BIOLOGICAL SCIENCEFACULTY MEMBER Dr. Debra A. Fadool
Personal Home Page Research and Professional Interests: We are researching learning, memory, and neural plasticity at the level of
the ion channel protein. Our main stay in the laboratory is biophysics, specifically
a technique called patch-clamp electrophysiology, where we can measure single
conformational changes in ion channel proteins that elicit electrical signals,
essentially the language of the brain. One of the most ubiquitous ways of modulating
electrical activity of ion channels is a biochemical process called phosphorylation,
whereby negative phosphate groups are added to the channel at specific residues.
Hence we combine our skills in electrophysiology with those of protein biochemistry
(phosphorylation assays; protein-protein interactions), molecular biology (creating
mutant ion channels and signaling proteins), and molecular genetics (genetically
targeted "knock-out" mice to study cell signaling as guided by loss of function).
We were very much excited that the 2000 Nobel Prize in Physiology or Medicine
was attributed to several scientists that discovered the importance of phosphorylation.
Perhaps the importance of phosphorylation in regulating cellular activity can
be underscored by the large portion (2-3%) of the eukaryotic genome set aside
to code for kinases, enzymes that initiate phosphorylation. Humans have 2000
conventional kinase genes and most of those exist in the brain. Abnormality
in these genes and correlate enzyme activity could contribute to the onset or
severity of specific neuronal diseases such as Alzheimer's functional, inflammatory
responses, deregulated cell proliferation, and to diseases such as cancer (especially
mammary), atherosclerosis, psoriasis, and diabetes. Most recently we have discovered
that hormones and neurotrophins (insulin and brain-derived neurotrophic factor
(BDNF)) modulate electrical activity in the brain at the level of the ion channel.
Thus we are studying the neuropathology of diabetes and nerve damage through
disease or injury. Since perfusion of BDNF induces new nerve cell growth, it
may have this capacity by acting at the level of the ion channel. Marks DR, Tucker K, Cavallin MA, Mast TG, Fadool DA. 2009.
Awake intranasal insulin delivery modifies protein complexes and alters memory, anxiety, and olfactory behaviors.
J Neurosci.29(20):6734-51. Colley BS, Cavallin MA, Biju K, Marks DR, Fadool DA. 2009.
Brain-derived neurotrophic factor modulation of Kv1.3 channel is disregulated by adaptor proteins Grb10 and nShc.
Neurosci. 10:8. Biju KC, Mast TG, Fadool DA. 2008.
Olfactory sensory deprivation increases the number of proBDNF-immunoreactive mitral cells in the olfactory bulb of mice.
Neurosci Lett. 447(1):42-7. Tucker K, Overton JM, Fadool DA. 2008.
Kv1.3 gene-targeted deletion alters longevity and reduces adiposity by increasing locomotion and metabolism in melanocortin-4 receptor-null mice.
Int J Obes (Lond). 32(8):1222-32 Biju KC, Marks DR, Mast TG, Fadool DA. 2008.
Deletion of voltage-gated channel affects glomerular refinement and odorant receptor expression in the mouse olfactory system.
J Comp Neurol. 506(2):161-79. Colley, B.S., K.C. Biju, A. Visegrady, S. Campbell, and D.A. Fadool. 2007. TrkB
increases Kv1.3 ion channel half-life and surface expression. Neuroscience
144(2):531-46. Marks DR, Fadool DA. 2007.
Post-synaptic density perturbs insulin-induced Kv1.3 channel modulation via a clustering mechanism involving the SH3 domain.
J Neurochem. 103(4):1608-27 Brann, J.H. and D.A. Fadool. 2006. Vomeronasal sensory neurons (VSNs) from Sternotherus
odoratus (Stinkpot/Musk Turtle) respond to chemosignals via the phospholipase C (PLC)
system. J. Exp. Biol. 209: 914-927 Fadool, D.A., K. Tucker, R. Perkins, G. Fasciani, R.N. Thompson, A.D. Parsons,
J.M. Overton, P.A. Koni, R.A. Flavell, and L.K. Kaczmarek. 2004. Kv1.3 channel
gene-targeted deletion produces "super-smeller mice" with altered glomeruli,
interating scaffolding proteins, and biophysics. Neuron. 41: 1-20. Tucker, K. and D.A. Fadool. 2002. Neurotrophin modulation of voltage-gated
potassium channels in rat through TrkB receptors is time and sensory-experience
dependent. J. Physiol. 542.2: 413-429. Graduate Students: |
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Dr. Debra A. Fadool - FSU Biological Science Faculty Member
