LABORATORY OF MICHAEL FILL

Michael Fill, Ph.D.
Professor
Department of Molecular Biophysics & Physiology
Rush Medical College
Rush University Medical Center
1750 W. Harrison St.
Chicago, IL 60612
312.942.6434 (Voice)
312.942.8711 (Fax)
mfill@rush.edu



            Dr. Fill’s research focuses on defining the mechanisms that control intracellular Ca signaling in excitable cells. He is particularly interested in the origin/control of local intracellular Ca signals mediated by ryanodine receptor (RyR) and/or Inositol trisphosphate receptor (InsP3R) Ca release channels. Since this is critical to modulation of many cellular phenomena (contraction, secretion, transcription, etc), his work is clinically relevant because it defines potential sites for pathological failure and/or therapeutic intervention.

            Dr. Fill’s previous research accomplishments (published) include, 1) amoung the first to define RyR function at the single channel level, 2) defined abnormal single RyR function in Malignant Hyperthermia, 3) discovered/defined the single RyR adaptation phenomena, 4) showed that the apoptotis protein Bcl-xl forms an ion channel, 5) defined structure-function of recombinant InsP3R, 6) defined single InsP3R ligand regulation using InsP3R chimeras and 7) first to measure RyR physiological unit Ca current.

            Dr.Fill’s current research efforts (unpublished) are NIH funded. His current efforts seek to, 1) define role of feed-through Ca local control during RyR operation, 2) identify candidate lumenal local RyR Ca control mechanisms and, 3) determine local control mechanisms underlying the coordinated RyR channel. Dr. Fill is also working on a project that will better define RyR permeation and its ramifications to RyR-mediated Ca2+ release including its potential involvement in a RyR-linked myopathy. He is also working with Dr. Josefina Ramos-Franco to define the origin Ca puffs, the elementary unit of InsP3R-mediated Ca2+ release.


Publications:

Györke, S., and M. Fill.  Ryanodine receptor adaptation:  Control mechanism of Ca2+-induced Ca2+ release in heart.  Science  260: 807-809, 1993.

Tu, Q., P. Vélez, M. Cortes-Gutierrez and M. Fill.  Surface charge at the lumenal mouth of the cardiac ryanodine receptor channel. Journal of General Physiology 103: 1-15, 1994.

Minn, A.J., P. Velez, S.L. Schendel, H. Liang, S.W. Muchmore, S.W. Fesik, C.B. Thompson* and M. Fill*. Bcl-xl forms an ion channel in synthetic lipid membranes. Nature 385:353-357, 1997. (*co-senior authors)

Fill, M., and J. Copello.  Ryanodine receptor calcium release channels. Physiological Reviews 82(4):893-922, 2002.

Ramos, J., W. Jung, J. Ramos-Franco, G.A. Mignery and M. Fill. Single Channel Function of Inositol 1,4,5-trisphosphate Receptor Type-1 and -2 Isoform Domain-Swap Chimeras. Journal of General Physiology  121(5):399-411, 2003.

Rosales R., A. Escobar and M. Fill. Calcium Regulation of Single Ryanodine Receptor Channel Gating
Analyzed Using HMM/MCMC Statistical Methods. Journal of General Physiology 123(5):533-553, 2004.


Ryanodine Receptor - Single Channel Recording


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