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My research program started from the observation that the modality of glucose transport evolves during the process of cancer development. Our studies in lung cancer showed that pre-malignant and early-stage lesions utilize sodium-dependent transporters (SGLTs) to take up glucose from the environment, whereas advanced and poorly differentiated tumors switch to transporters of the GLUT family. Our current research aims at answering the following questions: – Why do cancer cells need to change their glucose transport system as tumors progress? – Are there metabolic differences between SGLT- and GLUT-dependent cells? – What regulates SGLT and GLUT expression in different disease grades and stages? – What is the relationship between glucose transport system and cellular differentiation? – What are the consequences of SGLT2 knockout or pharmacological blockade on the progression from pre-malignant lesions to invasive cancer, including effects on cellular epigenetics, on the microenvironment, and on the tumor-specific immune response? To answer these questions, we are using a variety of experimental models, including monolayer and 3D cell culture, genetically engineered mouse models, patient-derived xenografts, and chorioallantoic membrane assays. We employ a variety of experimental methods, from molecular biology to metabolic analyses, imaging, and whole genome studies.
A selected list of publications:
Saggese P, Martinez CA, Tran LM, Lim R, Dumitras C, Grogan T, Elashoff D, Ramin SR, Dubinett SM, Liu B, Scafoglio C. Genotoxic Treatment Enhances Immune Response in a Genetic Model of Lung Cancer.. Cancers, 2021.
Saggese P, Sellitto A, Martinez CA, Giurato G, Nassa G, Rizzo F, Tarallo R, Scafoglio C. Metabolic Regulation of Epigenetic Modifications and Cell Differentiation in Cancer.. Cancers, 2020.
Martinez CA, Scafoglio C. Heterogeneity of Glucose Transport in Lung Cancer.. Biomolecules, 2020.
Barrio JR, Huang SC, Satyamurthy N, Scafoglio CS, Yu AS, Alavi A, Krohn KA. Does 2-FDG PET Accurately Reflect Quantitative In Vivo Glucose Utilization?. Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 2019.
Hsieh MH, Choe JH, Gadhvi J, Kim YJ, Arguez MA, Palmer M, Gerold H, Nowak C, Do H, Mazambani S, Knighton JK, Cha M, Goodwin J, Kang MK, Jeong JY, Lee SY, Faubert B, Xuan Z, Abel ED, Scafoglio C, Shackelford DB, Minna JD, Singh PK, Shulaev V, Bleris L, Hoyt K, Kim J, Inoue M, DeBerardinis RJ, Kim TH, Kim JW. p63 and SOX2 Dictate Glucose Reliance and Metabolic Vulnerabilities in Squamous Cell Carcinomas.. Cell reports, 2019.
Scafoglio CR, Villegas B, Abdelhady G, Bailey ST, Liu J, Shirali AS, Wallace WD, Magyar CE, Grogan TR, Elashoff D, Walser T, Yanagawa J, Aberle DR, Barrio JR, Dubinett SM, Shackelford DB. Sodium-glucose transporter 2 is a diagnostic and therapeutic target for early-stage lung adenocarcinoma.. Science translational medicine, 2018.
Kepe V, Scafoglio C, Liu J, Yong WH, Bergsneider M, Huang SC, Barrio JR, Wright EM. Positron emission tomography of sodium glucose cotransport activity in high grade astrocytomas.. Journal of neuro-oncology, 2018.
Ghezzi C, Yu AS, Hirayama BA, Kepe V, Liu J, Scafoglio C, Powell DR, Huang SC, Satyamurthy N, Barrio JR, Wright EM. Dapagliflozin Binds Specifically to Sodium-Glucose Cotransporter 2 in the Proximal Renal Tubule.. Journal of the American Society of Nephrology : JASN, 2016.
Scafoglio C, Hirayama BA, Kepe V, Liu J, Ghezzi C, Satyamurthy N, Moatamed NA, Huang J, Koepsell H, Barrio JR, Wright EM. Functional expression of sodium-glucose transporters in cancer.. Proceedings of the National Academy of Sciences of the United States of America, 2015.
Scafoglio C, Smolka M, Zhou H, Perissi V, Rosenfeld MG. The co-repressor SMRT delays DNA damage-induced caspase activation by repressing pro-apoptotic genes and modulating the dynamics of checkpoint kinase 2 activation.. PloS one, 2013.
Perissi V, Scafoglio C, Zhang J, Ohgi KA, Rose DW, Glass CK, Rosenfeld MG. TBL1 and TBLR1 phosphorylation on regulated gene promoters overcomes dual CtBP and NCoR/SMRT transcriptional repression checkpoints.. Molecular cell, 2008.
Olson LE, Tollkuhn J, Scafoglio C, Krones A, Zhang J, Ohgi KA, Wu W, Taketo MM, Kemler R, Grosschedl R, Rose D, Li X, Rosenfeld MG. Homeodomain-mediated beta-catenin-dependent switching events dictate cell-lineage determination.. Cell, 2006.