Paul Valdmanis, PhD | Division of Medical Genetics

Assistant Professor

Medical Genetics

Adjunct Assistant Professor

Genome Sciences

Adjunct Assistant Professor

Pathology

Faculty Information

Biography

I grew up in Toronto, Canada and received a Bachelor’s in Science (Biochemistry) Summa cum laude from the University of Ottawa. Following this, I completed my PhD in the laboratory of Guy Rouleau in the Department of Human Genetics at McGill University in Montreal, Canada. My research focused on the identification of mutations in genes that are responsible for Amyotrophic Lateral Sclerosis and other neurodegenerative diseases. During this time, I was supported by fellowships from the Natural Sciences and Engineering Research Council of Canada (NSERC), the Canadian Institutes of Health Research (CIHR) and the Fonds de Recherche Sante Quebec (FRSQ).

I conducted my postdoctoral research at Stanford University in the lab of Mark Kay in the Departments of Pediatrics and Genetics where I was a Bisby Postdoctoral Fellow as well as a Banting Postdoctoral Fellow. I established methods to identify how to safely and effectively reduce target genes by utilizing adeno-associated viral delivery of small hairpin RNAs.

In August of 2017 I opened my lab in the Division of Medical Genetics at the University of Washington where I am excited to train a new generation of scientists in genetics and gene therapy.

Pronouns: He/Him/His

Education & Training:

Bachelor's Degree in Science

University of Ottawa

2003

PhD

McGill University

2009

Honors:

Roger Guindon Scholarship

2000

Centre Hospitalier de l’Universite de Montreal Award of Excellence

2005

CIHR Institute of Neurosciences Brain Star Award

2008

Governor General’s Gold Medal, McGill University

2009

Gordon A. Maclachlan Prize, McGill University

2009

American Society of Gene and Cell Therapy Research Excellence Award

2011

American Society of Gene and Cell Therapy Travel Award

2011-2012

American Society of Gene and Cell Therapy Travel Award

2014

American Society of Gene and Cell Therapy Travel Award

2016

Contact

Email:

paulnv@uw.edu

Phone:

(206) 685-3982

Mailing Address:

University of Washington

Division of Medical Genetics

1705 NE Pacific St

Box 357720

Seattle, WA 98195-7720

Research & Clinical Interests

Research Interests:

The Valdmanis lab's research focus is to identify pathogenic variants that cause or modify human disease, determine the mechanisms of action of these genes in disease pathogenesis and correct the variants through gene therapy approaches including RNA interference and genome editing.

Our lab focuses on the following research goals:

1. Identify novel genetic contributors to Amyotrophic Lateral Sclerosis and Alzheimer's disease, including tandem repeat expansions using long-read sequencing technology.

2. Develop gene therapy methods for safe and effective gene knockdown using recombinant adeno-associated viral vectors (AAVs) to target genes implicated in neurodegeneration.

3. Perform mechanistic characterization of the role of microRNAs including miR-122 and an imprinted cluster of microRNAs at the DLK1-DIO3 locus in the development of hepatocellular carcinoma.

Publications

My NCBI:

My NCBI Bibliography

Publications:

Valdmanis PN, Kay MA. Future of rAAV Gene Therapy: Platform for RNAi, Gene Editing, and Beyond. Human Gene Therapy. 2017 Apr;28(4):361-372.

Valdmanis PN, Gu S, Chu K, Jin L, Zhang F, Munding EM, Huang Y, Kutay H, Ghoshal K, Lisowski L, Kay MA. RNA interference-induced hepatotoxicity results from loss of the first synthesized isoform of microRNA-122 in mice. Nature Medicine 2016 May;22(5)557-62.

Valdmanis PN, Roy-Chaudhuri B, Kim HK, Sayles LC, Zheng Y, Chuang CH, Caswell DR, Chu K, Zhang Y, Winslow MM, Sweet-Cordero EA, Kay MA. Upregulation of the microRNA cluster at the Dlk1-Dio3 locus in lung adenocarcinoma. Oncogene. 2015 Jan 2;34(1):94-103.

Barzel A, Paulk NK, Shi Y, Huang Y, Chu K, Zhang F, Valdmanis PN, Spector, LP, Porteus MH, Gaensler KM, Kay MA. Promoterless gene targeting without nucleases ameliorates haemophilia B in mice. Nature 2015 Jan 15;517(7534):360-4.

Roy-Chaudhuri B, Valdmanis PN, Zhang Y, Wang Q, Luo QJ, Kay MA. Regulation of microRNA-mediated gene silencing by microRNA precursors. Nature Structural & Molecular Biology 2014 Sep;21(9):825-32.

Gu S, Jin L, Zhang Y, Huang Y, Zhang F, Valdmanis PN, Kay MA. The loop position of shRNAs and pre-miRNAs is critical for the accuracy of dicer processing in vivo. Cell 2012 Nov 9;151(4):900-11.

Valdmanis PN, Gu S, Schüermann N, Sethupathy P, Grimm D, Kay MA. Expression determinants of mammalian argonaute proteins in mediating gene silencing. Nucleic Acids Research 2012 Apr;40(8):3704-13.

Valdmanis PN, Dupré N, Lachance M, Stochmanski S, Belzil VV, P.A. Dion PA, I. Thiffault, B. Brais, L. Weston, L. Saint-Amant, M.E. Samuels and Rouleau GA. A mutation in the RNF170 gene causes autosomal dominant sensory ataxia. Brain 2011 Feb;134(Pt 2):602-7.

Kwiatkowski TJ Jr, Bosco DA, Leclerc AL, Tamrazian E, Vanderburg CR, Russ C, Davis A, Gilchrist J, Kasarskis EJ, Munsat T, Valdmanis P, Rouleau GA, Hosler BA, Cortelli P, de Jong PJ, Yoshinaga Y, Haines JL, Pericak-Vance MA, Yan J, Ticozzi N, Siddique T, McKenna-Yasek D, Sapp PC, Horvitz HR, Landers JE, Brown RH Jr. Mutations in the FUS gene on chromosome 16 cause familial amyotrophic lateral sclerosis. Science 2009 Feb 27;323(5918):1205-8.

Kabashi E*, Valdmanis PN*, Dion PA, Spiegelman D, McConkey BJ, Vande Velde C, Bouchard J-P, Lacomblez L, Pochigayeva K, Salachas F, Pradat P-F, Camu W, Meininger V, Dupré N and Rouleau GA. TARDBP mutations in sporadic and familial ALS patients. Nature Genetics 2008 May; 40(5):572-4.

Valdmanis PN*, Meijer IA*, Reynolds A, Lei A, MacLeod P, Schlesinger D, Zatz M, Reid E, Dion PA, Drapeau P, and Rouleau GA. Mutations in the KIAA0196 gene at the SPG8 locus cause Hereditary Spastic Paraplegia. American Journal of Human Genetics 2007 Jan; 80(1): 152-61.

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