Kurt F. Hauser, Ph.D.
Department: Department of Pharmacology and Toxicology
Phone: (804) 628-7579
Fax: (804) 828-0676
Hermes A. Kontos Building, Room 439
1217 East Marshall Street
Richmond, Virginia 23298-06
- University of Medicine and Dentistry of New Jersey, Ph.D., 1983
- Columbia University, postdoctoral training, 1983-86
- Pennsylvania State University, postdoctoral training, 1986-87
Drug abuse and central nervous system plasticity with emphasis on the effects of opioids
- Drug-induced modulation of human immunodeficiency virus type 1
- Developmental neurobiology
- Glial biology
- Endogenous opioids and the pathobiology of dynorphins
Drug abuse and central nervous system (CNS) plasticity with emphasis on the effects of opioids in the context of neuro-acquired immunodeficiency syndrome (neuroAIDS) and the modulation of human immunodeficiency virus type 1 (HIV-1) neuropathogenesis; developmental neurobiology; glial biology; neuroimmunology; endogenous opioids and the pathobiology of dynorphins
Our research attempts to understand the mechanisms by which drug abuse causes lasting changes in CNS organization and function. During development, as well as in the mature brain, we have found that drug abuse can disrupt the production and organization of neurons and glia. We propose that the organizational changes are maladaptive and especially revealed when the drug-exposed CNS is further challenged with insults such as disease, trauma, and/or aging.
The effects of substance abuse to CNS function are particularly evident in individuals infected with HIV-1. Opioid abuse can dramatically exacerbate the neuroinflammatory and neurodegenerative consequences of HIV-1. We discovered that opioid drugs can interact synergistically with HIV-1 proteins to directly increase neuronal injury and death. Our lab also found that opioids can potentiate the production of inflammatory and excitotoxic molecules in HIV-1-exposed microglia and astroglia, which further contribute to neuronal damage. These studies have also added significant insight into mechanisms underlying the pathogenesis of neuroAIDS in non-substance abusers. To tackle these problems, a wide variety of cell, molecular, genetic, neuropharmacological, and neuroimmune strategies are used to understand the complex mechanisms by which substance abuse and HIV-1 disrupt the nervous system.
Sorrell, M.E., K.F. Hauser. 2014. Ligand-gated purinergic receptors regulate HIV-1 Tat and morphine related toxicity in primary mouse striatal neuron-glia co-cultures. J Neuroimmune Pharmacology, 9:233-244. PMC3959217.
Dever, S.M., B.N. Costin, R. Xu, N. El-Hage, J. Balinang, A. Samoshkin, M.A. O’Brien, M.P. McRae, L. Diatchenko, P.E. Knapp, K.F. Hauser. 2014. Differential expression of the alternatively spliced OPRM1 isoform μ-opioid receptor-1K in HIV-infected subjects. AIDS, 28:19-30. PMC3939043.
Beardsley, P.M., K.F. Hauser. 2014. Glial modulators as potential treatments of psychostimulant abuse. Advances in Pharmacology, 69: 1-69.PMC4103010.
El-Hage, N., M. Rodriquez, E. Podhaizer, S. Zou, S., S.E. Snider, S.M. Dever, P.E. Knapp, P.M. Beardsley, K.F. Hauser. 2014. Ibudilast (AV411), and its AV1013 analog, reduces HIV-1 replication and neuronal death induced by HIV-1 and morphine. AIDS, 28(10):1409-1419. PMC4300098.
Bull C., K.C. Freitas, S. Zou, R.S. Poland, W.A. Syed, D.J. Urban, S.C. Minter, K.L. Shelton, K.F. Hauser, S.S. Negus, P.E Knapp, and M.S. Bowers. 2014. Rat nucleus accumbens core astrocytes modulate reward and the motivation to self-administer ethanol after abstinence. Psychoneuropharmacology, 39: 2835-45. PMC4200494.
Masvekar, R.R., N. El-Hage, K.F. Hauser, and P.E. Knapp. 2014. Morphine enhances HIV-1SF162-mediated neuron death and delays recovery of injured neurites. PLoS ONE, 9(6):e100196. PMC4064991.
Hauser, K.F., and P.E. Knapp. 2014. Interactions of HIV and drugs of abuse: the importance of glia, neural progenitors, and host genetic factors.International Review of Neurobiology, 118C: 231-313. PMC4304845.
Fitting, S., P.E. Knapp, S. Zou, W.D. Marks, M.S. Bowers, H.I. Akbarali, and K.F. Hauser. 2014. Interactive HIV-1 Tat and morphine-induced synaptodendritic injury is triggered through focal disruptions in Na+ influx, mitochondrial instability, and Ca2+overload, Journal of Neuroscience, 34: 12850-12864. PMC4166164.
Ngwainmbi, J., D.D. De, T.H. Smith, N. El-Hage, S. Fitting, M. Kang, W.L. Dewey, K.F. Hauser, H.I. Akbarali. 2014. Effects of HIV-1 Tat on enteric neuropathogenesis, Journal of Neuroscience, 34: 14243-14251. PMC4205550.
Watanabe H., S. Fitting, M.Z. Hussain, O. Kononenko, A. Iatsyshyna, T. Yoshitake, J. Kehr, K. Alkass, H. Druid, H. Wadensten, P. Andren, I. Nylander, D.H. Wedell, O. Krishtal, K.F. Hauser, F. Nyberg, V.M. Karpyak, T. Yakovleva, G. Bakalkin. 2015. Asymmetry of the endogenous opioid system in the human anterior cingulate: a putative molecular basis for lateralization of emotions and pain. Cerebral Cortex, 25(1):97-108. PMC4259275.
Hahn Y.-K., E.M. Podhaizer, S.P. Farris, M.F. Miles, K.F. Hauser, P.E. Knapp. 2015. Effects of chronic HIV-1 Tat exposure in the CNS: heightened vulnerability of males versus females to changes in cell numbers, synaptic integrity, and behavior. Brain Structure and Function, 220(2): 605-623. PMC4341022.
Ellis, K., J. Marlin, S. Fitting, T.A.H. Taylor, K.F. Hauser, G. Rice, M. McRae. 2015. The effects of HIV infection on the expression of the drug efflux proteins P-glycoprotein and breast cancer resistance protein in a human intestine model, Journal Pharmacy and Pharmacology, 67(2):178-188. PMC4306588.
Maximyuk, O., V. Khmyz, C-J. Lindskog, V. Vukojević, T. Ivanova, A. Rajnisz, J. Solecka, A.W. Lipkowski, K.F. Hauser, G. Bakalkin, O. Krishtal. 2015. Plasma membrane poration by opioid neuropeptides: a prototypical mechanism of signal transduction, Cell Death & Disease, 6:e1683. PMC4385918. PMC4385918.
Masvekar, R.R., N. El-Hage, K.F. Hauser, and P.E. Knapp. 2015. GSK3β-activation is a point of convergence for HIV- and opiate-mediated Interactive neurotoxicity, Molecular & Cellular Neuroscience, 65C:11-20. PMC4393771.
Fitting, S., J. Ngwainmbi, M. Kang, F.A. Khan, D.L. Stevens, W.L. Dewey, P.E. Knapp, K.F. Hauser, H.I. Akbarali. 2015. HIV-1 Tat increases neuronal sensitivity to morphine in enteric ileal neurons, Neurogastroenterology and Motility, 27(4):468-80.PMC4380805.
Bhardwaj, R., J.W. Yester, S.K. Singh, D. Biswas, M.J. Surace, M. Waters, K.F. Hauser, Y. Yao, B.F. Boyce, and T. Kordula. 2015. RelB/p50 complexes regulate cytokine-induced YKL-40 expression. Journal of Immunology,194(6):2862-70. PMC4355396.
Fitting, S., S. Zou, N. El-Hage, M. Suzuki, J.W. Rodríguez, M. Rodriguez, P.E. Knapp, K.F. Hauser. 2014. Opiate addiction therapies and HIV-1 Tat: interactive effects on glial [Ca2+]i, oxyradical and neuroinflammatory chemokine production and correlative neurotoxicity, Current HIV Research, 12(6):424-434. PMC4475822.
Hahn, Y.-K., R. Masvekar, R. Xu, S. Zou, N. K.F. Hauser, P.E. Knapp. 2015. Chronic HIV-1 Tat and HIV reduce Rbfox3/NeuN: Evidence for sex-related effects, Current HIV Research, 13(1):10-20.
Sahu, G, Farley, F., N. El-Hage, B. Aiamkitsumrit, R. Fassnacht, F. Kashanchi, A. Ochem, G.L. Simon, J. Karn, K.F. Hauser, and M. Tyagi. 2015. Cocaine promotes both initiation and elongation phase of HIV-1 transcription by activating NF-ĸB and MSK1 and inducing selective epigenetic modifications at HIV-1 LTR, Virology, 483:185-202. PMID: 25980739.
Zou, S., S. Fitting, Y.K. Hahn, B. Fuss, K.F. Hauser, and P.E. Knapp. 2015. Oligodendrocytes are targets of HIV-1 Tat: NMDA and AMPA receptor-mediated effects on survival and development. Journal of Neuroscience, 35: 11384-11398. PMC4532766.
Kadri, F., M. Pacifici, A. Wilk, A. Parker-Struckhoff, L. Del Valle, K.F. Hauser, P.E. Knapp, C. Parsons, D. Jeansonne, A. Lassak, F. Peruzzi. 2015. HIV-Tat inhibits SC35-mediated Tau exon 10 inclusion through upregulation of DYRK1A and activation of GSK-3β, Journal of Biological Chemistry, in press. doi: jbc.M115.675751.
Fitting, S., D.L. Stevens, F.A. Khan, K.L. Scoggins, R.M. Enga, P.M. Beardsley, P.E. Knapp, W.L. Dewey, and K.F. Hauser. 2015. Morphine tolerance and physical dependence are altered in conditional HIV-1 Tat transgenic mice. Journal of Pharmacology & Experimental Therapeutics, in press. doi: jpet.115.226407.