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Lab Phone: 617-726-8463
Neurology Access Center: 1-855-644-6387
Research Investigator Profile
Dimitri Krainc, MD, PhD
Gene Transcription and Disease
Dimitri Krainc, MD PhD is using molecular and genomic approaches to identify mechanisms that lead to neurodegeneration. In particular, his research interest involves deciphering the molecular pathways of transcriptional deregulation and mutant protein accumulation in Huntington's disease (HD) and related neurodegenerative disorders. In order to identify biologically relevant targets of this transcriptional dysfunction in HD, Dr. Krainc's group showed that huntingtin inhibits gene expression of PGC-1alpha, a transcriptional coactivator that regulates several metabolic processes including mitochondrial biogenesis and respiration. These studies demonstrated that deregulation of transcription by mutant huntingtin leads to defects in energy metabolism and dysfunction of neurons that are most vulnerable to metabolic stress in HD. In an effort to help develop new therapies, Dr. Krainc's group conducts studies to correct these transcriptional and metabolic abnormalities in HD and related neurodegenerative disorders.
Clearance of Disease Proteins
A recurrent observation of accumulation and aggregation of mutant proteins in different neurodegenerative disorders indicates the possibility of a shared clearance mechanism. Dr. Krainc's group identified a novel mechanism of autophagic-lysosomal degradation that promotes selective clearance of the mutant huntingtin protein. Finding the modifiers of these pathways will identify needed targets for treatment.
Read more: Krainc Laboratory
Christine Klein (Germany)Pamela McLean (MGH) Leonard Guarente (MIT)Ai Yamamoto (Columbia) Naoko Tanese (NYU) Robert Tjian (HHMI) Francis Collins (NIH) John Yates (Scripps) Jeff Savas (Scripps) Anne Hart (Brown) Guy Caldwell (U of Alabama) Elena Cattaneo (U of Milan)Ellen Sidransky (NIH)
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