Research Investigator Profile

  • Assistant Professor of Neurology,
    Harvard Medical School
  • Assistant in Neurology,
    Massachusetts General Hospital





Research Description

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 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 will direct 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 regulating survival and 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. An important goal of her work is to establish a mouse embryonic stem cell model 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.

Research interests Huntingtin, membranes, lipids, embryonic stem cells, drug discovery, protease
Research techniques Embryonic stem cells, liposomes, phosphoinositide phosphate
Diseases studied Neurodegenerative diseases: Huntington’s disease
Selected publications
  1. Kegel KB, Sapp E, Yoder J, Cuiffo B, Sobin L, Kim YJ, Qin ZH, Hayden MR, Aronin N, Scott D, Isenberg G, Goldmann WH, DiFiglia. Huntingtin associates with acidic phospholipids at the plasma membrane. J Biol Chem 2005;280:36464-36473.
  2. Kegel, KB, Kim M, Sapp E, McIntire C, Aronin N, DiFiglia M.  Huntingtin expression stimulates endosomal/lysosomal activity, endosomal tubulation, and autophagy.   J Neurosci 2000; 20: 7268-7278.
  3. Kegel, KB, Meloni A, 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;277:7466-7476.
  4. 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’s Disease brain.  J Neuropathol Exper Neurol 2001; 60: 161-172.
  5. Kim, Yun J.,  Sapp E, Cuiffo B, Sobin L, Yoder J, Kegel KB, Qin Z-H, Detloff P, Aronin N, DiFiglia M. Lysosomal proteases are involved in generation of N-terminal huntingtin fragments. Neurobiol Dis 2006;22;346-356.
NCBI PubMed link NCBI PubMed Publications
E-mail address
Lab mailing address MassGeneral Institute for Neurodegenerative Disease
CNY B114, 2-2150
114 16th Street
Charlestown, MA 02129

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