Shinya Yamamoto, DVM, PhD
Baylor College of Medicine (BCM)
Investigator, Jan & Dan Duncan Neurological Research Institute (NRI), Texas Children's Hospital (TCH)
Associate Director, Genetics & Genomics Graduate Program, BCM
Co-Director, Model Organisms Screening Center, Undiagnosed Diseases Network (UDN)
Co-Lead, Disease Modeling Unit, Center for Precision Medicine Models (CPMM), BCM
Model Organisms: Goat/Sheep ➔ Mouse ➔ Fruit Fly ➔ Human
I was originally trained as a veterinarian at the University of Tokyo Veterinary Medical School, and also gained three years of research experience during this DVM training. The first set of model organisms I worked with were goats and sheep, which are used as models to study molecular mechanisms of pregnancy in ruminants (e.g. cattle). Next, I used mice to study molecular mechanisms of implantation during pregnancy, early embryogenesis, and inflammatory bowel diseases. While I became fascinated in biomedical research through these experiences, I also learned the challenges and limitations in working with mammalian model organisms.
After obtaining my BS and DVM degrees in Japan, I moved to the US and joined the Program of Developmental Biology at Baylor College of Medicine (BCM) to pursue basic research using a more genetically trackable model organism towards my PhD. I joined the laboratory of Dr. Hugo J. Bellen, who is one of the most charismatic and influential fruit fly (Drosophila melanogaster) geneticists. In his laboratory, I designed and led a large forward genetic screen on the Drosophila X-chromosome to isolate thousands of mutations in essential genes that are involved in proper development, function, or maintenance of the nervous system. Through detailed phenotypic characterization and further molecular and cell biological analyses, our team of graduate students, postdocs and technicians have successfully uncovered novel regulatory mechanisms underlying Notch signaling, Hedgehog signaling, central and peripheral nervous system development, phototransduction, and neurodegeneration. Many of these studies have direct relevance to human diseases.
By combining my strengths in Drosophila research with my earlier training and research experience in veterinary medicine and mammalian biology, I was fortunate to 'skip-a-postdoc' and obtained an independent position in 2013 as a Fellow of the Jan and Dan Duncan Neurological Research Institute (NRI) at Texas Children’s Hospital (TCH) through Dr. Huda Zoghbi's enormous support and encouragement. I was promoted to a tenure-track Assistant Professor in the Department of Molecular & Human Genetics at BCM in 2017, and also obtained a secondary appointment in the Department of Neuroscience. I actively participate in three PhD programs at BCM [Genetics & Genomics, Neuroscience, and DDMT (Development, Disease Models & Therapeutics)], and run an vibrant basic/translational research laboratory that studies various topics related to the nervous system using state-of-the-art Drosophila genetic technologies.
Many projects in my lab are related to rare and undiagnosed diseases. In fact, >25 million individuals (about the population of Texas) are affected by rare or ultra-rare diseases in the US alone. This number is more staggering at the global scale (affecting >300 million people worldwide, which is about the population of the US), and many experience a long and winding 'diagnostic odyssey' to try to find out the cause of their disorders. While state-of-the-art genomic technologies such as whole-exome sequencing (WES) and whole-genome sequencing (WGS) may provide answers to a subset of these individuals, many are often left with a handful of candidate genetic variants that require experimental studies to understand their functional consequences. As a co-director/co-lead of the Model Organisms Screening Center (MOSC) of the Undiagnosed Diseases Network (UDN) and BCM Center for Precision Medicine Models (CPMM), my lab utilizes Drosophila to test whether a genetic variant identified in a patient is the cause of their disease, which is pursued in close collaboration with clinicians and human geneticists across the country and around the world. I am also a member of the recently established BCM Undiagnosed Disease Center (UDC), a clinical/research initiative at BCM to support patients and families who are struggling to receive an accurate diagnosis. In collaboration with bioinformaticians and programmers at BCM/NRI (Dr. Zhandong Liu's lab), I am also involved in the development of novel computational tools such as MARRVEL and ModelMatcher to facilitate rare disease diagnosis, research, and collaborations on a global scale. Over the years, my interest has expanded to include more common neurological disorders such as autism spectrum disorders (ASD), Alzheimer's disease, psychiatric diseases and drug addiction. More recently, we are also developing creative strategies to study infectious diseases such as Zika virus mediated microcephaly and COVID-19, given their socioeconomic importance.
In summary, while members of my lab and I work on diverse research topics, all projects are built on a common foundation that harnesses the 'awesome power of fly genetics'.
U54 NS093793-07S2 (NIH: NINDS)
Bellen (PD/PI) 7/01/2022-6/30/2023
The major goal of this administrative supplement is to sustain the activity of the Model Organisms Screening Center (MOSC) to support the mission of the Undiagnosed Diseases Network.
Role: Co-I of overall, Project Lead of Drosophila Core.
R24 OD022005-07S1 (NIH: ORIP)
Bellen (PD/PI) 06/01/2022 - 05/31/2023
The major goal of this administrative supplement is to expand and complete a genetic tool kit of SARS-CoV-2 and human cDNAs to study the functional interaction of host-protein proteins involved in COVID-19, especially in the context of the nervous system.
RESEARCH AWARD (SATB2 Gene Foundation)
Yamamoto (PD/PI) 12/1/2021-11/30/2022
The major goal of this project is study the function of pathogenic variants identified in SATB2-associated syndrome and to further functionally characterize the role of this gene in the nervous system using Drosophila.
R01 HG011795 (NIH: NHGRI)
Bellen/Wangler (PD/PI) 7/13/2021-4/30/2026
The major goal of this project is to facilitate the implementation of genomic medicine in a medically underserved population by combining the latest clinical diagnostics, bioinformatics and Drosophila genetics tools in a clinical setting.
U54 NS093793-07S1 (NIH: NINDS)
Bellen (PD/PI) 7/01/2021-6/30/2022
The major goal of this administrative supplement is to increase the utility of MARRVEL and ModelMatcher by integrating these two online resources to facilitate rare and undiagnosed disease research.
Role: Project Lead.
R01 AG071557 (NIH: NIA)
Yamamoto (PD/PI) 5/1/2021-4/30/2024
The major goal of this proposal is to study the function of TM2D3 and its related genes in the context of Alzheimer’s disease pathogenesis in Notch signaling.
U54 OD030165 (NIH: ORIP)
Heaney/Lee/Milosavljevic (PD/PI) 9/15/2020-9/14/2025
The major goal of this project is to establish a BCM Center for Precision Medicine Models, which will develop precision animal models that will facilitate the diagnostic and therapeutic research of rare diseases.
Role: Co-I of the whole proposal, and Project Co-Lead of Disease Modeling Unit.
R24 OD022005-05S1 (NIH: ORIP)
Bellen (PD/PI) 07/01/2020 - 06/30/2022
The major goal of this administrative supplement is to establish a genetic tool kit of SARS-CoV-2 and human cDNAs to study the functional interaction of host-protein proteins involved in COVID-19.
U54 NS093793-06S1 (NIH: NINDS)
Bellen (PD/PI) 7/01/2020-6/30/2021
The major goal of this administrative supplement is to establish a global matchmaking system between scientist and clinicians called ModelMatcher to facilitate rare and undiagnosed disease research.
Role: Project Lead.
U01 HG007530-07 subaward (NIH: NHGRI)
Kohane/McCray/Might (PD/PI) 7/1/2020-6/30/2021
The major goal of this administrative supplement is to study the function of GLS, a gene identified as a in the Undiagnosed Disease Network as a disease causing gene, using Drosophila.
Role: Project Lead.
Nancy Chang, Ph.D. Award for Research Excellence (BCM)
Yamamoto (PI) 07/01/2019-06/30/2020
The major goal of this project is to understand the function of TM2D family proteins in the context of Notch signaling and late-onset Alzheimer’s disease using Drosophila.
Junior Faculty Seed Funding Award (BCM)
Yamamoto (PI) 07/01/2017-06/30/2018
The major goal of this project is to understand the function of proteins and non-coding RNAs encoded in the Zika viral genome using Drosophila to understand the mechanism by which this virus cause microcephaly in humans.
R24 OD022005 (NIH: ORIP)
Bellen (PD/PI) 06/01/2016 - 05/31/2024
The goal of this study is to generate a large library of human cDNA expressing constructs and transgenic Drosophila strains to facilitate the use of fruit flies in biomedical research.
R01 DC014932 (NIH: NIDCD)
Groves (PI) 12/1/2016-11/30/2022
The goal of this proposal is to study the role of the Ubr3 gene in regulating proteins involved in Usher syndrome, the most common form of deaf-blindness, and MYH9-related disease syndromes that can also cause deafness. In addition, we will perform genetic screens to identify additional genes involved in hearing in insects and mice.
New Investigator Research Grant (Alzheimer’s Association)
Yamamoto (PI) 10/1/2015-9/30/2017
The major goal of this project is to understand the functional effect of a late-onset Alzheimer’s disease associated variant in TM2D3 using Drosophila.
U54 NS093793 (NIH: NINDS & CommonFund)
Bellen (PD/PI) 9/15/2015-6/30/2023
The major goal of this project is to establish a Model Organisms Screening Center (MOSC) that will use Drosophila and Zebrafish to support the diagnostic mission of the Undiagnosed Disease Network (UDN).
Role: Co-I of overall, Project Lead of Drosophila Core.
Targeted-Functional Screen of Autism-Associated Variants Award (Simons Foundation)
Wangler/Yamamoto (Co-PIs) 8/1/2015-7/31/2018
The major goal of this project is to perform functional analyses of rare variants in conserved autism genes found in the Simons Simplex Cohort using Drosophila.
R13 HD080297-01 (NIH: NCI & NICHD)
Blacklow (PI) 5/10/2014-4/30/2015
This grant supported a Gordon Research Conference (GRC) and Seminar (GRS) on “Notch Signaling in Development, Regeneration & Disease” held in July 19-25, 2014 at Bates College, Maine.
Role: Chair of GRS.
NRI Fellowship (TCH)
Yamamoto (PI) 3/1/2013-2/28/2017
This fellowship is designed to recruit and support candidates that have just received their terminal degrees (e.g., Ph.D.) to start up an independent laboratory in the Jan and Dan Duncan Neurological Research Institute (NRI) at Texas Children's Hospital (TCH).
Nakajima Foundation Fellowship (Nakajima Foundation)
Yamamoto (Fellow) 5/1/2005-4/30/2010
This competitive fellowship is awarded to 3-4 Japanese students annually to pursue graduate studies in the life science field in a foreign country. Fellows receive a generous stipend up to 5 years.
Role: Pre-Doctoral Fellow.