University of Pittsburgh Cancer Institute (UPCI)

Molecular Targets

Molecular targetsMTTDP researchers are evaluating a variety of key cancer cell signaling mechanisms, which might be targeted as a therapeutic approach. These molecular targets include nuclear and cellular matrix proteins, transcription factors, growth factors, kinase receptors and other transmembrane proteins, and hormone and hormone receptors, among others.

Selected Publications

  • Abnormal activities of histone lysine demethylases and lysine deacetylases are associated with aberrant gene expression in breast cancer development. A MTTDP study suggests that the histone lysine-specific demethylase 1 intimately interacts with histone deacetylases in human breast cancer cells. Inhibition of histone demethylation and deacetylation exhibits cooperation and synergy in regulating gene expression and growth inhibition, and may represent a promising and novel approach for epigenetic therapy of breast cancer (Huang Y et. al., Breast Cancer Res Treat. 2012 Feb;131(3):777-89).
  • The risk of radionuclide release in terrorist acts or exposure of healthy tissue during radiotherapy demand potent radioprotectants/radiomitigators. Ionizing radiation induces cell death by initiating the selective peroxidation of cardiolipin in mitochondria by the peroxidase activity of its complex with cytochrome c leading to apoptosis. CTP investigators designed and synthesized mitochondria-targeted triphenylphosphonium-conjugated imidazole-substituted oleic and stearic acids that blocked peroxidase activity of cytochrome c/cardiolipin complex. Both compounds prevent cell death, and protect mice against lethal doses of irradiation (Atkinson J et. al., Nat Commun. 2011 Oct 11;2:497).

Members

Altschuler, Daniel, PhD
Pharmacology & Chemical Biology
Kagan, Valerian, PhD, DSc
Environmental & Occupational Health
Chu, Edward, MD
Medicine
Lagasse, Eric, Pharm, PhD
Pathology
Crowley, Rebecca, MD
Biomedical Informatics (DBMI)
Schmitz, John, PhD
Medicine
Deiters, Alexander PhD
Chemistry
Vogt, Andreas, PhD
Computational & Systems Biology
Jiang, Yu, PhD
Pharmacology & Chemical Biology