The Scharenberg laboratory has two major areas of interest: Mg2+ transport and cation channel function in the immune system, and the development of cell engineering technology.
Current effort is centered in two areas:
1) Mg2+ transport and cation channel function.
We have characterized novel divalent cation entry pathways mediated by TRPM7 and SLC41A1, and have shown that these proteins play important roles in Mg2+ homeostasis and control of cell proliferation. With the recent demonstration that a 3rd class of Mg2+ transporters, the MAGT1 family, plays a key role in early TCR signaling, we have begun to dissect the differing roles and functions of each Mg2+ transport pathway in lymphocyte physiology using a unique suite of Mg2+ transport reagents, electrophysiology, atomic mass spectrometry, and cell engineering technology.
2) Development of cell engineering technolog:
a) We have had a longstanding interest in developing gene repair methods for hematopoietic genetic diseases, and working within the Northwest Genome Engineering Consortium, we have pioneered homing endonuclease engineering technology for this purpose. Present efforts are centered on optimizing nuclease and repair template delivery to primary and pluripotent stem cells using viral vectors and advanced electroporation methods, and on implementing gene repair in primary cells and animal models.
b) Two recent reports this past summer demonstrated that adoptive cell therapy for cancer has the potential for curative therapy of a range of malignancies for which present standard therapies are limited capacity. Our group is working with Dave Rawlings laboratory at the Center for Immunity and Immunotherapies and Michael Jensen’s laboratory at the Center for Childhood Cancer to apply a variety of cell engineering tools, including TAL effector nucleases, homing endonucleases, lentiviral and foamy viral gene transfer vectors, and advanced electroporation techniques to develop the next generation of safe and controlled adoptive cell therapies.
