Irving L. Weissman's research encompasses the phylogeny and developmental biology of the cells that make up the blood-forming and immune systems. His laboratory identified and isolated the blood-forming stem cell from mice, and has defined, by lineage analysis, the stages of development between the stem cells and mature progeny (granulocytes, macrophages, etc.). This required developing and cloning stromal cells of the hematolymphoid microenvironments—from the bone marrow for myeloid and B cells, and from the thymus for T cells. While the adhesion molecules and factors from these stromal cells proved important as molecules (and the genes that encode them) for myeloid and B cells, the analysis of T cell development required in vivo studies of thymic development. In addition, the Weissman laboratory has pioneered the study of the genes and proteins involved in cell adhesion events required for lymphocyte homing to lymphoid organs in vivo, either as a normal function or as events involved in malignant leukemic metastases.

The Weissman laboratory also has a small group at Hopkins Marine Station, where they have developed a model organism for laboratory and field study of allorecognition—the invertebrate counterpart of transplantation immunity. Working with the protochordate Botryllus schlosseri (which has a chordate larval stage and an invertebrate adult form) they have identified a single major gene locus that governs rapid allorecognition, and 2-3 other loci involved in delayed allorecognition events. They are using this model to study the genes, proteins, and cells that govern protochordate allorecognition, and the effects of these genes on their population dynamics in the field.

• Narala SR, Allsopp RC, Wells TB, Zhang G, Prasad P, Coussens MJ, Rossi DJ, Weissman IL, Vaziri H "SIRT1 Acts as a Nutrient-sensitive Growth Suppressor and its Loss is Associated with Increased AMPK and Telomerase Activity." Mol Biol Cell 2008; More
• Bababeygy SR, Cheshier SH, Hou LC, Higgins DM, Weissman IL, Tse VC "Hematopoietic Stem Cell-Derived Pericytic Cells in Brain Tumor Angio-Architecture." Stem Cells Dev 2008; More
• Karsunky H, Inlay MA, Serwold T, Bhattacharya D, Weissman IL "Flk2+ common lymphoid progenitors possess equivalent differentiation potential for the B and T lineages." Blood 2008; More
• Xiong A, Austin TW, Lagasse E, Uchida N, Tamaki S, Bordier BB, Weissman IL, Glenn JS, Millan MT "Isolation of Human Fetal Liver Progenitors and Their Enhanced Proliferation by Three-Dimensional Coculture with Endothelial Cells." Tissue Eng Part A 2008; More
• Bhattacharya D, Ehrlich LI, Weissman IL "Space-time considerations for hematopoietic stem cell transplantation." Eur J Immunol 2008; 38: 8: 2060-2067 More