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John William Hanna, M.D., Ph.D.



Available: 11/18/19, Expires: 11/18/22

Misfolded proteins are toxic to all cells are major contributors to many human diseases, including most neurodegenerative diseases and some cancers. Cells have developed complex stress responses to identify and eliminate misfolded proteins. The Hanna lab studies these stress responses, with an emphasis on their basic mechanisms. PI is a practicing physician scientist and former HMS MD-PhD trainee.

The student will have their own project and be mentored directly by Dr. Hanna. The time commitment is flexible and will be agreed upon in advance of starting the project.

Available: 06/16/22, Expires: 06/30/26

My lab studies how cells destroy proteins, a process which is critical for many human diseases, including most neurodegenerative diseases and some cancers. We focus on the basic mechanisms of the ubiquitin-proteasome system, and use a variety of biochemical, structural, genetic, and cell biologic methods. One part of the lab is focused on the detailed mechanisms of the proteasome, and we use cutting edge cryo-electron microscopy methods to gain insight. The other part of the lab is focused on the cellular stress responses that identify and eliminate misfolded proteins. Here we use powerful proteomics and lipidomics methods to inform our work. This would be an opportunity to learn or further develop basic scientific skills while being mentored by an HMS-trained practicing physician-scientist.

Available: 01/10/22, Expires: 03/01/24

The accumulation of misfolded proteins contributes to many diseases, including most neurodegenerative diseases. The proteasome is the complex multisubunit machine in cells that destroys proteins. We are studying the basic mechanisms of the proteasome using a combination of structural biology (cryo-EM), biochemistry, genetics, and cell biology. This is an opportunity to contribute to the fundamental mechanisms of an important group of diseases, and to be mentored by an HMS MD-PhD alum who is also a practicing physician.

The research activities and funding listed below are automatically derived from NIH ExPORTER and other sources, which might result in incorrect or missing items. Faculty can login to make corrections and additions.
  1. R01GM135337 (HANNA, JOHN W) Aug 1, 2020 - Jul 31, 2024
    Role of very long chain fatty acids in protein quality control and membrane homeostasis
    Role: Principal Investigator
  2. DP5OD019800 (HANNA, JOHN W) Sep 13, 2014 - Aug 31, 2020
    New Ubiquitin-Proteasome System Components that Protect against Proteotoxicity
    Role: Principal Investigator

Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
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PMC Citations indicate the number of times the publication was cited by articles in PubMed Central, and the Altmetric score represents citations in news articles and social media. (Note that publications are often cited in additional ways that are not shown here.) Fields are based on how the National Library of Medicine (NLM) classifies the publication's journal and might not represent the specific topic of the publication. Translation tags are based on the publication type and the MeSH terms NLM assigns to the publication. Some publications (especially newer ones and publications not in PubMed) might not yet be assigned Field or Translation tags.) Click a Field or Translation tag to filter the publications.
  1. Caballero JRI, Lalande BM, Hanna JW, Klopfenstein NB, Kim MS, Stewart JE. Genomic Comparisons of Two Armillaria Species with Different Ecological Behaviors and Their Associated Soil Microbial Communities. Microb Ecol. 2022 Mar 21. PMID: 35312808.
    Citations:    Fields:    
  2. Hanna JW, Klopfenstein NB, Cram MM, Olatinwo RO, Fraedrich SW, Kim MS. First Report of Armillaria Root Disease Pathogen, Armillaria gallica, on Rhododendron and Quercus rubra in Georgia, USA. Plant Dis. 2020 Nov 11. PMID: 33174801.
    Citations:    Fields:    
  3. Duarte-Mata E, Elias R, Hanna JW, Klopfenstein NB, Kim MS. First Report of the Armillaria Root-Disease Pathogen, Armillaria gallica, Associated with Several Woody Hosts in Three States of Central Mexico (Guanajuato, Jalisco, and Michoacan). Plant Dis. 2020 Jul 28. PMID: 32720881.
    Citations: 1     Fields:    
  4. Hanna J, Guerra-Moreno A, Ang J, Micoogullari Y. Protein Degradation and the Pathologic Basis of Disease. Am J Pathol. 2019 01; 189(1):94-103. PMID: 30312581; PMCID: PMC6315326.
    Citations: 23     Fields:    Translation:HumansCells
  5. Elías-Román RD, Medel-Ortiz R, Alvarado-Rosales D, Hanna JW, Ross-Davis AL, Kim MS, Klopfenstein NB. Armillaria mexicana, a newly described species from Mexico. Mycologia. 2018 Mar-Apr; 110(2):347-360. PMID: 29608410.
    Citations: 1     Fields:    Translation:Animals
  6. Klopfenstein NB, Stewart JE, Ota Y, Hanna JW, Richardson BA, Ross-Davis AL, Elías-Román RD, Korhonen K, Keca N, Iturritxa E, Alvarado-Rosales D, Solheim H, Brazee NJ, Lakomy P, Cleary MR, Hasegawa E, Kikuchi T, Garza-Ocañas F, Tsopelas P, Rigling D, Prospero S, Tsykun T, Bérubé JA, Stefani FO, Jafarpour S, Antonín V, Tomšovský M, McDonald GI, Woodward S, Kim MS. Insights into the phylogeny of Northern Hemisphere Armillaria: Neighbor-net and Bayesian analyses of translation elongation factor 1-a gene sequences. Mycologia. 2017; 109(1):75-91. PMID: 28402796.
    Citations: 6     Fields:    Translation:Animals
  7. Sun ZJ, Bhanu MK, Allan MG, Arthanari H, Wagner G, Hanna J. Solution Structure of the Cuz1 AN1 Zinc Finger Domain: An Exposed LDFLP Motif Defines a Subfamily of AN1 Proteins. PLoS One. 2016; 11(9):e0163660. PMID: 27662200.
    Citations: 1     Fields:    
  8. Laga AC, Shroba SM, Hanna J. Atypical hand, foot and mouth disease in adults associated with coxsackievirus A6: a clinico-pathologic study. J Cutan Pathol. 2016 Nov; 43(11):940-945. PMID: 27445155.
    Citations: 10     Fields:    Translation:HumansCells
  9. Guerra-Moreno A, Hanna J. Tmc1 Is a Dynamically Regulated Effector of the Rpn4 Proteotoxic Stress Response. J Biol Chem. 2016 Jul 08; 291(28):14788-95. PMID: 27226598.
    Citations: 7     Fields:    Translation:AnimalsCells
  10. Guerra-Moreno A, Isasa M, Bhanu MK, Waterman DP, Eapen VV, Gygi SP, Hanna J. Proteomic Analysis Identifies Ribosome Reduction as an Effective Proteotoxic Stress Response. J Biol Chem. 2015 Dec 11; 290(50):29695-706. PMID: 26491016.
    Citations: 25     Fields:    Translation:AnimalsCells
  11. Klopfenstein NB, Hanna JW, Cannon PG, Medel-Ortiz R, Alvarado-Rosales D, Lorea-Hernández F, Elías-Román RD, Kim MS. First Report of the Armillaria Root-Disease Pathogen, Armillaria gallica, Associated with Several Woody Hosts in Three States of Mexico. Plant Dis. 2014 Sep; 98(9):1280. PMID: 30699636.
    Citations: 1     Fields:    
  12. Hanna J, Waterman D, Isasa M, Elsasser S, Shi Y, Gygi S, Finley D. Cuz1/Ynl155w, a zinc-dependent ubiquitin-binding protein, protects cells from metalloid-induced proteotoxicity. J Biol Chem. 2014 Jan 17; 289(3):1876-85. PMID: 24297164.
    Citations: 9     Fields:    Translation:AnimalsCells
  13. Nelson EV, Fairweather ML, Ashiglar SM, Hanna JW, Klopfenstein NB. First Report of the Armillaria Root Disease Pathogen, Armillaria gallica, on Douglas-fir (Pseudotsuga menziesii) in Arizona. Plant Dis. 2013 Dec; 97(12):1658. PMID: 30716834.
    Citations: 1     Fields:    
  14. Hanna J, Reimann JD, Haddad RI, Krane JF. Human papillomavirus-associated adenocarcinoma of the base of the tongue. Hum Pathol. 2013 Aug; 44(8):1516-23. PMID: 23465278.
    Citations: 6     Fields:    Translation:Humans
  15. Hanna J, Waterman D, Boselli M, Finley D. Spg5 protein regulates the proteasome in quiescence. J Biol Chem. 2012 Oct 05; 287(41):34400-9. PMID: 22904326.
    Citations: 9     Fields:    Translation:Animals
  16. Ropper AE, Cahill KS, Hanna JW, McCarthy EF, Gokaslan ZL, Chi JH. Primary vertebral tumors: a review of epidemiologic, histological and imaging findings, part II: locally aggressive and malignant tumors. Neurosurgery. 2012 Jan; 70(1):211-9; discussion 219. PMID: 21768918.
    Citations: 16     Fields:    Translation:Humans
  17. Ropper AE, Cahill KS, Hanna JW, McCarthy EF, Gokaslan ZL, Chi JH. Primary vertebral tumors: a review of epidemiologic, histological, and imaging findings, Part I: benign tumors. Neurosurgery. 2011 Dec; 69(6):1171-80. PMID: 21725252.
    Citations: 26     Fields:    Translation:Humans
  18. Kim MS, Hanna JW, Klopfenstein NB. First Report of an Armillaria Root Disease Pathogen, Armillaria gallica, Associated with Several New Hosts in Hawaii. Plant Dis. 2010 Dec; 94(12):1503. PMID: 30743375.
    Citations: 1     Fields:    
  19. Lee BH, Lee MJ, Park S, Oh DC, Elsasser S, Chen PC, Gartner C, Dimova N, Hanna J, Gygi SP, Wilson SM, King RW, Finley D. Enhancement of proteasome activity by a small-molecule inhibitor of USP14. Nature. 2010 Sep 09; 467(7312):179-84. PMID: 20829789.
    Citations: 458     Fields:    Translation:HumansAnimalsCells
  20. Lee MJ, Lee BH, Hanna J, King RW, Finley D. Trimming of ubiquitin chains by proteasome-associated deubiquitinating enzymes. Mol Cell Proteomics. 2011 May; 10(5):R110.003871. PMID: 20823120.
    Citations: 130     Fields:    Translation:HumansAnimals
  21. Kim MS, Klopfenstein NB, Hanna JW, Cannon P, Medel R, López A. First Report of Armillaria Root Disease Caused by Armillaria tabescens on Araucaria araucana in Veracruz, Mexico. Plant Dis. 2010 Jun; 94(6):784. PMID: 30754323.
    Citations:    Fields:    
  22. Klopfenstein NB, Lundquist JE, Hanna JW, Kim MS, McDonald GI. First Report of Armillaria sinapina, a Cause of Armillaria Root Disease, Associated with a Variety of Forest Tree Hosts on Sites with Diverse Climates in Alaska. Plant Dis. 2009 Jan; 93(1):111. PMID: 30764271.
    Citations: 1     Fields:    
  23. Hanna J, Meides A, Zhang DP, Finley D. A ubiquitin stress response induces altered proteasome composition. Cell. 2007 May 18; 129(4):747-59. PMID: 17512408.
    Citations: 102     Fields:    Translation:AnimalsCells
  24. Hanna JW, Klopfenstein NB, Kim MS. First Report of the Root-Rot Pathogen, Armillaria nabsnona, from Hawaii. Plant Dis. 2007 May; 91(5):634. PMID: 30780721.
    Citations:    Fields:    
  25. Hanna J, Finley D. A proteasome for all occasions. FEBS Lett. 2007 Jun 19; 581(15):2854-61. PMID: 17418826; PMCID: PMC1965587.
    Citations: 71     Fields:    Translation:HumansAnimals
  26. Crosas B, Hanna J, Kirkpatrick DS, Zhang DP, Tone Y, Hathaway NA, Buecker C, Leggett DS, Schmidt M, King RW, Gygi SP, Finley D. Ubiquitin chains are remodeled at the proteasome by opposing ubiquitin ligase and deubiquitinating activities. Cell. 2006 Dec 29; 127(7):1401-13. PMID: 17190603.
    Citations: 159     Fields:    Translation:Animals
  27. Hanna J, Hathaway NA, Tone Y, Crosas B, Elsasser S, Kirkpatrick DS, Leggett DS, Gygi SP, King RW, Finley D. Deubiquitinating enzyme Ubp6 functions noncatalytically to delay proteasomal degradation. Cell. 2006 Oct 06; 127(1):99-111. PMID: 17018280.
    Citations: 186     Fields:    Translation:HumansAnimals
  28. Kirkpatrick DS, Hathaway NA, Hanna J, Elsasser S, Rush J, Finley D, King RW, Gygi SP. Quantitative analysis of in vitro ubiquitinated cyclin B1 reveals complex chain topology. Nat Cell Biol. 2006 Jul; 8(7):700-10. PMID: 16799550.
    Citations: 208     Fields:    Translation:AnimalsCells
  29. Schmidt M, Hanna J, Elsasser S, Finley D. Proteasome-associated proteins: regulation of a proteolytic machine. Biol Chem. 2005 Aug; 386(8):725-37. PMID: 16201867.
    Citations: 74     Fields:    Translation:Cells
  30. Elsasser S, Chandler-Militello D, Müller B, Hanna J, Finley D. Rad23 and Rpn10 serve as alternative ubiquitin receptors for the proteasome. J Biol Chem. 2004 Jun 25; 279(26):26817-22. PMID: 15117949.
    Citations: 148     Fields:    Translation:AnimalsCells
  31. Hanna J, Leggett DS, Finley D. Ubiquitin depletion as a key mediator of toxicity by translational inhibitors. Mol Cell Biol. 2003 Dec; 23(24):9251-61. PMID: 14645527.
    Citations: 110     Fields:    Translation:AnimalsCells
  32. Leggett DS, Hanna J, Borodovsky A, Crosas B, Schmidt M, Baker RT, Walz T, Ploegh H, Finley D. Multiple associated proteins regulate proteasome structure and function. Mol Cell. 2002 Sep; 10(3):495-507. PMID: 12408819.
    Citations: 277     Fields:    Translation:AnimalsCells
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Funded by the NIH National Center for Advancing Translational Sciences through its Clinical and Translational Science Awards Program, grant number UL1TR002541.