Hematopoietic stem and progenitor cells are often characterized by their biochemical properties, including size, granularity, expression of specific protein markers, etc. as well as their ability to perform in ex vivo assays such as how well they grow in culture. However, our previous work and other groups have shown that these properties don't always truly reflect functional or potent hematopoietic stem and progenitor cells. Furthermore, different applications (i.e., different forms of cell therapies) may depend on different functional properties of stem and progenitor cells. This project seeks to elucidate global mechanisms associated with stem and progenitor cell potency and to flesh out these mechanisms to find ways to improve the use of these cells in various therapies.

Relevant publications include:
The fulfilled promise and unmet potential of umbilical cord blood

Insights into highly engraftable hematopoietic cells from 27-year cryopreserved umbilical cord blood

Protocol for enrichment and functional analysis of human hematopoietic cells from umbilical cord blood 

Previous work by one of Jim's postdoctoral mentors revealed that Dipeptidyl peptidase 4 (DPP4/CD26) is a critical regulatory molecule in stress hematopoiesis. This work led to several clinical trials, the results of which made it clear that DPP4 inhibition is a viable strategy to improve hematopoietic cell transplantation by modulating the homing of stem and progenitor cells. Furthermore, a study in the New England Journal of Medicine by a clinician at IUSM found that prophylactic treatment with DPP4 inhibitors could reduce post transplantation complications. Finally, recent studies have suggested that DPP4 inhibition might inhibit the growth of malignant hematopoietic cells. Thus, this DPP4 is a multi-faceted molecule that plays a role in many different hematopoietic processes. However, its contrasting roles in healthy and diseased hematopoiesis as well as the mechanisms by which it works are unclear. Further, it is currently limited to high-dose treatments yielding modest effects in these contexts, suggesting this approach can still be improved upon.

Relevant publications include:
An expanded role for dipeptidyl peptidase 4 in cell regulation

Leukemia inhibitory factor promotes survival of hematopoietic progenitors ex vivo and is post-translationally regulated by DPP4 

This project involves targeting various gene programs that we have identified as important for healthy hematopoietic cell potency in the context of diseased hematopoiesis, such as acute myeloid leukemia.