Current Environment:

Research Overview

The goals of the Mochida Laboratory are: 1] to understand the molecular basis of genetic disorders of human brain development, 2] to understand neuropathogenesis of congenital infections, particularly Zika virus, and 3] to develop novel treatment strategies for genetic and non-genetic developmental brain disorders. The Mochida Laboratory combines human subject research with cellular and animal models in order to achieve these goals.

Laboratory Projects

  1. Molecular basis of genetic microcephaly and disorders of the cerebellum: We collaborate with clinicians worldwide to enroll individuals and their families with rare genetic disorders affecting the growth of the cerebrum (microcephaly) and cerebellum (cerebellar hypoplasia and cerebellar atrophy). High-throughput sequencing and genomic approaches are applied to identify novel genetic mutations associated with these human disorders. We particularly focus on highly consanguineous populations in the Middle East to effectively identify autosomal recessive disease genes and have published four new genes associated with these disorders since 2013.
  2. Cellular and animal models of human cerebral and cerebellar development: Once candidate pathogenic mutations in novel genes are identified, we create cellular and animal models to understand their function during normal development and the effect of the mutations we identified. We utilize various model systems from cultured cells to vertebrates (zebrafish and mice) and take advantage of cutting-edge technologies, including induced pluripotent stem cells (iPSCs) and CRISPR/Cas9-mediated genome editing. Some of the biological pathways we currently focus on include amino acid metabolism, energy metabolism, and intracellular trafficking.
  3. Neuropathogenesis of congenital Zika syndrome: Congenital Zika virus infection causes serious neurodevelopmental consequences, including microcephaly, collectively known as congenital Zika syndrome. How Zika virus leads to severe brain malformations is poorly understood, and there are no effective prevention or treatment strategies. We have developed a new mouse model of congenital Zika virus infection and are studying this model to understand the effect of Zika virus infection in the developing brain. Further, we are using this model as a platform for developing novel prevention and therapeutic strategies for congenital Zika virus infection.

Research Background

Ganeshwaran H. Mochida, M.D., M.M.Sc. is a Principal Investigator in the Division of Genetics and Genomics at Boston Children’s Hospital and Assistant Professor of Pediatrics at Harvard Medical School. He is a native of Tokyo and graduated summa cum laude from Keio University School of Medicine. After his pediatric internship at Keio University Hospital, Dr. Mochida moved to Boston and completed residency training in pediatric neurology at Massachusetts General Hospital. Subsequently, his postdoctoral research training was in the laboratory of Professor Christopher A. Walsh at Beth Israel Deaconess Medical Center. He also completed the Clinical Investigator Training Program at Beth Israel Deaconess Medical Center and Harvard-MIT Division of Health Sciences and Technology, and received a Master of Medical Sciences degree from Harvard Medical School. He established his research laboratory in the Division of Genetics and Genomics at Boston Children’s Hospital in 2013.

Selected Publications

  1. Mochida GH*, Ganesh VS*, de Michelena MI, Dias H, Atabay KD, Kathrein KL, Huang HT, Hill RS, Felie JM, Rakiec D, Gleason D, Hill AD, Malik AN, Barry BJ, Partlow JN, Tan WH, Glader LJ, Barkovich AJ, Dobyns WB, Zon LI, Walsh CA. CHMP1A encodes an essential regulator of BMI1- INK4A in cerebellar development. Nat Genet. 2012;44(11):1260-4. PMCID: PMC3567443. (*equal contribution)
  2. Ahmed MY, Chioza BA, Rajab A, Schmitz-Abe K, Al-Khayat A, Al-Turki S, Baple EL, Patton MA, Al-Memar AY, Hurles ME, Partlow JN, Hill RS, Evrony GD, Servattalab S, Markianos K, Walsh CA, Crosby AH*, Mochida GH*. Loss of PCLO function underlies pontocerebellar hypoplasia type III. Neurology 2015;84:1745-50. PMCID: PMC4424132. (*equal contribution)
  3. Nakayama T, Al-Maawali A, El-Quessny M, Rajab A, Khalil S, Stoler JM, Tan WH, Nasir R, Schmitz-Abe K, Hill RS, Partlow JN, Al-Saffar M, Servattalab S, LaCoursiere CM, Tambunan DE, Coulter ME, Elhosary PC, Gorski G, Barkovich AJ, Markianos K, Poduri A, Mochida GH. Mutations in PYCR2, encoding pyrroline-5-carboxylate reductase 2, cause microcephaly and hypomyelination. Am J Hum Genet 2015;96:709-19. PMCID: PMC4570282.

Publications