neurotropic virusBS are a major cause of morbidity and mortality worldwide, the proposed program is designed to develop investigators derived from 2 sources: (a) PHYSICIANS, with prior training in neurology (including pediatric neurology), pediatrics or neuropathology;and (b) PhDs, with a background in virology or molecular biology. The goal is to steer them into problems in neurological disease which can be attacked by these disciplines. This is a laboratory research training program which includes experience with important methods in virology and molecular biology. The disciplines currently being used are protein purification and nucleic acid hybridization, molecular genetics, production and characterization of cDNA libraries, DNA sequencing, molecular cloning, virology, production of monoclonal and polyclonal antibodies, cell sorting, quantization of humoral and cell-mediated immune responses, preparation of subunit viral vaccine and its expression, and molecular aspects of viral pathogenesis. Each trainee. In collaboration with one of 9 experienced trainers, undertakes an independent study over a 3-year period, which provides experience in the design and analysis of experiments, and in the presentation and publication of results. Weekly formal meetings and presentations provide constant interchange between trainees and frequent exposure to many trainers. Research is also often supplemented by formal courses and informal seminars. This training program builds on several strengths: (a) well-established Graduate Faculty in Microbiology & Immunology and in Molecular Biology which grant the PhD degree;(b) an NIH-funded Neuroscience Center of Excellence;(c) a cadre of investigators at the Univ. Colo. School of Medicine and at the Eleanor Roosevelt Institute at the Univ. Denver with proven track records and commitment to research in neurovirology and the molecular biology of neurologic disease;(d) 3 NIH-supported program project grants focused on neurologic disease produced by neurotropic virus infection, and by somatic or mitochondrial DNA defects;and (e) considerable individual experience of the trainers with postdoctoral fellows as detailed in the body of this proposal. Training facilities for programs are extensive not only within immediate surroundings of the individual trainer's laboratories, but also extend to collaborating laboratories at the U. Colo. School of Medicine when necessary. Laboratories are well equipped for biochemical, molecular biological, immunological, genetic and neuroscience investigations. Upon completion, postdoctorals are qualified to begin junior faculty positions as independent investigators to study neurovirologic or molecular biologic aspects of neurologic diseases. The training program in Neurovirology-Molecular Biology at the Univ. Colo. School of Medicine has been successfully training 4 postdoctoral fellows a year for the past 20 years.

Public Health Relevance

Neurological diseases caused by highly neurotropic viruses are a major cause of morbidity and mortality worldwide. Just a few examples include the HIV virus that causes AIDS, as well as multiple herpes viruses, enteroviruses (formerly polio and now the Coxsackie and ECHO viruses), and the Togaviruses (the viruses that cause Eastern, Western and Venezuelan Equine encephalitis) and various Flaviviruses (most notably West Nile Virus). Analysis of the clinical features and molecular mechanisms by which these viruses produce neurological disease is essential to the eventual prevention and treatment of neurological deficit and death produced by these viruses.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Institutional National Research Service Award (T32)
Project #
3T32NS007321-24S1
Application #
8840780
Study Section
Program Officer
Korn, Stephen J
Project Start
1988-07-01
Project End
2015-06-30
Budget Start
2013-07-01
Budget End
2014-06-30
Support Year
24
Fiscal Year
2014
Total Cost
$60,789
Indirect Cost
$4,503
Name
University of Colorado Denver
Department
Neurology
Type
Schools of Medicine
DUNS #
041096314
City
Aurora
State
CO
Country
United States
Zip Code
80045
Cohrs, Randall J; Badani, Hussain; Baird, Nicholas L et al. (2017) Induction of varicella zoster virus DNA replication in dissociated human trigeminal ganglia. J Neurovirol 23:152-157
Keller, Amy C; Badani, Hussain; McClatchey, P Mason et al. (2016) Varicella zoster virus infection of human fetal lung cells alters mitochondrial morphology. J Neurovirol 22:674-682
Henderson, Heather H; Timberlake, Kensey B; Austin, Zoe A et al. (2016) Occupancy of RNA Polymerase II Phosphorylated on Serine 5 (RNAP S5P) and RNAP S2P on Varicella-Zoster Virus Genes 9, 51, and 66 Is Independent of Transcript Abundance and Polymerase Location within the Gene. J Virol 90:1231-43
Cohrs, Randall J; Badani, Hussain; Bos, Nathan et al. (2016) Alphaherpesvirus DNA replication in dissociated human trigeminal ganglia. J Neurovirol 22:688-694
Badani, Hussain; White, Teresa; Schulick, Nicole et al. (2016) Frequency of varicella zoster virus DNA in human adrenal glands. J Neurovirol 22:400-2
Gilden, Don; Nagel, Maria; Cohrs, Randall et al. (2015) Varicella Zoster Virus in the Nervous System. F1000Res 4:
Blauth, Kevin; Soltys, John; Matschulat, Adeline et al. (2015) Antibodies produced by clonally expanded plasma cells in multiple sclerosis cerebrospinal fluid cause demyelination of spinal cord explants. Acta Neuropathol 130:765-81
Baird, Nicholas L; Bowlin, Jacqueline L; Hotz, Taylor J et al. (2015) Interferon Gamma Prolongs Survival of Varicella-Zoster Virus-Infected Human Neurons In Vitro. J Virol 89:7425-7
Diebel, Kevin W; Oko, Lauren M; Medina, Eva M et al. (2015) Gammaherpesvirus small noncoding RNAs are bifunctional elements that regulate infection and contribute to virulence in vivo. MBio 6:e01670-14
Nagel, Maria A; James, Stephanie F; Traktinskiy, Igor et al. (2014) Inhibition of phosphorylated-STAT1 nuclear translocation and antiviral protein expression in human brain vascular adventitial fibroblasts infected with varicella-zoster virus. J Virol 88:11634-7

Showing the most recent 10 out of 69 publications