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Faculty Detail    
Name ANDREW B WEST
Co-Director, Center for Neurodegeneration and Experimental Therapeutics
John A. and Ruth R. Jurenko Professor of Neurology
Professor of Neurology and Neurobiology
 
Campus Address CIRC 552 Zip 0021
Phone  205-996-7697
E-mail  abwest@uab.edu
Other websites West laboratory
     

Education
Graduate  Mayo Clinic School of Medicine    2003  Ph.D. 
Fellowship  University of California at Los Angeles    2004  Post-doctoral Fellowship 
Fellowship  Johns Hopkins University    2006  Post-doctoral Fellowship 


Faculty Appointment(s)
Appointment Type Department Division Rank
Primary  Civitan International Research Center  Civitan International Research Center
Primary  Neurology   Neurology Chair Office Professor
Secondary  Neurobiology  Neurobiology Assistant Professor
Center  Neurology   Alzheimer's Disease Center Professor
Center  Comprehensive Ctr for Healthy Aging  Comprehensive Ctr for Healthy Aging
Center  General Clinical Research Center  Comprehensive Neuroscience Center
Center  General Clinical Research Center  Ctr for Clinical & Translational Sci Professor
Center  Ctr for Glial Bio in Med  Ctr for Glial Bio in Med Professor
Center  Neurology   Ctr Neurodegeneration & Exp Ther (CNET)
Center  GL Ctr for Craniofacial, Oral, & Dental Disorders  GL Ctr for Craniofacial, Oral, & Dental Disorders
Center  General Clinical Research Center  Nephrology Research & Training Center Professor

Graduate Biomedical Sciences Affiliations
Biochemistry and Molecular Genetics Program 
Biochemistry and Structural Biology 
Cell, Molecular, & Developmental Biology 
Cellular and Molecular Biology Program 
Genetics, Genomics and Bioinformatics 
Hughes Med-Grad Fellowship Program 
Medical Scientist Training Program 
Neuroscience 
Neuroscience Graduate Program 

Biographical Sketch 
Andrew West, Ph.D. is an Associate Professor of Neurology and holds the John A. and Ruth R. Jurenko Endowed Professorship in Neurology. Dr. West received his undergraduate degree from Alma College and his PhD in Molecular Neuroscience from the Mayo Clinic School of Medicine in Rochester, MN. He then went on to complete a Postdoctoral Fellowship at UCLA Neuropsychiatric Institute in Los Angeles in the laboratory of Nigel Maidment and a second postdoctoral fellowship in the laboratory of Ted Dawson at Johns Hopkins, followed by an Instructor faculty position in the Department of Neurology at Johns Hopkins. Work from the students of the West laboratory frequently appears in national news: http://www.foxnews.com/health/2014/12/10/brain-inflammation-shared-trait-in-autism-study-finds/ http://www.sciencedaily.com/releases/2014/06/140610144402.htm http://www.birminghammedicalnews.com/news.php?viewStory=1090

Society Memberships
Organization Name Position Held Org Link
Society for Neuroscience     



Research/Clinical Interest
Title
Genetic and biochemical mechanisms in neurodegeneration and neurological disorders
Description
Our primary goal is to utilize emerging genetic and genomic approaches to help understand the molecular basis of neurological disorders, particularly Parkinson disease, and develop targeted therapeutic strategies. The laboratory has a major focus on the new and exciting molecule recently discovered as a major cause of familial Parkinson disease, the LRRK2 protein kinase. We have developed innovative biochemical approaches over the last few years that demonstrate that this kinase may be overactive in Parkinson's disease, and therapeutic approaches to knockdown this activity may provide neuroprotective benefit to Parkinson disease patients. We are vested in all aspects of pursuing this protein as a drug target, including biomarker assays, antibody and transgenic animal development, and discovery of specific compounds that modify LRRK2 activity together with our collaborators in the pharmaceutical industry. An emerging area of interest in the laboratory is to help contribute to the understanding of autism and identification of new genetic-based models and therapeutic strategies. Our laboratory has assembled together one of the largest collections of post-mortem brain material and is analyzing this material using state of the art genetic approaches including RNAseq and whole genome resequencing, together with collaborators. In addition, we are developing new mouse models of autism based on our discoveries in the pathological tissue.

Selected Publications 
Publication PUBMEDID
West Lab Publications
2012 to Present

• Moehle MS, Webber PJ, Tse T, Sukar N, Standaert DG, DeSilva TM, Cowell RM, West AB. “LRRK2 Inhibition Attenuates Microglial Inflammatory Responses” J Neurosci. 2012 Feb 1;32(5):1602-11.

• Stafa, K, Trancikova, A., Webber, PJ, Glauser, L., West, AB, Moore, DJ. “'GTPase Activity and Neuronal Toxicity of Parkinson's Disease-Associated LRRK2 is Regulated by ArfGAP1” PLoS Genet. 2012 Feb;8(2):e1002526. Epub 2012 Feb 9.

• Trancikova A, Mamais A, Webber PJ, Stafa K, Tsika E, Glauser L, West AB, Bandopadhyay R, Moore DJ. “Phosphorylation of 4E-BP1 in the mammalian brain is not altered by LRRK2 expression or pathogenic mutations.” PLoS One. 2012;7(10):e47784

• Davies P, Hinkle KM, Sukar NN, Sepulveda B, Mesias R, Serrano G, Alessi DR, Beach TG, Benson DL, White Iii CL, Cowell RM, Das SS, West AB, Melrose HL. “Comprehensive Characterization and Optimization of Leucine Rich Repeat Kinase 2 (LRRK2) Monoclonal Antibodies.” Biochem J. 2013 Jul 1;453(1):101-13

• Day K, Waite LL, Thalacker-Mercer A, West AB, Bamman MM, Brooks JD, Myers RM, Absher D. “Differential DNA methylation with age displays both common and dynamic features across human tissues that are influenced by CpG landscape.” Genome Biol. 2013 Sep 13;14(9):R102

• Fraser KB, Moehle MS, Daher JP, Webber PJ, Williams JY, Stewart CA, Yacoubian TA, Cowell RM, Dokland T, Ye T, Chen D, Siegal GP, Galemmo RA, Tsika E, Moore DJ, Standaert DG, Kojima K, Mobley JA, West AB.” LRRK2 secretion in exosomes is regulated by 14-3-3.” Hum Mol Genet. 2013 Aug 6.

• Day K, Waite LL, Thalacker-Mercer A, West AB, Bamman MM, Brooks JD, Myers RM, Absher D. “Differential DNA methylation with age displays both common and dynamic features across human tissues that are influenced by CpG landscape.” Genome Biol. 2013 Sep 13;14(9):R102.

• Sampath, S., Bhat, S., Gupta, S., O'Connor, A., West, AB., Arking, D., Chakravarti, A. “Defining the Contribution of CNTNAP2 to Autism Susceptibility” PLoS One. 2013 Oct 17;8(10):e77906.

• Dougherty,S, Hollimon, J, McMeekin, L, Bohannon, A, West, AB, Lesort, M, Hablitz, J, Cowell, R. “Hyperactivity and Cortical Disinhibition in Mice with Restricted Expression of Mutant Huntingtin to Parvalbumin-Positive Cells” Neurobiol Dis. 2014 Feb;62:160-71.

• Daher JP, Volpicelli-Daley LA, Blackburn JP, Moehle MS, West AB “Abrogation of α-synuclein-mediated dopaminergic neurodegeneration in LRRK2-deficient rats.” Proc Natl Acad Sci U S A. 2014 Jun 24;111(25):9289-94.

• West AB, Cowell RM, Daher JP, Moehle MS, Hinkle KM, Melrose HL, Standaert DG, Volpicelli-Daley LA. “Differential LRRK2 expression in the cortex, striatum, and substantia nigra in transgenic and nontransgenic rodents.” J Comp Neurol. 2014 Aug 1;522(11):2465-80.

• Ellis SE, Gupta S, Ashar FN, Bader JS, West AB, Arking DE. “RNA-Seq optimization with eQTL gold standards.” BMC Genomics. 2013 Dec 17;14:892.

• Liu Z, Galemmo RA Jr, Fraser KB, Moehle MS, Sen S, Volpicelli-Daley LA, DeLucas LJ, Ross LJ, Valiyaveettil J, Moukha-Chafiq O, Pathak AK, Ananthan S, Kezar H, White EL, Gupta V, Maddry JA, Suto MJ, West AB. "Unique Functional and Structural Properties of the LRRK2 ATP-Binding Pocket" J. Biol. Chem., J Biol Chem. 2014 Sep 16.

• Lucas, E., Dougherty, S., McMeekin, L., Reid, C., Dobrunz, L., West, AB, Hablitz, J, Cowell, R. “PGC-1α provides a transcriptional framework for synchronous neurotransmitter release from parvalbumin-positive interneurons” J Neurosci. 2014 Oct 22;34(43):14375-87.

• Moehle, M., West, AB. “M1 and M2 Immune Activation in Parkinson's Disease: Foe and Ally”. Neuroscience. 2014 Nov 25. pii: S0306-4522(14)00975-0.

• West, AB “10 Years and Counting: Moving LRRK2 Inhibitors to the Clinic” Mov Disord. 2014 Dec 1.

• Gupta, S., Ellis, S., Ashar, F., Moes, A., Bader, J., Zhan, J., West, AB*., Arking, D* “Transcriptome Analysis Reveals Dysregulation of Innate Immune Response Genes and Neuronal Activity-Dependent Genes in Autism” Nat Commun. 2014 Dec 10;5:5748.

• Volpicelli-Daley, LA, Gamble, KL, Schultheiss, CE, Riddle, DM, West, AB, Lee, VMY. “Formation of α-Synuclein Lewy Neurite-like aggregates in Axons Impedes the Transport of Distinct Endosomes”, Mol Biol Cell. 2014 Dec 15;25(25):4010-23.

• Moehle MS, Daher JP, Hull TD, Boddu R, Abdelmotilib HA, Mobley J, Kannarkat GT, Tansey MG, West AB. “The G2019S LRRK2 mutation increases myeloid cell chemotactic responses and enhances LRRK2 binding to actin-regulatory proteins.” Hum Mol Genet. 2015 Apr 29

• Boddu R, Hull TD, Bolisetty S, Hu X, Moehle MS, Daher JP, Kamal AI, Joseph R, George JF, Agarwal A, Curtis LM, West AB. “Leucine-rich repeat kinase 2 deficiency is protective in rhabdomyolysis-induced kidney injury.” Hum Mol Genet. 2015 Apr 22.

• Daher, J., Hu, X., Moehle, M., Hirst, W., West, AB., “Pharmacological Inhibition of LRRK2 Blocks Alpha-Synuclein Induced Neurodegeneration” J Biol Chem. 2015 Aug 7;290(32):19433-44.

• Rosenthal LS, Drake D, Alcalay RN, Babcock D, Bowman FD, Chen-Plotkin A, Dawson TM, Dewey RB Jr, German DC, Huang X, Landin B, McAuliffe M, Petyuk VA, Scherzer CR, Hillaire-Clarke CS, Sieber BA, Sutherland M, Tarn C, West AB, Vaillancourt D, Zhang J, Gwinn K; PDBP consortium. “The NINDS Parkinson’s Disease Biomarker Program” Mov Disord. 2015 Oct 7.

• Liu, Z., Mobley, J., DeLucas, L., West, AB. “LRRK2 Autophosphorylation Enhances its GTPase Activity” FASEB J. 2015 Sep 22.

• Lavalley NJ, Slone SR, Ding H, West AB, Yacoubian TA. “14-3-3 proteins regulate LRRK2 kinase activity and neurite shortening”. Hum Mol Genet. 2015 Nov 5

• Fraser, KB, Moehle, MS, Alcalay, RN., West, AB “Urinary LRRK2 phosphorylation predicts parkinsonian phenotype in G2019S LRRK2 carriers” Neurology. 2016 Feb 10

• Ellis, SE, Panitch, R, West, AB, Arking, DE. "Transcriptome Analysis of Cortical Tissue Reveals Shared Sets of Down-Regulated Genes in Autism and Schizophrenia" Transl Psychiatry. 2016 May 24;6:e817.

• Fraser, KB, Rawlins, AB, Clark, RG, Alcalay, RN, Standaert, DG, Liu, N, West, AB. “Ser(P)-1292 LRRK2 in urinary exosomes is elevated in idiopathic Parkinson's disease.” Mov Disord. 2016 Oct;31(10):1543-1550.

• West, AB, Cookson, MR. “Identification of bona-fide LRRK2 kinase substrates.” Mov Disord. 2016 Aug;31(8):1140-1.

• Volpicelli-Daley, LA, Stoyka, L, Abdelmotilib, H, Fraser, K, Daher, JP, Milnerwood, A., Hirst, W., Yue, Z., Zhao, HT, Fraser, K, Kennedy, RE, West, AB. “G2019S-LRRK2 Expression Augments α-Synuclein Sequestration into Inclusions in Neurons.” J Neurosci. 2016 Jul 13;36(28):7415-27.

• Galemmo, RA, West, AB, Maddry, JA, Ananthan, S., Pathak, A., Vailyaveetitil, J. “Triazolopyridazine compounds, use as inhibitors of the kinase LRRK2, and methods for preparation thereof” 2015 US Patent 9,187,484

• Alcalay, R., Fraser, K., West, AB., “Phosphorylated pS1292 LRRK2 to Total LRRK2 Concentration Ratio in Urine Exosomes Distinguishes LRRK2-PD and Idiopathic PD” Neurology 84 14 Supplement S7.002, 2015

• Ellis, SE, Gupta, S., Moes, A., West, AB, Arking, DE “Exaggerated CpH Methylation in the Autism-Affected Brain” Molecular Autism. 2017 Feb 17;8:6. doi: 10.1186/s13229-017-0119-y.

• Liu, Z., West, AB. “The dual enzyme LRRK2 hydrolyzes GTP in both its GTPase and kinase domains in vitro” Biochimica et Biophysica Acta (BBA), 2017 Mar;1865(3):274-280

• Ivanova AA, Caspary T, Seyfried NT, Duong DM, West AB, Liu Z, Kahn RA.Biochemical characterization of purified mammalian ARL13B protein indicates that it is an atypical GTPase and ARL3 guanine nucleotide exchange factor (GEF). J Biol Chem. 2017 Jun 30;292(26):11091-11108. doi: 10.1074/jbc.M117.784025. Epub 2017 May 9.

• Gwinn K, David KK, Swanson-Fischer C, Albin R, Hillaire-Clarke CS, Sieber BA, Lungu C, Bowman FD, Alcalay RN, Babcock D, Dawson TM, Dewey RB Jr, Foroud T, German D, Huang X, Petyuk V, Potashkin JA, Saunders-Pullman R, Sutherland M, Walt DR, West AB, Zhang J, Chen-Plotkin A, Scherzer CR, Vaillancourt DE, Rosenthal LS. “Parkinson's disease biomarkers: perspective from the NINDS Parkinson's Disease Biomarkers Program.” Biomark Med. 2017 May;11(6):451-473. doi: 10.2217/bmm-2016-0370. Epub 2017 Jun 23.

• Cook DA, Kannarkat GT, Cintron AF, Butkovich LM, Fraser KB, Chang J, Grigoryan N, Factor SA, West AB, Boss JM, Tansey MG.“LRRK2 levels in immune cells are increased in Parkinson's disease.” NPJ Parkinsons Dis. 2017 Mar 28;3:11. doi: 10.1038/s41531-017-0010-8.
• Abdelmotilib H, Maltbie T, Delic V, Liu Z, Hu X, Fraser KB, Moehle MS, Stoyka L, Anabtawi N, Krendelchtchikova V, Volpicelli-Daley LA, West A. “α-Synuclein fibril-induced inclusion spread in rats and mice correlates with dopaminergic Neurodegeneration.” Neurobiol Dis. 2017 May 30;105:84-98. doi: 10.1016/j.nbd.2017.05.014

• West, AB. “Achieving neuroprotection with LRRK2 kinase inhibitors in Parkinson disease” Exp Neurol. 2017 Jul 29. pii: S0014-4886(17)30203-0. doi: 10.1016/j.expneurol.2017.07.019. Review.

• HT Zhao, N John, V Delic, K Ikeda-Lee, A Kim, A Weihofen, EE Swayze, HB Kordasiewicz, AB West, LA Volpicelli-Daley. “LRRK2 Antisense Oligonucleotides Ameliorate α-Synuclein Inclusion Formation in a Parkinson’s Disease Mouse Model” Mol Ther Nucleic Acids. 2017 Sep 15;8:508-519.

 
 

Keywords
Molecular Genetics & Disease; Neurobiology