My research encompasses the phylogeny and developmental biology of the cells that make up the blood-forming and immune systems.

My laboratory was first to identify and isolate the blood-forming stem cell [HSC] from mice, and has defined, by lineage analysis, the stages of development between the stem cells and mature progeny.  We have also discovered the human HSC, a human brain-forming stem cell population, mouse skeletal muscle stem cells, and an osteochondral stem cell in mice. I have worked in cancer research since 1977, and more recently have concentrated on cancer stem-cell biology. In recent years, my work has included studying the potential of CD47 as a cancer therapeutic, and identifying cancer stem cells from a variety of blood and solid cancers. My colleagues and I have found that CD47, a “don’t-eat-me” signal, is highly expressed beginning in the latter stages of progression of cancer stem cells from the benign to the highly malignant state, and this counteracts “eat me” signals on preneoplastic and highly malignant cancer cells, presumably as part of the evolution of cancer clones driven by self-renewing subsets of cells in the cancer. This research brings into focus the primary role of phagocytic cells such as macrophages of the innate immune system, in tumor surveillance.

I also have a laboratory at the Hopkins Marine Station of Stanford University, where I study the histocompatibility systems in colonial protochordate. I propose that this system evolved to prevent predatory germline stem-cell lineages from passing from one individual to another in multi-individual colonies that share a common extracorporeal blood vascular system. Only histocompatible stem cells can colonize allogeneic natural parabionts.

I direct a research group consisting of graduate students, medical student-scientists and postdoctoral fellows, all of whom study stem-cell biology and regenerative medicine. Over the years I have trained and supervised hundreds of students and fellows, and published more than 750 scientific articles.