Angela Savino is a postdoctoral fellow at Memorial Sloan Kettering Cancer Center (MSKCC) in Michael Kharas’s laboratory, focusing on translational laboratory-based research of hemato-oncology, with a particular emphasis on acute leukemia. I have experience in basic cancer biology as well as in translational research.

Prior to this position, she started her education in Italy where she obtained her bachelor degree in Industrial Biotechnology at University of Bari during which she spent a year in an analytical chemistry lab studying drug controlled-release devices under the supervision of Prof. Elvira De Giglio. Then she moved to Milano where she earned her Master Degree at University of Milano-Bicocca in Genomic Biotechnology and her master thesis was developed in the R&D department of a pharmaceutical company (Lofarma S.P.A), leader in production of vaccines for allergies in Italy. This time spent in the company made her experience a different reality compared to the academia and meet some patient and disease-oriented needs in a more concrete way. After that, she worked in the same company as Quality Control Technician before she started her PhD in translational medicine at Fondazione Tettamanti, a research center closely collaborating with University of Milano-Bicocca and leader for diagnosis and monitoring of genetic abnormalities in childhood leukemia for all Italy. As graduate student, she focused on novel therapeutic strategies to target CRLF2/JAK2 driven malignancies (Leukemia 2017). Importantly, in this work the HADAC inhibitor givinostat selectively killed the malignant cells in CRLF2/JAK2-driven ALL potentiating the effect of current chemotherapy and overcoming the well know effect of JAK-inhibition resistance. Most importantly, she learned critical thinking skill and how to ask salient research questions that have potential to make great impacts on the field. She got my PhD in 2015. Soon after she moved to Tel Aviv to Professor Shai Izraeli’s laboratory in Sheba Medical Center focusing on studying the pathogenesis of Acute Lymphoblastic Leukemia with signaling pathway alterations, mainly focusing on CRLF2/JAK2 driven ALLs. She contributed to characterize the USP9X loss in Down Syndrome JAK driven leukemia (published as a co-first author in May 2017 in PNAS). She made the discovery that JAK signaling requires buffering for survival of leukemic cells. Importantly, she discovered that Ruxolitinib, in the dose given in the clinic, may paradoxically promote the survival of JAK mutated lymphoid leukemic cells. Furthermore, she contributed to creating a mouse model for IL7/CRLF2/JAK driven lymphoid leukemia with the intention of dissecting an instructive role for IL7RA in the development of human B-cell precursor leukemia (under review in Nature Communications).

In the last part of her first post doc, she developed a growing interest towards metabolic adaptation of leukemic cells, especially to extramedullary sites. Motivated by this type of cancer research, she has spent last two years of her first post doc and the first year of her second, modeling and studying the pathogenesis of CNS (central nervous system) leukemia using in vitro and in vivo models of CNS-prone human xenografts. This study unraveled the dependency of this leukemia on de novo lipid synthesis and pointed out Steroyl CoA-desaturase (SCD) as a new metabolic driver of CNS lymphoid leukemia. This manuscript has been published in Nature Cancer (2020).

DESCRIPTION OF HER CURRENT WORK

Since 2019 the main focus of her research has been to determine the metabolic vulnerabilities of leukemia stem cells (LSCs) in relation to RNA Binding Proteins, specifically MSI2, with the goal of identifying novel therapeutic strategies that selectively target malignant cells in leukemia patients. To date, she has been actively involved in targeting metabolic adaptation of acute myeloid leukemia cells to alternative nutrients in a context of disease-induced stress. In the Bone Marrow (BM), high proliferative leukemic cells need to sustain rapid cell division and enhanced energetic demand, increasing the acquisition of nutrients from the environment and reprogramming their intermediary metabolism to produce more biomass. As consequence, these cells modify the local environment making the primary BM niche nutrient-scarce and hypoxic, forcing the cells to re-program their metabolism to sustain their enhanced fitness. Her work have provided the mechanistic evidence that metabolic adaptation of leukemic cells to utilize fructose in conditions of glucose deprivation can be inhibited by targeting phosphoglycerate dehydrogenase (PHGDH), a key enzyme of Serine Synthesis Pathway (SSP) leading to a new potent therapeutic strategy to eradicate the disease.