Vanderbilt-Ingram Cancer Center

My long-standing scientific interests have centered on understanding the mechanisms by which integrated signaling networks and growth factors from the tumor microenvironment initiate and sustain acute lymphoblastic leukemia (ALL) cell survival.  My research investigations have focused on PI3K/AKT/mTOR signaling and its interactions with cytokine-stimulated survival signaling in ALL as a strategy to unveil potential targets for rationally selected biologic agents that will be incorporated into current treatment regimens for ALL. To this end, my research endeavors have identified a number of potential relevant signaling nodes stimulated by the cytokines IL-7 and TSLP that are being tested as potential therapeutic targets for the treatment of ALL.

Specifically, my work has demonstrated that mTOR inhibitors, such as rapamycin, inhibit proliferation and induce cell death of ALL cells. As monotherapy, mTOR inhibitors also show efficacy in preclinical models of ALL. However, rapamycin-treated mice eventually relapse and die from ALL. These rapamycin-mediated inhibitory effects can be overcome by the cytokines IL-7 and TSLP, suggesting a role for IL-7Ralpha signaling as a compensatory survival signal in the context of mTOR inhibition. Furthermore, I have found that PI3K inhibitors can potentiate the effects of mTOR inhibitors as well as attenuate the pro-survival effect of IL-7 in ALL cells. We are working on finding novel therapies that will take into account these compensatory survival signals to optimize mTOR inhibition.

As the Leader of Translational Biology in the Division of Pediatric Hematology/Oncology, I plan to develop an experimental therapeutics program within the division in order to get  biologically-relevant targeted therapies that are being developed in the laboratory translated to novel treatment regimens in patients.

In addition to my basic science research interests, I am interested in primary immunodeficiencies and immune reconstitution following hematopoietic stem cell transplantation.