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Samuel Katz, MD, PhD

Associate Professor of Pathology

Contact Information

Samuel Katz, MD, PhD

Office Location

Mailing Address

  • Pathology

    310 Cedar Street, PO Box 208023

    New Haven, CT 06520-8023

    United States

Katz Lab
Yale Medicine

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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

  • Interaction between FOG-1 and the corepressor C-terminal binding protein is dispensable for normal erythropoiesis in vivo.Katz 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: 3121-8. PMID: 11940669, PMCID: PMC133767.
  • Endothelial lineage-mediated loss of the GATA cofactor Friend of GATA 1 impairs cardiac development.Katz 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: 14030-5. PMID: 14614148, PMCID: PMC283540, DOI: 10.1073/pnas.1936250100.
  • BAX activation is initiated at a novel interaction site.Gavathiotis E, Suzuki M, Davis ML, Pitter K, Bird GH, Katz SG, Tu HC, Kim H, Cheng EH, Tjandra N, Walensky LD. BAX activation is initiated at a novel interaction site. Nature 2008, 455: 1076-81. PMID: 18948948, PMCID: PMC2597110, DOI: 10.1038/nature07396.
  • 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. A stapled BIM peptide overcomes apoptotic resistance in hematologic cancers. The Journal Of Clinical Investigation 2012, 122: 2018-31. PMID: 22622039, PMCID: PMC3366394, DOI: 10.1172/JCI46231.
  • 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. Brain and testicular tumors in mice with progenitor cells lacking BAX and BAK. Oncogene 2013, 32: 4078-85. PMID: 22986529, PMCID: PMC3529761, DOI: 10.1038/onc.2012.421.
  • 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. Mantle cell lymphoma in cyclin D1 transgenic mice with Bim-deficient B cells. Blood 2014, 123: 884-93. PMID: 24352880, PMCID: PMC3916879, DOI: 10.1182/blood-2013-04-499079.
  • Distinct BimBH3 (BimSAHB) stapled peptides for structural and cellular studies.Bird GH, Gavathiotis E, LaBelle JL, Katz SG, Walensky LD. Distinct BimBH3 (BimSAHB) stapled peptides for structural and cellular studies. ACS Chemical Biology 2014, 9: 831-7. PMID: 24358963, PMCID: PMC4131438, DOI: 10.1021/cb4003305.
  • 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. 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: 7201-6. PMID: 26015568, PMCID: PMC4466744, DOI: 10.1073/pnas.1421063112.
  • GATA4 mediates gene repression in the mature mouse small intestine through interactions with friend of GATA (FOG) cofactors.Beuling E, Bosse T, aan de Kerk DJ, 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: 179-89. PMID: 18692040, PMCID: PMC3031907, DOI: 10.1016/j.ydbio.2008.07.022.
  • Synthesis of stabilized alpha-helical peptides.Bernal F, Katz SG. Synthesis of stabilized alpha-helical peptides. Methods In Molecular Biology (Clifton, N.J.) 2014, 1176: 107-14. PMID: 25030922, PMCID: PMC6333094, DOI: 10.1007/978-1-4939-0992-6_9.
  • Expression of CD30 as a biomarker to predict response to brentuximab vedotin.Xu ML, Acevedo-Gadea C, Seropian S, Katz SG. Expression of CD30 as a biomarker to predict response to brentuximab vedotin. Histopathology 2016, 69: 155-8. PMID: 26648051, PMCID: PMC7064871, DOI: 10.1111/his.12914.
  • 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 proteins.Gross A, Katz SG. Non-apoptotic functions of BCL-2 family proteins. Cell Death And Differentiation 2017, 24: 1348-1358. PMID: 28234359, PMCID: PMC5520452, DOI: 10.1038/cdd.2017.22.
  • Methods to Probe Calcium Regulation by BCL-2 Family Members.Carpio MA, Katz SG. Methods to Probe Calcium Regulation by BCL-2 Family Members. Methods In Molecular Biology (Clifton, N.J.) 2019, 1877: 173-183. PMID: 30536006, DOI: 10.1007/978-1-4939-8861-7_12.
  • Minocycline mitigates the effect of neonatal hypoxic insult on human brain organoids.Boisvert 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.
  • BOK promotes erythropoiesis in a mouse model of myelodysplastic syndrome.Kang 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.
  • Proapoptotic protein BIM as a novel prognostic marker in mantle cell lymphoma.Wang 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.
  • A versatile flow-based assay for immunocyte-mediated cytotoxicity.Rabinovich 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.
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