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            Dr.Fill’s current research efforts (unpublished) are NIH funded.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.