Anti-Tumor Therapy, Apoptosis/Cell Death, Cancer, Cell Biology, Cell Transformation, Drug Resistance, Imaging, Lipid Signaling, Membrane Proteins/Channels, Membranes, Mitochondria, Molecular Biology, Oncogenes, Protein Kinases, Signal Transduction, Tumor Suppressor Genes, Tumorigenesis
Cancer Biology [CAB], Genetics and Genomic Sciences [GGS]
BS, Baldwin-Wallace College
PhD, Case Western Reserve University
Postdoctoral Training, La Jolla Institute for Allergy and Immunology
Postdoctoral Training, St. Jude Children’s Research Hospital
Career Development Award
Leukemia & Lymphoma Society
Irma T. Hirschl / Monique Weill-Caulier Research Trusts
Research Scholar Grant
American Cancer Society
Dr. Harold and Golden Lamport Research Award
Basil O'Connor Phase-In Award
March of Dimes
Young Scientist Cancer Research Fund
Basil O'Connor Award
March of Dimes
Ruth Kirschstein NRSA
National Institutes of Health
Thibaud T. Renault Ph.D.
Madhavika N. Serasinghe Ph.D.
Andrew P. Trotta Ph.D.
Mark Luna-Vargas Ph.D.
Rana Elkholi M.S.
Usman Hameedi B.S.
Jesse Gelles-Hurwitz B.A.
Julie C. Sung B.S.
Kent Li B.S.
Cuauhtlehuanitzin A. Rangel B.S.
Shira Y. Wieder M.D.
Our current research interests are divided into three areas, but adopt a unified theme to decipher the interplay between mitochondria and cell death signaling:
I. What are the biochemical, physiological, and structural consequences of protein·protein interactions within the BCL-2 family?
II. How does the mitochondrial environment influence BCL-2 family function and the core cell death machinery?
III. How do oncogenic and tumor suppressor signals intersect with the mitochondrial dynamics machinery to regulate tumorigenesis and chemosensitivity?
We explore the above questions using state-of-the-art apoptosis, metabolism, and cancer biology model systems --- usually focusing on hematological malignancies and melanoma.
Visit the Chipuk Laboratory
Luna-Vargas MP, Chipuk JE. The Deadly Landscape Of Pro-Apoptotic BCL-2 Proteins In the Outer Mitochondrial Membrane. The FEBS Journal 2015 Dec;.
Chipuk JE. BCL-2 proteins: melanoma lives on the edge. Oncoscience 2015 Aug 11; 2(9): 729-30.
Follis AV, Llambi F, Merritt P, Chipuk JE, Green DR, Kriwacki RW. Pin1-Induced Proline Isomerization in Cytosolic p53 Mediates BAX Activation and Apoptosis. Molecular Cell 2015 Aug 20; 59(4): 677-84.
Gelles JD, Elkholi R, Serasinghe MN, Luna-Vargas M, Chipuk JE. From zero to sixty: cell death signaling in the city that never sleeps. Oncogene 2015 Jul 6;.
Wieder SY, Serasinghe MN, Sung JC, Choi DC, Birge MB, Yao JL, Bernstein E, Celebi JT, Chipuk JE. Activation of the mitochondrial fragmentation protein DRP1 correlates with BRAFV600E melanoma. The Journal of Investigative Dermatology 2015 Oct; 135(10): 2544-7.
Serasinghe MN, Weider SY, Renault TT, Elkholi R, Asciolla JJ, Yao JL, Jabado O, Hoehn K, Kageyama Y, Sesaki H, Chipuk JE. Mitochondrial division is requisite to RAS-induced transformation and targeted by oncogenic MAPK pathway inhibitors. Molecular Cell 2015 Feb 5; 57(3): 521-536.
Renault TT, Floros KV, Elkholi R, Corrigan KA, Kushnareva Y, Wieder SY, Lindtner C, Serasinghe MN, Asciolla JJ, Buettner C, Newmeyer DD, Chipuk JE. Mitochondrial shape governs BAX-induced membrane permeabilization and apoptosis. Molecular Cell 2015 Jan 8; 57(1): 69-82.
Galluzzi L, Bravo-San Pedro JM, Vitale I, Aaronson SA, Abrams JM, Adam D, Alnemri ES, Altucci L, Andrews D, Annicchiarico-Petruzzelli M, Baehrecke EH, Bazan NG, Bertrand MJ, Bianchi K, Blagosklonny MV, Blomgren K, Borner C, Bredesen DE, Brenner C, Campanella M, Candi E, Cecconi F, Chan FK, Chandel NS, Cheng EH, Chipuk JE, Cidlowski JA, Ciechanover A, Dawson TM, Dawson VL, De Laurenzi V, De Maria R, Debatin KM, Di Daniele N, Dixit VM, Dynlacht BD, El-Deiry WS, Fimia GM, Flavell RA, Fulda S, Garrido C, Gougeon ML, Green DR, Gronemeyer H, Hajnoczky G, Hardwick JM, Hengartner MO, Ichijo H, Joseph B, Jost PJ, Kaufmann T, Kepp O, Klionsky DJ, Knight RA, Kumar S, Lemasters JJ, Levine B, Linkermann A, Lipton SA, Lockshin RA, López-Otín C, Lugli E, Madeo F, Malorni W, Marine JC, Martin SJ, Martinou JC, Medema JP, Meier P, Melino S, Mizushima N, Moll U, Muñoz-Pinedo C, Nuñez G, Oberst A, Panaretakis T, Penninger JM, Peter ME, Piacentini M, Pinton P, Prehn JH, Puthalakath H, Rabinovich GA, Ravichandran KS, Rizzuto R, Rodrigues CM, Rubinsztein DC, Rudel T, Shi Y, Simon HU, Stockwell BR, Szabadkai G, Tait SW, Tang HL, Tavernarakis N, Tsujimoto Y, Vanden Berghe T, Vandenabeele P, Villunger A, Wagner EF, Walczak H, White E, Wood WG, Yuan J, Zakeri Z, Zhivotovsky B, Melino G, Kroemer G. Essential versus accessory aspects of cell death: recommendations of the NCCD 2015. Cell Death and Differentiation 2015 Jan; 22(1): 58-73.
Elkholi R, Renault TT, Serasinghe MN, Chipuk JE. Putting the pieces together: How is the mitochondrial pathway of apoptosis regulated in cancer and chemotherapy. Cancer & Metabolism 2014 Sept; 2(16): 1-15.
Renault TT, Elkholi R, Bharti A, Chipuk JE. BH3 mimetics demonstrate differential activities dependent upon the functional repertoire of pro- and anti-apoptotic BCL-2 family proteins. Journal of Biological Chemistry 2014 Sept; 289(38): 26481-26491.
Chong RA, Wu K, Spratt DE, Yang Y, Lee C, Nayak J, Xu M, Elkholi R, Tappin I, Li J, Hurwitz J, Brown BD, Chipuk JE, Chen ZJ, Sanchez R, Shaw GS, Huang L, Pan ZQ. Pivotal role for the ubiquitin Y59-E51 loop in lysine 48 polyubiquitination. Proc Natl Acad Sci USA 2014 June 10; 111(23): 8434-9.
Serasinghe MN, Missert DJ, Asciolla JJ, Podgrabinska S, Wieder SY, Izadmehr S, Belbin G, Skobe M, Chipuk JE. Anti-apoptotic BCL-2 proteins govern cellular outcome following BRAFV600E inhibition and can be targeted to reduce resistance. Oncogene 2014 Mar 10;.
Zhang X, Lv H, Zhou Q, Elkholi R, Chipuk JE, Reddy MV, Reddy EP, Gallo JM. Preclinical pharmacological evaluation of a novel multiple kinase inhibitor, ON123300, in brain tumor models. Molecular Cancer Therapeutics 2014 May; 13(5): 1105-16.
Lopez-Rivera E, Jayaraman P, Parikh F, Davies MA, Ekmekcioglu S, Izadmehr S, Milton DR, Chipuk JE, Grimm EA, Estrada Y, Aguirre-Ghiso JA, Sikora AG. Inducible nitric oxide synthase drives mTOR pathway activation and proliferation of human melanoma by reversible nitrosylation of TSC2. Cancer Research 2014 Feb 15; 74(4): 1067-1078.
Elkholi R, Chipuk JE. How do I kill thee? Let me count the ways: p53 regulates PARP-1 dependent necrosis. BioEssays 2014 Jan; 36(1): 46-51.
Renault TT, Chipuk JE. Death upon a kiss: mitochondrial outer membrane composition and organelle communication govern sensitivity to BAK/BAX-dependent apoptosis. Chemistry & Biology 2014 Jan 16; 21(1): 114-123.
Fink MY, Chipuk JE. Survival of HER2-positive breast cancer cells: receptor signaling to apoptotic control centers. Genes & Cancer 2013 May 8; 4(5-6): 187-195.
Renault TT, Floros KV, Chipuk JE. BAK/BAX activation and cytochrome c release assays using isolated mitochondria. Methods 2013 June; 61(2): 146-155.
Beverly LJ, Howell LA, Hernandez-Corbacho M, Casson L, Chipuk JE, Siskind LJ. BAK activation is necessary and sufficient to drive ceramide synthase-dependent ceramide accumulation following inhibition of BCL2-like proteins. The Biochemical Journal 2013 May 15; 452(1): 111-9.
Renault TT, Chipuk JE. Getting away with murder: how do the BCL-2 family of proteins kill with immunity?. Annals of the New York Academy of Science 2013 May; 1285(1): 59-79.
Follis AV, Chipuk JE, Fisher JC, Yun MK, Grace CR, Nourse A, Baran K, Ou L, Min L, White SW, Green DR, Kriwacki RW. PUMA binding induces partial unfolding within BCL-xL to disrupt p53 binding and promote apoptosis. Nature Chemical Biology 2013 Mar; 9(3): 163-8.
Renault TT, Chipuk JE. Inter-organellar communication with mitochondria regulates both the intrinsic and extrinsic pathways of apoptosis. Communicative & Integrative Biology 2013 March/April; 6(2): 1-4.
Anvekar RA, Asciolla JJ, Lopez-Rivera E, Floros KV, Izadmehr S, Elkholi R, Belbin G, Sikora AG, Chipuk JE. Sensitization to the mitochondrial pathway of apoptosis augments melanoma tumor cell responses to conventional chemotherapeutic regimens. Cell Death and Disease 2012 Nov 15; 3(e420): 1-11.
Asciolla JJ, Renault TT, Chipuk JE. Examining BCL-2 family function with large unilamellar vesicles. Journal of Visualized Experiments 2012 Oct 5; 68: 1-6.
Greter M, Helft J, Chow A, Hashimoto D, Mortha A, Agudo-Cantero J, Bogunovic M, Gautier EL, Miller J, Leboeuf M, Lu G, Aloman C, Brown BD, Pollard JW, Xiong H, Randolph GJ, Chipuk JE, Frenette PS, Merad M. GM-CSF controls nonlymphoid tissue dendritic cell homeostasis but is dispensable for the differentiation of inflammatory dendritic cells. Immunity 2012 Jun; 36(6): 1031-46.
Chipuk JE, McStay GP, Bharti A, Kuwana T, Clarke CJ, Siskind LJ, Obeid LM, Green DR. Sphingolipid metabolism cooperates with BAK and BAX to promote the mitochondrial pathway of apoptosis. Cell 2012 March; 148(5): 988-1000.
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 and Differentiation 2012 Apr; 18(4): 642-9.
Elkholi R, Floros KV, Chipuk JE. The role of BH3-Only proteins in tumor cell development, signaling, and treatment. Genes & Cancer 2011 May; 2(5): 523-37.
Anvekar RA, Asciolla JJ, Missert DJ, Chipuk JE. Born to be alive: a role for the BCL-2 family in melanoma tumor cell survival, apoptosis, and treatment. Frontiers in Molecular Oncology 2011 Oct; 1(34).
Du H, Wolf J, Schafer B, Moldoveanu T, Chipuk JE, Kuwana T. BH3 domains other than BIM and BID can directly activate BAX/BAK. The Journal of Biological Chemistry 2011 Jan; 286(1): 491-501.
McAuley JL, Chipuk JE, Boyd KL, Van De Velde N, Green DR, McCullers JA. PB1-F2 proteins from H5N1 and 20th century pandemic influenza viruses cause immunopathology. PLoS Pathogens 2010; 6(7).
Chipuk JE, Moldoveanu T, Llambi F, Parsons MJ, Green DR. The BCL-2 family reunion. Molecular Cell 2010 Feb; 37(3): 299-310.
Chipuk JE, Green DR. PUMA cooperates with direct activator proteins to promote mitochondrial outer membrane permeabilization and apoptosis. Cell Cycle 2009 Sep; 8(17): 2692-6.
Chipuk JE, Green DR. How do BCL-2 proteins induce mitochondrial outer membrane permeabilization? . Trends in Cell Biology 2008 April; 18(4): 157-164.
Cassidy-Stone A, Chipuk JE, Ingerman E, Song C, Yoo C, Kurth MJ, Hinshaw J, Shaw J, Green DR, Nunnari J. Mitochondrial division inhibitors reveal the role of the mitochondrial division dynamin in BAX/BAK-dependent mitochondrial cytochrome c release. Developmental Cell 2008 February; 14(2): 193-204.
Green D, Chipuk J. Stabbed in the BAX. Nature 2008 October; 455(7216): 1047-1049.
Chipuk JE, Fisher JC, Dillon CP, Kuwana T, Kriwacki RW, Green DR. Mechanism of apoptosis induction by the inhibition of BCL-2 proteins. Proceedings of the National Academy of Science - USA 2008 Dec; 105(51): 20327-20332.
Chipuk JE, Green DR. Do inducers of apoptosis trigger caspase-independent cell death?. Nature Reviews Molecular Cellular Biology 2005 March; 6(3): 268-275.
Kuwana T, Bouchier-Hayes L, Chipuk JE, Bonzon C, Sullivan BA, Green DR. BH3 domains of BH3-only proteins differentially regulate BAX-mediated membrane permeabilization both directly and indirectly. Molecular Cell 2005 Feb; 17(4): 525-35.
Chipuk JE, Bouchier-Hayes L, Newmeyer DD, Green DR. PUMA couples the nuclear and cytoplasmic pro-apoptotic function of p53. Science 2005 Sept; 309(5741): 1732-1735.
Spierings D, McStay GP, Saleh M, Bender C, Chipuk JE, Maurer U, Green DR. Connected to death: the (unexpurgated) mitochondrial pathway of apoptosis. Science 2005 Oct; 310(5745): 66-67.
Chipuk JE, Kuwana T, Bouchier-Hayes L, Droin NM, Newmeyer DD, Schuler M, Green DR. Direct activation of BAX by p53 mediates mitochondrial outer membrane permeabilization and apoptosis. Science 2004 Feb; 303(5660): 1010-1014.
Chipuk JE, Maurer U, Green DR, Schuler M. Pharmacologic activation of p53 elicits BAX-dependent apoptosis in the absence of transcription. Cancer Cell 2003 Nov; 4(5): 371-381.
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