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Papapetrou Lab

This post features the laboratory of Dr. Eirini Papapetrou, an Associate Professor of Oncological Sciences and Associate Professor of Medicine, Hematology, and Medical Oncology. Her lab is located at the Leon and Norma Hess Center for Science and Medicine at the Icahn School of Medicine at Mount Sinai, New York, New York and is also part of the Tisch Cancer Institute and the Black Family Stem Cell Institute (BFSCI).

Focus on the Study of Human Disease Using Pluripotent Stem Cell Models

The Papapetrou Lab uses technologies related to the reprogramming of somatic cells and genome editing such as CRISPR and others. They aim to develop models of blood diseases out of human pluripotent stem cells, specifically of premalignant and malignant hematopoietic diseases including Myelodysplastic Syndromes (MDS) and Acute Myeloid Leukemia (AML). Using such models, the Papapetrou team focuses on the exploration of disease mechanisms as well as the development of possible, new therapies.

The team seeks to understand the consequences involving the phenotypes and functions of induced pluripotent stem cells (iPSCs) derived from patients once they have been engineered to harbor certain mutations characteristic of blood disease as well as larger abnormalities in chromosomes including chromosomal deletions. Additionally, the team is determined to find new targets for therapy through chemical and genetic screening.

Latest Findings

  1. Studying Myelodysplastic Syndromes with Human iPSCs Models

Myelodysplastic syndromes (MDS) are clonal hematologic disorders which have the following characteristics:

  • Ineffective hematopoiesis.
  • risk to progress into acute myeloid leukemia (AML)

Previously thought of as rare disorders, MDS are currently considered as one of the most common types of blood cancers. However, little is known about them in terms of their pathogenesis. That said, there is lack of present tools used to study MDS. Certain limitations are contributory such as the non-existence of cell lines, the heterogeneity of primary cells, the difficulty in growing them ex vivo, and the inability of animal models that effectively recapitulate human myelodysplastic syndromes.

At the Papapetrou Lab, they have recently generated primary iPSC models which are iPSCs derived from the MDS clone or normal iPSCs derived from the residual hematopoietic cells. This is done by basically reprogramming hematopoietic cells that have been derived from the bone marrows of patients affected by MDS.

As a result, the study offers new possibilities to understand the cellular and molecular pathogenesis of MDS which also include its genetics and clonal evolution. It further offers a powerful basis for genetic and chemical screens based on their phenotypes thus introducing the possibility of identifying new therapeutic targets.

  1. Disease-Associated Chromosomal Deletions with CRISPR Models

Chromosomal deletions found in human diseases are not extraordinary in normal and cancer genomes. In fact, they could play an essential role in complex diseases as well as cancer.

The difficulty of studying chromosomal deletions is indubitable because of the limitations of physical mapping approaches of primary patient material. Informative cases are often few in numbers while conservation of synteny is very incomplete thus complicating the modeling in mice.

In lieu of these limitations, the Papapetrou Lab has established a novel approach for modeling disease-related chromosomal deletions in human iPSCs. They have modified Cre-loxP and CRISPR/Cas9 technologies in order to delete specific terminal or interstitial chromosomal fragments in a hemizygous manner. As a result, they were able to map disease phenotypes according to function as well as identify specific disease genes that could be possible candidates by way of phenotype-rescue screens.

Newer lab projects include: the development of patient-derived iPSC models to study disease progression from MDS to full-blown AML; studying the effects of mutations in spliceosome genes (SRSF2, SF3B1, U2AF1) in MDS; studying the stem and progenitor cell populations derived from normal human pluripotent stem cells, their lineage and engraftment potential; modeling JAK2 and CALR mutations in myeloproliferative neoplasms.

Please leave a comment below with any questions you have for Dr.Papapetrou or any other labs you would like to see us feature.

The Stem Cell Podcast Team
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