Currently, he is focusing on the molecular and cellular mechanisms of inherited myopathies with a special emphasis on inclusion body myopathy and its relation to protein degradative pathways in skeletal muscle and normal aging. In addition he treats patients with neuromuscular disorders in the Washington University Comprehensive Neuromuscular Clinic. He is the recipient of an NIH K08 career development award and Muscular Dystrophy Association development grant.

Inclusion body myopathies are a group of disabling skeletal muscle disorders. The most common form, inclusion body myositis (IBM), affects patients over the age of 50. There is no effective treatment. IBM muscle tissue contains characteristic "rimmed vacuoles" and eosinophilic cytoplasmic aggregates. These structures contain ubiquitin, ß-amyloid, apolipoprotein E, and phosphorylated tau, the same pathologic proteins present in Alzheimers Disease (AD) brains.

Mutations in the protein p97, also known as VCP (valosin containing protein), cause a dominantly inherited syndrome with an IBM phenotype. The pathologic consequence of these mutations has not been studied. p97/VCP belongs to the AAA ATPase (ATPases associated with other cellular activities) protein family and is implicated protein degradation via the ubiquitin-proteasome pathway.

My research uses both cellular and animal models of hereditary IBM to explore the underlying pathogenesis of this disease. These models allow us to understand mechanisms of protein misfolding and degradation in skeletal muscle and its relation to other inherited myopathies, muscular dystrophies, cachexia and normal aging.

To read more about his research visit the Weihl Laboratory website.

Medical Training

Dr. Weihl received his B.S. degree with high distinction from the University of Illinois at Urbana-Champaign in Cell and Structural Biology in 1994. While at the University of Illinois, he participated in the characterization of a novel testis specific isoform of calnexin in the laboratory of Dr. David Bunick. He received several honors related to his research project including the Cell and Structural Biology Undergraduate Research Award and the School of Life Science Director's Award for Excellence in Research.

He received both MD and PhD degrees from the University of Chicago in 2001 and was supported by an NIH Individual National Research Service Award for MD/PhD candidates. His PhD thesis focused on the role of presenilin-1 in the pathogenesis of Alzheimer's disease under the mentorship of Dr. Raymond Roos. He was awarded the American Academy of Neurology Saul R. Korey Award, American Federation for Aging Research/Glenn Foundation Scholarship for Research in the Biology of Aging and the Steven Lukes Memorial Prize for excellence in neurology and internal medicine.

He completed an internship in Internal Medicine in 2002 and Neurology residency in 2005, both at Barnes-Jewish Hospital. In 2003, he received the Washington University School of Medicine Resident Teaching Award and in 2005, the Leonard Berg Prize for research conducted during residency.

Selected Publications

Weihl CC, Lopate G. Motor neuron disease associated with copper deficiency. Muscle Nerve. 2006 Aug 23; [Epub ahead of print] PMID: 16929546 [PubMed - as supplied by publisher]

Weihl CC, Connolly AM, Pestronk A. Valproate may improve strength and function in patients with type III/IV spinal muscle atrophy. Neurology. 2006 Aug 8;67(3):500-1. Epub 2006 Jun 14. PMID: 16775228 [PubMed - in process]

Weihl CC, Dalal S, Pestronk A, Hanson PI. Inclusion body myopathy-associated mutations in p97/VCP impair endoplasmic reticulum-associated degradation. Hum Mol Genet. 2006 Jan 15;15(2):189-99. Epub 2005 Dec 1. PMID: 16321991 [PubMed - indexed for MEDLINE]

Weihl CC, Dalal S, Pestronk A, and Hanson PI. (2005) Inclusion body myopathy associated mutations in p97/VCP impair endoplasmic reticulum associated degradation. Human Molecular Genetics Advance Access. December 1, 2005.

Weihl CC and Roos RP. (1999) Creutzfeldt-Jakob Disease, New Variant Creutzfeldt-Jakob Disease and Bovine Spongiform Encephalopathy. Neurology Clinics. 17: 835-859.

Weihl CC. (1999) ß-catenin and Presenilin-1. Alzheimer's Reports. 2: 195-198.

Weihl CC, Ghadge GD, Kennedy SG, Hay N, Miller RJ, Roos RP. (1999) Mutant presenilin-1 induces apoptosis and downregulates Akt/PKB. J. Neuroscience. 19: 5360-5369.

Weihl CC, Ghadge GD, Miller RJ, Roos RP. (1999) Processing of wild-type and mutant familial Alzheimer's Disease-associated presenilin-1 in cultured neurons. J. Neurochem. 73: 31-40.

Weihl CC, Miller RJ, Roos RP. (1999) The role of ß-catenin stability in mutant presenilin-1 associated apoptosis. NeuroReport. 10: 2527-2532.

Yamasaki K, Weihl CC, Roos RP. (1999) Alternative translation of Theiler's Murine Encephalomyelitis Virus. J. Virology. 73: 8519-8526.

Luders JC, Weihl CC, Lin G, Ghadge GD, Stoodley M, Roos RP, Macdonald RL. (2000) Adenoviral gene transfer of nitric oxide synthase increases cerebral blood flow in rats. Neurosurgery. 47: 1206-1214

Stoodley M, Weihl CC, Zhang Z, Lin G, Johns, LM, Kowalczuk A, Ghadge GD, Roos RP, Macdonald RL. (2000) The effect of adenovirus-mediated nitric oxide synthase gene transfer on vasospasm after experimental subarachnoid hemorrhage. Neurosurgery. 46: 1193-1203.

Weihl CC, Macdonald RL, Stoodley M, Luders JC, Lin G. (1999) Gene therapy for cerebrovascular disease. Neurosurgery. 44: 239-253.