Research and teaching
Area of Focus
- Multiple Myeloma
Summary of Research
Multiple Myeloma: Interrogate the genome of myeloma cells to understand the biology of the disease and mechanisms of drug resistance.
Advances in genome technology and their increased use in translational research have increased our current understanding of Myelomagenesis.The goal of my research is to interrogate the myeloma genome to elucidate mechanisms of drug resistance to anti-MM agents, identify druggable therapeutic targets in myeloma and discover new biomarkers of response to novel agents. In addition over the past 5 years I have also focused on identifying biomarkers for a better targeting of therapeutics in this disease and the delivery of individualized medicine. As such, I have established in Calgary a Myeloma tissue bank that consists of a library of bone marrow biopsies from myeloma patients as well genomic materials to interrogate the genome of primary myeloma cells and define mechanisms of drug resistance. As such we have shown that loss of cereblon (CRBN) or increased expression of a CRBN splice isoform lacking exon 10, are associated with resistance to immunomodulatory drugs. Defining the exact mechanisms that mediate the efficacy or resistance to this class of drug in myeloma will surely permit to design therapeutic strategies to maximize their therapeutic potential and possibly overcome drug resistance.
Moreover, studying the chromosomal instability of myeloma cells we have identified a novel therapeutic approach that relies on the contextual synthetic lethality between proteasome and PARP inhibitors. We have demonstrated that the proteasome inhibitor bortezomib induces a BRCAness state in MM cells and results in a contextual synthetic lethality when combined with PARP inhibitors. This work was translated into the clinic with recently completed phase I clinical trial combining bortezomib with veliparib in multiply relapsed myeloma patients. This work has led to the understanding that targeting DNA repair defects present only in tumor cells can represent a promising area of clinical investigation in Multiple Myeloma.
Dr. Paola Neri, MD, PhD is an Associate Professor of Medicine, attending physician in the Hematology division at University of Calgary and member of the Arnie Charbonneau Cancer Institute. Since January 2019 she is the Scientific Director of the Precision Oncology Hub, Translational Research Laboratory, at the Tom Baker Cancer Centre (TBCC) in Calgary. Dr. Neri received her medical degree at Magna Græcia University, Catanzaro, Italy in 2000. She completed her specialty in Medical Oncology at Magna Græcia University, Catanzaro, Italy in 2005 and received a PhD in Molecular Oncology and Experimental Immunology in 2011. From 2003-2006 she was Research Associate at Dana-Farber Cancer Institute, Harvard Medical School, Boston, USA under the mentorship of Dr. Kenneth Anderson. In June 2008, she joined the University of Calgary.
The main focus of her research is the study of multiple myeloma (MM) with a particular interest in drug development and genomic studies with the goal of discovering novel therapeutic targets for this incurable disease. As such she has investigated the genome signature associated with MM cell response or resistance to anti-MM agents to identify druggable therapeutic targets in MM and new biomarkers of response to novel agents.
Dr. Neri is well published in the field and received national and international grants from several agencies including International Myeloma Society, Leukemia and Lymphoma Society, Multiple Myeloma Research Foundation and Canadian Institute of Health Research (CIHR). In 2021 she was selected by the International Myeloma Society to receive the Ken Anderson Young Investigator Award for her impressive translational work in multiple myeloma.
She is currently member of the American Society of Hematology and the scientific board of Myeloma Canada, very active both in preclinical and clinical trial research in Myeloma.