The Graham lab is a part of regeneration expert Nadia Rosenthal’s group at The Jackson Laboratory. The Graham lab is focused on the intersection of the mammalian immune system, cancer, and tissue regeneration.
In particular, we are interested in testing an 82-year-old hypothesis formulated by the noted British developmental biologist Conrad Waddington. By comparing the uncontrolled growth of cancer to the controlled process of embryonic development, Waddington proposed that cancer develops because of the interference with or loss of “developmental fields” mediating tissue organization. Like embryonic development, tissue regeneration requires a coordinated orchestration of factors mediating the restoration of cells, tissues, and organs that have been physically or functionally lost. Like a developmental field, a regenerative field must be capable of precisely regulating the cell cycle, it must guide cells to correct locations, and, once regeneration is complete, it must signal termination of the entire process. Implicit to Waddington’s hypothesis is the existence of a “field” of cell extrinsic factors regulating the activities of cells within a tissue; we think that perhaps these fields can also regulate the activities of cells burdened with cancer causing mutations.
Recently, a small rodent called the spiny mouse (Acomys spp.) was demonstrated to have true regeneration capability within its skin and ear tissue. Thus, for the first time since 1935, scientists have a regenerating mammalian model suitable to test Waddington’s hypothesis. As such, we are testing Waddington’s hypothesis by determining whether or not the regeneration-capable skin of the spiny mouse is resistant to carcinogen-induced skin cancer. Correspondingly, we are testing the skin wound healing ability and carcinogen-induced skin cancer susceptibility of a large panel of genetically diverse recombinant inbred mice (>75 strains). These studies will not only allow us to compare the spiny mouse cancer susceptibility to a non-regenerating rodent species, but they will allow us to further test Waddington’s hypothesis by determining if there is a correlation between strains with exceptional wound healing ability and cancer resistance.