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Science at the Center - Research


Raymond Roos, M.D.

Marjorie and Robert E. Strauss Professor, Department of Neurology
Co-Director, Center for Peripheral Neuropathy
Co-Director, Clinical Neuroimmunology Lab

Dr. Roos' main clinical and research interests are neurodegenerative disease (amyotrophic lateral sclerosis [ALS], Alzheimer's disease, and prion disease), multiple sclerosis and neuropathy.

As a result of these clinical interests, he co-directs a Muscular Dystrophy Association ALS/Motor Neuron Disease clinic. This clinic takes care of patients with a number of neuromuscular problems related to motor neuron disease and neuropathy. This clinic also serves as a core for an NIH-funded Motor Neuron Disease Program Project and is a source of patients for clinical trials and clinical research studies. Other patients with more varied neurodegenerative diseases, multiple sclerosis, or other neurological conditions are seen in a general neurological disease clinic.

A basic goal of Dr. Roos' research studies is to use molecular techniques to better understand the pathogenesis of these diseases. The lab has the following main research directions:

One aim of our studies is the delineation of genes and gene products critical to the death and survival of neurons, especially related to neurodegenerative diseases such as ALS and Alzheimer's disease. The lab uses viruses as vectors to deliver normal or mutant disease-associated (familial ALS or familial Alzheimer's disease) genes in order to clarify the mechanisms by which the mutant genes kill the target neurons. These vectors can also deliver genes to the central nervous system (CNS), and will be important in the development of tools for somatic cell gene therapy of inherited and acquired CNS disease.

The lab is investigating Theiler's virus (TV)-induced disease in order to identify molecular determinants for neurovirulence and demyelination and the mechanisms involved. Certain strains from one subgroup produce a chronic persistent infection in mice in which autoimmune factors are believed to contribute to the demyelinating disease. The demyelination caused by these strains provides one of the best experimental models for MS because of the similarity in their pathology and because the immune system appears to contribute to disease in both cases. Other strains from a second TV subgroup cause an acute, fatal polioencephalomyelitis. The TMEV model is a valuable one for these studies because of the powerful molecular tools that are available, the interesting phenotypes of the strains, and the ease with which one can study this simple virus in a mouse. The identification of these genes may not only clarify the pathogenesis of TV disease, but also lead to an understanding of genes important in the normal CNS and in human CNS disease states (such as MS).

Original Articles (comprehensive list):

Lee, J., Palfrey, C., Bindokas, V.P., Ghadge, G.D., Miller, R.J., and Roos, R.P. The role of immunophilins in mutant superoxide dismutase-1-linked FALS (familial amyotrophic lateral sclerosis). Proc. Natl. Acad. Sci. 96:3251-3256, 1999.

BDNF Study Group (Phase III). A controlled trial of recombinant methionyl human BDNF in ALS. Neurology 52:1427-1433, 1999.

Lin, X., Roos, R. P., Pease, L.R., Wettstein, P., and Rodriguez, M. A Theiler's virus alternatively-initiated protein inhibits the generation of H-2-K-restricted virus-specific cytotoxicity. J. Immunol. 162:17-24, 1999.

Weihl, C.C., Ghadge, G.D., Miller, R.J., and Roos, R.P. Processing of wild-type and mutant familial Alzheimer's disease-associated presenilin-1 in cultured neurons. J. Neurochem. 73 (1):31-40, 1999.

Weihl, C.C., Ghadge, G.D., Kennedy, S.G., Hay, N., Miller, R.J., and Roos, R.P. Mutant presenilin-1 induced apoptosis in cultured neurons via downregulation of Akt/PKB. J. Neurosci. 19: (13) 5360-5369, 1999.

Weihl, C.C., Miller, R.J., and Roos, R.P. The role of b-catenin stability in mutant PS-associated apoptosis. NeuroReport 10 (12) 1-6, 1999.

Yamasaki, K., Weihl, C.C., and Roos, R.P. Alternative Translation Initiation of Theiler's Murine Encephalomyelitis Virus. J. Virol. 73(10) :8519-8526, 1999.

Rodriguez, M., Roos, R.P., McGavern, D., Zoecklein, L., Pavelko, K., Sang, H., and Lin, X. The CD4-mediated immune response is critical in determining the outcome of infection using Theiler's viruses with VP1 capsid protein point mutations. Virology Sept15: 275(1):9-19, 2000.

Stoodley, M., Weihl, C., Zhang, Z.D., Lin, G., Johns, L., Kowalczuk, A., Ghadge, G., Roos, R.P., Macdonald, R.L. Effect of adenoviral-mediated nitric oxide synthase gene transfer on vasospasm after experimental subarachnoid hemorrhage. J. Neurosurg 46:1193-1203, 2000.

Luders, J.C., Weihl, C.C., Lin, G., Ghadge, G., Stoodley, M., Roos, R.P., Macdonald, R.L.: Intrathecal adenoviral gene transfer of intric oxide synthase increases cerebral blood flow in rats. Neurosurgery Nov; 47 (5):1206-14 - Discussion 1214-5, 2000.

Hentati, A., Deng, H.X., Zhai, H., Chen, W., Yang, Y., Hung, W.Y., Azim, A.C., Bohlega, S., Tandan, R., Warner, C., Laing, N.G., Cambi, F., Gascon, G., Mitsumoto, H., Roos, R.P., Boustany, R.M., Phillips, J.P., Powell, B.R., Hamida, M.B., Siddique, T. Novel mutations in spastin and absence of correlation with age at onset of symptoms. Neurology Nov 14; 55 (9)>:1388-90, 2000.

Weihl, C.C., Ghadge, G.D., Kennedy, S.G., Hay, N., Miller, R.J., and Roos, R.P. Mutant presenilin-1 induced apoptosis in cultured neurons via downregulation of Akt/PKB. J. Neurosci. 19 (13):5360-5369, 1999.

Weihl, C.C., Ghadge, G.D., Miller, R.J., and Roos, R.P. Processing of wild-type and mutant familial Alzheimer's disease-associated presenilin-1 in cultured neurons. J. Neurochem. 73 (1) :31-40, 1999.

Weihl, C.C., Miller, R.J., and Roos, R.P. The role of b-catenin stability in mutant PS-associated apoptosis. NeuroReport 10(12): 1-6, 1999.

Weihl, C.C. and Roos, R.P. Creutzfeldt-Jakob disease, new variant Creutzfeldt-Jakob disease, and bovine spongiform encephalopathy. In: Infectious Diseases of the CNS. [Ed. Marra, C.] W.B. Saunders Co., Philadelphia, PA, 17(4), 1999, pp 835-861.

Miller, R.J. and Roos, R.P. Why mutant neuroserpins are in bad shape. Lancet 355:590-591, 2000.

Roos, R.P. Amyotrophic Lateral Sclerosis (ALS). WebMD on Internet, 2000.

Roos, R.P. Book Review - Amyotrophic Lateral Sclerosis: A Synthesis of Research and Clinical Practice. (Ed. Eisen, A. and Krieger, C.) N Eng J Med 342(7):523-524, 2000.

Mastrianni, J.A. and Roos, R.P. The Prion Diseases. Seminars in Neurology. 2000: 20 (3):337-52. Review.

Pallansch, M.A. and Roos, R.P. Enteroviruses: Polioviruses, Coxsackieviruses, Echoviruses, and Newer Enteroviruses. Fields' Virology. 4th Edition. In press.


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