Conrad C Weihl, MD, PhD

Associate Professor of Neurology

Phone314-555-6981

Fax314-362-3752

Emailweihlc@neuro.wustl.edu

Related Links

Recognition

  • The Hope Center Prize for Post-Doctoral Research, 2006
  • The Myositis Association Research Fellowship (declined), 2005
  • Leonard Berg Prize for Research Conducted During Residency, 2005
  • Washington University School of Medicine Resident Teaching Award, 2003
  • NIH Individual National Research Service Award for MD/PhD candidates (F30), 1996-2001
  • American Federation for Aging Research/Glenn Foundation Scholarship for Research in the Biology of Aging – national award to M.D./Ph.D., 1996
  • American Geriatrics Society Student Research Award, American Federation for Aging Research/American Geriatric Society, 1996

Publications

  • Johnson JO, Pioro EP, Boehringer A, Chia R, Feit H, Renton AE, Pliner HA, Abramzon Y, Marangi G, Winborn BJ, Gibbs JR, Nalls MA, Morgan S, Shoai M, Hardy J, Pittman A, Orrell RW, Malaspina A, Sidle KC, Fratta P, Harms MB, Baloh RH, Pestronk A, Weihl CC, Rogaeva E, Zinman L, Drory VE, Borghero G, Mora G, Calvo A, Rothstein JD; ITALSGEN, Drepper C, Sendtner M, Singleton AB, Taylor JP, Cookson MR, Restagno G, Sabatelli M, Bowser R, Chiò A, Traynor BJ. Mutations in the Matrin 3 gene cause familial amyotrophic lateral sclerosis. Nat Neurosci. 2014 May;17(5):664-6.
  • Bibee KP, Cheng YJ, Ching JK, Marsh JN, Li AJ, Keeling RM, Connolly AM, Golumbek PT, Myerson JW, Hu G, Chen J, Shannon WD, Lanza GM, Weihl CC, Wickline SA. Rapamycin nanoparticles target defective autophagy in muscular dystrophy to enhance both strength and cardiac function. FASEB J. 2014 May;28(5):2047-61.
  • Udan-Johns M, Bengoechea R, Bell S, Shao J, Diamond MI, True HL, Weihl CC, Baloh RH. Prion-like nuclear aggregation of TDP-43 during heat shock is regulated by HSP40/70 chaperones. Hum Mol Genet. 2014 Jan 1;23(1):157-70.
  • Wignes JA, Goldman JW, Weihl CC, Bartley MG, Andley UP. p62 expression and autophagy in αB-crystallin R120G mutant knock-in mouse model of hereditary cataract. Exp Eye Res. 2013 Oct;115:263-73
  • Ching JK, Weihl CC. Rapamycin-induced autophagy aggravates pathology and weakness in a mouse model of VCP-associated myopathy. Autophagy. 2013 May;9(5):799-800.
  • Weihl CC. Monitoring autophagy in the treatment of protein aggregate diseases: steps toward identifying autophagic biomarkers. Neurotherapeutics. 2013 Jul;10(3):383-90.
  • Ching JK, Elizabeth SV, Ju JS, Lusk C, Pittman SK, Weihl CC. mTOR dysfunction contributes to vacuolar pathology and weakness in valosin-containing protein associated inclusion body myopathy. Hum Mol Genet. 2013 Mar 15;22(6):1167-79.
  • Harms MB, Sommerville RB, Allred P, Bell S, Ma D, Cooper P, Lopate G, Pestronk A, Weihl CC, Baloh RH. Exome sequencing reveals DNAJB6 mutations in dominantly-inherited myopathy. Ann Neurol. 2012 Mar;71(3):407-16.
  • Fuentealba RA, Marasa J, Diamond MI, Piwnica-Worms D, Weihl CC. An aggregation sensing reporter identifies leflunomide and teriflunomide as polyglutamine aggregate inhibitors. Hum Mol Genet. 2012 Feb 1;21(3):664-80.
  • Weihl CC. Another VCP interactor: NF is enough. J Clin Invest. 2011 Dec;121(12):4627-30.
  • Weihl CC. Valosin containing protein associated fronto-temporal lobar degeneration: clinical presentation, pathologic features and pathogenesis. Curr Alzheimer Res. 2011 May;8(3):252-60. Review.
  • Andley UP, Hamilton PD, Ravi N, Weihl CC. A knock-in mouse model for the R120G mutation of αB-crystallin recapitulates human hereditary myopathy and cataracts. PLoS One. 2011 Mar 18;6(3):e17671.
  • Weihl CC, Miller SE, Zaidman CM, Pestronk A, Baloh RH, Al-Lozi M. Novel GNE mutations in two phenotypically distinct HIBM2 patients. Neuromuscul Disord. 2011 Feb;21(2):102-5.
  • Varadhachary AS, Weihl CC, Pestronk A. Mitochondrial pathology in immune and inflammatory myopathies. Curr Opin Rheumatol. 2010 Nov;22(6):651-7.
  • Weihl CC, Pestronk A. Sporadic inclusion body myositis: possible pathogenesis inferred from biomarkers. Curr Opin Neurol. 2010 Oct;23(5):482-8

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.