestell RG, Sotgia F, Lisanti MP, Capozza F. CAV1 inhibits metastatic potential in melanomas through suppression of the integrin/Src/FAK signaling pathway. Cancer Res. 2010 Oct 1;70(19):7489-99.

Bonuccelli G, Tsirigos A, Whitaker-Menezes D, Pavlides S, Pestell RG, Chiavarina B, Frank PG., Flomenberg N, Howell A, Martinez-Outschoorn UE, Sotgia F, Lisanti MP. Ketones and lactate "fuel" tumor growth and metastasis: Evidence that epithelial cancer cells use oxidative mitochondrial metabolism. Cell Cycle. 2010 Sep;9(17):3506-14.

Bonuccelli G, Whitaker-Menezes D, Castello-Cros R, Pavlides S, Pestell RG, Fatatis A, Witkiewicz AK, Heiden MG, Migneco G, Chiavarina B, Frank PG, Capozza F, Flomenberg N, Martinez-Outschoorn UE, Sotgia F, Lisanti MP. The reverse Warburg Effect: Glycolysis inhibitors prevent the tumor promoting effects of caveolin-1 deficient cancer associated fibroblasts. Cell Cycle. 2010 Dec 14;9(10):1960-71.

Gazzerro E, Assereto S, Bonetto A, Sotgia F, Scarfì S, Pistorio A, Bonuccelli G, Cilli M, Bruno C, Zara F, Lisanti MP, Minetti C. Therapeutic potential of proteasome inhibition in Duchenne and Becker muscular dystrophies. Am J Pathol. 2010 Apr;176(4):1863-77.

Gu L, Dagvadorj A, Lutz J, Leiby B, Bonuccelli G, Lisanti MP, Addya S, Fortina P, Dasgupta A, Hyslop T, Bubendorf L, Nevalainen MT. Transcription Factor Stat3 Stimulates Metastatic Behavior of Human Prostate Cancer Cells In Vivo, whereas Stat5b Has a Preferential Role in the Promotion of Prostate Cancer Cell Viability and Tumor Growth. Am J Pathol. 2010 Apr;176(4):1959-72.

Witkiewicz AK, Casimiro MC, Dasgupta A, Mercier I, Wang C, Bonuccelli G, Jasmin JF, Frank PG, Pestell RG, Kleer CG, Sotgia F, Lisanti MP. Toward a new stromal-based classification system for human breast cancer prognosis and therapy. Cell Cycle. 2009 Jun 1;8(11):1654-8.

Bonuccelli G, Casimiro MC, Sotgia F, Wang C, Liu M, Katiyar S, Capozza F, Daumer K, Alpy F, Rio MC, Tomasetto C, Mercier  I, Frank PG, Pestell RG, Michael P. Lisanti. Caveolin-1 (P132L), A Common Breast Cancer Mutation, Confers Mammary Cell Invasiveness and Defines a Novel Metastasis-Associated Gene Signature. Am J Pathol. 2009 May;174(5) :1650-62.

Mercier I, Bryant KG, Sotgia F, Bonuccelli G, Witkiewicz AK, Dasgupta A, Jasmin JF, Pestell RG, Lisanti MP. Using Caveolin-1 epithelial immunostaining patterns to stratify human breast cancer patients  and predict the Caveolin-1 (P132L) mutation. Cell Cycle. 2009 May 26;8(9).

Mercier I, Casimiro MC, Zhou J, Wang C, Plymire C, Bryant KG, Daumer KM, Sotgia F, Bonuccelli G, Witkiewicz AK, Lin J, Tran TH, Milliman J, Frank PG, Jasmin JF, Rui H, Pestell RG, Lisanti MP. Genetic ablation of caveolin-1 drives estrogen-hypersensitivity and the development of DCIS-like mammary lesions. Am J Pathol. 2009 Apr;174(4):1172-9.

Sotgia F, Del Galdo F, Casimiro MC, Bonuccelli G, Mercier I, Whitaker-Menezes D, Daumer KM, Zhou J, Wang C, Katiyar S, Xu H, Bosco E, Quong AA, Aronow B, Witkiewicz AK, Minetti C, Frank PG, Jimenez SA, Knudsen ES, Pestell RG, Lisanti MP. Caveolin-1-/- null mammary stromal fibroblasts share characteristics with human breast cancer-associated fibroblasts. Am J Pathol. 2009 Mar;174(3):746-61.

Sotgia F, Casimiro MC, Bonuccelli G, Liu M, Menezes D, Er O, Daumer KM, Mercier I, Witkiewicz AK, Minetti C, Capozza F, Rui H, Frank PG, Millimam J, Knudsen ES, Zhou J, Wang C, Pestell RG, Lisanti MP. 2008. Loss of Caveolin-3 Induces a Lactogenic Microenvironment that is Protective Against Mammary Tumor Formation. Am J Pathol. 2009 Feb;174(2):613-29.

Abdulghani J, Gu L, Daqvadory A, Lutz J, Leiby B, Bonuccelli G, Lisanti MP, Zellweger T, Alanen K, Mirtti T, Visakorpi T, Bubendorf L, Nevalainen MT. Stat3 promotes metastatic progression of prostate cancer. Am J Pathol. Jun 2008; 172(6) :1717-28.

Mercier I, Casimiro MC, Wang C, Rosenberg AL, Quong J, Minkeu A, Allen KG, Danilo C, Sotgia F, Bonuccelli G, Jasmin JF, Xu H, Bosco E, Aronow B, Witkiewicz A, Pestell RG, Knudsen ES, Lisanti MP. Human breast cancer-associated fibroblasts (CAFs) show caveolin-1 downregulation and RB tumor suppressor functional inactivation: Implications for the response to hormonal therapy. Cancer Biol Ther. 2008 Aug;7(8):1212-25.

Bonuccelli G, Sotgia F, Capozza F, Gazzerro E, Minetti C, Lisanti MP. Localized treatment    with a novel FDA-approved proteasome inhibitor blocks the degradation of dystrophin and dystrophin-associated proteins in mdx mice. Cell Cycle. May 2007;6(10):1242-1248.

Muehlbauer SM, Evering TH, Bonuccelli G, et al. Anthrax lethal toxin kills macrophages in a strain-specific manner by apoptosis or caspase-1-mediated necrosis. Cell Cycle. Mar 15 2007;6(6):758-766.

Schubert W, Sotgia F, Cohen AW, Capozza F, Bonuccelli G, Bruno C, Minetti C, Bonilla E, Dimauro S, Lisanti MP. Caveolin-1(-/-)- and caveolin-2(-/-)-deficient mice both display numerous skeletal muscle abnormalities, with tubular aggregate formation. Am J Pathol. Jan 2007;170(1):316-333.

Sotgia F, Rui H, Bonuccelli G, Mercier I, Pestell RG, Lisanti MP. Caveolin-1, mammary stem cells, and estrogen-dependent breast cancers. Cancer Res. Nov 15 2006;66(22):10647-10651.

Williams TM, Sotgia F, Lee H, Hassan G, Di Vizio D, Bonuccelli G, Capozza F, Mercier I, Rui, Pestell RG, Lisanti MP. Stromal and epithelial caveolin-1 both confer a protective effect against mammary hyperplasia and tumorigenesis: Caveolin-1 antagonizes cyclin D1 function in mammary epithelial cells. Am J Pathol. Nov 2006;169(5):1784-1801.

Medina FA, de Almeida CJ, Dew E, Li J, Bonuccelli G, Williams TM, Cohen AW, Pestell RG, Frank PG, Tanowitz HB, Lisanti MP. Caveolin-1-deficient mice show defects in innate immunity and inflammatory immune response during Salmonella enterica serovar Typhimurium infection. Infect Immun. Dec 2006;74(12):6665-6674.

Assereto S, Stringara S, Sotgia F, Bonuccelli G, Broccolini A, Pedemonte M, Traverso M, Biancheri R, Zara F, Bruno C, Lisanti MP, Minetti C. Pharmacological rescue of the dystrophin-glycoprotein complex in Duchenne and Becker skeletal muscle explants by proteasome inhibitor treatment. Am J Physiol Cell Physiol. Feb 2006;290(2):C577-582.

Hotchkiss KA, Basile CM, Spring SC, Bonuccelli G, Lisanti MP, Terman BI. TEM8 expression stimulates endothelial cell adhesion and migration by regulating cell-matrix interactions on collagen. Exp Cell Res. Apr 15 2005;305(1):133-144.

Bonuccelli G, Sotgia F, Frank PG, Williams TM, De Almeida CJ, Tanowitz HB, Scherer PE, Hotchkiss KA, Terman BI, Rollman B, Alileche A, Brojatsch J, Lisanti MP. ATR/TEM8 is highly expressed in epithelial cells lining Bacillus anthracis' three sites of entry: implications for the pathogenesis of anthrax infection. Am J Physiol Cell Physiol. Jun 2005;288(6):C1402-1410.

Sotgia F, Bonuccelli G, Minetti C, Woodman SE, Capozza F, Kemp RG, Scherer PE, and Lisanti MP. Phosphofructokinase muscle-specific isoform requires caveolin-3 expression for plasma membrane recruitment and caveolar targeting: implications for the pathogenesis of caveolin-related muscle diseases. Am J Pathol. Dec 2003;163(6):2619-2634.

Bonuccelli G, Sotgia F, Schubert W, Park DS, Frank PG, Woodman SE, Insabato L, Cammer M, Minetti C, and Lisanti MP. Proteasome inhibitor (MG-132) treatment of mdx mice rescues the expression and membrane localization of dystrophin and dystrophin-associated proteins. Am J Pathol. Oct 2003;163(4):1663-1675.

Sotgia F, Woodman SE, Bonuccelli G, Capozza F, Minetti C, Scherer PE, and Lisanti MP. Phenotypic behavior of caveolin-3 R26Q, a mutant associated with hyperCKemia, distal myopathy, and rippling muscle disease. Am J Physiol Cell Physiol. Nov 2003;285(5):C1150-1160.

Sotgia F, Bonuccelli G, Bedford M, Brancaccio A, Mayer U, Wilson MT, Campos-Gonzalez R, Brooks JW, Sudol M, Lisanti MP. Localization of phospho-beta-dystroglycan (pY892) to an intracellular vesicular compartment in cultured cells and skeletal muscle fibers in vivo. Biochemistry. Jun 17 2003;42(23):7110-7123.

Sotgia F, Razani B, Bonuccelli G, Schubert W, Battista M, Lee H, Capozza F, Schubert AL, Minetti C, Buckley JT, Lisanti MP. Intracellular retention of glycosylphosphatidyl inositol-linked proteins in caveolin-deficient cells. Mol Cell Biol. Jun 2002;22(11):3905-3926.

Bonuccelli G, Di Natale P, Corsolini F, Villani G, Regis S, Filocamo M. The effect of four mutations on the expression of iduronate-2-sulfatase in mucopolysaccharidosis type II. Biochim Biophys Acta. Nov 29 2001;1537(3):233-238.

Regis S, Filocamo M, Mazzotti R, Cusano R, Corsolini F, Bonuccelli G, Stroppiano M, Gatti R. Prenatal diagnosis of Pelizaeus-Merzbacher disease: detection of proteolipid protein gene duplication by quantitative fluorescent multiplex PCR. Prenat Diagn. Aug 2001;21(8):668-671.

Filocamo M, Bonuccelli G, Corsolini F, Mazzotti R, Cusano R, Gatti R. Molecular analysis of 40 Italian patients with mucopolysaccharidosis type II: New mutations in the iduronate-2-sulfatase (IDS) gene. Hum Mutat. Aug 2001;18(2):164-165.

Filocamo M, Bonuccelli G, Mazzotti R, Corsolini F, Stroppiano M, Regis S, Gatti R. Somatic mosaicism in a patient with Gaucher disease type 2: implication for genetic counseling and therapeutic decision-making. Blood Cells Mol Dis. Dec 2000;26(6):611-612.

Stroppiano M, Bonuccelli G, Corsolini F, Filocamo M. Aberrant splicing at catalytic site as cause of infantile onset glycogen storage disease type II (GSDII): molecular identification of a novel IVS9 (+2GT-->GC) in combination with rare IVS10 (+1GT-->CT). Am J Med Genet. Jun 1 2001;101(1):55-58.

Filocamo M, Bonuccelli G, Mazzotti R, Giona F, Gatti R. Identification of a novel recombinant allele in three unrelated Italian Gaucher patients: implications for prognosis and genetic counseling. Blood Cells Mol Dis. Aug 2000;26(4):307-311.

Dagnino F, Stroppiano M, Regis S, Bonuccelli G, Filocamo M. Evidence for a founder effect in Sicilian patients with glycogen storage disease type II. Hum Hered. Nov-Dec 2000;50(6):331-333.

Bonuccelli G, Filocamo M, Regis S, Corsolini F, Mazzotti R, Gatti R. A novel mutation, Y103X, and exon skipping in a patient with Hunter disease. Hum Mutat. Apr 2000;15(4):389.

Bonuccelli G, Regis S, Filocamo M, Corsolini F, Caroli F, Gatti R. A deletion involving exons 2-4 in the iduronate-2-sulfatase gene of a patient with intermediate Hunter syndrome. Clin Genet. Jun 1998;53(6):474-477.

Book Chapters:

Gloria Bonuccelli, Philippe G. Frank and Michael P. Lisanti. Role of Caveolin-1 in Cancer and Therapeutic Implications- Pp. 3-27 (25). Cutting Edge Therapies for Cancer in the 21st Century by Pier P. Claudio, Paraskevi Vogiatzi, 2014.

Gloria Bonuccelli and Michael Lisanti. Caveolin-1 and breast cancer. Caveolin Proteins in Cancer Pathogenesis, Prevention and Therapy. Book edited by Mercier I, Jasmin JF, Lisanti MP. 2011: Springer Science.