Clinical Associate Professor/Academic Scientist
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.
I am a Clinical Associate Professor of Medicine, attending physician in the Hematology division at University of Calgary and member of the Arnie Charbonneau Cancer Institute. I received my medical degree at Magna Græcia University, Catanzaro, Italy in 2000. I have completed my 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 I was Research Associate at Dana-Farber Cancer Institute, Harvard Medical School, Boston, USA under the mentorship of Dr. Kenneth Anderson and Dr. Nikhil Munshi. The main focus of my research is to investigate the genome signature associated with myeloma resistance to anti-MM agents and to identify druggable therapeutic targets in myeloma. I am well published in the field and some of my research work included the development of the scid-hu myeloma model and the pre-clinical investigation of several classes of drugs in this disease. Several of these pre-clinically validated targets are currently in early phase I clinical studies (BAFF inhibitors, HDAC inhibitors, ITGB-7 and PARP inhibitors). I have received national and international grants from several agencies including Myeloma Canada, Leukemia and Lymphoma Society, The International Multiple Myeloma Research Foundation and Canadian Institute of Health Research (CIHR). I have presented my research at numerous national and international meetings, and has chaired and participated in numerous international forum including the American Society of Hematology and the International Myeloma Workshop. I am 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.