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Beverly L. Davidson, Ph.D.

Beverly L. Davidson, Ph.D.

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Professor of Pathology and Laboratory Medicine
Department: Pathology and Laboratory Medicine
Graduate Group Affiliations

Contact information
The Children's Hospital of Philadelphia
3501 Civic Center Boulevard, 5060 CTRB
Philadelphia, PA 19104
Office: 267-426-0929
Fax: 215-590-3660
Education:
B.S. (Biology Major/Chemistry Minor; High Distinction)
Nebraska Wesleyan University, 1981.
Ph.D. (Biological Chemistry)
University of Michigan, 1987.
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Description of Research Expertise

Keywords:
Neurodegenerative Disease
RNA biology
Gene therapy
Animal models
Human treatment

Research in the Davidson Laboratory is focused on inherited genetic diseases that cause central nervous system dysfunction, with a focus on:

i) recessive, childhood onset neurodegenerative disease, such as the lysosomal storage diseases mucopolysaccharidoses and Battens disease;
ii) dominant genetic diseases, specifically the CAG repeat disorders, Huntington’s disease and spinal cerebellar ataxia;
iii) understanding how changes in the transcriptome impact neural development and neurodegenerative disease processes.

Our research on childhood onset neurodegenerative diseases is focused on experiments to better understand the biochemistry and cell biology of proteins deficient in these disorders, and to develop small molecule or gene therapy based strategies for therapy. In recent work, we demonstrated that the application of recombinant viral vectors to various models of storage disease reversed CNS deficits and improved life span. We continue to develop novel vector systems to improve therapeutic outcomes.

Therapies for dominant disorders are an exciting challenge and require that the dominant disease allele be silenced. To approach this, we developed reagents for expressing inhibitory RNAs or editing machinery (e.g., CrispR/Cas9 approaches) in vivo to improve disease phenotypes in relevant animal models.

Finally, we investigate how the transcriptome is altered in neurological diseases. Evaluation of splicing changes has led us to discover novel players in disease pathogenesis that include noncoding RNAs and RNA binding proteins. This work is revealing new pathways of pathogenesis and novel targets for therapy.

Selected Publications

Dissen GA, Adachi K, Lomniczi A, Chatkupt T, Davidson BL, Nakai H, Ojeda SR: Engineering as a gene silencing viral construct that targets the cat hypothalamus to induce permanent sterility: An update. Reprod Dom Anim 52(Suppl 2): 354-358, April 2017 Notes: doi: 10.111/rda. 12834 [Epub ahead of print]

Carmona V, Cunha-Santos J, Onofre I, Simoes A, Vijayakumar U, Davidson BL, Pereira de Almeida L.: Unravelling endogenous MicroRNAs system dysfunction as a new pathophysiological mechanism in Machado-Joseph disease. Mol Ther 25(4): 1038-1055, Feb 2017.

Kim Y-C, Miller A, Lins LCRF, Han W-W, Keiser MS, Davidson BL, Nandakumar S.: RNA interference of human alpha-synuclein in mouse. Front Neurol 8, Jan 2017 Notes: 10.3389/fneur2017.00013. Volume 8, Article 13.

Monteys, AM, Ebanks SA, Keiser MS, Davidson BL: CRISPR/Cas9 editing of the mutant Huntingtin allele in vitro and in vivo. Mol Ther 25(1): 12-23, Jan 2017.

Machuca TN, Cypel M, Bonato R, Yeung J, Chun Y-M, Juvet S, Guan Z, Hwang DM, Chen M, Saito T, Harmantas C, Davidson BL, Waddell TK, Liu M, Keshavjee S. : Safety and efficacy of ex-vivo donor lung adenoviral IL-10 gene therapy in a large animal lung transplant survival model. Hum Gen Ther 28(9): 757-765, January 2017.

Keiser MS, Mas Monteys A, Corbau R, Gonzalez-Alegre P, Davidson BL.: RNAi prevents and reverses phenotypes induced by mutant human ataxin-1. Annals of Neurology 80(5): 754-765, Nov 2016 Notes: NIHMS820622; DOI: 10.1002/ana.24789.

Ramachandran S, Coffin SL, Tang T-Y, Jobaliya CD, Spengler RM, Davidson BL: cis-Acting sing nucleotide polymorphisms alter Micro RNA-mediated regulation of human brain expressed transcripts. Hum Mol Genet 25(22): 4939-4950, Sept 2016 Notes: Free text link: http://hmg.oxfordjournals.org/content/early/2016/10/18/hmg.ddw317.long

Spenger RM, Zhang X, Cheng C, McLendon JM, Skeie JM, Johnson FL, Davidson BL, Boudreau RL: Elucidation of transcriptome-side micro RNA binding sites in human cardiac tissues by Ago2 HITS-CLIP. Nucleic Acids Research 44(15): 7120-7131, Sept 2016 Notes: Advance Access published July 14, 2016 (Nucl. Acids Res.-2016-Spengler-nar_gkw640.pdf).

Lin L, Park JW, Ramachandran S, Zhang Y, Tseng YT, Shen S, Waldvogel H Curtis M, Faull R, Troncoso J, Ross C, Davidson BL*, Xing Y* (joint corresponding authors): Transcriptome sequencing reveals aberrant alternative splicing in Huntington's disease. Hum Mol Genet 15(25): 3545-3466, Aug 2016 Notes: pil: ddw187. [Epub ahead of print]. Free full advance access: http://hmg.oxfordjournals.org/content/early/2016/07/03/hmg.ddw187.long.

Thompson LM, Ochaba J, Mas Monteys A, O'Rourke JG, Reidling JC, Steffan JS, Davidson BL: PIAS1 regulates mutant Huntingtin accumulation and Huntington's disease-associated phenoytypes in vivo. Neuron 90(3): 507-520, May 2016.

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Last updated: 09/14/2017
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