Leukemia; Lymphoma; Stem Cells; Cell Death; Apoptosis; Genes, bcl-2; Endoplasmic Reticulum Stress
The goal of the Katz laboratory is to selectively control the cell death machinery for therapeutic benefit. Toward that end a multidisciplinary approach is applied to understand how mammalian cells are conditioned to expire, and how mutations in essential apoptotic regulators lead to developmental defects or malignancy. In particular, BCL-2 family proteins are vital regulators of mitochondrial integrity and have been implicated in the development, maintenance and chemoresistance of numerous cancers. While the basic mode of BCL-2 family action is established, how this pathway is integrated in the context of various cellular programs, including alternate survival and death pathways, is not nearly as well understood.
Thus, we focus on:
- severe apoptotic blockades in cancer stem cells;
- loss of pro-apoptotic BCL-2 family members in mantle cell lymphoma as well as other cancers; and
- the mechanism of key understudied family members.
- Brain and testicular tumors in mice with progenitor cells lacking BAX and BAK Brain and testicular tumors in mice with progenitor cells lacking BAX and BAK. Katz SG, Fisher JK, Correll M, Bronson RT, Ligon KL, Walensky LD. Oncogene 2013, 32(35):4078-85.
- A Stapled BIM peptide overcomes apoptotic resistance in hematologic cancers. A Stapled BIM peptide overcomes apoptotic resistance in hematologic cancers.. LaBelle JL, Katz SG, Bird GH, Gavathiotis E, Stewart ML, Lawrence C, Fisher JK, Godes M, Pitter K, Kung AL, Walensky LD. J Clin Invest. 2012 Jun;122(6):2018-31. doi: 10.1172/JCI46231. Epub 2012 May 24.
- BAX activation is initiated at a novel interaction site. Gavathiotis E, Suzuki M, Davis ML, Pitter K, Bird GH, Katz SG, Tu H-C, Kim H, Cheng EH-Y., Tjandra N, Walensky LD. Nature 2008; 455:1076-1081.
- Endothelial lineage mediated loss of the GATA cofactor FOG-1 impairs cardiac development. Katz SG, Williams A, Yang J, Fujiwara Y, Tsang AP, Epstein JA, Orkin SH. PNAS 2003; 100:14030-14035.
- Interaction between FOG-1 and the corepressor C-terminal binding protein is dispensable for normal erythropoiesis in vivo. Katz SG*, Cantor AB*, Orkin SH. Mol Cell Biol 2002; 22:3121-3128.
- Mantle cell lymphoma in cyclin D1 transgenic mice with Bim-deficient B cells. Katz SG, Labelle JL, Meng H, Valeriano RP, Fisher JK, Sun H, Rodig SJ, Kleinstein SH, Walensky LD. Blood. 2014 Feb 6;123(6):884-93.
- Distinct BimBH3 (BimSAHB) stapled peptides for structural and cellular studies. Bird GH, Gavathiotis E, LaBelle JL, Katz SG, Walensky LD. ACS Chem Biol. 2014 Mar 21;9(3):831-7.
- BCL-2 family member BOK promotes apoptosis in response to endoplasmic reticulum stress. Carpio MA, Michaud M, Zhou W, Fisher JK, Walensky LD, Katz SG. Proc Natl Acad Sci U S A. 2015 Jun 9;112(23):7201-6.