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profileKimberly B. Kegel, PH.D.

TitleAssistant Professor of Neurology
InstitutionMassachusetts General Hospital
DepartmentNeurology
AddressMassachusetts General Hospital
Bldg 114 - 2150
114 16th Street
Charlestown MA 02129
Phone617/724-8754
Fax617/726-1264
vCardDownload vCard (login for email)

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Dr. Kegel studies the normal and altered function of huntingtin (htt), the protein mutated in Huntington Disease (HD). Her early work revealed that autophagy and the lysosomal system were activated with htt accumulation in an HD cell system. More recently, she has mapped a cationic membrane association domain in htt and discovered a normal association of htt with specific phosphoinositol phosphates (PIPs). PIPs are lipids present in membranes that can act to target proteins to specific sites within cells. The finding that htt interacts with specific PIPs is directing investigations that will enable us to elucidate htt function at a molecular level. Different PIPs are generated by growth factor molecules such as IGF1, PDFG, and EGF to propagate signals to regulate survival and govern changes in cellular morphology. Specific PIPs are also used to regulate various steps of intracellular membrane trafficking pathways. Experiments addressing the mechanism, regulation and consequences of htt-PIP interactions are currently being pursued. Dr. Kegel also has expertise in drug discovery for HD. She has establish mouse neural stem cell models of HD for translational research. In collaboration with other investigators, small cell-permeable molecules capable of inhibiting htt proteolysis, a process thought to initiate HD pathology, are being identified.


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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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  1. Valencia A, Sapp E, Kimm JS, McClory H, Reeves PB, Alexander J, Ansong KA, Masso N, Frosch MP, Kegel KB, Li X, DiFiglia M. Retracted: Elevated NADPH oxidase activity contributes to oxidative stress and cell death in Huntington's disease. Hum Mol Genet. 2017 Nov 01; 26(21):4314. PMID: 28973680.
    View in: PubMed
  2. Vodicka P, Lim J, Williams DT, Kegel KB, Chase K, Park H, Marchionini D, Wilkinson S, Mead T, Birch H, Yates D, Lyons K, Dominguez C, Beconi M, Yue Z, Aronin N, DiFiglia M. Assessment of chloroquine treatment for modulating autophagy flux in brain of WT and HD mice. J Huntingtons Dis. 2014; 3(2):159-74. PMID: 25062859.
    View in: PubMed
  3. Valencia A, Sapp E, Kimm JS, McClory H, Ansong KA, Yohrling G, Kwak S, Kegel KB, Green KM, Shaffer SA, Aronin N, DiFiglia M. Striatal synaptosomes from Hdh140Q/140Q knock-in mice have altered protein levels, novel sites of methionine oxidation, and excess glutamate release after stimulation. J Huntingtons Dis. 2013; 2(4):459-75. PMID: 24696705; PMCID: PMC3970728.
  4. Valencia A, Sapp E, Kimm JS, McClory H, Reeves PB, Alexander J, Ansong KA, Masso N, Frosch MP, Kegel KB, Li X, DiFiglia M. Elevated NADPH oxidase activity contributes to oxidative stress and cell death in Huntington's disease. Hum Mol Genet. 2013 Mar 15; 22(6):1112-31. PMID: 23223017; PMCID: PMC3578411.
  5. Wu JC, Qi L, Wang Y, Kegel KB, Yoder J, Difiglia M, Qin ZH, Lin F. The regulation of N-terminal Huntingtin (Htt552) accumulation by Beclin1. Acta Pharmacol Sin. 2012 Jun; 33(6):743-51. PMID: 22543707; PMCID: PMC4010368.
  6. Li X, Valencia A, McClory H, Sapp E, Kegel KB, Difiglia M. Deficient Rab11 activity underlies glucose hypometabolism in primary neurons of Huntington's disease mice. Biochem Biophys Res Commun. 2012 May 18; 421(4):727-30. PMID: 22542623.
    View in: PubMed
  7. Ritch JJ, Valencia A, Alexander J, Sapp E, Gatune L, Sangrey GR, Sinha S, Scherber CM, Zeitlin S, Sadri-Vakili G, Irimia D, Difiglia M, Kegel KB. Multiple phenotypes in Huntington disease mouse neural stem cells. Mol Cell Neurosci. 2012 May; 50(1):70-81. PMID: 22508027; PMCID: PMC3383872.
  8. Sapp E, Valencia A, Li X, Aronin N, Kegel KB, Vonsattel JP, Young AB, Wexler N, DiFiglia M. Native mutant huntingtin in human brain: evidence for prevalence of full-length monomer. J Biol Chem. 2012 Apr 13; 287(16):13487-99. PMID: 22375012; PMCID: PMC3339996.
  9. Valencia A, Sapp E, Reeves PB, Alexander J, Masso N, Li X, Kegel KB, DiFiglia M. Reagents that block neuronal death from Huntington's disease also curb oxidative stress. Neuroreport. 2012 Jan 04; 23(1):10-5. PMID: 22045254.
    View in: PubMed
  10. Moscovitch-Lopatin M, Weiss A, Rosas HD, Ritch J, Doros G, Kegel KB, Difiglia M, Kuhn R, Bilbe G, Paganetti P, Hersch S. Optimization of an HTRF Assay for the Detection of Soluble Mutant Huntingtin in Human Buffy Coats: A Potential Biomarker in Blood for Huntington Disease. PLoS Curr. 2010 Dec 29; 2:RRN1205. PMID: 21278900; PMCID: PMC3015780.
  11. Kegel KB, Sapp E, Alexander J, Reeves P, Bleckmann D, Sobin L, Masso N, Valencia A, Jeong H, Krainc D, Palacino J, Curtis D, Kuhn R, Betschart C, Sena-Esteves M, Aronin N, Paganetti P, Difiglia M. Huntingtin cleavage product A forms in neurons and is reduced by gamma-secretase inhibitors. Mol Neurodegener. 2010 Dec 14; 5:58. PMID: 21156064; PMCID: PMC3018386.
  12. Li X, Valencia A, Sapp E, Masso N, Alexander J, Reeves P, Kegel KB, Aronin N, Difiglia M. Aberrant Rab11-dependent trafficking of the neuronal glutamate transporter EAAC1 causes oxidative stress and cell death in Huntington's disease. J Neurosci. 2010 Mar 31; 30(13):4552-61. PMID: 20357106; PMCID: PMC3842456.
  13. Valencia A, Reeves PB, Sapp E, Li X, Alexander J, Kegel KB, Chase K, Aronin N, DiFiglia M. Mutant huntingtin and glycogen synthase kinase 3-beta accumulate in neuronal lipid rafts of a presymptomatic knock-in mouse model of Huntington's disease. J Neurosci Res. 2010 Jan; 88(1):179-90. PMID: 19642201.
    View in: PubMed
  14. Li X, Standley C, Sapp E, Valencia A, Qin ZH, Kegel KB, Yoder J, Comer-Tierney LA, Esteves M, Chase K, Alexander J, Masso N, Sobin L, Bellve K, Tuft R, Lifshitz L, Fogarty K, Aronin N, DiFiglia M. Mutant huntingtin impairs vesicle formation from recycling endosomes by interfering with Rab11 activity. Mol Cell Biol. 2009 Nov; 29(22):6106-16. PMID: 19752198; PMCID: PMC2772576.
  15. Li X, Sapp E, Chase K, Comer-Tierney LA, Masso N, Alexander J, Reeves P, Kegel KB, Valencia A, Esteves M, Aronin N, Difiglia M. Disruption of Rab11 activity in a knock-in mouse model of Huntington's disease. Neurobiol Dis. 2009 Nov; 36(2):374-83. PMID: 19699304; PMCID: PMC2798579.
  16. Weiss A, Abramowski D, Bibel M, Bodner R, Chopra V, DiFiglia M, Fox J, Kegel K, Klein C, Grueninger S, Hersch S, Housman D, Régulier E, Rosas HD, Stefani M, Zeitlin S, Bilbe G, Paganetti P. Single-step detection of mutant huntingtin in animal and human tissues: a bioassay for Huntington's disease. Anal Biochem. 2009 Dec 01; 395(1):8-15. PMID: 19664996.
    View in: PubMed
  17. Kegel KB, Schewkunow V, Sapp E, Masso N, Wanker EE, DiFiglia M, Goldmann WH. Polyglutamine expansion in huntingtin increases its insertion into lipid bilayers. Biochem Biophys Res Commun. 2009 Sep 25; 387(3):472-5. PMID: 19607813.
    View in: PubMed
  18. Kegel KB, Sapp E, Alexander J, Valencia A, Reeves P, Li X, Masso N, Sobin L, Aronin N, DiFiglia M. Polyglutamine expansion in huntingtin alters its interaction with phospholipids. J Neurochem. 2009 Sep; 110(5):1585-97. PMID: 19566678.
    View in: PubMed
  19. Li X, Sapp E, Valencia A, Kegel KB, Qin ZH, Alexander J, Masso N, Reeves P, Ritch JJ, Zeitlin S, Aronin N, Difiglia M. A function of huntingtin in guanine nucleotide exchange on Rab11. Neuroreport. 2008 Oct 29; 19(16):1643-7. PMID: 18845944.
    View in: PubMed
  20. Kim YJ, Sapp E, Cuiffo BG, Sobin L, Yoder J, Kegel KB, Qin ZH, Detloff P, Aronin N, DiFiglia M. Lysosomal proteases are involved in generation of N-terminal huntingtin fragments. Neurobiol Dis. 2006 May; 22(2):346-56. PMID: 16423528.
    View in: PubMed
  21. Kegel KB, Sapp E, Yoder J, Cuiffo B, Sobin L, Kim YJ, Qin ZH, Hayden MR, Aronin N, Scott DL, Isenberg G, Goldmann WH, DiFiglia M. Huntingtin associates with acidic phospholipids at the plasma membrane. J Biol Chem. 2005 Oct 28; 280(43):36464-73. PMID: 16085648.
    View in: PubMed
  22. Qin ZH, Wang Y, Sapp E, Cuiffo B, Wanker E, Hayden MR, Kegel KB, Aronin N, DiFiglia M. Huntingtin bodies sequester vesicle-associated proteins by a polyproline-dependent interaction. J Neurosci. 2004 Jan 07; 24(1):269-81. PMID: 14715959.
    View in: PubMed
  23. Qin ZH, Wang Y, Kegel KB, Kazantsev A, Apostol BL, Thompson LM, Yoder J, Aronin N, DiFiglia M. Autophagy regulates the processing of amino terminal huntingtin fragments. Hum Mol Genet. 2003 Dec 15; 12(24):3231-44. PMID: 14570716.
    View in: PubMed
  24. Kegel KB, Meloni AR, Yi Y, Kim YJ, Doyle E, Cuiffo BG, Sapp E, Wang Y, Qin ZH, Chen JD, Nevins JR, Aronin N, DiFiglia M. Huntingtin is present in the nucleus, interacts with the transcriptional corepressor C-terminal binding protein, and represses transcription. J Biol Chem. 2002 Mar 01; 277(9):7466-76. PMID: 11739372.
    View in: PubMed
  25. Kim YJ, Yi Y, Sapp E, Wang Y, Cuiffo B, Kegel KB, Qin ZH, Aronin N, 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 U S A. 2001 Oct 23; 98(22):12784-9. PMID: 11675509; PMCID: PMC60131.
  26. Sapp E, Kegel KB, Aronin N, Hashikawa T, Uchiyama Y, Tohyama K, Bhide PG, Vonsattel JP, DiFiglia M. Early and progressive accumulation of reactive microglia in the Huntington disease brain. J Neuropathol Exp Neurol. 2001 Feb; 60(2):161-72. PMID: 11273004.
    View in: PubMed
  27. Qin ZH, Wang Y, Kikly KK, Sapp E, Kegel KB, Aronin N, DiFiglia M. Pro-caspase-8 is predominantly localized in mitochondria and released into cytoplasm upon apoptotic stimulation. J Biol Chem. 2001 Mar 16; 276(11):8079-86. PMID: 11102441.
    View in: PubMed
  28. Kegel KB, Kim M, Sapp E, McIntyre C, Castaño JG, Aronin N, DiFiglia M. Huntingtin expression stimulates endosomal-lysosomal activity, endosome tubulation, and autophagy. J Neurosci. 2000 Oct 01; 20(19):7268-78. PMID: 11007884.
    View in: PubMed
  29. Head MW, Hurwitz L, Kegel K, Goldman JE. AlphaB-crystallin regulates intermediate filament organization in situ. Neuroreport. 2000 Feb 07; 11(2):361-5. PMID: 10674487.
    View in: PubMed
  30. Kegel KB, Iwaki A, Iwaki T, Goldman JE. AlphaB-crystallin protects glial cells from hypertonic stress. Am J Physiol. 1996 Mar; 270(3 Pt 1):C903-9. PMID: 8638673.
    View in: PubMed
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