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Dr. J.Marie Hardwick

Ph.D.
J.Marie Hardwick
Titles

Professor of Molecular Microbiology and Immunology,The Johns Hopkins Bloomberg School of Public Health
Joint Appointments in Pharmocology and Molecular Sciences, Neurology, Oncology, and Pharmacology
Joint Appointment in Biochemistry Molecular Biology, Johns Hopkins Bloomberg School of Public Health

Schools\Degrees

Ph.D., Microbiology, University of Kansas

Training

Fellow, Molecular Virology (retroviruses), University of Alabama at Birmingham, Birmingham, AL

Research Summary

Dr. Hardwick’s research is focused on the cellular and molecular biology of programmed cell death. Her laboratory was a pioneer in this new field of study, demonstrating that viruses trigger cells to undergo apoptosis, a deliberate suicide process often occurring long before the cell succumbs to the direct damaging effects of a virus. Her research on viral and cellular mechanisms that regulate programmed cell death has uncovered surprising findings, challenged dogma and provided insight into basic cellular mechanisms that are conserved throughout phylogeny. 

Research projects currently under way in her laboratory include:
• The molecular, biophysical and physiological differences between the Bcl-2 proteins found in cells and those encoded by oncogenic viruses.
• The Hardwick laboratory suggests that the death-inducing proteins harbored inside healthy cells are not just “latent” death factors waiting to kill cells when called upon, but rather function as regulators of essential biochemical processes (e.g., metabolism, neuronal activity, mitochondrial structure) that can be converted into killing factors should the occasion arises.
• While programmed cell death is known to be essential for sculpting and maintaining all complex multicellular organisms, Dr. Hardwick promotes a new hypothesis that programmed cell death is an ancient and fundamental process conserved even in unicellular organisms, perhaps originating to protect these species from invasion and destruction by pathogens. Determining and understanding these basic properties is necessary to fully understand the pathogenic mechanisms of this family of proteins in human disease.

 

EM 5/06
 

Journal Citations

Bonanni, L.; Chachar, M.; Jover-Mengual, T.; Li, H.; Jones, A.; Yokota, H.; Ofengeim, D.; Flannery, R.J.; Miyawaki, T.; Cho, C.H.; Polster, B.M.; Pypaert, M.; Hardwick, J.M.; Sensi, S.L.; Zukin, R.S.; Jonas, E.A. Zinc-dependent multi-conductance channel activity in mitochondria isolated from ischemic brain. J Neurosci. 2006 Jun 21;26(25):6851-6862.
Chen, Y.B.; Seo, S.Y.; Kirsch, D.G.; Sheu, T.T.; Cheng, W.C.; Hardwick, J.M. Alternate functions of viral regulators of cell death. Cell Death Differ. 2006 Aug;13(8):1318-1324.
Cheng, W.C.; Berman, S.B.; Ivanovska, I.; Jonas, E.A.; Lee, S.J.; Chen, Y.; Kaczmarek, L.K.; Pineda, F.; Hardwick, J.M. Mitochondrial factors with dual roles in death and survival. Oncogene. 2006 Aug 7;25(34):4697-4705.
Galonek, H.L.; Hardwick, J.M. Upgrading the BCL-2 network. Nat Cell Biol. 2006 Dec;8(12):1317-1319.
Sauerwald, T.M.; Figueroa, B., Jr.; Hardwick, J.M.; Oyler, G.A.; Betenbaugh, M.J. Combining caspase and mitochondrial dysfunction inhibitors of apoptosis to limit cell death in mammalian cell cultures. Biotechnol Bioeng. 2006 Jun 5;94(2):362-372.
Cheng, W.C.; Hardwick, J.M. A quorum on bacterial programmed cell death. Mol Cell. 2007 Nov 30;28(4):515-517.
Qi, B.; Hardwick, J.M. A Bcl-xL timer sets platelet life span. Cell. 2007 Mar 23;128(6):1035-1036.
Basanez, G.; Hardwick, J.M. Unravelling the bcl-2 apoptosis code with a simple model system. PLoS Biol. 2008 Jun 17;6(6):e154.
Berman, S.B.; Pineda, F.J.; Hardwick, J.M. Mitochondrial fission and fusion dynamics: The long and short of it. Cell Death Differ. 2008 Jul;15(7):1147-1152.
Cheng, W.C.; Leach, K.M.; Hardwick, J.M. Mitochondrial death pathways in yeast and mammalian cells. Biochim Biophys Acta. 2008 Jul;1783(7):1272-1279.
Cheng, W.C.; Teng, X.; Park, H.K.; Tucker, C.M.; Dunham, M.J.; Hardwick, J.M. Fis1 deficiency selects for compensatory mutations responsible for cell death and growth control defects. Cell Death Differ. 2008 Dec;15(12):1838-1846.
Guo, J.Y.; Yamada, A.; Kajino, T.; Wu, J.Q.; Tang, W.; Freel, C.D.; Feng, J.; Chau, B.N.; Wang, M.Z.; Margolis, S.S.; Yoo, H.Y.; Wang, X.F.; Dunphy, W.G.; Irusta, P.M.; Hardwick, J.M.; Kornbluth, S. Aven-dependent activation of ATM following DNA damage. Curr Biol. 2008 Jul 8;18(13):933-942.
Hickman, J.A.; Hardwick, J.M.; Kaczmarek, L.K.; Jonas, E.A. Bcl-xL inhibitor ABT-737 reveals a dual role for Bcl-xL in synaptic transmission. Journal of neurophysiology. 2008 Mar;99(3):1515-1522.
Li, H.; Chen, Y.; Jones, A.F.; Sanger, R.H.; Collis, L.P.; Flannery, R.; McNay, E.C.; Yu, T.; Schwarzenbacher, R.; Bossy, B.; Bossy-Wetzel, E.; Bennett, M.V.; Pypaert, M.; Hickman, J.A.; Smith, P.J.; Hardwick, J.M.; Jonas, E.A. Bcl-xL induces Drp1-dependent synapse formation in cultured hippocampal neurons. Proc Natl Acad Sci U S A. 2008 Feb 12;105(6):2169-2174.
Qi, B.; Hardwick, J.M. Bcl-2 turns deadly. Nat Chem Biol. 2008 Dec;4(12):722-723.
Siskind, L.J.; Feinstein, L.; Yu, T.; Davis, J.S.; Jones, D.; Choi, J.; Zuckerman, J.E.; Tan, W.; Hill, R.B.; Hardwick, J.M.; Colombini, M. Anti-apoptotic Bcl-2 family proteins disassemble ceramide channels. J Biol Chem. 2008 Mar 14;283(11):6622-6630.
Berman, S.B.; Chen, Y.B.; Qi, B.; McCaffery, J.M.; Rucker, E.B., 3rd; Goebbels, S.; Nave, K.A.; Arnold, B.A.; Jonas, E.A.; Pineda, F.J.; Hardwick, J.M. Bcl-x L increases mitochondrial fission, fusion, and biomass in neurons. J Cell Biol. 2009 Mar 9;184(5):707-719.
Galluzzi, L.; Aaronson, S.A.; Abrams, J.; Alnemri, E.S.; Andrews, D.W.; Baehrecke, E.H.; Bazan, N.G.; Blagosklonny, M.V.; Blomgren, K.; Borner, C.; Bredesen, D.E.; Brenner, C.; Castedo, M.; Cidlowski, J.A.; Ciechanover, A.; Cohen, G.M.; De Laurenzi, V.; De Maria, R.; Deshmukh, M.; Dynlacht, B.D.; El-Deiry, W.S.; Flavell, R.A.; Fulda, S.; Garrido, C.; Golstein, P.; Gougeon, M.L.; Green, D.R.; Gronemeyer, H.; Hajnoczky, G.; Hardwick, J.M.; Hengartner, M.O.; Ichijo, H.; Jaattela, M.; Kepp, O.; Kimchi, A.; Klionsky, D.J.; Knight, R.A.; Kornbluth, S.; Kumar, S.; Levine, B.; Lipton, S.A.; Lugli, E.; Madeo, F.; Malomi, W.; Marine, J.C.; Martin, S.J.; Medema, J.P.; Mehlen, P.; Melino, G.; Moll, U.M.; Morselli, E.; Nagata, S.; Nicholson, D.W.; Nicotera, P.; Nunez, G.; Oren, M.; Penninger, J.; Pervaiz, S.; Peter, M.E.; Piacentini, M.; Prehn, J.H.; Puthalakath, H.; Rabinovich, G.A.; Rizzuto, R.; Rodrigues, C.M.; Rubinsztein, D.C.; Rudel, T.; Scorrano, L.; Simon, H.U.; Steller, H.; Tschopp, J.; Tsujimoto, Y.; Vandenabeele, P.; Vitale, I.; Vousden, K.H.; Youle, R.J.; Yuan, J.; Zhivotovsky, B.; Kroemer, G. Guidelines for the use and interpretation of assays for monitoring cell death in higher eukaryotes. Cell Death Differ. 2009 Aug;16(8):1093-1107.
Hardwick, J.M.; Youle, R.J. SnapShot: BCL-2 proteins. Cell. 2009 Jul 23;138(2):404, 404 e401.
Teng, X.; Hardwick, J.M. Reliable method for detection of programmed cell death in yeast. Methods Mol Biol. 2009;559:335-342.

 

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