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 made seminal contribution to the understanding of the biology of MDSCs and identified different genetic targets (PDE5, Arginase, NOS2, superoxide, IL4Ra) whose inhibition can reverse MDSCs ability to restrain effector T cells activity. Some of his findings had important repercussion on clinical trial design. For example, Dr. Serafini undisclosed a dual role of GM-CSF that can act as immune adjuvant or as immunosuppressive factor depending on the dose. This finding was extremely important in the design of Trial using GM-CSF as vaccine adjuvant (G-VAX vaccines) and allowed the definition of a maximum dose of GM-CSF in human vaccines. More recently, after identifying PDE5 as an important mediator of MDSCs suppressive activity, he started a Clinical Trial evaluating the immune-adjuvant role of PDE5 inhibitors in Head and Neck Squamous Cells Carcinoma. His preliminary results lead to opening similar trials in Johns Hopkins University (MD) and at Liverpool Cancer Center (UK). His work has been highlighted by Nature, Nature Business, The Faculty 1000, and other journals. His work has been cited more than 3900 times.
In the last years, Dr. Serafini established different nanoplatform to target MDSCs in vivo taking advantages of the progresses RNA aptamers selection and in PAMAM dendrimer modification. In particular, his team optimized the SELEX and Cell-SELEX techniques for aptamer selection. Using these new tools he was able to demonstrate the essential role of IL4Ra in MDSCs survival. Currently, his team is using these new tools to re-program MDSCs in vivo or for delivering therapeutics at the tumor site. In the field of nanotechnology, using peptide modified PAMAM dendrimer he was able to improve the efficacy of DNA vaccination and further analyze MDSCs biology in vivo.
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. Additionally, his laboratory is developing new aptamer based imaging reagents to track the desired cells in vivo or to measure beta cell mass in a setting of type 1 diabetes.
- 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
- He started the first clinical Trial using Tadalafil (Cialis) as immune modulator in HNSCC
- MDSCs can act as antigen presenting cell specific for regulatory T cells
- Selection of a blocking IL4Ra aptamer able to induce apoptosis in MDSCs and tumor associated macrophages in vivo.
Selected Cancer-Related Publications
Collaborating in the Multidisciplinary Research Program(s):