ULB Center for Diabetes Research

Inflammatory and Apoptotic Signaling in Diabetes

Group Leader: Prof.  Alessandra K. Cardozo

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Alessandra K. Cardozo utilizes cell biological, genomic, and proteomic approaches to identify and characterize the mechanisms leading to inflammation-mediated dysfunction and death of pancreatic β-cells in diabetes.

 

Group Leader, Prof.  Alessandra K. Cardozo

Alessandra K. Cardozo is a biologist that obtained a Master (1999) and PhD degrees (2003) from the Vrije Universiteit Brussel, Brussels Belgium. In 2006 she obtained a position of Research Associate/Chercheur Qualifié at the FRS-FNRS to develop her own research group at the ULB Center for Diabetes Research, Faculty of Medicine, ULB (former Laboratory of Experimental Medicine). Since 2015 she is engaged as a Chargé de Cours/Associate Professor at the Faculty of Medicine, Université Libre de Bruxelles, Brussels Belgium where she teaches and is the head of the group of Inflammatory and apoptotic signaling in diabetes.

 

Research Interests

Alessandra K. Cardozo utilizes cell biological, genomic, and proteomic approaches to identify and characterize the mechanisms leading to inflammation-mediated dysfunction and death of pancreatic β-cells in diabetes. She together with Prof Eizirik were pioneers in performing transcriptome profiling in primary pancreatic β-cells. These studies demonstrated that β-cells are not passive bystanders of their own destruction but they promote a “dialog” with immune-cells that contributes to islet inflammation and β-cell demise during type 1 diabetes. She has shown that activation of the transcription factor NF-κB is a crucial mediator of these β-cell pro-inflammatory and pro-apoptotic responses. By focusing her research on the pro-apoptotic mechanisms downstream NF-κB in β-cells she observed that pro-inflammatory cytokines induces endoplasmic reticulum stress in these cells.

AK Cardozo has also unveiled an important crosstalk between endoplasmic reticulum stress and the mitochondrial apoptotic pathway leading to β-cell apoptosis and suggested that endoplasmic reticulum stress may mediate pro-inflammatory responses in these cells. She has recently unveiled an atypical activation of the alternative NF-κB pathway by pro-inflammatory cytokines in pancreatic β-cells that constitutes a novel “feed forward” mechanism that contributes to the particularly pro-apoptotic effect of NF-κB in β-cells. The current research topics of Alessandra K. Cardozo are: Regulation of NF-κB activation and β-cell death in diabetes; the crosstalk between endoplasmic reticulum stress and mitochondrial apoptotic pathway leading to β cell demise; the role of endoplasmic reticulum stress in β-cell mediated pro-inflammatory and antiviral responses; the role of regulated necrosis on β-cell death during diabetes. The main aim of her research is to devise tools prevent β-cell loss during diabetes.

Honours & Awards

  • Sanofi-Aventis Award in Diabetes - 2009-2010
  • Paul Langerhans Research Award for the Research on the Physiology and Pathophysiology of the β-cells, from the European Association for the Study of Diabetes (EASD)/Amylin-Pharmaceuticals Inc., 2005
  • Victor Lange Prize for Diabetes Research in Belgium, 2004 - 2005
  • Postdoctoral Fellowship from the Juvenile Diabetes Research Foundation International, New York, USA, 2004-2006
  • Young Investigators Award, the Belgian Endocrine Society (BES). 10th Annual Meeting, Brussels, 2000
  • VUB scholarship for the course “Master in Medical and Pharmaceutical Research” from the VUB Advice Council for Development Cooperation (VUBAROS), 1998-1999

Selected Publications

  1. Meyerovich K, Violato NM, Fukaya M, Dirix V, Pachera N, Marselli L, Marchetti P, Strasser A, Eizirik DL, Cardozo AK. MCL-1 is  key anti-apoptotic protein in human and rodent pancreatic β-cells. Diabetes, 66: 2446-2458, 2017 (IF 8.684)
  2. Fukaya M, Brorsson CA, Catrysse L , Delaroche D, Vanzela EC, Meyerovich K, Ortis F, Beyaert R, Nielsen LB,  Andersen ML, Mortensen HB, Pociot F, van Loo G, Størling J, Cardozo AK. TNFAIP3/A20 inhibits β-cell apoptosis by multiple mechanisms and predicts residual β-cell function in children newly-diagnosed for type 1 diabetes. Molecular Endocrinology, 30:48-61, 2016 (IF 4.022)
  3. Meyerovich K, Fukaya M, Terra LF, Ortis F, Eizirik DL, Cardozo AK. The non-canonical NF-κB pathway is induced by cytokines in pancreatic β-cells and contributes to cell death and pro-inflammatory responses. Diabetologia, 59:512-21, 2016 (IF 6,671)
  4. Allagnat F, Fukaya M, Nogueira TC, Welsh N, Marselli L, Marchetti P, Eizirik DL, Cardozo AK. C/EBP Homologous Protein (CHOP) Contributes to Cytokine-induced Pro-Inflammatory Responses and Apoptosis in Beta Cells. Cell Death Diff, 19:1836-1846, 2012 (IF 8.371)
  5. Allagnat F, Cunha D, Moore F, Vanderwinden JM, Eizirik DL, Cardozo AK. Mcl-1 degradation by pro-inflammatory cytokines and palmitate is an early and major event for beta cell apoptosis. Cell Death Differ, 18:328-37, 2011 (IF 8.849)
  6. Allagnat F, Christulia F, Ortis F, Pirot P, Lortz S, Lenzen S, Eizirik DL, Cardozo AK. Sustained expression of spliced XBP1 induces pancreatic beta-cell dysfunction and apoptosis. Diabetologia. 53:1120-30, 2010 (Cover page of this issue) (IF 6.973)
  7. Pirot P, Ortis F, Yanjun M, Hendershot L, Eizirik DL, Cardozo AK. Transcriptional regulation of the endoplasmic reticulum (ER) stress gene CHOP in pancreatic β-cells. Diabetes, 56:1069-1077, 2007 (IF 8.261)
  8. Cardozo AK, Ortis F, Storling J, Feng Y-M, Rasschaert J, Tonnesen M, Van Eylen F, Mandrup-Poulsen T, Herchuelz A, Eizirik DL. Cytokines downregulate the sarcoendoplasmic-reticulum pump Ca2+-ATPase (SERCA)2b and deplete endoplasmic reticulum (ER)-Ca2+ leading to induction of ER-stress in pancreatic β-cells. Diabetes, 54:452-461, 2005 (IF 8.028)
  9. Cardozo AK, Proost P, Gysemans C, Chen MC, Mathieu C, Eizirik DL. IL-1β and IFN-γ induce the expression of diverse chemokines and IL-15 in human and rat pancreatic islet cells, and in islets from pre-diabetic NOD mice. Diabetologia 46:255-266, 2003 (IF 5.689)
  10. Cardozo AK, Heimberg H, Heremans Y, Leeman R, Kutlu B, Kruhoffer M, Orntoft T, Eizirik DL. A comprehensive analysis of cytokine-induced and NF-κB dependent genes in primary rat pancreatic β¬cells. J Biol Chem 52: 48876-48886, 2001 (IF 7.258)