Dr. Joya Chandra
The University of Texas MD Anderson Cancer Center
Department of Pediatrics
- Oxidative stress-dependent signaling
- Induction of oxidative stress by biologically targeted agents
- Apoptosis induction as a consequence of proteasome inhibition
- Biology of pediatric and adult leukemias
Research in my laboratory is directed towards two broad topics:understanding how oxidative stress promotes growth, proliferation and progression in oncogene-induced hematological malignancies; and using therapeutically derived oxidative stress to induce cell death.
Recent years have seen the development of a body of clinically relevant biologically targeted agents including various kinase inhibitors, farnesyl transferase inhibitors, and proteasome inhibitors. While many of these drugs are currently being tested in the clinic, their mechanism of action is often more complex than initially hypothesized. We will use some of these compounds as tools with which to better understand the biology of pediatric leukemias, and we will also address the preclinical efficacy of these agents in hematological malignancies using primary specimens from patients and animal models.
A tutorial in my laboratory will introduce a student to apoptosis detection methods, flow cytometry techniques, quantitative measurement of reactive oxygen species (ROS) and cellular defenses against ROS, protein detection techniques, ad handling and probing of primary patient material.
Chandra J, Tracy J, Loegering D, Flatten K, Verstovsek S, Beran M, Gorre M, Estrov Z, Donato N, Talpaz M, Sawyers C, Bhalla K, Karp J, Sausville E, Kaufmann SH (2006) Adaphostin-induced oxidative stress overcomes BCR/ABL mutation-dependent and -independent imatinib resistance. Blood 107:2501-2506.
Miller CP, Ban K, Dujka ME, McConkey DJ, Munsell M, Palladino M, Chandra J (2007) NPI-0052, a novel proteasome inhibitor, induces caspase-8 and ROS -dependent apoptosis alone and in combination with HDAC inhibitors in leukemia cells. Blood 110(1):267-277.
Ban K, Gao Y, Amin HM, Howard A, Miller C, Lin Q, Leng X, Munsell M, Bar-Eli M, Arlinghaus RB, Chandra J (2008) BCR-ABL1 mediates up-regulation of Fyn in chronic myelogenous leukemia. Blood 111(5):2904-8.
Program in Cancer Biology