ISCRM faculty members Smita Yadav, an Associate Professor of Pharmacology and Nobuhiko (Nobu) Hamazaki, an Assistant Professor in the Departments of Obstetrics & Gynecology and Genome Sciences, have received prestigious awards from the John H. Tietze Foundation Trust that will help fuel promising research underway in their labs.
Stem Cell Models for Neurodevelopmental Disorders
Neurodevelopmental disorders, including autism spectrum disorder, ADHD, intellectual disability, speech and language disorders, currently affect an estimated 15% of children worldwide. Genetic sequencing in patients have identified mutations in genes involved in early brain development. Mutations in one such enigmatic gene, known as TBCK, cause a devastating neurodegenerative disorder that has onset in infancy.
Analyses of brain tissue from patients afflicted with TBCK mutations have revealed abnormal accumulation of material that normally is degraded in healthy neurons. This suggests that the function of lysosomes, tiny organelles that degrade cellular debris within neurons, might be impaired. How TBCK might control lysosomal function, and how aberrant lysosomes impact brain development are unknown.
Understanding how TBCK mutations impact early human brain development is critical for therapeutic intervention. Due to the limitation of mouse models in studying brain development, human iPSC derived models provide the most disease relevant system to study.
With funding from the 2025 John H. Tietze Stem Cell Scientist Award, Dr. Smita Yadav and her lab will develop neuronal and 3D brain organoid models to understand how lysosomal function in neurons is affected by TBCK mutations. The Yadav lab has generated induced pluripotent stem cells with mutations in TBCK found in patients. They will generate organoid models that mimic brain development which will allow them to study which brain cell types and developmental processes are impacted by abnormal TBCK function.
Cell Fate and Developmental Diseases
During gastrulation, a pivotal process following embryo implantation, cell fates diversify rapidly. The complexity and sensitivity of this stage make it particularly susceptible to genetic, chemical, and environmental disturbances, leading to adverse pregnancy outcomes such as miscarriage, congenital anomalies, and other developmental disorders
Understanding how both inherited and environmental factors shape cell fate decisions is essential for advancing our knowledge of human development and the underlying causes of developmental diseases.
Funding from the Jaconette L. Tietze Young Scientist Award will enable ISCRM faculty member Dr. Nobuhiko (Nobu) Hamazaki and his lab to build a stem cell derived human embryo mode that will allow us to study how genetic variants and environmental fluctuations reshape early cell fate decisions, highlighting disease related pathways and ultimately guiding new strategies for prevention and therapy.
The knowledge gained from this research will accelerate the understanding of the origins of developmental diseases and will inform future strategies for their prevention and treatment. The implications of this work will be broad, impacting fields such as reproductive health, developmental biology, and regenerative medicine.