Athanasia Panopoulos Elizabeth and Michael Gallagher Assistant Professor
During embryonic development, differentiation of embryonic stem cells (ESCs) results in a loss of lineage potential as cells become more committed and functionally restricted. This process was always thought to be unidirectional. However, the discovery that somatic cells could be reprogrammed back into a pluripotent state (referred to as induced pluripotent stem cells, or iPSCs) after the transduction of four defined transcription factors forever altered our initially restricted view of cellular plasticity (Takahashi and Yamanaka, 2006), and enabled researchers new ways to study development and disease.
The long-term research goals of my laboratory are to utilize somatic cell reprogramming to provide new opportunities in targeted cancer therapeutics and regenerative medicine.
Using reprogramming to understand cancer: Increasing evidence supports the concept that instances of cancer recurrence may be due to a subpopulation of cells within a tumor that behave as stem cells. Many studies have demonstrated that these populations contain specific markers, which can vary between types of cancer. Being able to identify and target these cells is a critical step. But the fundamental question remains: how do these specific cancer cell populations acquire stem cell properties? Previous studies from our laboratory and others have demonstrated that pathways critical in oncogenesis parallel those necessary for the induction of pluripotency, suggesting that similar mechanisms regulate both processes. Could iPSC research guide us towards understanding how a cancer cell acquires stem cell properties? Can we identify novel molecular mechanisms required for reprogramming that can be utilized to target cancer cells with stem cell characteristics? One focus of my laboratory is to examine the specific mechanisms that govern reprogramming that have also been implicated in cancer. This will enable us to gain insight into the methods by which cancer cells acquire and exploit stem cell properties, in the hopes that we may be able to strategically target these cell populations to prevent malignant relapse.
Using reprogramming to understand blood cell development: Although human pluripotent stem cells (i.e. ESCs and iPSCs) 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 functional hematopoietic stem cells (HSCs), the cells that enable long-term reconstitution of the entire blood system. One focus of my laboratory uses reprogramming 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. Why blood? If we were able to successfully make HSCs from human iPSCs, 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.
- Gallagher Family Assistant Professor of Stem Cell Biology, University of Notre Dame, IN 2014-Present
- Director, Flow Cytometry Core Facility 2016-Present
- Postdoctoral Fellow, The Salk Institute, CA 2007-2013
- Ph.D. Immunology, MD Anderson Cancer Center, TX 2007
- Ruiz S*, Gore A*, Li Z, Panopoulos AD, Montserrat N, Fung HL, Giorgetti A, Bilic J, Batchelder EM, Zaehres H, Scholer HR, Zhang K, Izpisua Belmonte JC. Analysis of protein-coding mutations in hiPSCs and their possible role during somatic cell reprogramming. Nature Communications 4:1382 (2013).
- Panopoulos AD*, Yanes O*, Ruiz S, Kida YS, Diep D, Tautenhahn R, Herrerias A, Batchelder EM, Plongthongkum N, Lutz M, Berggren WT, Zhang K, Evans RM, Siuzdak G, Izpisua Belmonte JC. The metabolome of induced pluripotent stem cells reveals metabolic changes occurring in somatic cell reprogramming. Cell Research 22:168-177 (2012).
- Ruiz S, Panopoulos AD, Montserrat N, Multon MC, Daury A, Rocher C, Spanakis E, Batchelder EM, Orsini C, Deleuze JF, Izpisua Belmonte JC. Generation of a drug-inducible reporter system to study cell reprogramming in human cells. Journal of Biological Chemistry 287:40767-40778 (2012).
- Panopoulos AD, Izpisua Belmonte JC. Induced pluripotent stem cells in clinical hematology: potentials, progress, and remaining obstacles. Review. Current Opinion in Hematology 19:256-260 (2012).
- Gore A, Li Z, Fung HL, Young J, Agarwal S, Antosiewicz-Bourget J, Canto I, Giorgetti A, Israel M, Kiskinis E, Lee JH, Loh YH, Manos PD, Montserrat N, Panopoulos AD, Ruiz S, Wilbert M, Yu J, Kirkness E, Izpisua Belmonte JC, Rossi DJ, Thomson J, Eggan K, Daley GQ, Goldstein LSB, Zhang K. Somatic coding mutations in human induced pluripotent stem cells. Nature 471:63-67 (2011).
- Panopoulos AD*, Ruiz S*, Yi F, Herrerias A, Batchelder EM, Izpisua Belmonte JC. Rapid and highly efficient generation of induced pluripotent stem cells from human umbilical vein endothelial cells. PLoS One 6:e19743 (2011).
- Panopoulos AD, Ruiz S, Izpisua Belmonte JC. iPSCs: Induced back to controversy. Preview. Cell Stem Cell 8:347-348 (2011).
- Kelber JA, Panopoulos AD, Shani G, Booker EC, Belmonte JC, Vale WW, Gray PC. Blockade of Cripto binding to cell surface GRP78 inhibits oncogenic Cripto signaling via MAPK/PI3K and SMAD2/3 pathways. Oncogene 28:2324-2336 (2009).