Our Faculty : Primary Faculty

Paolo Serafini, Ph.D.

Dr. Serafini’s research interests focus principally on understanding the molecular and cellular pathways myeloid cells, and in particular myeloid derived suppressor cells (MDSC), employed to regulate immune tolerance in physiological status as well as in disease.

In tumor setting, Dr. Serafini laboratory 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 demonstrate that PDE5 inhibitors beneficially modulate the immune system in patients with Head and Neck Squamous Cells Carcinoma reducing both MDSC and regulatory T cells and increasing the number of tumor specific CTL.

In the last years, Dr. Serafini laboratory established different nanoplatforms 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 conjugating molecular biology, NSG –sequencing and bio-informatic analysis. 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 laboratory 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.
His work has been cited more than 5000 times and highlighted by Nature, Nature Business, The Faculty 1000, and other journals.

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
• Demonstration that Tadalafil (Cialis) can beneficially modulate the immune response in HNSCC
• Selection of a blocking IL4Ra aptamer able to induce apoptosis in MDSCs and tumor associated macrophages in vivo.
• Demonstration that MDSCs act as antigen presenting cell specific for regulatory T cells

Current Research Interests
1. Targeting tumor associated myeloid cells in vivo via RNA aptamer to vehicle chemotherapeutic drugs and therapeutic RNAs
2. Determining the role of chemokine receptors in myeloid cell polarization in tumor hosts
3. Evaluating the synergy of PDE5 inhibitors and anti-tumor vaccine in patients with HNSCC undergoing salvage surgery.
4. Use of MDSCs in Type 1 diabetes to induce long term tolerance
5. Use of RNA aptamers to vehicle imaging reagents and therapeutic RNAs to mouse and human islets.

Research Profile
Pubmed Link