PHONE: 757 683 7044
ADDRESS: IRP 2, 4211 Monarch Way, Norfolk, VA, 23508
- Postdoctoral Fellow: Frank Reidy Research Center for Bioelectrics, Old Dominion University, Norfolk, Virginia, From 2015 to 2016
- Postdoctoral Fellow: Institute for Cancer Research and Treatment, University of Turin, Turin, Italy, From 2009 to 2013
- Postdoctoral Fellow: Italian National Institute of Health, Rome, Italy, From 2006 to 2009
- Ph.D.: in Human Biology and Genetics, University of Rome La Sapienza, Rome, Italy, 2006
- M.S.: Major in Molecular Biology, University of Rome La Sapienza, Rome, Italy, 2002
Flavia Mazzarda, Postdoctoral fellow
Alexandra Chittams-Miles, Ph.D. student
The research in our lab is focused on understanding the biological responses initiated by short intense electric pulses, which include: the opening of stable pores in the cell membrane and internal cell structures; phospholipid scrambling; alteration of cell metabolism and function; initiation of diverse cell death pathways; and regulated release of danger signals. These basic research studies have broad relevance to human health topics, with prospective applications in cancer and antimicrobial treatment.
Cancer treatment by electro-immuno-stimulation. Activation of a robust immune response against cancerous cells is a significant enhancement for any cancer therapeutic modality. We are developing a new cancer therapy - Electro-immuno-stimulation - which combines electric-pulse-induced ablation of tumor tissue with stimulation of an immune response directed against disseminated metastases. In our experiments, brief bursts of intense electric pulses directly kill tumor cells, while at the same time activating an immune response that protects animals from a second tumor challenge. In both colorectal cancer and lymphoma cells, short pulsed electric fields (PEF) cause sustained endoplasmic reticulum stress accompanied by phosphorylation of translation initiation factor 2α (eIF2α), a biomarker of immunogenic cell death. PEF-induced cell death comes with the release of all major immunogenic damage associated molecular patterns (DAMPs). Moreover, we are studying the effect of these brief electrical stimuli on immune cells that infiltrate the tumor microenvironment. Specifically, we discovered that the electroporation damage is sensed by the innate immunity platform known as inflammasome. Inflammasome activation in electroporated macrophages triggers the release of the highly inflammatory cytokine IL-1beta. Recent literature has shown that inflammasome-dependent cytokines play a crucial role in stimulating adaptive immune responses, including those involved in anti-cancer immunosurveillance.
Antimicrobial effects of ultra-short electric pulses. We are investigating the antimicrobial effects of burst of intense electric pulses. Our results show that, contrary to other antimicrobial agents, bacteria growing as biofilms are more sensitive to PEF treatments than their planktonic counterpart. Currently we are extending our findings to more species of bacteria biofilms and assessing the relevance of pulse parameters such as pulse width and amplitude. Moreover, we are studying potential synergistic effects between PEF and antibiotics using methicillin-resistant Staphylococcus aureus skin and soft tissue infection models.
Most relevant publications
- Poudel A., Oludiran A., Sozer E., Casciola M., Purcell E., and Muratori C. Growth in a Biofilm Sensitizes Cutibacterium acnes to Nanosecond Pulsed Electric Fields. Bioelectrochemistry. 2021 Mar 9;140:107797. doi: 10.1016/j.bioelechem.2021.107797.
- Rossi A, Pakhomova ON, Mollica PA, Casciola M, Mangalanathan U, Muratori C. Nanosecond Pulsed Electric Fields Induce Endoplasmic Reticulum Stress Accompanied by Immunogenic Cell Death in Murine Models of Lymphoma and Colorectal Cancer. Cancers (Basel). 2019 Dec 17;11(12). pii: E2034. doi: 10.3390/cancers11122034.
- A. Rossi, O. N. Pakhomova, A. G. Pakhomov, S. Weygandt, A. Bulysheva, L. Murray, P. Mollica, and C. Muratori. Mechanisms and immunogenicity of nsPEF-induced cell death in B16F10 melanoma tumors. Nature Sci Rep. 2019 Jan 23;9(1):431. doi: 10.1038/s41598-018-36527-5.
- Muratori C, Pakhomov A, Gianulis E , Meads J., Casciola M, Mollica P, and Pakhomova O. Activation of the phospholipid scramblase TMEM16F by nanosecond pulsed electric field (nsPEF) facilitates its diverse cytophysiological effects. J. Biol. Chem. 2017 Nov 24;292(47):19381-19391. doi: 10.1074/jbc.M117.803049.
- Muratori C, Pakhomov AG, Gianulis EC, Jensen SD, Pakhomova ON. The cytotoxic synergy of nanosecond electric pulses and low temperature leads to apoptosis. Nature Sci Rep. 2016 Nov 11; 6:36835. doi: 10.1038/srep36835.
Awards and Honors
- Award for best presentation at the Frank Reidy Research Center for Bioelectrics retreat (2017).
- 2 years postdoctoral fellowship, Italian Ministry of Education, Universities and Research (2011-2012).
- 2 years postdoctoral fellowship, Italian Ministry of Education, Universities and Research (2009-2010).
- New investigator scholarship, 13th Conference on Retroviruses and Opportunistic Infections (CROI-2006).
- Federation of European Biochemical Societies (FEBS) Youth scholarship to attend the FEBS International School on Immunology (2002).
- Member of the editorial board of Bioelectricity, Mary Ann Liebert Inc.
- Member of the Scientific Organizing Committee for the 4th World Congress on Electroporation, Copenhagen, Denmark (2022).
- Member of the Scientific Organizing Committee for the 2nd World Congress on Electroporation, Norfolk, Virginia (2017).