Department of Biological Science

Biological Science Faculty Member

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Professor
Ph.D., University of Florida, 1993
Graduate Faculty Status

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.

Selected Publications:

Thiebaud, N., F. Gribble, F. Reimann, S. Trapp, and D.A. Fadool. 2019. Not all interneurons in the olfactory bulb are inhibitory - the uncovering of glutamatergic cells. Scientific Reports 9(1): 15542.

Chelette, B.M., A. M. Thomas, and D.A. Fadool. 2019. Long-term obesogenic diet and targeted deletion of potassium channel Kv1.3 have differing effects on voluntary exercise in mice. Physiological Reports 7(20): e14254.

Fadool, D.A. and L.J. Kolling. 2020. Role of olfaction for eating behavior. The Senses: A Comprehensive Reference, Second Edition, 43 pages, Elsevier, Netherlands, ed. Bernd Fritzsch and Wolfgang Meyerhoff.

Schwartz, A.B., A. Kapur, Z. Huang, R. Anangi, J.M. Spear, S. Stagg, E. Fardone, Z. Dekan, J.T. Rosenberg, S.C. Grant, G.F. King, H. Mattoussi, and D.A. Fadool. 2021. Olfactory bulb targeted QD bioconjugate and Kv1.3 blocking peptide improve metabolic health in obese male mice. J. Neurochem. 157(6):1876-1896.

Huang, Z., R. Tatti, A.M. Loeven, D. Conde Landi, and D.A. Fadool. 2021. Modulation of neuronal microcircuits that control complex dynamics in olfactory networks. Front. Cell. Neurosci. 15:662184.

Chelette, B.M., A.M. Loeven, D.N. Gatlin, D.R. Landi Conde, C.A. Huffstetler, M. Qi, and D.A. Fadool. 2022. Consumption of dietary fat causes loss of olfactory circuitry that is not mitigated by voluntary exercise in mice. J. Physiol. 600(6):1473-1495. Selected for Cover Art and Special Commentary - Manzini, I. 2022. Dietary-induced disruption of the olfactory system: not only obesity is to blame. J Physiol. 600(6):1273-1274.

Tice, A.L., J.A. Laudato, D.A. Fadool, B.S. Gordon, J.L. Steiner. 2022. Acute binge alcohol alters whole body metabolism and the time-dependent expression of skeletal muscle specific metabolic markers for multiple days in mice. Am. J. Physiol. Endocrinol. Metabol. 323(3):E215-E230.

Du, L, S. Helsper, W. Wang, N.A. Nosratabad, D.A. Fadool, C. Amiens, S. Grant, and H. Mattoussi. 2022. A multifunctional contrast agent for 19f-based magnetic resonance imaging. Biocon. Chem. 33(5):881-891.

Kolling, L.J., R. Tatti, T. Lowry, Loeven, A.M., J. M. Fadool, and D.A. Fadool. 2022. Modulating the excitability of olfactory output neurons affects whole-body metabolism. J. Neurosci. 42(30):5966-5990. Selected for Cover Art and Editor’s Commentary.

Huffstetler, C.M., B. Cochran, C.A. May, N. Maykut, C.R. Silver, C. Cedeno, E. Franck, A. Cox, and D.A. Fadool. 2022. Single cannabidiol administration affects anxiety-, obsessive compulsive-, object memory-, and attention-like behaviors in mice in a sex and concentration dependent manner. Pharmacol. Biochem. Behav. 222:173498.

Lowry, T.W., A.E. Kusi-Appiah, D.A. Fadool, and S. Lenhert. 2023. Odor discrimination by lipid membranes. Membranes 13(2):151.

Meizhu Qi, D.A. Fadool, and D.A. Storace. 2023. An anatomically distinct subpopulation of orexin neurons project from the lateral hypothalamus to the olfactory bulb. J. Comp. Neurol. 531(15):1510-1524.

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

Postdoctoral Associates:

Graduate Students: