Dimitri Krainc, MD, PhD

  • Lab Phone: 617-726-8463
  • Neurology Access Center: 1-855-644-6387

Research Investigator Profile

Dr. Dimitri Krainc

Dimitri Krainc, MD, PhD

  • Associate Professor,
    Harvard Medical School
  • Associate Neurologist,
    Massachusetts General Hospital

 

 

Research Description

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

Research interests Neurodegeneration, Gene Transcription, Mitochondrial Function, Energy Metabolism, Protein Degradation, Autophagy
Research techniques molecular and genomic research techniques
Diseases studied Huntington's and Parkinson's disease
Selected publications
  1. Dunah AW, Jeong H., Griffin A., Kim MJ, Standaert DG, Hersch SM, Mouradian
    MM, Young AB, Tanese N. and Krainc D. Sp1 and TAF130 transcriptional activity disrupted in early Huntington’s Disease. Science, 2002; 296, 2238
  2. Cui L., Jeong H., Borovecki F. Parkhurst C., Tanese, N. and Krainc D. Transcriptional Repression of PGC-1alpha by Mutant Huntingtin Leads to Mitochondrial Dysfunction and Neurodegeneration. Cell, 2006, 126, 59-69.
  3. Jeong H., Then F., Mazzulli JR., Melia, T. Savas J., Voisine C., Tanese, N., Hart C.A., Yamamoto A. and Krainc D. Acetylation targets mutant huntingtin to autophagosomes for degradation. Cell, 2009,137, 1-13
  4. Mazzulli, J.R., Sun, Y., Knight, A.L., McLean, P.J., Caldwell, G, Sidransky, E, Grabowski, G.A. and Krainc, D.: Gaucher’s Disease Glucocerebrosidase and alpha-synuclein form a bidirectional pathogenic loop in synucleinopathies. Cell, 2011, 146, 1-16.
  5. Jeong, H., Cohen, D.E., Cui, L.; Supinski, A;  Bordone, L; , Guarente, L.P, and Krainc, D. Sirt1 mediates  neuroprotection from mutant huntingtin by activation of TORC1 and CREB transcriptional pathway, Nature Medicine, (advance online publication, December 2011, doi:10.1038/nm.2558)

 

NCBI PubMed link NCBI PubMed Publications
Collaborators

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)

E-mail address dkrainc@partners.org
Lab mailing address MassGeneral Institute for Neurodegenerative Disease
114 16th Street
Charlestown, MA 02129
Clinical interests Neurology, Movement Disorders , Huntington’s disease
Clinical address Massachusetts General Hospital
Neurology, Suite 835
Wang Ambulatory Care Center
55 Fruit Street
Boston, MA 02114 USA
Clinical website address Movement Disorders Unit

 

 

Updated 1/19/2012