Henry Paulson, M.D., Ph.D.

Lucile Groff Professor of Neurology, Department of Neurology
Director, Michigan Alzheimer’s Disease Center

4001 BSRB
109 Zina Pitcher Place
Ann Arbor, MI 48109-5720


Areas of Interest

The Paulson lab explores the reasons why the aging brain degenerates in neurodegenerative diseases and seeks routes to therapy for these fatal disorders. They primarily study the polyglutamine expansion diseases (including spinocerebellar ataxia type 3 and Huntington disease), frontotemporal dementia and Alzheimer’s disease. Researchers incorporate diverse methods in their basic and translational studies, spanning from recombinant protein analysis to cell-based assays and engineered mouse models, with corroborating evidence from human disease tissue.  A common theme in neurodegeneration is the tendency for specific proteins to accumulate abnormally.  The Paulson research group investigates why these proteins are toxic to neurons and explore how the neuron's protein quality control machinery counteracts this toxicity. A major current focus is exploring the relationship of ubiquitin-linked pathways to neurodegenerative disease, with a secondary goal of identifying therapeutic targets for specific diseases.

Honors & Awards

In 2020, Paulson was elected to the National Academy of Medicine for his work in making fundamental discoveries regarding protein aggregation and nucleotide repeat expansions as causes of neurodegenerative diseases, and pioneering novel therapeutic strategies for this group of devastating disorders. Election to the Academy is considered one of the highest honors in the fields of health and medicine and recognizes individuals who have demonstrated outstanding professional achievement and commitment to service. 

In 2020, Paulson was honored with a National Institute of Neurological Disorders and Stroke (NINDS) Landis Outstanding Mentor Award. This annual award is named in honor of former NINDS Director Dr. Story Landis.

In 2020, Paulson received the Movement Disorders Award from the American Academy of Neurology for discoveries in the causes and treatment of nucleotide repeat expansion diseases.

Published Articles or Reviews

Ubiquilin-2 differentially regulates polyglutamine disease proteins.
Gerson JE, Safren N, Fischer S, Patel R, Crowley EV, Welday JP, Windle AK, Barmada S, Paulson HL, Sharkey LM. Hum Mol Genet. 2020 Aug 29; 29(15):2596-2610. DOI: 10.1093/hmg/ddaa152. PMID: 32681165

Modeling UBQLN2-mediated neurodegenerative disease in mice: Shared and divergent properties of wild type and mutant UBQLN2 in phase separation, subcellular localization, altered proteostasis pathways, and selective cytotoxicity
Sharkey LM, Sandoval-Pistorius SS, Moore SJ, Gerson JE, Komlo R, Fischer S, Negron-Rios KY, Crowley EV, Padron F, Patel R, Murphy GG, Paulson HLNeurobiol Dis. 2020 Sep;143:105016. DOI: 10.1016/j.nbd.2020.105016. Epub 2020 Jul 10. PMID: 32653673

Oligonucleotide therapy mitigates disease in spinocerebellar ataxia type 3 mice.
McLoughlin HS, Moore LR, Chopra R, Komlo R, McKenzie M, Blumenstein KG, Zhao H, Kordasiewicz HB, Shakkottai VG, Paulson HLAnn Neurol. 2018 Jul;84(1):64-77. DOI: 10.1002/ana.25264. Epub 2018 Aug 6. PMID: 29908063 Free PMC article.

Mutant UBQLN2 promotes toxicity by modulating intrinsic self-assembly.
Sharkey LM, Safren N, Pithadia AS, Gerson JE, Dulchavsky M, Fischer S, Patel R, Lantis G, Ashraf N, Kim JH, Meliki A, Minakawa EN, Barmada SJ, Ivanova MI, Paulson HLProc Natl Acad Sci U S A. 2018 Oct 30;115(44):E10495-E10504. DOI: 10.1073/pnas.1810522115. Epub 2018 Oct 17. PMID: 30333186 Free PMC article.

Paulson H. Repeat expansion diseases. Handb Clin Neurol. 2018;147:105-123. DOI: 10.1016/B978-0-444-63233-3.00009-9. PMID: 29325606; PMCID: PMC6485936.

Paulson HL, Shakkottai VG, Clark HB, Orr HT. Polyglutamine spinocerebellar ataxias - from genes to potential treatments. Nat Rev Neurosci. 2017 Oct;18(10):613-626. DOI: 10.1038/nrn.2017.92. Epub 2017 Aug 17. PMID: 28855740; PMCID: PMC6420820.

For a complete list, visit: https://paulson.lab.medicine.umich.edu/publications/publications-list

Web Sites