The long-term research goals of the Panopoulos Laboratory are to harness the power of stem cells/reprogramming to provide innovative and clinically relevant advances in targeted cancer therapeutics and regenerative medicine.
During embryonic development, differentiation of embryonic stem cells results in a loss of lineage potential as cells become more committed and functionally restricted to develop a complete organism. This process was always thought to be unidirectional. However, the Nobel Prize-winning discovery that mature cells could be reprogrammed back into an embryonic-like (or “pluripotent”) state (referred to as induced pluripotent stem cells, or iPSCs) using transcription factors forever altered our initially restricted view of cellular plasticity, and enabled new ways for scientists to study development and disease.
Using Stem Cells to Identify and Target Novel Embryonic Mechanisms Exploited in Aggressive Cancer
Finding reliable approaches to identify and target embryonic mechanisms that mediate aggressive, uncontrolled cancer growth would have great therapeutic value. This assertion is based on a number of reports that have shown evidence of embryonic stem cell programs in highly malignant and metastatic cancers. Despite these findings, fundamental questions remain: How are metastatic cancer cells repurposing embryonic mechanisms to mediate aggressive outcomes? Which embryonic mechanisms could be serving as functional biomarkers of aggressive disease, and how can we target them successfully? One focus of the Panopoulos Laboratory is to identify and target embryonic mechanisms in cancer. These studies enable us to gain novel insight into the methods by which cancer cells acquire and exploit stem cell properties, and to develop methods to strategically target these cell populations to prevent malignant relapse.
Using Reprogramming to Identify Critical Mechanisms Regulating Normal and Aberrant Blood Cell Development
Although human pluripotent stem cells (i.e., embryonic stem cells and induced pluripotent stem cells) have the potential to differentiate into any cell lineage in the human body, researchers have not yet been able to obtain fully functional cells for some cell types. A long-standing hurdle in the hematopoietic field has been the inability to differentiate human pluripotent stem cells into fully functional hematopoietic stem cells (HSCs), the cells that enable long-term reconstitution of the entire blood system. One focus of the Panopoulos Laboratory uses reprogramming and genomic analysis to identify novel developmental deficiencies that exist in current blood cell differentiation protocols, in hopes of obtaining fully functional human HSCs in vitro from pluripotent cells that could be used in the clinic. We are also using reprogramming to generate tissue culture models of leukemogenesis for comparative analysis, to collectively identify novel mechanisms regulating both normal and aberrant blood cell development. Why blood? If we were able to successfully make HSCs from human iPSCs (i.e., make blood stem cells “in a dish”), then it is our hope that patients in need of a bone marrow transplant would no longer have to wait to find a bone marrow matched donor, and we could treat numerous blood diseases in ways we were not able to before.