J. Marie Hardwick, Ph.D.

Categories:

• Viral Oncology

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

Basanez, G., and Hardwick, J.M. (2008). Unravelling the bcl-2 apoptosis code with a simple model system. PLoS Biol 6, e154.

Berman, S.B., Pineda, F.J., and Hardwick, J.M. (2008). Mitochondrial fission and fusion dynamics: The long and short of it. Cell Death Differ 15, 1147-1152.

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. (2006). Zinc-dependent multi-conductance channel activity in mitochondria isolated from ischemic brain. J Neurosci 26, 6851-62.

Chen, Y. B., Seo, S. Y., Kirsch, D. G., Sheu, T. T., Cheng, W. C. & Hardwick, J. M. (2006). Alternate functions of viral regulators of cell death. Cell Death Differ 13, 1318-24.

Cheng, W. C., and J. M. Hardwick. 2007. A quorum on bacterial programmed cell death. Mol Cell 28:515-7.

Cheng, W. C., Berman, S. B., Ivanovska, I., Jonas, E. A., Lee, S. J., Chen, Y., Kaczmarek, L. K., Pineda, F. & Hardwick, J. M. (2006). Mitochondrial factors with dual roles in death and survival. Oncogene 25, 4697-705.

Cheng, W.C., Leach, K.M., and Hardwick, J.M. (2008). Mitochondrial death pathways in yeast and mammalian cells. Biochim Biophys Acta 1783, 1272-1279.

Cheng, W.C., Teng, X., Park, H.K., Tucker, C.M., Dunham, M.J., and Hardwick, J.M. (2008). Fis1 deficiency selects for compensatory mutations responsible for cell death and growth control defects. Cell Death Differ 15, 1838-1846.

Galonek, H. L. & Hardwick, J. M. (2006). Upgrading the BCL-2 network. Nat Cell Biol 8, 1317-1319.

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., and Kornbluth, S. (2008). Aven-dependent activation of ATM following DNA damage. Curr Biol 18, 933-942.

Hickman, J.A., Hardwick, J.M., Kaczmarek, L.K., and Jonas, E.A. (2008). Bcl-xL inhibitor ABT-737 reveals a dual role for Bcl-xL in synaptic transmission. J Neurophysiol 99, 1515-1522.

Ivanovska, I. & Hardwick, J. M. (2005). Viruses activate a genetically conserved cell death pathway in a unicellular organism. J Cell Biol 170, 391-9.

Jonas, E. A., Hardwick, J. M. & Kaczmarek, L. K. (2005). Actions of BAX on mitochondrial channel activity and on synaptic transmission. Antioxid Redox Signal 7, 1092-100.

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., and Jonas, E.A. (2008). Bcl-xL induces Drp1-dependent synapse formation in cultured hippocampal neurons. Proc Natl Acad Sci U S A 105, 2169-2174.

Qi, B., and Hardwick, J.M. (2008). Bcl-2 turns deadly. Nat Chem Biol 4, 722-723.

Qi, B., and J. M. Hardwick. 2007. A Bcl-xL timer sets platelet life span. Cell 128:1035-6.

Sauerwald, T. M., Figueroa, B., Jr., Hardwick, J. M., Oyler, G. A. & Betenbaugh, M. J. (2006). Combining caspase and mitochondrial dysfunction inhibitors of apoptosis to limit cell death in mammalian cell cultures. Biotechnol Bioeng 94, 362-72.

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., and Colombini, M. (2008). Anti-apoptotic Bcl-2 family proteins disassemble ceramide channels. J Biol Chem 283, 6622-6630.

Collin-Ramos, D. A., Irusta, P., Gan, E. C., Olson, M. R., Song, J., Morimotom, R. I., et al. 2003. Inhibition of translation and induction of apoptosis by Bunyaviral nonstructural proteins bearing sequence similarity to Reaper. Mol. Biol. Cell. 14:4162-4172.  Dohm, J. A., Lee, S. J., Hardwick, J. M., Hill, R. B., & Gittis, A. G. 2004. Cytosolic domain of the human mitochondrial fission protein fis-1 adopts a TPR fold. Proteins. 54:153-156.

Figueroa, B., Jr., Sauerwald, T. M., Oyler, G. A., Hardwick, J. M., & Betenbaugh, M. J. 2003. A comparison of the properties of a Bcl-xL variant to the wild-type anti-apoptosis inhibitor in mammalian cell cultures. Metab. Eng. 5:230-245.  Jonas, E. A., Hickman, J. A., Hardwick, J. M., & Kaczmarek, L. K. 2005. Exposure to hypoxia rapidly induces mitochondrial channel activity within a living synapse. J. Biol. Chem. 280:4491-4497.

Kim, T. W., Hung, C. F., Juang, J., He, L., Hardwick, J. M., & Wu, T. C. 2004. Enhancement of suicidal DNA vaccine potency by delaying suicidal DNA-induced cell death. Gene Ther. 11:336-342.  Seo, S. Y., Chen, Y. B., Ivanovska, I., Hong, S. J., Dawson, V. L., Ranger, A. M., et al. Caspase cleavage converts BAD from an antiapoptotic to a proapoptotic factor. [In review].