Dhvanit I. Shah, PhD
Harvard Medical School
Our laboratory investigates the origin, development, and differentiation of hematopoietic stem cells (HSCs) to treat patients with leukemia, lymphoma, genetic blood disorders, and bone-marrow failure syndromes. We have expertise in utilizing zebrafish, mice, and human induced pluripotent stem (iPS) cells to clone and analyze novel genes and mechanisms important for blood formation. Our goal is to utilize our knowledge in developing mechanism-based therapies as well as generating functional HSCs from patient-derived tissues for the treatment of hematological diseases using state-of-the-art gene-editing, cell-engineering, and computational approaches.
HSC transplantation (HSCT) is used to treat patients with genetic blood disorders, bone marrow failure syndromes, leukemia and lymphoma. Despite advances in umbilical-cord and haplo-identical HSCT, its therapeutic use is restricted due to difficulty in finding HLA-matched donors, particularly for children born to multi-ethnic parents. Even if one finds a suitable match, immunologic complications such as graft-versus-host disease, donor rejection, and high treatment-related mortality can compromise patient survival. However, these complications are eliminated by autologous transplant. Therefore, there is a critical need to identify new methods and sources to generate compatible HSCs from patient-derived tissues.
Our laboratory analyzes how blood vessels give rise to hematopoietic stem cells (HSC) and investigates factors regulating this process. During fetal development, a subset of endothelial cells in the aorta-gonad-mesonephros, termed hemogenic endothelial cells, change their fate to become HSCs. However, the identity and molecular nature of hemogenic endothelial cells are enigmatic. We are investigating new cell-intrinsic, cell-extrinsic, and pharmacological targets that could stimulate endothelial emergence of HSCs.
Karp Family Research Building, Room 06.211
Boston, MA 02115