BBS Faculty Member - James Gusella

James Gusella

Department of Genetics

Massachusetts General Hospital
Simches Research Building CPZN 5.252
185 Cambridge St
Boston, MA 02114
Tel: 617-726-5724
Visit my lab page here.

My laboratory is focused on understanding nervous system disease using molecular genetic strategies, beginning with human patients and proceeding through in vitro and modeling studies, with the ultimate goal of improving diagnosis, management and treatment. In any given disorder, the research can usually be divided into four sequential stages:

1. Determination of the chromosomal location of a gene defect, susceptibility gene or genetic modifier, usually based on linkage or association studies with polymorphic genetic markers or delineation of structural rearrangements.
2. Identification of the gene responsible for the phenotypic effect based upon its chromosomal location by integrating a variety of genomic strategies.
3. Characterization of the mechanism of action based upon analysis of the allelic versions of the culprit gene in man, and in appropriate in vitro or in vivo model systems, including cultured human cells, genetically engineered mice, and lower organisms such as Drosophila and Dictyostelium.
4. Exploration of the potential for rational therapies, including genetic therapies.

We are currently searching for modifier genes for Huntington’s disease and neurofibromatosis and, in part with the Developmental Genome Anatomy Project, we are identifying genes at breakpoints of balanced translocations associated with developmental abnormality. Finally, we are examining the mechanism of pathogenesis of genetic defects in autism, Huntington's disease, Parkinson's disease, and neurofibromatosis, using both iPS cells and model organisms, as we persue assays to identify genetic and chemical modifiers, with the ultimate goal of contributing to effective rational therapies.

Last Update: 12/7/2016


For a complete listing of publications click here.



Genetic Modifiers of Huntington’s Disease (GeM-HD) Consortium. Identification of Genetic Factors that Modify Clinical Onset of Huntington's Disease. Cell. 2015 Jul 30;162(3):516-526. PubMed PMID: 26232222.

Sugathan A, Biagioli M, Golzio C, Erdin S, Blumenthal I, Manavalan P, Ragavendran A, Brand H, Lucente D, Miles J, Sheridan SD, Stortchevoi A, Kellis M, Haggarty SJ, Katsanis N, Gusella JF, Talkowski ME. CHD8 regulates neurodevelopmental pathways associated with autism spectrum disorder in neural progenitors. Proc Natl Acad Sci U S A. 2014 Oct 21;111(42):E4468-77. PubMed PMID: 25294932; PubMed Central PMCID: PMC4210312.

Dietz KN, Di Stefano L, Maher RC, Zhu H, Macdonald ME, Gusella JF, Walker JA. The Drosophila Huntington's disease gene ortholog dhtt
influences chromatin regulation during development. Hum Mol Genet. 2015 Jan 15;24(2):330-45. PubMed PMID: 25168387.

Lee JM, Galkina EI, Levantovsky RM, Fossale E, Anne Anderson M, Gillis T, Srinidhi Mysore J, Coser KR, Shioda T, Zhang B, Furia MD, Derry J, Kohane IS, Seong IS, Wheeler VC, Gusella JF, MacDonald ME. Dominant effects of the Huntington's disease HTT CAG repeat length are captured in gene-expression data sets by a continuous analysis mathematical modeling strategy. Hum Mol Genet. 2013 Aug 15;22(16):3227-38. PubMed PMID: 23595883; PubMed Central PMCID: PMC3723309.

Talkowski ME, Ordulu Z, Pillalamarri V, Benson CB, Blumenthal I, Connolly S, Hanscom C, Hussain N, Pereira S, Picker J, Rosenfeld JA, Shaffer LG, Wilkins-Haug LE, Gusella JF, Morton CC. Clinical diagnosis by whole-genome sequencing of a prenatal sample. N Engl J Med. 2012 Dec 6;367(23):2226-32. PubMed PMID: 23215558; PubMed Central PMCID: PMC3579222.

Kim HG, Kim HT, Leach NT, Lan F, Ullmann R, Silahtaroglu A, Kurth I, Nowka A, Seong IS, Shen Y, Talkowski ME, Ruderfer D, Lee JH, Glotzbach C, Ha K, Kjaergaard S, Levin AV, Romeike BF, Kleefstra T, Bartsch O, Elsea SH, Jabs EW, MacDonald ME, Harris DJ, Quade BJ, Ropers HH, Shaffer LG, Kutsche K, Layman LC, Tommerup N, Kalscheuer VM, Shi Y, Morton CC, Kim CH, Gusella JF. Translocations disrupting PHF21A in the Potocki-Shaffer-syndrome region are associated with intellectual disability and craniofacial anomalies. Am
J Hum Genet. 2012 Jul 13;91(1):56-72. PubMed PMID: 22770980; PubMed Central PMCID: PMC3397276.

HD iPSC Consortium. Induced pluripotent stem cells from patients with Huntington's disease show CAG-repeat-expansion-associated phenotypes. Cell Stem Cell. 2012 Aug 3;11(2):264-78. PubMed PMID: 22748968; PubMed Central PMCID: PMC3804072.

Talkowski ME, Rosenfeld JA, Blumenthal I, Pillalamarri V, Chiang C, Heilbut A, Ernst C, Hanscom C, Rossin E, Lindgren AM, Pereira S,
Ruderfer D, Kirby A, Ripke S, Harris DJ, Lee JH, Ha K, Kim HG, Solomon BD, Gropman AL, Lucente D, Sims K, Ohsumi TK, Borowsky ML, Loranger S, Quade B, Lage K, Miles J, Wu BL, Shen Y, Neale B, Shaffer LG, Daly MJ, Morton CC, Gusella JF. Sequencing chromosomal abnormalities reveals neurodevelopmental loci that confer risk across diagnostic boundaries. Cell. 2012 Apr 27;149(3):525-37. PubMed PMID: 22521361; PubMed Central PMCID: PMC3340505.

Lee JM, Gillis T, Mysore JS, Ramos EM, Myers RH, Hayden MR, Morrison PJ, Nance M, Ross CA, Margolis RL, Squitieri F, Griguoli A, Di Donato S, Gomez-Tortosa E, Ayuso C, Suchowersky O, Trent RJ, McCusker E, Novelletto A, Frontali M, Jones R, Ashizawa T, Frank S, Saint-Hilaire MH, Hersch SM, Rosas HD, Lucente D, Harrison MB, Zanko A, Abramson RK, Marder K, Sequeiros J, MacDonald
ME, Gusella JF. Common SNP-based haplotype analysis of the 4p16.3 Huntington disease gene region. Am J Hum Genet. 2012 Mar 9;90(3):434-44. PubMed PMID: 22387017; PubMed Central PMCID: PMC3309179.

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