Samuel Katz, MD, PhD
Research & Publications
Biography
News
Locations
Research Summary
Programmed cell death is crucial for the development of multiple cell lineages and organs, as well as the maintenance of normal tissue homeostasis. Whereas pathologic cellular survival is seen in cancer and autoimmune diseases, excessive cellular demise is found in diseases such as neurodegeneration and myocardial infarction. The goal of the laboratory is to rigorously define and elucidate the cellular signaling network that dictates life and death in appropriate cellular contexts. This knowledge is basic to developing selective therapeutics.
Extensive Research Description
A core focus of the laboratory is the expansive family of BCL-2 proteins. They comprise an intricate network of guardian and executioner proteins that govern the core pathway for programmed cell death in mammals. The role of the pro-apoptotic pore forming BCL-2 proteins in the development, maintenance and chemoresistance of malignancy is a fundamental molecular process studied by the laboratory
Of particular interest is a poorly understood family member called BOK, which is present in one of the 20 most frequently deleted genomic regions in all human cancers. Current evidence supports a role for BOK not only in the canonical apoptosis pathway, but in other cellular homeostasis pathways, such as the response to ER stress. How BCL-2 family members like BOK integrate these so-called "day-jobs" into their regulation of cell viability is of great interest. Using conditional mouse knockouts, biochemistry and genetic screening, we hope to unravel these complicated cellular signaling pathways. This knowledge will be important in devising therapeutic strategies to overcome blocks in apoptosis.
The immune system has an incredible capacity to selectively deliver cytotoxic strikes to defined targets. Understanding the determinants of both immune cell and cancer cell survival is important to optimize immunotherapy. Here we employ highly translational, synthetic engineering approaches to improve adoptive cellular therapy. Primary human T cells, Natural Killer (NK) cells and Tumor infiltrating lymphocytes (TILs) are reprogrammed using a multifactor mRNA approach developed by our collaborator, Sherman M. Weissman, Sterling Professor of Genetics. Our efforts are further strengthened by close collaborations with the Yale New Haven Hospital’s Advanced Cell Therapy core and several clinical oncologists.
Coauthors
Research Interests
Leukemia; Lymphoma; Stem Cells; Immunotherapy, Adoptive; Cell Death; Apoptosis; Genes, bcl-2; Mutant Chimeric Proteins; Endoplasmic Reticulum Stress; Cellular Reprogramming
Selected Publications
- OAB-033: Pre-clinical models of genetically heterogeneous multiple myeloma reveal mechanisms of immune escape and predict clinical immunotherapy outcomesLarrayoz M, Garcia-Barchino M, Celay J, Etxebeste A, Jimenez M, Perez C, Ordoñez R, Cobaleda C, Chesi M, Bergsagel L, Rodríguez-Otero P, Takahashi S, Katz S, Walensky L, Ruppert S, Lasater E, Amann M, Lasarte J, Kurilovich A, Cerchietti L, Agirre X, San-Miguel J, Paiva B, Prosper F, Martinez-Climent J. OAB-033: Pre-clinical models of genetically heterogeneous multiple myeloma reveal mechanisms of immune escape and predict clinical immunotherapy outcomes Clinical Lymphoma Myeloma & Leukemia 2022, 22: s19-s20. DOI: 10.1016/s2152-2650(22)00306-8.
- A Static Self-Directed Method for Generating Brain Organoids from Human Embryonic Stem CellsBoisvert E, Means R, Michaud M, Thomson J, Madri J, Katz S. A Static Self-Directed Method for Generating Brain Organoids from Human Embryonic Stem Cells Journal Of Visualized Experiments 2020 DOI: 10.3791/60379-v.
- A versatile flow-based assay for immunocyte-mediated cytotoxicityRabinovich PM, Zhang J, Kerr SR, Cheng BH, Komarovskaya M, Bersenev A, Hurwitz ME, Krause DS, Weissman SM, Katz SG. A versatile flow-based assay for immunocyte-mediated cytotoxicity Journal Of Immunological Methods 2019, 474: 112668. PMID: 31525367, PMCID: PMC6891822, DOI: 10.1016/j.jim.2019.112668.
- Proapoptotic protein BIM as a novel prognostic marker in mantle cell lymphomaWang JD, Katz SG, Morgan EA, Yang DT, Pan X, Xu ML. Proapoptotic protein BIM as a novel prognostic marker in mantle cell lymphoma Human Pathology 2019, 93: 54-64. PMID: 31425695, PMCID: PMC7038910, DOI: 10.1016/j.humpath.2019.08.008.
- BOK promotes erythropoiesis in a mouse model of myelodysplastic syndromeKang SH, Perales O, Michaud M, Katz SG. BOK promotes erythropoiesis in a mouse model of myelodysplastic syndrome Annals Of Hematology 2019, 98: 2089-2096. PMID: 31203423, PMCID: PMC6702064, DOI: 10.1007/s00277-019-03726-7.
- Minocycline mitigates the effect of neonatal hypoxic insult on human brain organoidsBoisvert EM, Means RE, Michaud M, Madri JA, Katz SG. Minocycline mitigates the effect of neonatal hypoxic insult on human brain organoids Cell Death & Disease 2019, 10: 325. PMID: 30975982, PMCID: PMC6459920, DOI: 10.1038/s41419-019-1553-x.
- Methods to Probe Calcium Regulation by BCL-2 Family MembersCarpio MA, Katz SG. Methods to Probe Calcium Regulation by BCL-2 Family Members 2018, 1877: 173-183. PMID: 30536006, DOI: 10.1007/978-1-4939-8861-7_12.
- Abstract 294: BCL-2 family compensation regulates T cell homeostasis and reveals a BIM:BCL-W axis in T-ALLLudwig L, Roach L, Katz S, Fisher J, Burns M, Schnorenberg M, Bao R, Zewde M, Nakamura Y, Gutierrez A, Walensky L, LaBelle J. Abstract 294: BCL-2 family compensation regulates T cell homeostasis and reveals a BIM:BCL-W axis in T-ALL Cancer Research 2018, 78: 294-294. DOI: 10.1158/1538-7445.am2018-294.
- Bok Promotes Erythropoiesis in a Mouse Model of Myelodysplastic SyndromeKang S, Perales O, Michuad M, Katz S. Bok Promotes Erythropoiesis in a Mouse Model of Myelodysplastic Syndrome Blood 2017, 130: 922-922. DOI: 10.1182/blood.v130.suppl_1.922.922.
- EZH! The IRE of DLBCL gets an UPR hand.Katz SG. EZH! The IRE of DLBCL gets an UPR hand. Blood 2017, 129: 2340-2342. PMID: 28450573, DOI: 10.1182/blood-2017-02-769067.
- Non-apoptotic functions of BCL-2 family proteinsGross A, Katz SG. Non-apoptotic functions of BCL-2 family proteins Cell Death & Differentiation 2017, 24: 1348-1358. PMID: 28234359, PMCID: PMC5520452, DOI: 10.1038/cdd.2017.22.
- Expression of CD30 as a biomarker to predict response to brentuximab vedotinXu ML, Acevedo-Gadea C, Seropian S, Katz SG. Expression of CD30 as a biomarker to predict response to brentuximab vedotin Histopathology 2016, 69: 155-158. PMID: 26648051, PMCID: PMC7064871, DOI: 10.1111/his.12914.
- SOX11 Cooperates with CCND1 in Mantle Cell Lymphoma PathogenesisKuo P, Jiang Z, Perumal D, Leshchenko V, Lagana' A, Katz S, Walensky L, Shaknovich R, Ye B, Parekh S. SOX11 Cooperates with CCND1 in Mantle Cell Lymphoma Pathogenesis Blood 2015, 126: 1253-1253. DOI: 10.1182/blood.v126.23.1253.1253.
- BCL-2 family member BOK promotes apoptosis in response to endoplasmic reticulum stressCarpio MA, Michaud M, Zhou W, Fisher JK, Walensky LD, Katz SG. BCL-2 family member BOK promotes apoptosis in response to endoplasmic reticulum stress Proceedings Of The National Academy Of Sciences Of The United States Of America 2015, 112: 7201-7206. PMID: 26015568, PMCID: PMC4466744, DOI: 10.1073/pnas.1421063112.
- Synthesis of Stabilized Alpha-Helical PeptidesBernal F, Katz SG. Synthesis of Stabilized Alpha-Helical Peptides 2014, 1176: 107-114. PMID: 25030922, PMCID: PMC6333094, DOI: 10.1007/978-1-4939-0992-6_9.
- Distinct BimBH3 (BimSAHB) Stapled Peptides for Structural and Cellular StudiesBird GH, Gavathiotis E, LaBelle JL, Katz SG, Walensky LD. Distinct BimBH3 (BimSAHB) Stapled Peptides for Structural and Cellular Studies ACS Chemical Biology 2014, 9: 831-837. PMID: 24358963, PMCID: PMC4131438, DOI: 10.1021/cb4003305.
- Mantle cell lymphoma in cyclin D1 transgenic mice with Bim-deficient B cellsKatz SG, LaBelle JL, Meng H, Valeriano RP, Fisher JK, Sun H, Rodig SJ, Kleinstein SH, Walensky LD. Mantle cell lymphoma in cyclin D1 transgenic mice with Bim-deficient B cells Blood 2013, 123: 884-893. PMID: 24352880, PMCID: PMC3916879, DOI: 10.1182/blood-2013-04-499079.
- Brain and testicular tumors in mice with progenitor cells lacking BAX and BAKKatz SG, Fisher JK, Correll M, Bronson RT, Ligon KL, Walensky LD. Brain and testicular tumors in mice with progenitor cells lacking BAX and BAK Oncogene 2012, 32: 4078-4085. PMID: 22986529, PMCID: PMC3529761, DOI: 10.1038/onc.2012.421.
- A stapled BIM peptide overcomes apoptotic resistance in hematologic cancersLaBelle JL, Katz SG, Bird GH, Gavathiotis E, Stewart ML, Lawrence C, Fisher JK, Godes M, Pitter K, Kung AL, Walensky LD. A stapled BIM peptide overcomes apoptotic resistance in hematologic cancers Journal Of Clinical Investigation 2012, 122: 2018-2031. PMID: 22622039, PMCID: PMC3366394, DOI: 10.1172/jci46231.
- Abstract 2367: Neural progenitor cells deficient in BAX and BAK manifest progressive hyperplasia and tumorigenesisKatz S, Fisher J, Bronson R, Ligon K, Walensky L. Abstract 2367: Neural progenitor cells deficient in BAX and BAK manifest progressive hyperplasia and tumorigenesis Cancer Research 2012, 72: 2367-2367. DOI: 10.1158/1538-7445.am2012-2367.
- Abstract 1775: Therapeutic reactivation of cell death in refractory hematologic cancers using a broad spectrum BIM BH3 death helixLaBelle J, Katz S, Bird G, Gavathiotis E, Stewart M, Fisher J, Godes M, Walensky L. Abstract 1775: Therapeutic reactivation of cell death in refractory hematologic cancers using a broad spectrum BIM BH3 death helix Cancer Research 2011, 71: 1775-1775. DOI: 10.1158/1538-7445.am2011-1775.
- A Stapled BIM BH3 Helix Restores Apoptosis In Bim-Null Mantle Cell LymphomaKatz S, Labelle J, Godes M, Fisher J, Bird G, Walensky L. A Stapled BIM BH3 Helix Restores Apoptosis In Bim-Null Mantle Cell Lymphoma Blood 2010, 116: 437-437. DOI: 10.1182/blood.v116.21.437.437.
- Structural Analysis of a BAX-BIM SAHB Complex Reveals a Novel BH3 Interaction Site on BAX for Therapeutic Activation of ApoptosisGavathiotis E, Suzuki M, Davis M, Pitter K, Bird G, Katz S, Tu H, Kim H, Cheng E, Tjandra N, Walensky L. Structural Analysis of a BAX-BIM SAHB Complex Reveals a Novel BH3 Interaction Site on BAX for Therapeutic Activation of Apoptosis Blood 2008, 112: 300-300. DOI: 10.1182/blood.v112.11.300.300.
- BAX activation is initiated at a novel interaction siteGavathiotis E, Suzuki M, Davis ML, Pitter K, Bird GH, Katz SG, Tu HC, Kim H, Cheng E, Tjandra N, Walensky LD. BAX activation is initiated at a novel interaction site Nature 2008, 455: 1076-1081. PMID: 18948948, PMCID: PMC2597110, DOI: 10.1038/nature07396.
- GATA4 mediates gene repression in the mature mouse small intestine through interactions with friend of GATA (FOG) cofactorsBeuling E, Bosse T, de Kerk D, Piaseckyj CM, Fujiwara Y, Katz SG, Orkin SH, Grand RJ, Krasinski SD. GATA4 mediates gene repression in the mature mouse small intestine through interactions with friend of GATA (FOG) cofactors Developmental Biology 2008, 322: 179-189. PMID: 18692040, PMCID: PMC3031907, DOI: 10.1016/j.ydbio.2008.07.022.
- Pharmacologic Replacement of BIM BH3 Reactivates Apoptosis in Hematologic Cancer and Lymphoproliferative Disease.LaBelle J, Fisher J, Katz S, Bird G, Lawrence C, Silverstein A, Walensky L. Pharmacologic Replacement of BIM BH3 Reactivates Apoptosis in Hematologic Cancer and Lymphoproliferative Disease. Blood 2007, 110: 524-524. DOI: 10.1182/blood.v110.11.524.524.
- Endothelial lineage-mediated loss of the GATA cofactor Friend of GATA 1 impairs cardiac developmentKatz SG, Williams A, Yang J, Fujiwara Y, Tsang AP, Epstein JA, Orkin SH. Endothelial lineage-mediated loss of the GATA cofactor Friend of GATA 1 impairs cardiac development Proceedings Of The National Academy Of Sciences Of The United States Of America 2003, 100: 14030-14035. PMID: 14614148, PMCID: PMC283540, DOI: 10.1073/pnas.1936250100.
- Interaction between FOG-1 and the Corepressor C-Terminal Binding Protein Is Dispensable for Normal Erythropoiesis In VivoKatz SG, Cantor AB, Orkin SH. Interaction between FOG-1 and the Corepressor C-Terminal Binding Protein Is Dispensable for Normal Erythropoiesis In Vivo Molecular And Cellular Biology 2002, 22: 3121-3128. PMID: 11940669, PMCID: PMC133767, DOI: 10.1128/mcb.22.9.3121-3128.2002.
- Friend of GATA-1 Represses GATA-3–dependent Activity in CD4+ T CellsZhou M, Ouyang W, Gong Q, Katz S, White J, Orkin S, Murphy K. Friend of GATA-1 Represses GATA-3–dependent Activity in CD4+ T Cells Journal Of Experimental Medicine 2001, 194: 1461-1471. PMID: 11714753, PMCID: PMC2193678, DOI: 10.1084/jem.194.10.1461.