Ernesto Diaz-Flores, PhD
Associate Professor, Pediatrics/Oncology, UCSF
As a leukemia researcher, my ultimate goal is to find new cures for high-risk leukemia through an understanding of mechanisms mediating leukemogenesis. Through my training and experience accumulated over the last two decades, I am poised to bring novel discoveries to advance the field of leukemia research.
My graduate studies in molecular biology provided me expertise on T cell leukemia signaling and helped me identify critical mediators of lymphoid activation. For my postdoctoral studies I focused my efforts on in vivo models of leukemia. During my first postdoc in Dr. Shannon's lab, I dissected signal transduction alterations resulting from expression of mutant KrasG12D. My studies informed several therapeutic candidates for cells harboring what is considered an undruggable target. For my second postdoc, I joined Dr. Loh’s laboratory, where I studied the biochemical mechanisms of childhood hypodiploid leukemia. During this period, I made the observation that p53 is deregulated in low hypodiploid (LH) patient samples, which lead to the discovery of mutations in TP53 in LH B-ALL (>90%) with 40% of those mutations being present in germline. These findings are now used in the clinic to screen for TP53 mutations and Li-Fraumeni syndrome in patients with hypodiploid ALL.
Since promoted to assistant professor, I identified BCL-2 as a promising therapeutic target and carried all the experiments to identify and validate ABT-199 (Venetoclax) as an effective drug against this leukemia. These studies contributed to the first clinical trial of ABT-199 (Venetoclax) for pediatric ALL.
In 2022, I published work identifying biomarkers of response to Inotuzumab immunotherapy in relapse/refractory B cell leukemia (Benhert et al., Blood Advances, 2022). Most recently, my work has provided evidence for a highly effective combinatorial therapy against hypodiploid B-ALL (Pariury et al., Haematologica, 2023)
My current work focuses on studying pharmacological and immunotherapeutic opportunities of targeting mutant p53 in the context of acute leukemia. This work represents a new paradigm in the field of p53 and hypodiploid leukemia and is expected to bring novel treatments to the clinic for aggressive and refractory cancers.
Universidad Complutense de Madrid, BS, 01/1997, Biochemistry
Universidad Autonoma de Madrid, PhD cum laude, 01/2003, Molecular Biology
University of California, San Francisco, (UCSF), Postdoc, 06/2010, Oncology
University of California, San Francisco, (UCSF), Postdoc, 03/2014, Oncology