Research Interests

  1. Hematopoietic stem cell biology and application in cancer therapy. Transplantation of hematopoietic stem cells is of considerable promise for treatment of some genetic defects, malignancies, and immune diseases. We study the biology of hematopoietic microenvironment and developing technology pertinent to the improvement of hematopoietic stem cell transplantation, particularly of haploidentical stem cells and the associated immunosuppression due to pre-transplant conditioning.
  2. Biology of dendritic cells and their interactions with T cells. We are investigating the role of T cells in induction of dendritic cell phenotype and function. We are focusing on the morphology of dendritic cell membrane rearrangement and redistribution of antigen presenting and co-stimulatory molecules in the membrane. In addition, we are studying mechanisms and functional consequences of membrane transfer among the cells of the immune system.
  3. Interactions of dendritic cells and T cells with drugs. Pharmacological agents in dendritic cells and T cells may modulate immunity. Thus, the understanding of this role is important for feasibility of immunotherapy and immunosuppression. Currently, we are studying the imatinib mesylate, a drug effective in the treatment of chronic myeloid leukemia and other malignant diseases. Our functional models include dendritic cell maturation (terminal differentiation) and mixed lymphocyte reaction that we study by use of transcriptome, proteome and phosphoproteome analysis.
  4. Engineering dendritic cell grafts for cancer immunotherapy. We are developing technology for clinical-grade manufacturing of dendritic cell grafts for clinical trials. The ongoing and planned clinical trials include chronic myelogenous leukemia, malignant melanoma, ovarian carcinoma, pancreatic carcinoma and others. We have accomplished major steps in optimizing ex vivo maturation of myeloid dendritic cells from precursors selected by CD14‑specific immunomagnetic adsorption such as reduction of manufacturing time, simplification of the maturation medium, replacement of research-grade components with pharmaceutical grade components and introduction of a closed system for manufacturing. The continuing optimization includes the use of completely synthetic media that will increase the purity and yield and increase the optimal phenotype and function of cellular grafts.
  5. Recombinant replication-defective adenoviruses for gene transfer to dendritic cells. We pioneered the use of recombinant replication-defective adenoviruses for gene transfer to human dendritic cells. We focused on the application of adenoviruses harboring the gene for human IL-2 in the hope that they will provide a powerful tool for preparation of dendritic cells that secrete IL-2 and stimulate expansion of cytotoxic T cells. We are designing the first clinical use of this technology in clinical trials of dendritic cell immunotherapy of malignant diseases.