Icahn School of Medicine at Mount Sinai
My research harnesses human induced pluripotent stem cell (iPSC) technology and CRISPR/Cas9 genome editing to create novel models of blood cancers. We are using these models to investigate disease mechanisms, identify new therapeutic targets and test new drugs.
I envision a new era of cancer research in which human cells and patient-derived tissues are increasingly utilized as primary discovery platforms and in which human iPSCs will be a valuable tool in the armamentarium of the modern cancer researcher.
Eirini Papapetrou obtained MD and PhD degrees from the University of Patras in Greece and did postdoctoral research in genetic engineering and stem cell biology at Memorial Sloan-Kettering Cancer Center, where she was one of the first investigators to derive patient-specific induced pluripotent stem cells (iPSCs) and use them in disease modeling and regenerative medicine applications. As an independent investigator, first at the University of Washington in Seattle and, since 2014, at the Icahn School of Medicine at Mount Sinai in New York, she developed iPSC models of myeloid malignancies, in particular Myelodysplastic Syndromes (MDS) and Acute Myeloid Leukemia (AML). Her lab harnesses somatic cell reprogramming, CRISPR genome editing and human pluripotent stem cell-derived hematopoiesis to develop novel iPSC-based models of MDS/AML-associated mutations and chromosomal deletions for genotype-to-phenotype studies, interrogation of disease mechanisms and genetic and small molecule screens with the goal to understand disease mechanisms, identify new therapeutic targets and repurpose drugs. Dr Papapetrou is the recipient of several awards, including the American Society of Gene and Cell Therapy (ASGCT) Outstanding New investigator Award, a Damon Runyon-Rachleff Innovation Award, the American Society for Clinical Investigation (ASCI) Young Physician-Scientist Award, a Sidney Kimmel Foundation Scholar Award, an American Society of Hematology (ASH) Scholar Award and an Ellison Medical Foundation New Scholar Award.
Therapeutic targets in myeloid neoplasms with splicing factor mutations
Myelodysplastic syndromes (MDS) are common disorders of the blood affecting primarily older adults. Over one third of cases progress to acute myeloid leukemia (AML). There is currently no effective treatment for MDS. No new drugs have been approved for MDS by the US FDA since 2006 and few of the compounds currently in development are likely to gain approval in the near future.
“It is a big honor to receive the Pershing Square Sohn Prize. It will allow me and my lab to take a high-risk approach to investigating the effects of splicing factor mutations in myeloid cancers.”
One of the most exciting discoveries of the large-scale sequencing of cancer genomes in recent years was the discovery of mutations in splicing factor genes in MDS. We now know that this new class of mutations is the most characteristic genetic feature of MDS. Over half of MDS patients harbor mutations in splicing factor genes in their blood cells and these seem to be very critical in the development of the disease. Therefore, targeting them presents a very promising approach to the development of new therapies for MDS.
“Innovation is conceiving a radical idea to explain a phenomenon or inventing a new technology to address a limitation of current methods and using it as a vehicle to take you somewhere that no one has been before. Innovation often needs to transcend scientific fields and requires a healthy disregard for established norms, ideas and models of a given scientific field. For example, our project uses a radically new model system to study the effects of cancer genes in human cells.”
My laboratory has pioneered a new approach to model MDS using cutting-edge technologies from the fields of stem cell research and CRISPR genome editing. Our system provides for the first time the opportunity to study MDS and the effects of splicing factor mutations in human induced pluripotent stem cell (iPSC)-based models that mimic many of the disease conditions more faithfully than animal models. Here we propose to perform a large-scale screen based on CRISPR technology to uncover new therapeutic targets. This work can uncover new therapeutic opportunities for MDS with splicing factor mutations for subsequent drug development.