Age related diseases

Enrico Milan

Enrico Milan

Email: milan.enrico@hsr.it
Location: DIBIT1 A2, Floor 4, Room 23b

Project Leader, Age related diseases Unit

Enrico obtained his master’s degree in biotechnology at Università Vita-Salute San Raffaele, specializing himself in proteomics and identifying serum biomarkers able to predict patient response to EGFR inhibitor in non-small cell lung cancer (Milan et al., 2012).

In 2014, he received his PhD in Molecular Medicine at Università Vita- Salute San Raffaele in the lab of Dr. Simone Cenci investigating the role of autophagy in multiple myeloma (Milan et al. 2015). During these years he characterized the functions of the autophagic receptor of ubiquitinated proteins p62/SQSTM1 in multiple myeloma through an extensive and unbiased proteomic analysis of its interactors.

In 2015, he was visiting postdoctoral fellow in Prof. Jorge Moscat Lab at Sanford Burnham Prebys Medical Discovery Center, La Jolla CA.

He was awarded by national and international funding agencies with the Multiple Myeloma Research Foundation (MMRF) Junior Research Award 2016, the International Myeloma Foundation (IMF) Brian D. Novis Research grant 2019 and by Fondazione Cariplo with the Ricerca Biomedica Condotta da Giovani Ricercatori 2018 grant.

As principal investigator, he characterized the biological role and the related molecular circuits of multiple myeloma tumor suppressor FAM46C in regulating antibody secretion (Fucci et al., 2020, Perini et al., 2022). This opened new lines of research focused on investigating new molecular pathway impacting on plasma cell and multiple myeloma proteostasis, antibody production and drug sensitivity. His research activity is supported by Fondazione Telethon and Cariplo (Joint Grant on Rare Diseases) and Ministero della Sanità (Ricerca Giovani Ricercatori 2018 and 2019).

 

Research ACTIVITY

Multiple myeloma is a still incurable tumor of plasma cells responsible for 2% of all cancer deaths. Plasma cells are highly specialized secretory factories, derived from B lymphocyte differentiation, professionally devoted to antibody production and secretion. This massive effort causes a dependency of myeloma cells on pathways ensuring equilibrium between immunoglobulin synthesis, folding, secretion and degradation, as witnessed by the extraordinary success of proteasome inhibitors in the clinic.

Strengthening the relevance of this delicate coordination, mutations in genes driving plasma cell differentiation and antibody production have been identified in multiple myeloma patients. In particular, we have recently contributed to discover that the myeloma tumor suppressor FAM46C/TENT5C, which is lost in up of 20% of patients, is a non-canonical poly(A)polymerase that rapidly and potently promotes antibody secretion. Our discoveries reveal a selective pressure in multiple myeloma to reduce the cellular stress associated with immunoglobulin production to favor tumor growth. Projects funded by Fondazione Telethon and Cariplo and the Italian Ministry of Health are open in the lab to investigate the molecular circuits by which plasma cells regulate the levels and the efficiency of antibody synthesis to discover new vulnerabilities against this still uncurable cancer.