Aberrant signaling in hematopoietic cells can have dramatic effects on both normal hematopoiesis and the progression of leukemia. T cell protein tyrosine phosphatase (TC-PTP;gene name PTPN2) was one of the first PTPs to be cloned (Cool DE, 1989). TC-PTP is ubiquitously expressed in murine embryonic and adult tissues, with highest expression in hematopoietic tissues (Mosinger B Jr, 1992).
The first knockout mouse model of a PTP was in fact the TC-PTP-/- mouse created in our lab (You-Ten KE, 1997). Since then, we have been at the forefront of all the major discoveries of TC-PTP function using this interesting mouse model. TC-PTP play essential roles in bone marrow erythropoiesis (You-Ten KE, 1997), inflammation (Heinonen KM, 2004)(Simoncic PD, 2002), lymphocyte development (Bourdeau A, 2007), and stem cell expansion (Bourdeau A, 2013).
Our molecular characterization of TC-PTP activity, demonstrated it as a negative regulator of JAK-STAT signaling in response to growth factor and cytokine stimulation. TC-PTP therefore plays a crucial role in immune cell homeostasis, differentiation and activation.
As such, we are currently working on strategies to target TC-PTP to re-activate or boost immune cell activity to treat chronic diseases such as cancer. Similarly, we are continuing our investigating into how TC-PTP modulates the number and status of hematopoietic stem cells (HSCs) to design strategies to enhance stem cell expansion for therapeutic adoptive transfers. These research objectives will bring us to understand this enzyme in the context of its function in chronic diseases and identify new therapeutics such as small molecule inhibitors.