Joseph T. Opferman, PhD
Joseph T. Opferman, PhD

Joseph T. Opferman, PhD

Associate Member, St. Jude Faculty

Departments

Education

BS – Notre Dame University, Notre Dame, Indiana (1995)
PhD – University of Chicago, Chicago, Illinois (2000)
Fellowship - Dana-Farber Cancer Institute/ Harvard Medical School

Honors & Awards

  • 2001 Damon-Runyon Post-Doctoral Fellow
  • 2006 Pew Scholar in the Biomedical Sciences
  • 2010 American Cancer Society Research Scholar 

Research Interests

My laboratory’s mission is to understand the programmed cell death pathway (apoptosis) with the goal of gaining fundamental insight into how cellular homeostasis is controlled. Using the hematopoietic and other systems as models, we seek to define the roles of individual BCL2 family members and to comprehend their normal regulation. Understanding this basic biology is important for human diseases such as cancer because the programmed cell death pathway is commonly corrupted in malignant cells. By better understanding how the cell death machinery is regulated we can identify important signaling nodes that can be targeted to improve cancer responses to therapy. The availability of drugs which can modulate the cell death machinery, including BH3-mimetic agents, has the potential to revolutionize cancer therapy. Therefore, we seek to identify additional strategies to incorporate these therapeutic agents into cancer treatments with a focus on lymphoid and myeloid leukemia using state of the art cellular and genetic models.

Opferman Research Lab

Contact Information

Joseph T. Opferman, PhD Cell & Molecular Biology MS 340, Room 4007C St. Jude Children's Research Hospital 262 Danny Thomas Place Memphis, TN 38105-3678

St. Jude Faculty List

Related Topics

News Releases

Selected Publications

Rockfield SM, Turnis ME, Rodriguez-Enriquez R, Bathina M, Ng SK, Kurtz N, Becerra Mora N, Pelletier S, Robinson CG, Vogel P, Opferman JT. Genetic ablation of Immt induces a lethal disruption of the MICOS complex. Life Sci Alliance Jun 1;7(6), 2024.

Wright T, Turnis ME, Grace CR, Li X, Brakefield LA, Wang YD, Xu H, Kaminska E, Climer LK, Mukiza TO, Chang CL, Moldoveanu T, Opferman JT. Anti-apoptotic MCL-1 promotes long-chain fatty acid oxidation through interaction with ACSL1. Mol Cell Apr 4;84(7):1338-1353, 2024.

Turnis ME, Kaminska E, Smith KH, Kartchner BJ, Vogel P, Laxton JD, Ashmun RA, Ney PA, Opferman JT. Requirement for antiapoptotic MCL-1 during early erythropoiesis. Blood Apr 8;137(14):1945-1958, 2021.

Smith KH, Budhraja A, Lynch J, Roberts K, Panetta JC, Connelly JP, Turnis ME, Pruett-Miller SM, Schuetz JD, Mullighan CG, Opferman JT. The heme-regulated inhibitor pathway modulates susceptibility of poor prognosis B-lineage acute leukemia to BH3-mimetics. Mol Cancer Res Apr 1;19(4):636-650, 2021.

Turnis ME, Kaminska E, Smith KH, Kartchner BJ, Vogel P, Laxton JD, Ashmun RA, Ney PA, Opferman JT. Requirement for Anti-Apoptotic MCL-1 during Early Erythropoiesis. Blood, 2021. In Press. PMID: 33512417.

Lacayo NJ, Jabbour E, Rubnitz J, Bajel A, Laetsch TW, Leonard J, Colace SI, Khaw SL, Fleming S, Mattison RJ, Norris RE, Opferman JT, Roberts K, Zhao Y, Qu C, Badawi M, Schmidt M, Tong B, Pesko JC, Sun Y, Ross JA, Vishwamitra D, Rosenwinkel L, Kim SY, Jacobson A, Mullighan CG, Alexander TB, Stock W. Venetoclax and Navitoclax in Combination with Chemotherapy in Patients with Relapsed or Refractory Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma. Cancer Discovery, 2021. In Press.

Karol SE, Alexander TB, Budhraja A, Pounds SB, Canavera K, Wang L, Wolf J, Klco JM, Mead PE, Das Gupta S, Kim SY, Salem AH, Palenski T, Lacayo NJ, Pui CH, Opferman JT, Rubnitz JE. Venetoclax in combination with cytarabine with or without idarubicin in children with relapsed or refractory acute myeloid leukaemia: a phase 1, dose-escalation study. Lancet Oncol 21:551-560, 2020. PMID: 32171069.

Smith KH, Budhraja A, Lynch J, Roberts K, Panetta JC, Connelly JP, Turnis ME, Pruett-Miller SM, Schuetz JD, Mullighan CG, Opferman JT. Heme-Sensing Pathway Modulates Susceptibility of Poor Prognosis B-Lineage Acute Leukemia to BH3-Mimetics. Molecular Cancer Research, 2020. In Press. PMID: 33288732.

Villalobos-Ortiz M, Ryan J, Mashaka TN, Opferman JT, Letai A. BH3 profiling discriminates on-target small molecule BH3 mimetics from putative mimetics. Cell Death Differ 27:999-1007, 2020. PMID: 31332296

Escudero S, Zaganjor E, Lee S, Mill CP, Morgan AM, Crawford EB, Chen J, Wales TE, Mourtada R, Luccarelli J, Bird GH, Steidl U, Engen JR, Haigis MC, Opferman JT, Walensky LD. Dynamic regulation of long-chain fatty acid oxidation by a noncanonical interaction between the MCL-1 BH3 helix and VLCAD. Mol Cell. 69(5):729-743.e7. 2018

Budhraja A, Turnis ME, Churchman ML, Kothari A, Yang X, Xu H, Kaminska E, Panetta JC, Finkelstein D, Mullighan CG, Opferman JT. Modulation of navitoclax sensitivity by dihydroartemisinin-mediated MCL-1 repression in BCR-ABL(+) B-lineage acute lymphoblastic leukemia. Clin Cancer Res. 23(24):7558-7568. 2017

Koss B, Ryan J, Budhraja A, Szarama K, Yang X, Bathina M, Cardone MH, Nikolovska-Coleska Z, Letai A, Opferman JT. Defining specificity and on-target activity of BH3-mimetics using engineered B-ALL cell lines. Oncotarget. 7(10):11500-11. .2016

Delbridge AR, Opferman JT, Grabow S, Strasser A. Antagonism between MCL-1 and PUMA governs stem/progenitor cell survival during hematopoietic recovery from stress. Blood.  125(21):3273-80. 2015

Koss B, Morrison J, Perciavalle RM, Singh H, Rehg JE, Williams RT, Opferman JT. Requirement for anti-apoptotic MCL-1 in the survival of BCR-ABL B-lineage acute lymphoblastic leukemia. Blood 122(9):1587-1598, 2013.

Wang X, Bathina M, Lynch J, Koss B, Calabrese C, Frase S, Schuetz JD, Rehg JE, Opferman JT. Deletion of MCL-1 causes lethal cardiac failure and mitochondrial dysfunction. Genes Dev 27(12):1351-64, 2013.

Perciavalle RM, Opferman JT. Delving deeper: MCL-1's contributions to normal and cancer biology.Trends Cell Biol 23(1):22-29, 2012.

Malone CD, Hasan SMM, Roome RB, Xiong J, Furlong M, Opferman JT, Vanderluit JL. Mcl-1 regulates the survival of adult neural precursor cells. Mol Cell Neurosci 49(4):439-47, 2012.

Perciavalle RM, Stewart DP, Koss B, Lynch J, Milasta S, Bathina M, Temirov J, Cleland MM, Pelletier S, Schuetz JD, Youle RJ, Green DR, Opferman JT. Anti-apoptotic MCL-1 localizes to the mitochondrial matrix and couples mitochondrial fusion to respiration. Nat Cell Biol 14(6):575-83, 2012.

Garrison SP, Phillips DC, Jeffers JR, Chipuk JE, Parsons MJ, Rehg JE, Opferman JT, Green DR, Zambetti GP. Genetically defining the mechanism of Puma- and Bim-induced apoptosis. Cell Death Differ 19(4):642-9, 2012.

Germain M, Nguyen AP, Le Grand JN, Arbour N, Vanderluit JL, Park DS, Opferman JT, Slack RS. MCL-1 is a stress sensor that regulates autophagy in a developmentally regulated manner. Embo J 30(2):395-407, 2011.

Kurtulus S, Tripathi P, Opferman JT, Hildeman DA. Contracting the 'mus cells'- does down-sizing suit us for diving into the memory pool? Immunol Rev 236: 54-67, 2010.

Opferman JT, Green DR. DUB-le trouble for cell survival. Cancer Cell 17(2):117-9, 2010.

Weber A, Boger R, Vick B, Urbanik T, Haybaeck J, Zoller S, Teufel A, Krammer PH, Opferman JT, Galle PR, Schuchmann M, Heikenwalder M, Schulze-Bergkamen H. Hepatocyte-specific deletion of the antiapoptotic protein myeloid cell leukemia-1 triggers proliferation and hepatocarcinogenesis in mice. Hepatology 51(4):1226-1236, 2010.

Xiang Z, Luo H, Payton JE, Cain J, Ley TJ, Opferman JT, Tomasson MH. Mcl1 haploinsufficiency protects mice from Myc-induced acute myeloid leukemia. J Clin Invest 120(6):2109-2118, 2010.

Stewart DP, Koss B, Bathina M, Perciavalle RM, Bisanz K, Opferman JT. Ubiquitin independent degradation of anti-apoptotic MCL-1. Mol Cell Biol 30(12):2099-2110, 2010.

Sano R, Annunziata I, Patterson A, Moshiach S, Gomero E, Opferman J, Forte M, d'Azzo A. GM1-ganglioside accumulation at the mitochondria-associated ER membranes links ER stress to Ca2+-dependent mitochondrial apoptosis. Molecular Cell 36(3):500-11, 2009.

Brunelle JK, Ryan J, Yecies D, Opferman JT, Letai A. MCL-1-dependent leukemia cells are more sensitive to chemotherapy than BCL-2-dependent counterparts. J Cell Biol 187(3):429-42, 2009.

Steimer DA, Boyd K, Takeuchi O, Fisher JK, Zambetti GP, Opferman JT. Selective Roles for Anti-Apoptotic MCL-1 during granulocyte development and macrophage effector function. Blood 113:2805-15, 2009.

Vick B, Weber A, Urbanik T, Krammer PH, Opferman JT, Schuchmann M, Galle PR, Schulze-Bergkamen H. Knock-out of Myeloid cell leukemia-1 induces liver damage and increases apoptosis susceptibility of murine hepatocytes. Hepatology 49:627-36, 2009.

Steimer DA, Boyd K, Takeuchi O, Fisher JK, Zambetti GP, Opferman JT. Selective roles for antiapoptotic MCL-1 during granulocyte development and macrophage effector function. Blood 113(12):2805-2815, 2008.

Arbour N, Vanderluit JL, Le Grand JN, Jahani-Asl A, Ruzhynsky VA, Cheung ECC, Kelly MA, MacKenzie AE, Park DS, Opferman JT, Slack RS. MCL-1 is a key regulator of apoptosis during CNS development and following DNA damage. J Neuroscience 28:6068-6078, 2008.

Chao JR, Parganas E, Boyd K, Hong CY, Opferman JT, Ihle JN. Hax-1 mediated processing of HrtA2/Omi by PARL allows survival of lymphocytes and neurons. Nature 452:98-102, 2008.

Podar K, Gouill SL, Zhang J, Opferman JT, Zorn E, Tai YT, Hideshima T, Amiot M, Chauhan D, Harousseau JL, Anderson KC. A pivotal role for Mcl-1 in Bortezomib-induced apoptosis. Oncogene 27:721-731, 2007.

Woodland RT, Fox CJ, Schmidt MR, Hammerman PS, Opferman JT, Korsmeyer SJ, Hilbert DM, Thompson CB. Multiple signaling pathways promote B lymphocyte stimulator (BLyS)-dependent B cell growth and survival. Blood 111:750-760, 2008.

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Schweers RL, Zhang J, Randall MS, Loyd MR, Li W, Dorsey FC, Kundu M, Opferman JT, Cleveland JL, Miller JL, Ney PA. NIX is required for programmed mitochondrial clearance during reticulocyte maturation. Proc Natl Acad Sci USA 104:19500-19505, 2007.

Opferman JT. Life and death during hematopoietic differentiation. Curr Opin Immunol 19:497-502, 2007.

Opferman JT. Apoptosis in the development of the immune system. Cell Death Differ 15:234-242, 2007.

Wei G, Twomey D, Lamb J, Schlis K, Agarwal J, Stam RW, Opferman JT, Sallan SE, den Boer ML, Pieters R, Golub TR, Armstrong SA. Gene expression-based chemical genomics identifies rapamycin as a modulator of MCL-1 and glucocorticoid resistance. Cancer Cell 10:331-342, 2006.

Opferman JT. Unraveling MCL-1 degradation. Cell Death Differ 13:1260-1262, 2006.

Ruiz-Vela A, Opferman JT, Cheng EH, Korsmeyer SJ. Proapoptotic BAX and BAK control multiple initiator caspases. EMBO J 6:379-385, 2005.

Opferman JT, Iwasaki H, Ong CC, Suh H, Mizuno S-I, Akashi K, Korsmeyer SJ.  Obligate Role of Anti-apoptotic MCL-1 in the Survival of Hematopoietic Stem Cells. Science Science 307:1101-1104, 2005.

Oakes SA, Scorrano L, Opferman JT, Bassik MC, Nishino M, Pozzan T, Korsmeyer SJ. Proapoptotic BAX and BAK regulate the type I inositol triphosphate receptor and calcium leak from the endoplasmic reticulum. Proc Natl Acad Sci USA 102:105-110, 2005.

Phillips T, Opferman JT, Shah R, Liu N, Froelich CJ, Ashton-Rickardt PG. A Role for the Granzyme B Inhibitor Serine Protease Inhibitor 6 in CD8 Memory Cell Homeostasis. J Immunol 173:3801-3809, 2004.

Liu N, Phillips T, Zhang M, Wang Y, Opferman JT, Shah R, Ashton-Rickardt PG. Serine protease inhibitor 2A is a protective factor for memory T cell development. Nature Immunology 5:919-926, 2004.

Mori M, Burgess DL, Gefrides LA, Foreman PJ, Opferman JT, Korsmeyer SJ, Cavalheiro EA, Naffah-Mazzacoratti MdG, Noebels JL. Expression of apoptosis inhibitor protein Mcl1 linked to neuroprotection in CNS neurons. Cell Death and Differentiation 11:1223-1233, 2004.

Opferman JT, Letai A, Beard C, Sorcinelli MD, Ong CC, Korsmeyer SJ. Development and Maintenance of B and T Lymphocytes Requires Anti-Apoptotic MCL-1. Nature 426:671-676, 2003.

Oakes SA, Opferman JT, Pozzan T, Korsmeyer SJ, Scorrano L. Regulation of endoplasmic reticulum Ca(2 ) dynamics by proapoptotic BCL-2 family members. Biochem Pharmacol 66:1335-40, 2003.

Opferman JT, Korsmeyer SJ. Apoptosis in the Development and Maintenance of the Immune System. Nature Immunology 4:410-415, 2003.

Scorrano L, Oakes SA, Opferman JT, Cheng EH, Sorcinelli MD, Pozzan T, Korsmeyer SJ. Regulation of endoplasmic reticulum Ca2 dynamics by BAX, BAK is a control point for apoptosis.Science 300:135-139, 2003.

Hettmann T, Opferman JT, Leiden JM, Ashton-Rickardt PG. A critical role for NF-[kappa]B transcription factors in the development of CD8 memory-phenotype T cells. Immunology Letters 85:297-300 2003.

Opferman JT, Ober BT, Narayanna R, Ashton-Rickardt PG. Suicide induced by cytolytic activity controls the differentiation of memory CD8 T lymphocytes. Int Immunol 13:411-419, 2001.

Ober BT, Hu Q, Opferman JT, Hagevich S, Chiu N, Wang CR, Ashton-Rickardt PG. Affinity of thymic self-peptides for the TCR determines the selection of CD8 T lymphocytes in the thymus. Int Immunol 12:1353-1363, 2000.

Ashton-Rickardt PG, Opferman JT. Memory T lymphocytes. CMLS: Cellular and Molecular Life Sciences 56:69-77, 2000.

Thompson CB, Rathmell JC, Frauwirth KA, Lindsten T, Rudin CM, Opferman JT, Ashton-Rickardt PG, Harris MH, Chandel NS, Schumacker PT, Vander Heiden MG. What keeps a resting T cell alive?Cold Spring Harb Symp Quant Biol 64:383-387, 1999.

Opferman JT, Ober BT, Ashton-Rickardt PG. Linear differentiation of cytotoxic effectors into memory T lymphocytes. Science 283:1745-1748, 1999.

Markiewicz M, Girao C, Opferman JT, Sun J, Hu Q, Agulnik A, Bishop C, Thompson CB, Ashton-Rickardt PG. Long-term T cell memory requires the surface expression of self-peptide/major histocompability complex molecules. Proc Natl Acad Sci USA 95:3065-3070, 1998.

Hu Q, Walker CRB, Girao C, Opferman JT, Sun J, Shabanowitz J, Hunt DF, Ashton-Rickardt PG. Specific recognition of thymic self-peptides induces the positive selection of cytotoxic T lymphocytes.Immunity 7:221-231, 1997.

McAbee DD, Nowatzke W, Oehler C, Sitaram M, Sbaschnig E, Opferman JT, Carr J, Ebensen K. Endocytosis and degradation of bovine apo- and holo-lactoferrin by isolated rat hepatocytes are mediated by recycling calcium-dependent binding sites. Biochemistry 32:13749-13760, 1993.

Last update: April 2024

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