Beverly Davidson, Ph.D. (Full Member)
Roy J Carver Biomedical Reearch Chair, Internal M, University of Iowa
Associate Director, Center for Gene Therapy, University of Iowa
Director, Gene Transfer Vector Core, University of Iowa
Professor, Internal Medicine, Neurology, Physiolog, University of Iowa
Vice Chair for Research, Internal Medicine, University of Iowa

http://www.healthcare.uiowa.edu/labs/davidson/

Research Interest    

Cystic Fibrosis | Other Gentic Diseases

Cystic Fibrosis
Dr. Davidson's research objective includes the development of improved vector systems for preclinical testing in animal models of cystic fibrosis (CF) and other genetic diseases. With regards to her CF-related research, Dr. Davidson collaborates with Dr. Paul McCray to obtain and test novel glycoproteins for their ability to pseudotype lentiviruses. These lentiviruses are then tested for their abilities to transduce the respiratory epithelium from the apical surface. Some of these novel envelopes also have interesting properties when tested for brain or liver transduction. More recent work in the Davidson laboratory has been in the field of RNA interference. Dr. Davidson is now collaborating with Drs. McCray, Engelhardt, and Welsh to test if inhibitory RNAs, designed to silence pro-inflammatory cytokines, can protect or prevent the CF phenotype in the new porcine and ferret models of CF.

Selected Publications:

Quinn K, Brindley MA, Weller ML, Kaludov N, Kondratowicz A, Hunt CL, Sinn PL, McCray PB Jr, Stein CS, Davidson BL, Flick R, Mandell R, Stapleton W, Maury W, Chiorini JA. Rho GTPases Modulate Entry of Ebola and Vesicular Stomatitis Pseudotyped Vectors. J Virol, In Press.

Kang Y, Moressi CJ, Scheetz TE, Xie L, Tran DT, Casavant TL, Ak P, Benham CJ, Davidson BL, McCray PB Jr. Integration site choice of a feline immunodeficiency virus vector. J Virol 80(17):8820-3, 2006.

Kang Y, Xie L, Tran DT, Stein CS, Hickey M, Davidson BL, McCray PB Jr. Persistent expression of factor VIII in vivo following nonprimate lentiviral gene transfer. Blood 106(5):1552-8, 2005.

Other Genetic Diseases
Research in the Davidson laboratory is focused on inherited genetic diseases that cause central nervous system dysfunction, with a focus on (1) recessive, childhood onset neurodegenerative disease, in particular the lysosomal storage diseases such as the mucopolysaccharidoses and Battens disease; and (2) dominant genetic diseases for example the CAG repeat disorders, Huntington?s disease and spinal cerebellar ataxia type I, and (3), understanding how noncoding RNAs participate in neural development and neurodegenerative diseases 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 gene small molecule based medicines for therapy. In recent work we demonstrated that the application of recombinant viral vectors to animal models of storage disease reversed CNS deficits.

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 RNA in vivo. This approach improved disease phenotypes in relevant models of dominantly inherited human neurodegenerative diseases.

Finally, we investigate how naturally occurring noncoding RNAs, miRNAs, participate in cell fate decisions in normal development, and how their expression is altered in disease states. We find that miRNAs with altered expression in Huntington?s disease or spinocerebellar ataxia brains target proteins that themselves contribute to disease phenotypes. This work may reveal new targets for drug therapy

Selected Publications.

Borchert GM, Lanier W, Davidson BL. RNA polymerase III transcribes human microRNAs. Nat. Struct. Mol Biol. 13(12): 1097-1101, 2006.

Boudreau RL, Mas Moneys A, Davidson BL. Minimizing variables among hairpin-based RNA vectors reveals the potency of shRNAs. RNA 14: 1-11, 2008.

McBride JL, Boudreau RL, Harper SQ, Staber PD, Mas Monteys A, Martins I, Gilmore BL, Burstein H, Peluso RW, Polisky B, Carter BJ, Davidson BL. Artificial miRNAs mitigate shRNA-mediated toxicity in the brain: Implications for the therapeutic development of RNAi. PNAS 15(15): 5868-73, 2008.

Chen YH, Chang M, Davidson BL. Unique molecular signatures of disease brain endothelia provide a novel site for CNS-directed enzyme therapy. Nature, In Press.

Publications from Gene Therapy Center

Publications from PubMed