Linda O'Reilly

  • Lecturer

Contact

Office: (412) 624-4832
A354 Langley Hall
4249 Fifth Avenue
Pittsburgh, PA 15260

Dr. O’Reilly’s background is in biochemistry and she is particularly interested in how various human diseases arise from protein misfolding events. Misfolding occurs when a genetic mutation causes in an incorrect amino acid to be placed in the polypeptide sequence. The polypeptide is then unable to fold up into the protein’s correct 3-dimensional structure. When a protein is unable to achieve the correct structure, it is unable to preform its cellular function, and this can result in disease. Misfolded protein can also aggregate, become toxic, and kill the cells where it is expressed, leading to organ damage. Dr. O’Reilly’s past research has focused on both these problems. She has investigated two misfolded protein models, medium-chain acyl CoA dehydrogenase deficiency (a defect in the ability to metabolize fats), and alpha 1 antitrypsin deficiency (a liver disease caused by toxic aggregation).

O’Reilly L.P., Knoerdel R.R.,

O’Reilly L.P., Knoerdel R.R., Silverman G.A., Pak S.C., (2016) High-throughput, liquid based genome-wide RNAi screening in C. elegans; Methods in Molecular Biology, p 151-62 (ISBN: 978-1-4939-6335-5)

Luke C.J., O’Reilly L.P., (201

Luke C.J., O’Reilly L.P., (2015) Microscopic Investigation of Protein Function in C. elegans Using Fluorescent Imaging; Curr. Protoc. Cytom. 74:12.41.1-12.41.17.

Benson J.A., Cummings E.E., O’Reilly L.

Benson J.A., Cummings E.E., O’Reilly L.P., Lee M.H., Pak S.C., (2014) A high-content assay for identifying small molecules that reprogram C.elegans germ fate; 68(3):529-35

Luke C.J., Niehaus J.Z., O’Reilly L.P.

Luke C.J., Niehaus J.Z., O’Reilly L.P., Watkins S.C., (2014) Non-microfludic methods for imaging live C.elegans; Methods 68(3):542-7.

O’Reilly L.P., Benson J.A., Cu

O’Reilly L.P., Benson J.A., Cummings E.E., Perlmutter D.H., Silverman G.A., Pak S.C., (2014) Worming our way to novel drug discovery with the C.elegans proteostasis network, stress response and insulin-signaling pathways; Expert Opin. Drug Discov. 9(9):1021-32.

O’Reilly L.P., Perlmutter D.H.

O’Reilly L.P., Perlmutter D.H., Silverman G.A., Pak S.C., (2014) alpha 1-antitrypsin deficiency and the hepatocytes-An elegans solution to drug discovery; Int. J. Biochem. Cell Biol. 47:109-12.

O’Reilly L.P., Luke C.J., Perl

O’Reilly L.P., Luke C.J., Perlmutter D.H., Silverman G.A., Pac S.C., (2014) C.elegans in high-throughput drug discovery; Adv. Drug Deliv. Rev. 69-70:247-53.

Cummings E.E.*, O’Reilly L.P.*

Cummings E.E.*, O’Reilly L.P.*, King D.E., Silverman R.M., Miedel M.T., Luke C.J., Perlmutter D.H., Silverman G.A., Pak S.C., (2015) Deficient and Null Variants of SERPINA1 Are Proteotoxic in a Caenorhabditis elegans Model of a alpha1-Antitrypsin Deficiency; PLoS One 10(10):e0141542. (*contributed equally).

Silverman R.M., Cummings E.E., O’Reilly

Silverman R.M., Cummings E.E., O’Reilly L.P., Miedel M.T., Silverman G.A., Luke C.J., Perlmutter D.H., Pak S.C., (2015) The aggregation-prone intracellular serpin SRP-2 fails to transit the ER in Caenorhabditis elegans; Genetics, 200(1):207-19.

Long O.S., Benson J.A., Kwak J.H., Luke C.J., G

Long O.S., Benson J.A., Kwak J.H., Luke C.J., Gosai S.J., O’Reilly L.P., Wang Y., Li J., Vetica A.C., Miedel M.T., Stolz D.B., Watkins S.C., Zuchner S., Perlmutter D.H., Silverman G.A., Pak S.C., (2014) A C.elegans model of human alpha 1-antitrypsin deficiency links components of the RNAi pathway to misfolded protein turnover; Hum. Mol. Genet. 23(19):5109-22.

O’Reilly L.P.*, Long O.S.*, Co

O’Reilly L.P.*, Long O.S.*, Cobanoglu M.C.*, Benson J.A., Luke C.J., Miedel M.T., Hale P., Perlmutter D.H., Bahar I., Silverman G.A., Pak S.C., (2014) A genome-wide RNAi screen identifies potential drug targets in a C.elegans model of alpha 1-antitrypsin deficiency; Hum. Mol Genet. 23(19):5123-32. Cover Illustration (*contributed equally)

Li J., Pak S.C., O’Reilly L.P.

Li J., Pak S.C., O’Reilly L.P., Benson J.A., Wang Y., Hidvegi T., Hale P., Dippold C., Ewing M., Silverman G.A., Perlmutter D.H., (2014) Fluphenazine reduces proteotoxicity in C. elegans and mammalian models of alpha-1-antitrypsin deficiency; PLoS One 9(1):e87260.

O’Reilly L.P., Zhang X., Smith

O’Reilly L.P., Zhang X., Smithgall T.E., (2013) Individual Src-family tyrosine kinases direct the degradation or protection of the mammalian clock protein timeless via differential ubiquitylation; Cellular Signaling 25:860-66.

O’Reilly L.P., Watkins S.C., S

O’Reilly L.P., Watkins S.C., Smithgall T.E., (2011) An Unexpected Role for the Clock Protein Timeless in Developmental Apoptosis; PLoS ONE 6(2):e17157.

Estep J.M., O’Reilly L., Grant

Estep J.M., O’Reilly L., Grant G., Piper J., Jonsson J., Afendy A., Chandhoke V., Younossi Z.M., (2010) Hepatic Stellate Cell and Myofibroblast-Like Cell Gene Expression in the Explanted Cirrhotic Livers of Patients Undergoing Liver Transplantation; Dig. Dis. Sci. 55:496-504.

Chen S., O’Reilly L.P., Smithg

Chen S., O’Reilly L.P., Smithgall T.E., Engen J.R., (2008) Tyrosine phosphorylation in the SH3 domain disrupts negative regulatory interactions within the c-Abl kinase core; J. Mol. Biol. 383:414-23.

O’Reilly L., Andresen B.S., En

O’Reilly L., Andresen B.S., Engel P., (2005) Two clinical variants of medium chain CoA dehydrogenase (MCAD); K364R, a folding mutation, and R256T, a totally inactive but well-folded protein; FEBS Journal 272:4549-57.

Linda O’Reilly, Peter Bross, T

Linda O’Reilly, Peter Bross, Thomas Croydon, Simon E. Olpin, Jakob Hansen, John M. Kenney, Shawn McCandless, Dianne M. Frazier, Vibeke Winter, Niels Gregersen, Paul Engel, Brage Storstein Andresen, (2004) The Y42H mutation in medium chain acyl CoA dehydrogenase, which is screening, is temperature sensitive prevalent in babies identified by MS/MS-based newborn; Eur. J. Biochem; 271:4053-63. Cover Illustration.

Andresen BS, Dobrowolski SF, O’Reilly L

Andresen BS, Dobrowolski SF, O’Reilly L, Muenzer J, McCandless SE, Frazier DM, Udvari S, Bross P, Knudsen I, Banas R, Chace DH, Engel P, Naylor EW, Gregersen N., (2001) Medium-chain acyl-CoA dehydrogenase (MCAD) mutations identified by MS/MS-based prospective screening of newborns differ from those observed in patients with clinical symptoms: identification and characterisation of a new, prevalent mutation that results in mild MCAD deficiency; Am. J. Hum. Genet. 68(6):1408-18.
Dr. O’Reilly received her Ph.D. in 2003 from University College Dublin, Ireland, under the mentorship of Prof. Paul Engel. She preformed her post-doctoral studies at the University of Pittsburgh with Prof. Tom Smithgall (2004-12), and then moved to Children’s Hospital of Pittsburgh to study childhood liver disease, under the mentorship of Dr. Gary Silverman (2012-2016) and joined the department in 2016.