Val Sheffield, MD, PhD
Research Profile

Research Interests: Gene discovery: genes causing human hereditary disease

Model System: Mouse and zebrafish models of Bardet-Biedl syndrome

Affiliations:

• Roy J. Carver College of Medicine
• Department of Pediatrics
• Department of Ophthalmology
• Howard Hughes Medical Institute
• Interdepartmental Research Program in Human Molecular Genetics

Publications 2006-2008:

1. Wang, W-H., McNatt, L.G., Pang, I-H., Millar, J.C., Hellberg, P.E., Hellberg, M.H., Steely, H.T., Rubin, J.S., Fingert, J.H., Sheffield, V.C., Stone, E.M.,, Clark A.F.  Increased expression of the WNT antagonist sFRP-1 in glaucoma elevates intraocular pressure.  J of Clin Invest 10.1172/JCI33871 (epub ahead of publication)
2. Tayeh, M.K., Yen, H-J., Beck, J.S., Searby, C.C., Westfall, T.A., Griesbach, H., Sheffield, V.C., Slusarski, D.C. Genetic interaction between Bardet-Biedl syndrome genes and implications for polydactyly. Hum Mol Genet 2008  Submitted.
3. Fingert, J.H., Oh, K., Chung, M., Scheetz, T.E., Andorf, J.L., Johnson, R.M., Sheffield, V.C., Stone, E.M. Novel mutation in the retinol dehydrogenase 12 (RDH12) gene is associated with autosomal dominant retinitis pigmentosa.  Archives of Ophthalmology, 2008 in press.
4. Hjortshoj, T.D., Grenskov, K., Philp, A.R., Nishimura, D.Y., Adeyemo, A., Rotimi, C.N., Sheffield, V.C., Rosenberg, T., Brendum-Nielson, K.  Novel mutations in BBS5 highlight the importance of this gene in non-Caucasian Bardet-Biedl syndrome patients.  Am J Med Genet 2008 in Press.
5. Shah, A., Farmen, S.L.,  Moniger, T.O., Businga, T.R., Andrews, M.P., Searby, C.C., Nishimura, D.,  Brogden, K.A., Kline, J.N., Sheffield, V.C., Welsh, M.J. Loss of Bardet-Biedl syndrome proteins alters the morphology and function of motile cilia in mouse airway epithelia.  Proc. Natl. Acad. Sci. 2008 in Press.
6. Rahmouni, K., Fath, M.A., Seo, S., Thedens, D.R., Berry, C.J., Weiss, R., Nishimura, D.Y., Sheffield, V.C. Pathophysiological role of leptin in Bardet-Biedl syndrome: Evidence from knockout mouse models. J. Clin. Invest. 2008 in press.
7. Fingert, J.H., Alward, W.L., Kwon, Y.H., Wang, K., Streb, L.M., Sheffield, V.C., Stone, E.M.  LOXL1 mutations are associated with exfoliation syndrome in patients from the Midwestern United States. Am J Ophthalmol 2007, 144(6)-974-975
8. O’Leary, B.M., Davis, S.G., Smith, M.F., Brown, B., Kemp, M.B., Almabrazi, H., Grundstad, J.A., Burns, T., Leontiev, V., Andorf, J., Clark, A.F., Sheffield, V.C., Casavant, T.L., Scheetz, T.E., Stone, E.M., Braun, T.A.  Transcript annotation prioritization and screening system (TrAPSS) for mutation screening.  J Bioinform Comput Bio, 2007 5(6):1155-72
9. Davis, R.E., Swiderski, R.E., Rahmouni, K., Nishimura, D.Y., Mullins, R.F., Agassandian, K., Philp, A.R., Searby, C.C., Andrews, M.P., Thompson, S., Berry, C.J., Thedens, D.R., Yang , B., Weiss, R.M., Cassell, M.D., Stone, E.M., Sheffield  V.C. A knock-in mouse model of the Bardet-Biedl syndrome1 M390R mutation has cilia defects, ventriculomegaly, retinopathy and obesity  Proc Natl Acad Sci  2007, 104 (49) 19422-7
10. Swiderski, R.E., Nishimura, D.Y., Mullins, R.F., Olvera, M.A., Ross, J.L., Huang, J., Stone, E.M., Sheffield, V.C.  Gene expression analysis of photoreceptor cell loss in bbs-4-knockout mice reveals an early stress gene response and photoreceptor cell damage.  Invest Ophthalmol Vis Sci 2007, 48(7):3329-40
11. Nachury, M.V., Loktev, A.V., Zhang, Q., Westlake, C.J., Peranen, J., Merdes, A., Slusarski, D.C., Scheller R.H., Bazan, J.F., Sheffield, V.C., Jackson, P.K.  A core complex of BBS proteins cooperates with the GTPase Rab8 to promote ciliary membrane biogenesis.  Cell 2007, 15:129(6):1041-3
12. Fingert, J.H., Grassi, M.A., Janutka, J.C., East, J.S., Howard, J.G., Sheffield, V.C., Jacobson, D.M., Hayreh S.S., Stone, E.M.  Mitochondrial variant G4132A is associated atiht familial non-arteritic anterior ischemic optic neuropathy in one large pedigree.  Ophthalmic Genet 2007, 28(1):1-7
13. Gao, X., Gordon, D., Zhang, D., Browne, R.., Helms, C., Gillum, J., Weber, S., Devroy, S., Swangey, S., Dobbs, M., Morcuende, J., Sheffield, V., Lovett, M., Bowcock, A., Herring, J., Wise, C.  CHD7gene polymorphisms are associated with susceptibility to idiopathic scoliosis.  Am J Hum Genet 2007 80(5):957-65
14. Fingert, J.H., Honkanen, R.A., Shankar, S.P., Affatigato, L.M., Eblinger, M.A., Moore, M.D., Jampol, L.M., Sheffield, V.C., Stone, E.M., Alward, W.L.  Familial cavitary optic disk anomalies:  Identification of a novel genetic locus.  Am J Ophthalmol 2007 143 (5):795-800
15. Fingert, J.H., Alward, W.L., Kwon, Y.H., Shankar, S.P., Andorf, J.L., Mackey, D.A., Sheffield, V.C., Stone, E.M.  No association between variations in the WDR36 gene and primary open-angle glaucoma.  Arch Ophthalmol 2007 125(3):434-6
16. Autism Genome Project Consortium:  Szatmari, P., Paterson, A.D., et al. Mapping autism risk loci using geneic linkage and chromosomal rearrangements.  Nat Genet 2007 39(3):319-28
17. Shepard, A.R., Jacobson, N., Miller, J.C., Pang, I.H., Steely, H.T., Searby, C.C., Sheffield, V.C., Stone, E.M., Clark, A.F.  Glaucoma-causing myocilin mutants require the Peroxixomal targeting signal-1 receptor (PTS1R) to elevate intraocular pressure.  Hum Mol Genet 2007 3 16(6):609-17
18. Grassi, M.A., Folk, J.C., Scheetz, T.E., Taylor, C.M., Sheffield, V.C., Stone, E.M.  Complement factor H polymorphism p.Tyr402His and cuticular Drusen.  Arch Ophthalmol 2007 125 (1):93-7
19. White, D.R., Ganesh, A., Nishimura, D., Rattenberry, E., Ahmed, S., Smith, U.M., Pasha, S., Raeburn, S., Trembath, R.C., Rajab, A., Macdonald, F., Banin, E., Stone, E.M., Johnson, C.A,, Sheffield, V.C., Maher, E.R.  Autozygosity mapping of Bardet-Biedl syndrome to 12q21.2 and confirmation of FLJ23560 as BBS10.  Eur J Hum Genet 2007 15(2):173-8
20. Wassink, T.H., Losh, M., Piven, J., Sheffield, V.C., Ashley, E., Westin, E.R., Patil, S.R.  Systematic screening for subtelomeric anomalies in a clinical sample of autism.  J Autism Dev Disord 2007 37(4):703-8
21. Azari, A.A., Aleman, T.S., Cideciyan, A.V,, Schwartz, S.B., Windsor, E.A., Sumaroka, A., Cheung, A.Y., Steinberg, J.D., Roman, A.J., Stone, E.M., Sheffield, V.C., Jacobson, S.G.  Retinal disease expression in Bardet-Biedl syndrome-1 (BBS1) is a spectrum from maculopathy to retina-wide degeneration.  Invest Ophthalmol Vis Sci 2006 47 (11):5004-10
22. Scheetz, T.E., Kim, K.Y., Swiderski, R.E., Philp, A.R., Braun, T.A., Knudtson, K.L., Dorrance, A.M., Dibona, G.F., Huang, J., Casavant, T.L., Sheffield, V.C., Stone. E,M.  Regulation of gene expression in the mammalian eye and its relevance to eye disease.  Proc Natl Acad Sci USA 2006 103(39):14429-34
23. Fingert, J.H., Eliason, D.A., Phillips, N.C., Lotery, A.J., Sheffield, V.C., Stone, E.M.  Case of Stargardt disease caused by uniparental isodisomy.  Arch Ophthalmol 2006 124(5):744-5
24. Fingert, J.H., Kwon, Y.H., Moore, P.A., Johnston, R.M., Kim, K.Y., Sheffield, V.C., Alward, W.L., Stone, E.M.  The C677T variant in the methylenetetrahydrofolate reductase gene is not associated with disease in cohorts of pseudoexfoliation glaucoma and primary open-angle glaucoma patients from Iowa.  Ophthalmic Genet 2006 27(2):39-41
25. Bischof, J.M., Chiang, A.P., Scheetz, T.E., Stone, E.A., Casavant, T.L., Sheffield, V.C., Braun, T.A.  Genome-wide identification of pseudogenes capable of disease-causing gene conversion.  Human Mutation 2006 27(6):545-552
26. Chiang, A.P., Beck, J.S., Yen, H.J., Tayeh, M.K., Scheetz, T.E., Swiderski, R.E., Nishimura, D.Y., Braun, T.A., Kim, K.Y., Huang, J., Elbedour, K., Carmi, R., Slusarski, D.C., Casavant, T.L., Stone, E.M., Sheffield, V.C.  Homozygosity mapping with SNP arrays identifies TRIM32, an E3 ubiquitin ligase, as a Bardet-Biedl syndrome gene (BBS11).  Proc Natl Acad Sci 2006, 103(16):6287-92
27. Yen, H.-J., Tayeh, M.K., Mullins, R.F., Stone, E.M., Sheffield, V.C., Slusarski, D.C.  Bardet-Biedl syndrome genes are important in retrograde intracellular trafficking and Kupffer’s vesicle cilia function.  Hum Mol Genet 2006, 1:15(5):667-77
28. Braun, T.A., Shankar, S.P., Davis, S., O’leary, B., Scheetz, T.E., Clark, A.F., Sheffield, V.C., Casavant, T.L., Stone, E.M.  Prioritizing regions of candidate genes for efficient mutation screening.  Hum Mutat 2006, 27(2):195-200

Personnel:

• Darryl Nishimura, Research Scientist
• Ruth Swiderski, Associate Research Scientist
• Qihong Zhang, Assistant Research Scientist
• Denise Aguiar Crouch, Administrative Assistant
• Seongjin Seo, Postdoctoral Associate
• Pam Pretorious, Graduate Student
• Charles Searby, Research Technician
• John Beck, Research Technician
• Gretel Beck, Research Assistant
• Erik Berg, Research Assistant
• Kevin Bugge, Research Assistant
• Amanda Ferguson, Research Assistant
• Gretel Beck, Research Assistant
• Valerie Buffard,Research Assistant
• Kevin Bugge, Support Staff
• GunHee Lee, Research Assistant
• Amy Librant, Research Assistant
• Gregg Webster, Info Tech Support