Genetic Neurobiology Laboratory

Faculty:  Russell L. Margolis, M.D., Director

Link to PubMed publications for Margolis RL
              
The Laboratory of Genetic Neurobiology currently focuses on four interrelated projects:

1. A search for the genetic causes of neurodegenerative diseases, particularly those that affect the basal ganglia or the cerebellum. In the last two years we have found the cause of two of these disorders, as described below. We are searching for additional mutations in our collection of DNA from several hundred individuals with unidentified disorders of the basal ganglia and cerebellum.
2. A search for the genetic etiology of psychiatric disorders, such as bipolar disorder and schizophrenia, using a candidate-gene approach. Our current work is designed to test the hypotheses that repeat expansions or copy number variations may contribute to the genetic vulnerability of these disorders (Margolis et al, 1999).
3. A search for genetic factors that influence the diagnosis, onset age or progression of Huntington's disease. This work is carried out in conjunction with the Baltimore Huntington's Disease Center, and has led to changes in the recommended diagnostic test for HD (Margolis et al, 1999).
4. Investigation of the pathogenesis of Huntington's disease like-2 (HDL2), another disorder clinically (Margolis et al, 2001) and genetically (Holmes, 2001) characterized in our laboratory. HDL2 is clinically indistinguishable from HD but is caused by a CTG expansion in an alternatively spliced exon of the gene junctophilin-3. Current research is focused on developing cell and animal models of HDL2 pathogenesis, and further defining the clinical, genetic, and epidemiological characteristics of the disease in humans.

Staff and Fellows
   Doda Rudnicki, Ph.D.
   Nancy Sachs, Ph.D.  
   Heather Bruce

Laboratory Technician
   Colleen Callahan, B.A.

Recent Publications

Holmes SE, O'Hearn E, Callahan C, Hwang HS, Rosenblatt A, Ingersoll-Ashworth RG, Fleisher A, Stevanin G, Brice A, Potter NT, Ross CA, Margolis RL. A CTG trinucleotide repeat expansion in Junctophilin 3 is associated with Huntington's Disease-Like 2 (HDL2). Nature Genetics, 29 (2001): 377-378, 2001.

Margolis RL, McInnis MG, Rosenblatt A, Ross CA. Trinucleotide repeat expansion and neuropsychiatric disease. Archives of General Psychiatry, 56 (1999):1019-1031.

Holmes SE, O'Hearn E, McInnis MG, Kwak NG, Gorelick-Feldman DA, Kleiderlein JK, Callahan C, Sherr M, Sharp AH, Sumner AJ, Ashworth RG, Ananth U, Seltzer W, Vieria-Saecker AM, Epplen JT, Reiss O, Ross CA, Margolis RL. Expansion of a novel CAG trinucleotide repeat in the 5' region of PPP2R2B is associated with SCA12, Nature Genetics, 23 (1999): 391-392.

Acknowledgements

Work on all of these projects is performed in close collaboration with Dr. Christopher Ross, Dr. Adam Rosenblatt, and Dr. Akira Sawa within the Division of Neurobiology, Drs. Troncoso and Borchelt in the Division of Neuropathology, Drs. McInnis, Potash, and DePaulo of the Division of Psychiatric Genetics, and Dr. Elizabeth O'Hearn in the Department of Neurology.

See also the Department's Schizophrenia Program