Research Interests
Our
laboratory is interested in deciphering the role of DEG/ENaC ion
channels in sensory perception and neurodegeneration and primarily
employs the powerful model organism C. elegans. DEG/ENaCs
are two-transmembrane domain subunits of voltage-independent Na +
channels that function as trimers in an extraordinary range of biological
processes.
Furthermore, a subset of neuronally-expressed DEG/ENaCs can potently
induce neurodegeneration when hyperactivated in ischemia models.
Despite clear patho-physiological relevance of deciphering the mechanism
of DEG/ENaC action, understanding of how channel features and associated
proteins confer specificity of function and dysfunction is in its
infancy. Our lab focuses on C. elegans DEG/ENaC channel
MEC-4 which functions within a mechanosensory ion channel complex
comprised of pore-forming and accessory subunits to mediate touch
perception in C. elegans.
| Interestingly, we recently unexpectedly discovered that
the hyperactivated mutant MEC-4(d) channel is Ca 2+-permeable
and may induce neurodegeneration by conducting toxic levels of
Ca 2+ into the cell. |
| IImportantly, hyperactivated DEG/ENaC ASIC1a also
conducts Ca 2+ in an analogous model of neurotoxicity in mouse. These
data revealed a novel channel feature in some DEG/ENaC family
members—Ca 2+ permeability—and suggested a
new mechanism of neurotoxicity. We are interested in further
investigating the role of Ca 2+ permeability and of each subunit
within the channel complex in DEG/ENaC function in physiological
and neurotoxic conditions. |
 |
Selected Publications
- Bianchi L. *, Tsechpenakis G. *, Metaxas D., Driscoll M. (2007) A novel computational approach for simultaneous tracking and feature extraction of C. elegans populations in fluid environments. *These two authors contributed equally to this work. IEEE Transactions in Biomedical Engineering, in press.
- Bianchi L., (2007) Mechanotransduction: touch and feel at the molecular level as modeled in Caenorhabditis elegans. Molecular Neurobiology, 2007 Dec;36(3):254-71. Epub 2007 Sep 27. PMID: 17955200.
- Bianchi L and Driscoll M (2006) Culture of embryonic C. elegans cells for electrophysiological and pharmacological analyses. Book Chapter in WormBook, ed. The C. elegans Research Community.
- Bianchi L and Driscoll M (2006) Heterologous expression of C. elegans channels in Xenopus oocytes. Book Chapter in WormBook, ed. The C. elegans Research Community.
- Royal DC, Bianchi L, Royal MA, Lizzio M Jr, Mukherjee G, Nunez YO, Driscoll M (2005) Temperature-sensitive mutant of the Caenorhabditis elegans neurotoxic MEC-4(d) DEG/ENaC channel identifies a site required for trafficking or surface maintenance. J Biol Chem. 280(51):41976-86.
- Bianchi L, Gerstbrein B, Frokjaer-Jensen C, Royal DC, Mukherjee G, Royal MA, Xue J, Schafer WR, Driscoll M (2004) The neurotoxic MEC-4(d) DEG/ENaC sodium channel conducts calcium: implications for necrosis initiation. Nat Neurosci. 7(12):1337-44.
- Bianchi L and Driscoll M (2004) The molecular basis of touch sensation as modeled in Caenorhabditis elegans. Book Chapter in "Transduction channels in sensory cells", (eds. Frings, S. & Bradley J.), 1-29 (Wiley-VCH, Weinheim, Germany).
- Suzuki H, Kerr R, Bianchi L, Frokjaer-Jensen C, Slone D, Xue J, Gerstbrein B, Driscoll M, Schafer WR (2003) In vivo imaging of C. elegans mechanosensory neurons demonstrates a specific role for the MEC-4 channel in the process of gentle touch sensation. Neuron. 39(6):1005-17.
- Bianchi L, Kwok SM, Driscoll M, Sesti F (2003) A potassium channel-MiRP complex controls neurosensory function in Caenorhabditis elegans. J Biol Chem. 278(14):12415-24.
- Bianchi L, Driscoll M (2002) Protons at the gate: DEG/ENaC ion channels help us feel and remember. Neuron. 2002 34(3):337-40.
Curriculum Vitae
- 1992 B.S. and M.A. in Biology, University of Milan, Italy
- 1997 PhD Physiology, University of Florence, Italy
- 1997-1998 Postdoctoral Fellowship, Physiology and Biophysics, Case Western Reserve
- 1998-2001 Postdoctoral Fellowship, Department of Medicine, Vanderbilt University
- 2001-2006 Research Assistant Professor, Dept. of Molecular Biology and Biochemistry, Rutgers University
- 2006-present Assistant Professor, Dept. of Physiology and Biophysics, University of Miami School of Medicine
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