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You are here: FRIAS Fellows Fellows 2017/18 Dr. Milena Bertolotti

Dr. Milena Bertolotti

University of Freiburg
Junior Fellow
June 2017 - 2019

Phone +49 (0)761 203 97229
Fax +49 (0)761 203 97451


I currently work as a post-doctoral researcher in the group of Prof. Michael Reth, where I study the nanoscale organization of the B cell receptor (BCR) redox machinery. After obtaining my Bachelor and Master Degree in Biotechnology at the University of Milano-Bicocca in Italy, I started my PhD at the International PhD School of “Molecular Medicine” at the University Vita-Salute San Raffaele. I worked on redox homeostasis and hydrogen peroxide fluxes in B cells, and had my PhD defense on the subject “Regulation of diverse cellular functions through AQP8-mediated hydrogen peroxide transport”.  In 2008 and 2009 I had the opportunity to work as a visiting scientist in the laboratory of Prof. Sue Goo Rhee at the Ewha Womans University in Seoul, where I analyzed the antibody production in various redox-related genes knock-out mice. From 2010 to 2015 I worked also as a teaching assistant at the University Vita-Salute San Raffaele, presenting lectures in “Cell and molecular biology” for the Degree course in “Medicine and Surgery”. I was Master Thesis supervisor for some students of the MSc in “Industrial Biotechnology” and MSc in “Biology” at the University of Milano-Bicocca. I am a member of the Society for Free Radical Biology and Medicine and of the Differentiation Cell Biology Association, being my research expertise mainly focused on the fields of cell biology, immunology and redox signaling.

Selected Publications

  • Bertolotti M, Farinelli G, Galli M, Aiuti A, Sitia R., AQP8 transports NOX2-generated H2O2 across the plasma membrane to promote signaling in B cells. J Leukoc Biol. 2016
  • Bertolotti M., Bestetti S, García-Manteiga JM, Medraño-Fernandez I, Dal Mas A, Malosio ML, Sitia R., Tyrosine kinase signal modulation: a matter of H2O2 membrane permeability? Antioxid Redox Signal. 2013 Nov;19(13):1447-51.
  • Bertolotti M., Sitia R, Rubartelli A, On the redox control of B lymphocyte differentiation and function Antioxid Redox Signal. 2012 May;16(10):1139-49.
  • Bertolotti M., Yim Sh, Garcia-Manteiga Jm, Masciarelli S, Kim Yj, Kang Mh, Iuchi Y, Fujii J, Vené R, Rubartelli A, Rhee Sg, Sitia R, B to plasma cell terminal differentiation entails oxidative stress and profound reshaping of the antioxidant responses, Antioxid Redox Signal. 2010 Oct;13(8):1133-44.
  • Masciarelli S, Fra AM, Pengo N, Bertolotti M, Cenci S, Fagioli C, Ron D, Hendershot LM and Sitia R, CHOP-independent apoptosis and pathway-selective induction of the UPR in developing plasma cells, Mol Immunol. 2010 Mar;47(6):1356-65

FRIAS Research Project

Mapping the nanoscale organization of the BCR redox machinery

Through the B cell antigen receptor (BCR) mature B cells recognize the presence of antigens in the external world and adapt their responses. The signaling output from this receptor is tightly controlled by co-stimulatory and inhibitory receptors, so as to prevent its hypo- or hyper-stimulation, respectively. The host lab has employed a Fab-based proximity ligation assay (Fab-PLA) that allows a precise mapping of the localization and interactions of proteins on the B cell surface at nm distances. It is known that reactive oxygen species (ROS) can amplify BCR signaling. However, ROS fluxes have never been studied at the nanoscale level. I recently showed that the NADPH oxidase complex 2 (NOX2) produces ROS molecules, such as H2O2, on the B cell surface and that the water channel aquaporin 8 (AQP8) is consequently needed to transport H2O2 through the plasma membrane for BCR signal amplification. A major open question in the redox field is the nanoscale organization of the signaling components. Furthermore, little is known about the nanoscale location and interactions of BCR inhibitory receptors, and the second aim of my research project is to thoroughly investigate this issue. My project will provide new insights on normal B cells membrane organization and signaling mechanisms, and consequently on the molecular background associated with diseases such as B cell leukemia.