Hematologic Malignancies, Multiple Myeloma
multiple myeloma disease progression; stem cell biology; epigenetics ...read more
The goal of our laboratory is to elucidate the basic mechanisms responsible for multiple myeloma disease relapse and progression and translate these laboratory findings into novel and effective therapies. We have investigated regulators of tumor initiation and self-renewal that are required tumor regrowth after treatment. We have found that a novel inhibitor of RAS signaling can target myeloma stem cell activity. In addition, we have identified regulators of protein translation as critical mediators of chemoresistance and self-renewal. We are currently working to develop better models to study RAS function in multiple myeloma and to develop novel methods of targeting patients with RAS-mutated multiple myeloma. We are also working to identify novel inhibitors/targets that mediate myeloma relapse by promoting stem cell functions.
Yang M, Gocke CB, Luo X, Borek D, Tomchick DR, Machius M, Otwinowski Z, Yu H. Structural basis for CoREST-dependent demethylation of nucleosomes by the human LSD1 histone demethylase. Mol Cell. 2006 Aug 4;23(3):377-87. PubMed PMID: 16885027
Gocke CB, Yu H. ZNF198 stabilizes the LSD1-CoREST-HDAC1 complex on chromatin through its MYM-type zinc fingers. PLoS One. 2008 Sep 22;3(9):e3255. PubMed PMID: 18806873; PubMed Central PMCID: PMC2532748
Alonso S, Hernandez D, Chang YT, Gocke CB, McCray M, Varadhan R, Matsui WH, Jones RJ, Ghiaur G. Hedgehog and retinoid signaling alters multiple myeloma microenvironment and generates bortezomib resistance. J Clin Invest. 2016 Dec 1;126(12):4460-4468. PubMed PMID: 27775549; PubMed Central PMCID: PMC5127663
Gocke CB, McMillan R, Wang Q, Begum A, Penchev VR, Ali SA, Borrello I, Huff CA, Matsui W. IQGAP1 Scaffold-MAP Kinase Interactions Enhance Multiple Myeloma Clonogenic Growth and Self-Renewal. Mol Cancer Ther. 2016 Nov;15(11):2733-2739. PubMed PMID: 27573425; PubMed Central PMCID: PMC5097000.
Park EH, Soori M, Wang Q, Gondek L, Matsui W, Gocke CB. Protein Synthesis Rates Regulate Tumor-Initiating Potential and Chemoresistance in Multiple Myeloma. Abstract #4390. 59th ASH Annual Meeting & Exposition; 2017 December; Atlanta, GA
Sidney Kimmel Comprehensive Cancer Center
1650 Orleans St.
CRB I, Room 388
Baltimore, MD 21287 map
Phone: 410-955-8839
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