The main focus of our lab is to study stem cell biology and stem cell gene transfer with the goal of developing novel stem cell based treatment strategies for patients with genetic, infectious and malignant diseases. Most of our work has been with hematopoietic stem cells (HSCs) although more…
more recently we have also initiated studies using embryonic stem (ES) cells. Hematopoietic stem cells are attractive targets for gene therapy because of their ability to permanently reconstitute the hematopoietic and immune systems. However, in order to efficiently modify HSCs one has to be able to 1) identify and isolate HSCs and 2) identify vector systems that allow for efficient transduction of HSCs. Unfortunately stem cell gene transfer studies in the mouse have not been predictive for outcomes in large animal studies or patients. Thus we have focused on 1) studying and characterizing stem cells from large animal models and 2) developing and testing novel vector systems that allow efficient transduction of HSCs in these models. Findings in large animals models are generally very predictive for human applications, in particular with regard to stem cell gene transfer and transplantation. Thus current research in our laboratory focuses on studies to: 1) characterize HSCs from large animal models, 2) determine plasticity of hematopoietic and nonhematopoietic stem cells, 3) investigate hematopoietic differentiation of monkey ES cells, 4) analyze the integration site pattern of different retroviruses, 5) analyze the clonal composition of hematopoiesis after transplantation of gene-modified HSCs, 6) decrease or eliminate immune responses against gene-modified cells, 7) develop preclinical protocols using stem cell gene therapy to facilitate allogeneic nonmyeloablative stem cell transplantation, and 8) develop clinical gene therapy protocols for genetic and acquired diseases including cancer.
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