Mechanisms of disease

Together with our numerous collaborators, we have been and continue to use these CSC-directed chemical tools to understand the complex proteome alterations that occur in specific chronically stressed cells/organisms such as in cancer, neurodegenerative diseases and microorganisms living in conditions of stress. Examples are the discovery of mechanisms behind: transforming ability of BCL6 in a subset of BCL6-driven Diffuse Large B-Cell Lymphomas (DLBCL) [Nature Medicine 2009] (collaboration with A. Melnick lab); regulation of apoptosis in small-cell lung carcinomas [Nature Chem Biol 2007] (collaboration with Jiang and Massague labs); the altered proteome and its addiction to tumor HSP90 in a subset of triple negative breast cancer [PNAS 2009]; regulation of HER2 activity in HER2 overexpressing breast cancers [Nature Chem Biol 2013]; transformation in JAK2-driven MPDs and potential mechanisms associated with resistance to JAK inhibitors [J Clinical Investigation 2010, Nature 2012, Blood 2014]; (collaboration with R. Levine lab); regulation of the viral oncoproteome in Kaposi sarcoma herpes virus (KHSV)-associated lymphomas [Blood 2013]; (collaboration with E. Cesarman lab); regulation of the activated STAT5 signaling and increased transcriptional activity in chronic myeloid leukemia [Nature Chem Biol 2011]; molecular signature of HSP90-addicted AML [Cell Reports 2015] (collaboration with M Guzman lab); the biochemical nature of the CSC/epichaperome networks in cancer and their therapeutic implications (interdisciplinary multimember team Nature 2016 and Nature Medicine 2018); the nature of CSC networks in PD neurons (Nature Communications 2018, collaboration with Studer lab) to list a few.

  1. Zong H, Gozman A, Caldas-Lopes E, Taldone T, Sturgill E, Brennan S, Ochiana SO, Gomes-DaGama EM, Sen S, Rodina A, Koren J, 3rd, Becker MW, Rudin CM, Melnick A, Levine RL, Roboz GJ, Nimer SD, Chiosis G, Guzman ML. A Hyperactive Signalosome in Acute Myeloid Leukemia Drives Addiction to a Tumor-Specific Hsp90 Species. Cell Rep. 2015;13(10):2159-73. PMCID: PMC4699804. PubMed [PMID: 26628369]