Blood cancer and heat shock factors

Nahid F. Mivechi, PhD, received a $1.3M, 5-year R01 grant from NIH/NCI for “Role of Heat Shock Factors (Hsfs) in Tumorigenesis.”

This research will investigate the molecular mechanisms that cause and drive the T-cell subtype of acute lymphoblastic leukemia (T-ALL), a form of blood cancer. Studies have shown that patients with primary and relapse T-ALLs, as well as laboratory models of T-ALL, have a very high incidence of activated Notch1 protein and mutated (inactivated) tumor suppressor protein, TP53. Dr. Mivechi’s group has found that deletion of heat shock factors (Hsfs) Hsf4, Hsf2, or Hsf1 in TP53-deficient mice leads to significant protection against the development of T-ALL, suggesting that therapeutic inhibition of Hsfs could be a key to eliminating T-ALL. Research funded by this R01 will test the hypothesis that although Hsfs are not essential for T cell development, they cooperate with oncogenes and tumor suppressor genes to control T-ALL development, and that depletion of Hsfs result in the inability of T-ALL cells to survive.