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J. Marie Hardwick, Ph.D.

Photo of Dr. J. Marie Hardwick, Ph.D.

Joint Appointment in Neurology

Background

Titles

  • Joint Appointment in Neurology
  • Joint Appointment in Oncology
  • Joint Appointment in Pharmacology and Molecular Sciences

Research & Publications

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.

Lab Website: J. Marie Hardwick Lab

Selected Publications

  1. Teng, X.; Hardwick, J.M. Reliable method for detection of programmed cell death in yeast. Methods Mol Biol. 2009;559:335-342.
  2. Hardwick, J.M.; Youle, R.J. SnapShot: BCL-2 proteins. Cell. 2009 Jul 23;138(2):404, 404 e401.
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. 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.
  8. 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.
  9. 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.
  10. 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.
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