Adult and pluripotent stem cell research not only has huge potential for the future of regenerative medicine, but also holds promise to elucidate pathways altered in malignant transformation due to parallels between stem cells and cancer. Embryonic stem cells (ESC) and induced pluripotent stem cells (iPSC) exhibit the rare characteristics that they can contribute to all three germ layers in vivo and are capable of self-renewal in vitro. Where as, one example of adult stem cell, the hematopoietic stem cell (HSC), maintains hematopoiesis throughout life and has the potential to both self-renew and differentiate to the multiple cell lineages of the hematopoietic system. Both intrinsic and extrinsic molecular mechanisms such as cytokine signaling and transcription factors play a key role in stem cell fate decisions. However recent studies by our lab and others have suggested that ubiquitin proteasome system (UPS), a key modulator of protein stability and function, also regulates self-renewal and lineage specification adding an additional layer to molecular mechanisms regulating stem cells.
My research interest centers on the molecular mechanisms regulating stem cell fate decisions that may also be linked to cancer. My goal is to utilize genomic and proteomic approaches to identify key ubiquitin ligases and their substrates that regulate mechanisms of pluripotency, self-renewal, differentiation, and hematopoietic malignant transformation. The dynamic reversibility of the ubiquitin modification (by kinases, phosphatases, E3 ligases and de-ubiquitinases) and recent success of a UPS inhibitor (Velcade) for the treatment of multiple myeloma and mantle cell lymphoma proves the translational importance of the UPS system. This suggests that targeting of specific elements of the UPS could lead to future breakthroughs in both basic research and cancer therapy by leading to more efficient generation of induced pluripotent stem cells, promoting lineage differentiation for cell therapy, and provide potential targets for drug discovery.
Shannon Buckley- Assistant Professor
Rachel Willow Hynes - Graduate student
Qulsum Akhter Mir- Research Technologist
Lab Publications (PubMed)