Neil Aronin, M.D.

Academic Role: Professor

Faculty Appointment(s) In:
   Endocrinology
   Medicine
   Physiology

Other Affiliation(s):
   Cell Biology
   Program in Neuroscience

Huntington's Disease

My clinical interests focus on neuroendocrinology (pituitary and hypothalamic diseases), inherited endocrine diseases, and adrenal problems. We are currently conducting research in the treatment of patients with impaired pituitary function. My basic research centers on the pathogensis of neurodegenerative diseases, especially Parkinson's disease and Huntington's disease.

Dr. Aronin's Clinical Site

Representative Publications

Aronin N, Sagar SM, Sharp FK and Schwartz WJ: Light regulates expression of a Fos-related protein in rat suprachiasmatic nuclei. Proc Nat Acad  Sci   87:5959-5962, 1990. 

Takeuchi J, Shannon W, Aronin N, and Schwartz WJ: Compositional changes of AP-1 DNA-binding proteins are regulated by light in a mammalian circadian clock. Neuron 11:825-836, 1993.

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

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.

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

Aronin N, Kim M, Laforet GS and DiFiglia M: Are there multiple pathways to cell death in Huntington's disease? Phil Trans Roy Soc Lond B 354:995-1003, 1999.

Kim M, Lee HS, Laforet G, McIntyre C, Martin EM, Chang P, Kim TW, Williams M, Reddy PH, Tagle D, Boyce FM, Won LA, Heller A, Aronin N and DiFiglia M: Mutant huntingtin expression in clonal striatal cells: dissociation of inclusion formation and neuronal survival by caspase inhibition. J Neurosci 19: 964-973, 1999.

Kegel KB, Kim M, Sapp E, McIntyre C, Castano JG, Aronin N and DiFiglia M: Huntingtin expression stimulates endosomal-lysosomal activity, endosome tubulation, and autophagy. J Neurosci  20:7268-7278, 2000.

Laforet GA, Sapp E, Chase K, McIntyre C, Boyce FM, Campbell M, Cadigan BA, Warzecki L, Tagle DA, Reddy H, Cepeda C, Calvert CR, Jokel ES, Klapstein GJ, Ariano MA, Levine MS, DiFiglia M and Aronin N: Mutant huntingtin dependent cellular changes in the cortex predict behavior and electrophysiological abnormalities.   J Neurosci 21:9112-9123, 2001.

Kim YJ, Yi Y, Sapp E, Wang Y, Cuiffo B, Kegel KB, Qin Z-H, Aronin N and DiFiglia M: Caspase 3-cleaved N-terminal fragments of wild-type and mutant huntingtin are present in normal and Huntington’s disease brains, associate with membranes, and undergo calpain-dependent proteolysis.  Proc Natl Acad Sci USA 98:12784-12789, 2001.

Kegel KB, Meloni AR, Yi Y, Kim YJ, Doyle E, Cuiffo BG, Sapp E, Wang Y, Qin ZH, Chen JD, Nevins JR, Aronin N and DiFiglia M: Huntingtin is present in the nucleus, interacts with the transcriptional corepressor C-terminal binding protein, and represses transcription.  J Biol Chem 277:7466-7476, 2002.

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.

Qin ZH, Wang, Y, Kegel KB, Kazantsev A, Apostol BL, Thompson LM, Yoder J, Aronin N, and DiFiglia M: Autophagy regulates the processing of amino terminal huntingtin fragments.  Human Molec Genet 12:3231-3244, 2003.

Qin ZH, Wang Y, Sapp E, Cuiffo B, Wanker E, Hayden MR, Kegel KB, Aronin N, and DiFiglia M: Huntingtin bodies sequester vesicle-associated proteins by a polyproline-dependent interaction. J Neurosci 24:269-281, 2004.

Kegel KB, Sapp E, Yoder J, Cuiffo B, Sobin L, Kim YJ, Qin Z-H, Hayden MR,          Aronin N, Scott D, Isenberg G, Goldmann WH, and DiFiglia M: Huntingtin associates with acidic phospholipids at the plasma membrane. J Biol Chem 280:36464-46473, 2005.

Dahia PLM, Hao K, Rogus J, Colin C, Pujana MAG, Ross K, Magoffin D, Aronin N, Cascon A, Hayashida CY, Li C, Toledo SPA, Stiles C, for the Familial Pheochromocytoma Consortium: Novel pheochromocytoma susceptibility loci identified by integrative genomics. Cancer Res 65:9651-9658, 2005.

Kim YJ, Sapp E, Cuiffo BG, Sobin L, Yoder J, Kegel KB, Qin Z-H, Detloff P, Aronin N, and DiFiglia M: Lysosomal proteases are involved in generation of N-terminal huntingtin fragments. Neurobiology of Disease 22:346-356, 2006. 

Aronin N: Target selectivity in mRNA silencing. Gene Therapy 13:509-516, 2006.

Potential Rotation Projects

Project #1: Molecular Mechanisms in the Pathogenesis of Neurodegenerative Disease. The student can select projects emphasizing either molecular mechanisms of huntingtin in trafficking in neurons or receptor stimulated effects on gene expression in neurons. Techniques include:

1. Generation of fusion proteins, raising antisera
2. Preparation of organelles
3. Immunocytochemistry, light microscopy and electron microscopy
4. Immunoprecipitation methods
5. PCR
6. Protein separation techniques, gel electrophoresis, immunoblotting
7. Autoradiography

Background

• Undergraduate: Duke University, 1966-1970
  
• Medical School: University of Pennsylvania, 1970-1974
  
• Internship and Residency: Duke University Medical Center, 1974-1977
  
• Research Fellowship: Massachusetts General Hospital and Harvard Medical School, 1979-1981
  

Positions

• University of Massachusetts Medical School, 1981 - present,
  
• Professor of Medicine and Cell Biology,
  
• Director of Endocrinology and Metabolism

Board Certifications

• Internal Medicine, Endocrinology and Metabolism

Office: 225 LRB
Phone: 508-856-3239
E-mail: Neil.Aronin@umassmed.edu
Keywords: Neurobiology, Clinical Research, Cell Cycle

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