Faculty Research

John K. Fink, M.D. ( jkfink@umich.edu )
Professor Department of Neurology
Director, Neurogenetic Disorders Program

Dr. Fink's laboratory investigates the molecular basis of inherited neurologic and psychiatric disorders. We use molecular genetic methods to genetically map, positionally clone, and analyze the functions of functions of genes responsible for these conditions. We create animal models in which to study the pathophysiology and develop treatments for these disorders.

We identified genetic loci for two forms of the inherited spinal cord disorder, hereditary spastic paraplegia (HSP) as well as genetic loci for an episodic movement disorder (paroxysmal dystonic choreoathetosis, PDC), and X-linked mental retardation/epilepsy. Recently, we demonstrated that SPG3A/atlastin gene mutations and SPG6/ NIPA1 gene mutations cause two forms dominantly inherited HSP. We are developing animal models of HSP through targeted mutation of HSP genes. We also identified the cause of an episodic movement disorder by showing that myofibrilogenesis regulator 1 (MR1) gene mutations cause PDC. Work is underway to learn the mechanisms by which MR1 gene mutations cause episodic involuntary movements.

Representative publications

Zhao X, Alvarado, D, Rainier S, Lemons R, Hedera P, Weber C, Tukel T, Apakl M, Heiman-Patterson T, Ming L, Bui M, Fink JK. Mutations in a novel GTPase cause autosomal dominant hereditary spastic paraplegia. Nature Genetics, 2001;29:326-331.

Rainier S, Chai J-H, Tokarz D, Nicholls RD, Fink JK. NIPA1 gene mutations cause autosomal dominant hereditary spastic paraplegia (SPG6). Am J Hum Genet 2003;73:967-971.

Rainier S, Thomas D, Tokarz D, Ming L, Bui M, Plein E, Zhao X, Lemons R, Delaney C, Alvarado A, Fink JK. Myofibrillogenesis regulator 1 (MR-1) gene mutations cause paroxysmal dystonic choreoathetosis. Archives of Neurology 2004;61:1025-1029

Hedera P, Alvarado A, Beydoun A, Fink JK. Novel mental retardation-epilepsy syndrome linked to Xp21.1-p11.4. Annals of Neurology, 2002;51:45-50

Hedera P, Rainier S, Alvarado D, Zhao X, Williamson J, Otterud B, Leppert M, Fink, JK. Novel locus for autosomal dominant hereditary spastic paraplegia on chromosome 8q. Am J Hum Genet, 1999;64:563-569.

Fink JK, Heiman-Patterson T. et al. Hereditary Spastic Paraplegia: Advances in Genetic Research Neurology, 1996;46:1507-1514.

Fink JK, Rainier S, Wilkowski J, Jones SM, Kume A, Hedera P, Albin R, Mathay J, Girbach L, Varvil T, Otterud B, Leppert M. Paroxysmal dystonic choreoathetosis: tight linkage to chromosome 2q. Am J Hum Genet, 1996;59:140-145.

Fink JK, Wu C-T B, Jones SM, Sharp GB, et al. Autosomal dominant, familial spastic paraplegia: tight linkage to chromosome 15q. Am J Hum Genet 1995;56:188-192.

Fink JK. The Hereditary Spastic Paraplegias: Nine Genes and Counting. Arch Neurol: 2003;60:1045-1049

Fink JK. Hereditary spastic paraplegia. Emery and Rimoin's Principles and Practice of Medical Genetics, fourth edition, 2001. Rimoin DL, Pyeritz RE, Connor JM, Korf BR, eds. London : Churchill Livingston. ISBN 0-443-06434-2; Chapter 116, 3124-3145, 2001.

Fink, JK. Progressive spastic paraparesis: hereditary spastic paraplegia and it's relation to primary and amyotrophic lateral sclerosis. Seminars in Neurology, 2001; 21:199-208.