Shahin Rafii's laboratory focuses on stem cell biology and angiogenesis uses in vivo mouse model and mouse and human genetics, tissue culture approaches and molecular biology to model angiognesis, cancer and stem cell metabolic regulation. Genetic, genomic, molecular and cell biological techniques are combined to achieve a systems level understanding of these complex processes.

Currently, Rafii's work is focused on identifying the molecular and cellular pathways involved in organ regeneration and tumor growth. He has established the concept that vascular endothelial cells are not just inert plumbing to deliver oxygen and nutrients, but also by production of tissue-specific growth factors, defined as angiocrine factors, support organ regeneration and tumor proliferation. He has shown that bone marrow endothelial cells by elaboration of angiocrine factors, such as Notch ligands, support stem cell self-renewal and differentiation into lymphoid and myeloid progenitors. He has recently demonstrated that liver and lung endothelial cells are endowed with unique phenotypic and functional attributes and by production of unique instructive growth factors contribute to the hepatic and alveolar regeneration.