Andy Hudmon, Ph.D.
Assistant Professor
Department of Biochemistry and Molecular Biology
Indiana University School of Medicine
Stark Neurosciences Research Institute
950 W. Walnut Street, Room E480
Indianapolis, Indiana 46202-5188
Phone: (317) 278-8513
Facsimile: (317) 274-4686
E-mail: ahudmon@iupui.edu
B.S., 1988, Auburn University
M.S., 1991, Auburn University
Ph.D., 1997, The University of Texas Health Science Center at Houston
Post Doc., 2003, Stanford University
Area of Study
Molecular mechanisms underlying normal and aberrant Ca2+ signaling in neurons: kinases, molecular machines, and signaling modules. More details...
Selected Recent Publications
Ashpole NM, Song W, Brustovetsky T, Engleman EA, Brustovetsky N, Cummins TR, Hudmon A. Calcium/calmodulin-dependent protein kinase II (CaMKII) inhibition induces neurotoxicity via dysregulation of glutamate/calcium signaling and hyperexcitability. Journal of Biological Chemistry 2012; 287(11):8495–8506. PMID: 22253441
Ashpole NM, Herren AW, Ginsburg KS, Johnson DA, Brogan JD, Cummins TR, Bers DM, Hudmon A. CaMKII regulates cardiac sodium channel Nav1.5 by phosphorylation in the loop between domain I and II. Journal of Biological Chemistry 2012; in press.
Brittain JM, Duarte DB, Wilson SM, Wang Y, Ballard C, Zhu W, Brustovetsky T, Schmutller BS, Xiong W, Ripsh MS, Ashpole NM, Hudmon A, Hingtgen CM, Vasko MR, Brustovetsky N, Jin X, Fehrenbacher JC, Hurley JH, White FA, Khanna R. Suppression of inflammatory and neuropathic pain by uncoupling CRMP-2 from the presynaptic Ca2+ channel complex. Nature Medicine 2011 Accepted 3-2-2011.
Li L, Khanna M, Jo I, Wang F, Ashpole NM, Hudmon A, Meroueh SO. Target-Specific Support Vector Machine Scoring in Structure-Based Virtual Screening: Computational Validation, In Vitro Testing in Kinases, and Effects on Lung Cancer Cell Proliferation. Journal of Chemical Information and Modeling, 2011; Epub Mar 25
Ashpole NM and Hudmon A. Excitotoxic neuroprotection and vulnerability with CaMKII inhibition. Molecular and Cellular Neuroscience. 2011 46(4):720-730.
Hudmon A, Davenport G, Coleman ES, Sartin JL. Low doses of estradiol partly inhibit release of GH in sheep without affecting basal levels. Domestic Animal Endocrinology, 2009; 37(3):181-187.
Hudmon A, Choi JS, Tyrrell L, Black JA, Rush AM, Waxman SG and Dib-Hajj SD. Phosphorylation of sodium channel NaV1.8 by p38 mitogen-activated protein kinase increases current density in dorsal root ganglion neurons. Journal of Neuroscience 2008, March 19; 28(12):3190-3201.
Yu X, Sun JP, He Y, Guo X, Liu S, Zhou B, Hudmon A, Zhang ZY. Structure, inhibitor and regulatory mechanism of Lyp, a lymphoid-specific tyrosine phosphatase implicated in autoimmune disease. Proc. Natl. Acad. Sci., 2007, 104(50):19767-72.
Merrill Ma, Malik Z, Akyol Z, Bartos JA, Leonard AS, Hudmon A, Shea MA, Hell JW. Displacement of alpha-actinin from the NMDA receptor NR1 C-domain by Ca2+/calmodulin promotes CaMKII binding. Biochemistry 2007; 46(29):8485-8497.
Takagi Y, Calero G, Komori H, Brown JA, Ehrensberger AH, Hudmon A, Asturias F, and Kornberg RD. Head module control of meditor interactions. Molecular Cell 2006;22(3):355-364.
Choi J-S, Hudmon A, Waxman SG, Dib-Hajj SD. Calmodulin regulates current density and frequency-dependent inhibition of sodium channel NaV1.8 in DRG neurons. Journal of Neurophysiology, 2006; 96(1):97-108.
Hudmon A, Schulman H, Kim J, Maltez J, Nunziato D, Tsien RW, Pitt G. CaMKII tethers to L-type Ca2+ channels, establishing a local and dedicated integrator of Ca2+ signals for facilitation. Journal of Cell Biology 2005; 171(3):537-547.
Hudmon A, LeBel E, Roy H, Sik A, Schulman H, Waxham MN, DeKoninck P. A mechanism for CaMKII clustering at synaptic and non-synaptic sites based on self-association. Journal of Neuroscience 2005; 25(30):6971-6983.
Whittmack EK, Rush A, Hudmon A, Waxman SG, Dibb-Hajj SD. Voltage-gated sodium channel Nav1.6 is regulated by P38 Map kinase. Journal of Neuroscience 2005; 25(28):6621–6630.
Takagi Y, Komori H, Chang WH, Hudmon A, Erdjument-Bromage H, Tempst P, Kornberg RD. Revised subunit structure of yeast transcription factor IIH (TFIIH) and reconciliation with human TFIIH. Journal of Biological Chemistry 2003;278(45):43897–43900.
Hudmon A, Schulman H. Neuronal Ca2+/calmodulin dependent protein kinase II: Role of structure and autoregulation in cellular function. Annual Review of Biochemistry 2002;71:473¬–510.
Bradshaw JM, Hudmon A, Schulman H. Chemical quench flow kinetic studies indicate an intra-holoenzyme autophosphorylation mechanism for Ca2+/calmodulin dependent protein kinase II. Journal of Biological Chemistry 2002;277(23):20991–20998. [Top-50 download]
Hudmon A, Schulman H. The structure and autoregulation of Ca2+/calmodulin dependent protein kinase II. Biochemical Journal 2002;364:593–611.
Kim SA, Hudmon A, Volmer A, Waxham MN. A novel mechanism for dephosphorylation of calcium/calmodulin-dependent protein kinase II: Reversal of the autodephosphorylation reaction. Biochemical and Biophysical Research Communications 2001;282:773–780.
Singla SI, Hudmon A, Smith JL, Schulman H. Molecular interactions that contribute to calmodulin trapping by CaM kinase II. Journal of Biological Chemistry 2001;276(31):29353–29360.
Hudmon A, Kim SA, Stoops JK, Waxham MN. Characterization of CaM-kinase II self-association by light scattering and transmission electron microscopy. Journal of Neurochemistry 2001;76:1364–1375.
Pitt GS, Zuhlke RD, Hudmon A, Schulman H, Reuter H, Tsien RW. Molecular basis of CaM tethering and Ca2+-dependent inactivation of L-type calcium channels. Journal of Biological Chemistry 2001;276(33):30794–30802.
Kolodziej SJ, Hudmon A, Waxham MN, Stoops JK. Three-dimensional reconstruction of CaM kinase IIα and truncated CaM kinase IIα reveal a unique organization for its structural core and functional domains. Journal of Biological Chemistry 2000;275(19):14354–14359.
Kolb SJ, Hudmon A, Ginsberg TR, Waxham MN. Identification of domains essential for the assembly of calcium/calmodulin-dependent protein kinase II holoenzymes. Journal of Biological Chemistry 1998;273(47):31555–31564.
Hudmon A, Aronowski JA, Kolb SJ, Waxham MN. Inactivation and self-association of Ca2+/calmodulin-dependent protein kinase II during autophosphorylation. Journal of Biological Chemistry 1996;271(15):8800–8808.
Kolb SJ, Hudmon A, Waxham MN. Ca2+/calmodulin-dependent protein kinase II translocates in a hippocampal slice model of ischemia. Journal of Neurochemistry 1995;64:2147–2152.
Thompson K, Coleman ES, Hudmon A, Kemppainen RJ, Soyoola EO, Sartin JL. Effects of short-term cortisol infusion on growth hormone-releasing hormone stimulation of growth hormone release in sheep. American Journal of Veterinary Research 1995;56(9):1228–1231.
Research Interests
Ranging from fertilization and cell death to contraction and secretion, transient increases in intracellular calcium (Ca2+) levels regulate fundamental biological processes throughout the body. In the nervous system, neuronal communication requires Ca2+ signaling, as does the regulation of the strength and specificity of neuronal connections. Ca2+ alters cell function by altering the biological activity of proteins. This process may involve a direct affect through Ca2+ altering a protein’s conformation as well indirect affects through the activation of kinases and phosphorylation. Understanding the mechanisms by which protein kinases and Ca2+ binding proteins translate Ca2+ signals into specific changes in cell function is the focus of my laboratory.
My current research efforts are concentrated on two Ser/Thr protein kinases: 1) a Ca2+/calmodulin activated protein kinase (CaMKII) essential to synaptic plasticity and 2) mitogen-activated protein kinases (MAP kinases), which are activated by cell stress and growth factors to regulate pain, synaptic plasticity, and addiction. Although CaMKII is found throughout the body, it’s best known as a “cognitive kinase” due to its role in learning and memory and “machine-like” behavior in decoding Ca2+ signals. MAP kinases are downstream effectors of multiple kinases, including CaMKII. MAP kinase activity may produce long-term changes in cell function by changes in gene transcription. Thus, the universal role of CaMKII in Ca2+ signal transduction as well the potential for MAP kinases to remodel long-term changes in cell function, make these kinases, as well as their regulators and substrates, important therapeutic targets for a number of important diseases throughout the body, ranging from heart disease and diabetes to addiction and cerebral ischemia.
The primary goal of my laboratory is to elucidate how protein kinases function as specialized molecular machines and assemble with their substrates and regulators to form signaling modules. In doing so, we combine traditional biochemical and biophysical techniques in conjunction with fluorescent imaging approaches to characterize kinases and their substrates in vitro and in living cells. The long-term goals of our research efforts are to identify novel protein interactions and regulatory mechanisms that underlie synaptic function and plasticity in the nervous system.
