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Mauricio Reginato

Mauricio Reginato, PhD

Professor; Director, Graduate Program in Cancer Biology


Department: Biochemistry & Molecular Biology

Education

  • Postdoctoral Fellow, Harvard Medical School (1998-2004)
  • PhD - Pharmacology, University of Pennsylvania (1998)

Dr. Reginato is a professor in the Department of Biochemistry & Molecular Biology, and director of the Graduate Program in Cancer Biology at Drexel University College of Medicine.

Research Overview

Research Interests

Molecular mechanisms underlying breast cancer growth, survival and spread to distinct organs, in particular how cancer genes alter metabolic pathways and how these pathways may be exploited to target cancers.

Research

Breast cancer is the second leading cause of cancer death in women. About 1 in 8 women in the U.S. will develop invasive breast cancer during her lifetime. Our lab is interested in understanding altered signaling pathways that lead to breast cancer initiation and progression. Identifying and understanding these pathways will lead to development of novel therapies. Recently our lab has become interested in understanding how signaling pathways regulate metabolic reprogramming in cancer cells.

Every year approximately 200,000 new cases of breast cancer are diagnosed, and 40,000 women are expected to die from this disease in the U.S. alone. Our lab's long-term goal is to identify novel therapeutic targets for treatment of breast cancer. We are trying to understand alterations in cellular signaling pathways between normal and cancer cells and exploit these differences for possible therapeutic gain.

Mauricio Reginato - use of 3D human epithelail cell cultures in breast cancer research

Our lab uses in vitro three-dimensional human mammary epithelial cell cultures that allow organization of cells into duct-like structures with properties similar to mammary ducts in vivo. Overexpression of oncogenes such as wildtype or mutant HER2/ErbB2 (tyrosine kinase receptor) induces changes in tissue architecture that resemble human breast cancer lesions. Our lab is interested in understanding molecular, cell biological and signaling events associated with cancer progression.

Our lab has two major areas of interest:

  1. We are trying to understand how oncogenes regulate cancer cell signaling and progression to more aggressive phenotypes using standard and three-dimensional (3D) culture assays. In 3D culture, normal cells form polarized, hollow duct-like structures that resemble mammary ducts in vivo. Cancer cells, and oncogenes such as tyrosine kinase family of receptors, including HER2/ErbB2, provide signals that allow disruption of morphogenesis including increase in cell growth and inhibition of cell death pathways. However, these structures remain surrounded by intact basement membrane and are considered to have properties of pre-cancers. Our lab is very interested in understanding signals that drive cells from pre-cancer to malignant state. Cells expressing constitutively active form of ErbB2, or very aggressive breast cancer cells, are able to invade through the matrix and have properties of malignant cells. We are also examining how low oxygen levels (hypoxia) regulate signaling pathways associated with cancer progression and chemoresistance.
  2. Our lab is also interested in understanding how oncogenes alter metabolic reprogramming in cancer cell. Tumor cells take up ten times more glucose then normal cells and switch to glycolysis to meet energy needs. Our lab was the first to show that a nutrient-sensing pathway that regulates sugar-based protein modification, called O-GlcNAcylation, is highly elevated in cancer. Our lab has shown that reducing O-GlcNAcylation in breast and prostate cancer cells inhibits growth, invasion and metastasis thus targeting the enzyme that regulates O-GlcNAcylation, O-GlcNAc transferase, may provide novel way of to treat cancers. We are currently investigating how O-GlcNAcylation regulates oncogenic signaling pathways using in vitro and in vivo cancer models. In addition, we are analyzing how O-GlcNAcylation regulates cancer metabolomics.
Mauricio Reginato - research into how reducing OGT in breast cancer cells blocks metastasis

Reducing OGT levels in breast cancer cells blocks metastasis to brain in vivo.
A. Human breast cancer cells (MDA-MB-231) expressing control or OGT RNAi were intracardiacly injected into nu/nu mice. Mice were imaged four weeks post-injection using the IVIS Lumina Imaging System. B. To verify tumor metastasis, brains were excised and subjected to immunohistochemical analysis. Representative H&E coronal section of the brain (arrows indicate metastasis). Image provided by Christina Ferrer, Christos Katsetos and Mauricio Reginato.

In the Media

Publications

Selected Publications

See all of Dr. Reginato's publications in ResearchGate.

“Nutrient sensor O-GlcNAcylation controls cancer lipid metabolism via SREBP-1 regulation”
Sodi VL, Bacigalupa ZA, Ferrer CM, Lee J, Gocal W, Mukherjee D, Wellen KE, Ivan M, and Reginato MJ
Submitted, 2016

“Proapoptotic protein Bim attenuates estrogen-enhanced survival in lymphangioleiomyomatosis”
Li C, Li N, Liu X, Zhang EY, Sun Y, Masuda K, Li J, Sun J, Morrison T, Li X, Chen Y, Wang J, Karim NA, Zhang Y, Blenis J, Reginato MJ, Henske EP, Yu JJ.
J. of Clinical Investigation Insight; 1(19): e86629, Nov 17, 2016

"O-GlcNAcylation regulates breast cancer metastasis via SIRT1 modulation of FoxM1 pathway"
Ferrer CM, Lu TY, Bacigalupa ZA, Katsetos CD, Sinclair DA, and Reginato, MJ
Oncogene, Jun 27 2016 [Epub ahead of print]

“O-GlcNAcylation in Cancer Biology: Linking Metabolism and Signaling”
Ferrer CM, Sodi VL and Reginato MJ
Journal of Molecular Biology, Jun 22 2016 [Epub ahead of print](add link)

"Progress towards overcoming hypoxia-induced resistance to solid tumor therapy"
Karakashev SV, and Reginato MJ
Cancer Management and Research, 12;7:253-64 Aug 2015

"Sweet Connections: O-GlcNacylation links cancer metabolism and survival"
Ferrer CM, and Reginato MJ
Molecular & Cellular Oncology, Oct 29; 2(1) 2014

"Emerging microtubule targets in glioma therapy"
Katsetos CD, Reginato MJ, Baas PW, D’Agostino L, Legido A, Tuszyn Ski JA, Draberova E, and Draber P
Seminars in Pediatric Neurology; 22(1):49-72, March 2015

"mTOR/c-MYC axis regulates O-GlcNAc transferase (OGT) expression and O-GlcNAcylation in breast cancer "
Sodi VL, Khaku S, Schwab LP, Vocadlo DJ, Seagroves TN and Reginato MJ
Molecular Cancer Research, 13(5):923-33, May 2015
Publication listed in Highlights of This Issue

"Epithelial-to-mesenchymal transition alters interstitial fluid flow-induced signaling in ERBB2-positive breast cancer cells"
Tchafa AM, Ta M,  Reginato MJ and Shieh AC
Molecular Cancer Research, 13(4):755-64, Apr 2015

"Hypoxia/HIF-1a induces lapatinib resistance in ERBB2-positive breast cancer cells via regulation of DUSP2"
Karakashev SV, and Reginato MJ
Oncotarget, 6(4):1967-80, Feb 10, 2015

Book Chapter: "Cancer Metabolism: Cross Talk Between Signaling and O-GlcNAcylation"
Ferrer CM, and Reginato MJ
Cancer Genomics and Proteomics: Methods and Protocols, Methods in Molecular Biology, Vol. 1176 pp 73-88, Springer, Narendra Wajapeyee (Ed.), 2014

"O-GlcNAcylation regulates cancer metabolism and survival stress signaling via regulation of HIF-1 pathway."
Ferrer CM, Lynch TP, Sodi V, Falcone JN, Schwab L, Peacock D, Vocadlo DJ, Seagroves TN, and Reginato MJ 
Molecular Cell; (54(5); 820-831, June 5, 2014

"Sticking to Sugars at the Metastatic Site: Sialyltransferase ST6GalNAc2 Acts as Breast Cancer Metastasis Suppressor"
Ferrer, CM, and Reginato, MJ
Cancer Discovery; March 4(3); 275–7, March 2014

"Activated ERBB2/HER2 licenses sensitivity to apoptosis upon endoplasmic reticulum stress through a PERK-dependent pathway"
Martin-Perez, R, Palacios, C, Yerbes, R, Cano-Gonzales, A, Iglesias-Serret, D, Gil, J, Reginato, MJ and López-Rivas A  
Cancer Research; 74(6): 1766-77, March 15, 2014

"ErbB2, FoxM1, and 14-3-3ζ prime breast cancer cells for invasion in response to ionizing radiation."
Kambach DM, Sodi VL, Lelkes PI, Azizkhan-Clifford J, and Reginato MJ 
Oncogene Jan 30; 33(5):589-98 (2014)

"HINCUTs in Cancer: Hypoxia-induced non-coding ultraconserved transcripts"
Ferdin J, Wu X, Nishida N Nicoloso MS, Shah NM, Devlin C, Ling H, Shimizu M, Kumar K, Cortez MA, Ferracin M, Bi Y, Yang D, Czerniack BA, Zhang W, Schmittgen TD, Voorhoeve MP, Reginato MJ, Negrini M, Davuluri RV, Kunej T, Iva, M, and Calin GA
Cell Death Differ Sep 13 2013 [Epub ahead of print]

"The oncogene HER2/neu (erbB2) requires the Hypoxia-inducible factor HIF-1 for mammary tumor growth and anoikis resistance." 
Whelan KA, Schwab L, Karakashev S, Franchetti L, Johannes GJ, Seagrove, TN, and  Reginato MJ
J. Biol Chem May 31; 288(22):15865-77   (2013)

"ERK2 regulated TIMP1 induces hyperproloferation of K-Ras (G12D)-transformed pancreatic ductal cells."
Botta GP, Reichert M, Reginato MJ, Heeg S, Rustgi AK and Lelkes PI
Neoplasia Apr 15 (4): 359-72 (2013)

"Control of FLIPL expression and TRAIL resistance by the extracellular signal regulated kinase (ERK)1/2 pathway in breast epithelial cells"
Yerbes R, López-Rivas A, Reginato MJ, and Palacios C
Cell Death Differ; 19:1908-16, Dec 2012

"Critical role of O-GlcNAc transferase in prostate cancer invasion, angiogenesis, and metastasis." 
Lynch TP, Ferrer C, Jackson SR, Shahriari KS, Vosseller K, and Reginato MJ 
J. Biol. Chem. Mar 30; 287: 11070-81  (2012)

"K-Ras activation of ERK2 in a three-dimensional model of human pancreatic cells regulates invasion via induction of matrix metalloproteinase-1"
Botta, GP, Reginato, MJ, Rustgi, AK, and Lelkes, PI
Mol. Cancer Research, Feb; 10: 183-96. (2012)

"Surviving without oxygen: Hypoxia regulation of mammary morphogenesis and anoikis"
Whelan, KA and Reginato, MJ
Cell Cycle Jul 15: 10, 2287-94 (2011)

"Cellular FLIP(L) plays a survival role and regulates morphogenesis in breast epithelial cells"
Yerbes, R, Palacios, C, Reginato, MJ, and Lopez-Rivas, A
Biochim Biophys Acta Jan: 1813, 168-78 (2011)

"O-GlcNAc transferase: A sweet new cancer target"
Lynch, TP and Reginato, MJ
Cell Cycle June 1: 10, 1712-13 (2011)

"Hypoxia suppression of Bim and Bmf blocks anoikis and luminal clearing during mammary morphogenesis"
Whelan, KA, Caldwell, SA, Shahriari, KS, Jackson, SR, Jones, L, Johannes, G and Reginato, MJ
Mol. Biol. Cell. Nov 15: 21, 3829-37 (2010)

"Nutrient sensor O-GlcNAc transferase regulates breast cancer tumorigenesis via targeting of the oncogenic transcription factor FoxM1"
Caldwell, SA, Jackson, SR, Shahriari, KS, Lynch, TP, Sethi, G, Walker, S, Vosseller, K, and Reginato, MJ
Oncogene May 13: 29, 2831-42 (2010)

"ErbB2 requires integrin alpha5 for anoikis resistance via c-Src regulation of receptor activity in human mammary epithelial cells"
Haenssen, KK, Caldwell, SA, Shahriari, K, Jackson, R, Whelan, K, Klein-Szanto, A, and Reginato, MJ
J. of Cell Science  April 15: 123, 1373-82 (2010)

"Micropatterns of matrigel for three-dimensional epithelial cultures"
Sodunke, TR, Turner, KK, Caldwell, SA, McBride, KW, Reginato, MJ and Noh, N
Biomaterials 28, 4006-16 (2007)

"Illuminating the center: mechanisms regulating lumen formation and maintenance in mammary morphogenesis"
Reginato, MJ, and Muthuswamy, SK
J Mammary Gland Biology & Neoplasia 11, 205-11 (2006)


Contact Information


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