Paolo Serafini, Ph.D.
Assistant Professor of Microbiology & Immunology
Description of Research
Dr. Serafini’s research interests focus principally on understanding the molecular and cellular pathways that regulate immune tolerance in physiological status as well as in disease. Two cellular populations appear to be particularly important in these processes: Myeloid Derived Suppressor Cells (MDSC) and regulatory T cells (Treg). Recent data from his laboratory reveal that these populations do not act only independently but can interact and synergize to create an immunosuppressive environment promoting long term, antigen specific tolerance.
In tumor setting Dr. Serafini's team is evaluating the molecular mechanisms that promote MDSCs activation and promote Treg expansion. Different genetic targets have been found (PDE5, Arginase, NOS2 superoxide, IL4Ra), and drugs able to block these pathways are being evaluated in murine models and in clinical trials. Moreover, they are developing new nanodrugs based either on RNA aptamers or in PAMAM dendrimer for the in vivo modulation of MDSCs and Treg pathways.
In autoimmune disease and transplantation settings Dr. Serafini is evaluating new therapeutic approaches based on the in vivo induction/ adoptive cell transfer of MDSCs and/or Treg to induce antigen specific T cell tolerance. These approaches are based on what they are learning from studying tumor induced tolerance, are developed in collaboration with the DRI, and might be a solution toward the cure of type 1 diabetes and other autoimmune diseases.
Different projects are currently under development in Dr. Serafini’s laboratory:
- Cross-talking between MDSCs and Treg during tumor progression in murine models
- Inhibition/depletion of MDSCs in tumor bearing mice using RNA based aptamer
- In vivo genetic manipulation of MDSCs using PAMAM dendrimers in tumor bearing mice
- In vivo APC targeted genetic vaccination by the use of PAMAM dendrimer (in collaboration with Dr. Daftarian)
- Evaluation of the immune-modulatory properties of PDE5 inhibitors in patients with Head and Neck Squamous Cell Cancer (HNSCC) (in collaboration with Dr. Weed, Dept of Otolaryngology)
- Retrospective analysis of tumor infiltrating leukocytes in patient with HNSCC (in collaboration with Dr. Weed, Dept of Otolaryngology)
- Generation of MDSC from cord blood as a tool for promoting tolerance in Type 1 Diabetes (in collaboration with Dr. Inverardi, Diabetes Research Institute)
- In vivo induction of MDSCs and Treg to prevent allograft rejection (in collaboration with Dr. Inverardi, Diabetes Research Institute)
Highlights
- Identification of MDSCs as a population able to suppress immune response
- Molecular characterization of MDSCs and their mechanisms of immunosuppression in tumor bearing mice
- Identification of PDE5 inhibitors as a tool to reverse tumor induced immunosuppression and prime a spontaneous immune response
- MDSCs can act as antigen presenting cell specific for regulatory T cells
Selected Cancer-Related Publications
Programs
Collaborating in the Multidisciplinary Research Program(s):