DMM Outstanding Paper Prize 2019 winner: Alessandro Bailetti

Dr Alessandro Bailetti grew up in Pisco, a small port city in the south of Peru. In his family's farm, he saw his father and grandfather use basic genetics to improve the crops and cattle of their farm. His family immigrated to northwest Florida in the United States in 2004. After finishing high school, Alessandro decided to attend his local community college, Pensacola State College (PSC; Pensacola, FL, USA). Quickly, Alessandro became involved in campus life and joined the Phi Theta Kappa Honors Society. Alessandro graduated from PSC in 2009 with an associate's degree in mathematics. He was awarded the very competitive Jack Kent Cooke Undergraduate Transfer Scholarship and transferred to Cornell University (Ithaca, NY, USA). He joined the Lin laboratory to study Jagged1 and Notch signalling in mammalian neurogenesis. He was awarded the National Science Foundation (NSF)-Cornell University Undergraduate Research Fellowship to undergo his undergraduate research. His honours research focused on the roles of Jagged1 in neurogenesis during mouse development. In collaboration with a PhD student, Chris Blackwood, part of his work was published in Frontiers of Biology (Blackwood et al., 2020).

He graduated with honours with a bachelor's degree in biological sciences from Cornell University in 2012. He was awarded the NSF Graduate Research Fellowship and the Jack Kent Cooke Graduate Scholarship to pursue his PhD degree at New York University (New York, NY, USA). Alessandro joined Dr Erika Bach's laboratory for his doctoral studies. In the Bach laboratory, Alessandro worked on using Drosophila as a model for myeloproliferative neoplasms (MPNs). MPN patients carry a JAK2 mutation that increases JAK/STAT signalling and proliferation of myeloid lineage cells. A mutation in the fly JAK gene (hop) called hop^Tum increases JAK/STAT activity and myeloid-like cells, a similar phenotype to that found in MPN patients (Anderson et al., 2017).

In collaboration with a postdoc, Dr Abigail Anderson, Alessandro performed a deficiency screen looking for modifiers in the tumour burden in the JAK hyperactive mutant hop^Tum. They and colleagues found 32 enhancers and 11 suppressors of the tumor burden (Anderson et al., 2017). Alongside Dr Anderson, Alessandro validated one of the enhancers, expanded, which is part of the Hippo pathway. They and colleagues found a novel role of the Hippo pathway in the circulating haemocytes, concluding that Hippo activity contributes to the suppression of haemocyte proliferation, and that Yki activation, owing to Hippo mutations or ectopic expression of yki, increases haemocyte proliferation (Anderson et al., 2017).

Dr Bailetti also explored a second enhancer from the deficiency screen, Enhancer of Polycomb [E(Pc)] (Anderson et al., 2017; Bailetti et al., 2019). Unlike its name suggests, E(Pc) is a member of the Tip60 complex. The Tip60 complex transfers acetyl groups to lysine residues, which is reversed by the action of lysine deacetylases (KDACs). Bailetti and colleagues found that depletion of E(Pc) in the haematopoietic system increased the hop^Tum tumour burden (Bailetti et al., 2019). More interestingly, depletion of E(Pc), Tip60 and other members of the Tip60 complex in a healthy wild-type animal was sufficient to lead to development of lamellocytes and tumour formation. This showed that the Tip60 complex was necessary for tumour suppression and lamellocyte differentiation in flies. In addition, Alessandro showed that depletion of E(Pc) and Tip60 in the haematopoietic system increased the JAK/STAT activity without increasing the expression of its ligands, JAK or STAT. Finally, he showed that depletion of E(Pc) or the inhibition of Tip60, using KDAC inhibitors, increased the Hop protein level. This elucidated that the role of E(Pc) through the Tip60 complex in the haematopoietic system was to attenuate Hop protein levels and, hence, JAK/STAT activity (Bailetti et al., 2019).

Alessandro is an avid promoter of equality and inclusion in science. He has been a member of multiple mentoring programmes aimed at increasing minority students in the science, technology, engineering and mathematics (STEM) field. Alessandro was a mentor and director of the Clear Directions mentoring program at New York University designed to help high-school minority students discover careers in the STEM field. He is also an active member of the Research Experience for Peruvian Undergrads (REPU) programme that helps current undergraduate students in Peru find international research experience. Dr Bailetti is currently a postdoctoral fellow at Stanford University (Stanford, CA, USA) in Dr Anthony Oro's laboratory. His current research aims to understand how the genomic landscape changes and contributes during stem cell differentiation to skin.