Sonia Rodriguez-Rodriguez, Ph.D.

The long-term goal of my research is to better understand the mechanisms involved in the regulation of normal and malignant hematopoietic stem cells that would lead to the identification of novel approaches for treating bone marrow failures and leukemias. Dr. Carlesso’s laboratory has been focused for several years on understanding how the Notch signaling pathway senses the microenvironment and contributes to hematopoietic stem cell regulation. Specifically, my research activity in the past few years has being focused on understanding the mechanisms that control cell fate decisions, self-renewal and differentiation of hematopoietic stem cells, especially in response to stress. More in particular, I have being studying the role of SKP2 in hematopoiesis.

 

SKP2 is an important regulator of the cell cycle and has being studied in depth in several cellular systems. SKP2 transcription is regulated by the Notch family of protein receptors, and our recent studies show that SKP2 deficiency enhances HSC quiescence. As little is known about the role of SKP2 in leukemia, I recently started to explore the role of SKP2 in T cell leukemia. The majority of T cell leukemia is characterized by the constitutive activation of the Notch signaling pathway. However, little is known about the downstream mediators involved in the disease progression and relapse. Our laboratory has a wide experience with “in vivo” Notch-induced mouse and xenograft models. My previous results with those models show that the increase in Notch signaling correlates with an overexpression of SKP2, and an increase cell cycle. On the other hand, genetic ablation of SKP2 increases survival and delays disease progression, revealing for the first time the important role of SKP2 in leukemias, and making SKP2 a suitable target for new drug therapies. Our findings on SKP2 and leukemia, together with the discovery of new small compounds inhibiting SKP2 function, lead to the possibility of a new potential use of SKP2 inhibitors in the treatment of T-ALL.