Biological Science Faculty Member
Dr. Debra A. Fadool
Dr. Debra Fadool is currently recruiting new postdoctoral investigators for Spring 2020.
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 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.
I would welcome students wishing to gain experience with the techniques of electrophysiology (patch-clamp recording and single channel analysis), protein biochemistry, molecular biology (site-directed mutagenesis, gene-targeted deletions, 2 hybrid yeast, microarray), and immunochemistry, and to those wishing to answer questions about the physiology of olfaction, cell-signaling cascades, the regulation of neuronal excitability, and ion channel structure/function.
|Al Koborssy D, Palouzier-Paulignan B, Canova V, Thevenet M, Fadool DA, Julliard AK, Modulation of olfactory-driven behavior by metabolic signals: role of the piriform cortex, Brain Struct Funct, 2019 PubMed|
|Fardone E, Celen AB, Schreiter NA, Thiebaud N, Cooper ML, Fadool DA, Loss of odor-induced c-Fos expression of juxtaglomerular activity following maintenance of mice on fatty diets, J Bioenerg Biomembr, 2019 PubMed|
|Julliard AK, Al Koborssy D, Fadool DA, Palouzier-Paulignan B, Nutrient Sensing: Another Chemosensitivity of the Olfactory System, Front Physiol 2017 PubMed|
|Huang Z, Thiebaud N, Fadool DA, Differential serotonergic modulation across the main and accessory olfactory bulbs, J Physiol, 2017 PubMed|
|Thiebaud N, Llewellyn-Smith IJ, Gribble F, Reimann F, Trapp S, Fadool DA, The incretin hormone glucagon-like peptide 1 increases mitral cell excitability by decreasing conductance of a voltage-dependent potassium channel, J Physiol, 2016 PubMed|
|Spear JM, Koborssy DA, Schwartz AB, Johnson AJ, Audhya A, Fadool DA, Stagg SM, Kv1.3 contains an alternative C-terminal ER exit motif and is recruited into COPII vesicles by Sec24a, BMC Biochem, 2015 PubMed|
|Thiebaud N, Johnson MC, Butler JL, Bell GA, Ferguson KL, Fadool AR, Fadool JC, Gale AM, Gale DS, Fadool DA, Hyperlipidemic diet causes loss of olfactory sensory neurons, reduces olfactory discrimination, and disrupts odor-reversal learning, J Neurosci, 2014PubMed|
|Johnson MC, Biju KC, Hoffman J, Fadool DA, Odor enrichment sculpts the abundance of olfactory bulb mitral cells, Neurosci Lett, 2013 PubMed|
|Tucker K, Cho S, Thiebaud N, Henderson M, Fadool DA, Glucose sensitivity of mouse olfactory bulb neurons is conveyed by a voltage-gated potassium channel, J Physiol, 2013 PubMed|
|Tucker K, Michael Overton J, Fadool DA, Diet-induced obesity resistance of Kv1.3-/- mice is olfactory bulb dependent, J Neuroendocrinol, 2012 PubMed|
|Mast TG, Fadool DA, Mature and precursor brain-derived neurotrophic factor have individual roles in the mouse olfactory bulb, PLoS One, 2012 PubMed|
|Palouzier-Paulignan B, Lacroix MC, Aimé P, Baly C, Caillol M, Congar P, Julliard AK, Tucker K, Fadool DA, Olfaction Under Metabolic Influences, Chem Senses, 2012 PubMed|
|Corthell JT, Fadool DA, Trombley PQ, Connexin and AMPA receptor expression changes over time in the rat olfactory bulb, Neuroscience, 2012 PubMed|
|Tucker KR, Godbey SJ, Thiebaud N, Fadool DA, Olfactory ability and object memory in three mouse models of varying body weight, metabolic hormones, and adiposity, Physiol Behav, 2012 PubMed|
|Fadool DA, Tucker K, Pedarzani P, Mitral cells of the olfactory bulb perform metabolic sensing and are disrupted by obesity at the level of the Kv1.3 ion channel, PLoS One, 2011 PubMed|
|Mast TG, Brann JH, Fadool DA, The TRPC2 channel forms protein-protein interactions with Homer and RTP in the rat vomeronasal organ, BMC Neurosci, 2010 PubMed|
|Tucker K, Cavallin MA, Jean-Baptiste P, Biju KC, Overton JM, Pedarzani P, Fadool DA, The Olfactory Bulb: A Metabolic Sensor of Brain Insulin and Glucose Concentrations via a Voltage-Gated Potassium Channel, Results Probl Cell Differ, 2010 PubMed|
|Marks DR, Tucker K, Cavallin MA, Mast TG, Fadool DA, Awake intranasal insulin delivery modifies protein complexes and alters memory, anxiety, and olfactory behaviors, J Neurosci, 2009 PubMed|