Neil Aronin, MD
Professor and Chief
Department of Medicine (Endocrinology and Metabolism)
Co-Director, Neurotherapeutics Institute

phone 508-856-3239
University of Massachusetts Medical School
55 Lake Avenue North
Worcester, MA 01655
Faculty page:

My research focuses on developing gene silencing for therapy in autosomal disease. The current genetic disease is Huntington’s disease, an autosomal dominant neurodegenerative disease. The laboratory uses allele selective RNAi to silence the mutant huntingtin and preserve wild type huntingtin, thereby exploring potential therapies and neuronal pathophysiology attributable to the mutant huntingtin. We also study viral delivery of allele selective shRNAmir, with single stranded and self-complementary adeno-associated virus. Thus, my laboratory studies next-generation therapeutics that will be applicable to a spectrum of autosomal dominant diseases. Furthermore, we study mechanisms of pathogenesis in Huntington’s disease: mutant huntingtin mRNA kinetics, vesicle recycling and roles of proteins that interact with mutant huntingtin.

List of key papers (from 1995 to present)

3. DiFiglia M, Sapp E, Chase K, Schwarz C, Meloni A, Young C, Martin E, Vonsattel, J-P, Carraway R, Reeves SA, Boyce FM and Aronin N: Huntingtin is a cytoplasmic protein associated with vesicles in human and rat brain neurons. Neuron 14:1075-1081, 1995. PMCID: PMC7748555

4. Aronin N, Chase K, Young C, Sapp E, Schwarcz C, Matta N, Kornreich R, Sheth A, Landwehrmeyer B, Bird E, Vonsattel J-P, Smith T, Carraway R, Boyce FM, Beal MF, Young AB, Penney JB, and DiFiglia M: CAG expansion affects the expression of mutant huntingtin in the Huntington’s disease brain. Neuron 15:1193-1201, 1995.

5. DiFiglia M, Sapp E, Chase KO, Davies SW, Bates GP, VonSattel JP and Aronin N: Aggregation of huntingtin in neuronal intranuclear inclusions and dystrophic neurites in brain. Science 277:1990-1993, 1997. PMCID: PMC9302293

6. Schwarz DS, Hutvagner G, Du T, Xu Z, Aronin N, and Zamore PD: Unexpected asymmetry in the assembly of the RNAi enzyme complex. Cell 115: 199-208, 2003. PMCID: PMC14567917

7. Schwarz DS, Ding H, Kennington L, Moore JT, Schelter J, Burchard J, Linsley PS, Aronin N, Xu Z, and Zamore PD. Designing siRNA that distinguish between genes that differ by a single nucleotide. PLOS-Genetics 2006, Sept. 8; 2:e140. PMCID: PMC16965178

8. DiFiglia M, Esteves MA, Chase K, Sapp E, Pfister E, Sass M, Yoder J, Reeves P, Pandey RK, Rajeev KG, Manoharan M, Sah DWY, Zamore PD, and Aronin N. Therapeutic silencing of mutant huntingtin with siRNA attenuates striatal and cortical neuropathology and behavioral deficits, Proc Natl Acad Sci USA 104:17204-17209, 2007. PMCID: PMC17940007

9. Liu W, Kennington L, Rosas HD, Hersch S, Cha J-H, Zamore PD, and Aronin N. Linking SNP identity to CAG repeat length in Huntington's Disease patients. Nature Methods 5: 951-953, 2008.

10. Pfister EL, Kennington L, Straubhaar J, Wagh S, Liu W, DiFiglia M, Landwehrmeyer B, Vonsattel J-P, Zamore PD, and Aronin N. Five siRNAs targeting three SNPs in Huntingtin may provide therapy for three-quarters of Huntington's disease patients. Current Biology 19: 774-778, 2009.

11. Li X, Sapp E, Chase K, Cmoer-Tierney LA, Masso N, Alexander J, Reeves P, Qin Z-H, Kegel KB, Valencia A, Esteves M, Aronin N, and DiFiglia M. Disruption of Rab11 activity in a knock-in mouse model of Huntington’s disease. Neurobiology of Disease 36:374-383, 2009.

12. Li X, Standley C, Sapp E, Valencia A, Qin Z-H, Kegel KB, Yoder J, Comer-Tierney LA, Esteves M, Chase K, Masso N, Sobin L, Bellve K, Tuft R, Lifshitz L, Fogarty K, Aronin N, and DiFiglia M. Mutant Huntington impairs vesicle formation from recycling endosomes by interfering with Rab11 activity. Molecular Cell Biology 29:6106-6116, 2009.

13. Qin YJ, Yao L, King EE, Buddavarapu K, Lenci RE, Chocron ES, Lechleiter JD, Sass M, Aronin N, Schiavi F, Boaretto F, Opocher G, Toledo RA, Toledo SPA, Stiles C, Aguiar RCT, Dahia PLM. Germline mutations in TMEM127 confer susceptibility to pheochromocytoma. Nature Genetics 42:229-234, 2010.

14. Li X, Valencia A, Sapp E, Masso N, Alexander J, Reeves P, Kegel KB, Aronin N, and DiFiglia M. Aberrant Rab11-dependent trafficking of the neuronal glutamate transporter EAAC1 causes oxidative stress and cell death in Huntington's disease. J Neurosci 30:4552-4561, 2010.

15. Sah DWH & Aronin N. Oligonucleotide therapeutic approaches for Huntington’s disease. J Clin Invest, in press (February, 2011)


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