Email

yamamoto@bcm.edu

Positions

Assistant Professor

Department of Molecular and Human Genetics (primary), Department of Neuroscience (secondary), Graduate Program in Developmental Biology
Baylor College of Medicine
Houston, Texas United States

Investigator

Jan and Dan Duncan Neurological Research Institute (NRI)
Texas Children's Hospital
Houston, Texas United States

Co-Director, Drosophila Core

Model Organisms Screening Center (MOSC) for the Undiagnosed Diseases Network (UDN)

SFARI Investigator

Simons Foundation Autism Research Initiative (SFARI)

Addresses

Jan and Dan Duncan Neurological Research Institute (Lab)

1250 Moursund St.
NRI-1025.12
Houston, TX 77030
United States

Education

BS from University of Tokyo

03/2005 - Tokyo, Japan

DVM from Ministry of Agriculture, Forestry and Fisheries of Japan

04/2005 - Tokyo, Japan

PhD from Baylor College of Medicine

03/2012 - Houston, Texas United States

Post-Doctoral Fellowship at Baylor College of Medicine

12/2013 - Houston, Texas United States

Professional Interests

• New Disease Gene Discovery
• Integration of Drosophila Genetics and Human Genomics
• Cell-Cell Communication in Development and Disease
• Facilitation of the Use of Model Organisms in Human Disease Diagnosis and Research

Professional Statement

Many pediatric diseases and conditions are caused by mutations found in the patients’ genomic DNA. Genetic mutations responsible for some of these disorders have been successfully identified, which has opened up new doors for researchers to develop better diagnostic tools and new treatments. However for most neurological and psychiatric diseases, the causes are yet to be identified.

The human genome contains ~25,000 genes, yet the biological functions of more than 80% of them are not well characterized. Yamamoto lab aims to bridge this gap using powerful genetic tools available in the model organism, Drosophila melanogaster (fruit flies) that allow for rapid discovery and functional elucidation of genes that play key roles in the development and maintenance of nervous system.

Using the information obtained from large-scale fly screens and combining this with large whole exome sequence (WES) datasets from thousands of patients with undiagnosed diseases (in collaboration with Drs. Jim Lupski, Richard Gibbs, Michael Wangler and the Baylor-Hopkins Center for Mendelian Genomics), we have identified a number of new human disease-causing genes. Furthermore, by extensively studying the function of the fly homologs of these disease genes, we have revealed molecular mechanisms by which mutations in these genes cause certain disease conditions.

We are especially interested in classes of genes that regulate cell-cell communication in development and disease. Notch signaling is a key pathway in the development of almost all organs, and defects in Notch signaling leads to different congenital disorders, stroke and cardiovascular diseases, as well as in many types of cancer in both children and adults. Dopamine signaling, on the other hand, regulates diverse aspects of neuronal function, and its dysfunction is seen in diverse neurodevelopmental (e.g. autism spectrum disorders, ADHD/ADD), neurological (e.g. dystonia, restless legs syndrome), psychiatric (e.g. schizophrenia, mood disorders, addiction), as well as neurodegenerative conditions (e.g. Parkinson’s disease).

We aim to identify and characterize novel genes in these pathways and understand their precise functions in vivo using genetic, cell/molecular biological, biochemical and electrophysiological methodologies. Our goal is to provide a better understanding of the molecular mechanisms underlying these diseases, allowing researchers to explore novel drug targets and potential therapies towards a cure.

Websites

Professional Development

GRS: Notch Signaling in Development, Regeneration and Disease

Conference (Organizer, 2014)

Sponsor: Gordon Research Conference

Selected Publications

• Liu N, Schoch K, Luo X, Pena DML, Bhavana VH, Kukolich MK...Undiagnosed Diseases Network (UDN)...Shashi V#, Yamamoto S#. (# Corresponding Authors) "Functional variants in TBX2 are associated with a syndromic cardiovascular and skeletal developmental disorder.." Hum. Mol. Genet..2018;In press: Pubmed PMID: 29726930
• Wangler MF*, Yamamoto S*, Chao HT, Posey JE, Westerfield M, Postlethwait J; Members of the Undiagnosed Diseases Network (UDN), Hieter P, Boycott KM, Campeau PM, Bellen HJ. (* Equal Contribution) "Model Organisms Facilitate Rare Disease Diagnosis and Therapeutic Research.." Genetics.2017/September1;207(1):9-27. Pubmed PMID: 28874452
• David-Morrison G, Xu Z, Rui YN, Charng WL, Jaiswal M, Yamamoto S, Xiong B, Zhang K, Sandoval H, Duraine L, Zhang S, Bellen HJ "WAC regulates mTOR activity through the TTT-Pontin/Reptin complex." Dev Cell.2016/January25;36(2):139-151. Pubmed PMID: 26812014
• Jakobsdottir J*, van der Lee SJ*, Bis JC*, Chouraki V*, Li-Kroeger D*, Yamamoto S*, et al., (*Equal Contribution) "Rare Functional Variant in TM2D3 is Associated with Late-Onset Alzheimer's Disease.." 2016/October20;12(10):e1006327. Pubmed PMID: 27764101