Flavia Pichiorri,
Assistant Professor,
The Ohio State University
The primary focus of my research has been elucidating the role of microRNAs (miRNAs) in multiple myeloma (MM) development. Specifically in this project we plan to characterize the functional role of circulating miRNAs free or encapsulated in small lipid drafts (exosome) in cell-cell communication and to identify differentially expressed peripheral blood biomarkers in MM patients at diagnosis. My long term goal is to provide the molecular basis to accurately risk stratify MM patients at diagnosis, thus advising on the best course of medical treatment. This will include the understanding of the functional relationship between circulating miRNAs and cytokines in vitro and directly in the patients setting and a deeper understanding of the miRNA structure and localization, setting the stage for developing a novel diagnostic tool and small RNA based therapy.My research program has been greatly facilitated by the development of next generation technologies for miRNome and proteome analysis, both available here at The Ohio State University. These technologies have already allowed direct assessment of circulating miRNAs in MM patients as possible new non-invasive molecular marker for high and low risk MM disease and response to the therapy. As a post-doctoral fellow and research scientist in Dr. Carlo M. Croce’s laboratory, I was the first to show that miRNAs are involved in the malignant transformation of plasma cells (PCs) and that miRNA-dependent deregulation of critical genes contribute to MM pathogenesis.. I also showed that recurrent molecular aberrations, such as p53 mutation/deletion, could affect the miRNA expression and therapeutic response in MM cells. I am a young scientist who has built a good record through scientific publications. I have nearly 40 peer-reviewed publications in major scientific journals, notably first authored and senior or co-senior authored papers published in Journal of Proteomics, Journal of Experimental Medicine, Cancer Cell, Blood, Proceedings of the National Academy of Science and many others. The current application builds logically on my prior work extending the knowledge of the role of circulating miRNAs as possible new players in MM pathogenesis and as new diagnostic biomarkers for disease progression. I have a demonstrated a record of high relevance publications in the field of Multiple Myeloma, and my scientific record has prepared me to lead the proposed project. I am also an extremely hard working, diligent, and self-motivated person with talent, creativity, and a friendly and approachable personality.
Patients’ Blood miRNA Profiling as a New Tool for Prognosis in Multiple Myeloma
Thursday, 12 September 2013 at 11:45
Add to Calendar ▼2013-09-12 11:45:002013-09-12 12:45:00Europe/LondonPatients’ Blood miRNA Profiling as a New Tool for Prognosis in Multiple MyelomaExosomes and Circulating Biomarkers Summit 2013 in San Diego, CASan Diego, CASELECTBIOenquiries@selectbiosciences.com
Multiple Myeloma (MM) is an incurable cancer where prognosis is determined by the combination of the International Staging System (ISS) and fluorescent in-situ-hybridization (FISH) analysis of MM plasma cells (MM-PCs). However, the outcome predictions based on the current criteria are not precise and patients with similar characteristics have different outcome, thereby supporting the need for novel and more accurate prognosticators. microRNAs are short- non-coding-RNAs whose expression levels change in the transition from normal PCs to MM-PCs. miRNAs are master regulators of gene expression and have been found altered in all cancers. Their identification in body fluids suggests their possible use as novel biomarkers in MM patients. A comprehensive profile of circulating miRNAs for disease prognostication has not been reported. We profiled more than 654 different miRNAs using nCounter technology (nanoString, Seattle, USA) on samples from 54 newly diagnosed MM patients enrolled on the randomized phase 3 study of Velcade Melphalan Prednisone Thalidomide versus Velcade Melphalan Prednisone (NCT#01063179). Stem loop real-time PCR (qRT-PCR) was performed on an additional 234 MM patients enrolled in the same trial. We found that 3 miRNAs [miR-16 (P=0.0019), -19b (P=0.043) and miR-25(P=0.0012)] were associated with overall survival (OS) of myeloma patients. By incorporating these indices into the ISS score, we generated a novel miRNA-integrated score that is highly predictive of survival duration (P<0.00001) and substantially improved the currently used prognostic scores. These observation are perfectly aligned with our previously published data in which these miRNAs, are tightly regulated in MM cells and are shown to regulate their survival. We can then conclude that circulating microRNAs can be considered a new class of non-invasive prognosticators in MM.
Add to Calendar ▼2013-09-12 00:00:002013-09-13 00:00:00Europe/LondonExosomes and Circulating Biomarkers Summit 2013Exosomes and Circulating Biomarkers Summit 2013 in San Diego, CASan Diego, CASELECTBIOenquiries@selectbiosciences.com
Add to Calendar ▼2013-09-12 11:45:002013-09-12 12:45:00Europe/LondonPatients’ Blood miRNA Profiling as a New Tool for Prognosis in Multiple MyelomaExosomes and Circulating Biomarkers Summit 2013 in San Diego, CASan Diego, CASELECTBIOenquiries@selectbiosciences.com
