Adolfo A. Ferrando, MD, PhD
Photo: Adolfo Ferrando



Elected 2012
Human T-cell acute lymphoblastic leukemia is a highly aggressive malignancy resulting from the malignant transformation of T-cell progenitors. Our group studies the genetic programs and molecular alterations responsible for uncontrolled growth, proliferation and survival in human leukemia cells. Activating mutations in the NOTCH1 gene result in oncogenic NOTCH signaling in over 50% of patients with T-cell leukemia. The fundamental importance of this finding resides in our capacity to block the activity of NOTCH1 with drugs known as gamma-secretase inhibitors. Over the last years, my laboratory has analyzed the oncogenic function of NOTCH1 and the antileukemic properties of blocking NOTCH1 signaling in T-ALL. These studies have uncovered the role of NOTCH1 as a master regulator of cell growth and metabolism upstream in leukemic cells and identified the interaction of NOTCH1 with major oncogenic factors such as MYC and the PI3K-AKT pathway. In addition, we have demonstrated that inhibition of NOTCH1 signaling can effectively reverse resistance to glucocorticoid therapy in T-cell leukemias. Over the last year, we have addressed the role of the TLX1 oncogene in the pathogenesis of T-ALL and identified new tumor suppressor genes mutated in T-ALL including such as WT1, BCL11B, RUNX1, EZH2, ETV6 and PHF6. Current work in our lab uses high throughput assays and animal models to analyze the mechanisms of transformation in T-ALL and to identify new therapeutic targets for the treatment of this disease.