As one of the first institutions in North America to establish a neurobiology research department, City of Hope has a long and robust history in studying the nervous system.
The Department of Developmental and Stem Cell Biology (formerly Neurosciences) offers a multidisciplinary research and training environment in neurobiology that focuses on developmental aspects of the nervous system and its relation to human disease. Research within the department encompasses molecular and cellular neurobiology, genetics, and neurophysiology, and includes ongoing studies in neurogenesis and tumorigenesis, migration and specification, degeneration, and regeneration.
Researchers in the department collaborate with colleagues in other basic science departments and divisions, as well as with clinical researchers in the neurosurgery and neuro-oncology programs, focusing on nanoparticle and neural stem cell delivery of cancer therapeutics, and on immunotherapy using genetically modified T cells.
The Department of Developmental and Stem Cell Biology groups its broad range of research interests into two major categories:
1. Stem and progenitor cells in developing and mature brains, the earliest periods of neurogenesis and lineage commitment, and application of these understandings to neural repair and regeneration.
Understanding the mechanisms that control self-renewal and differentiation of neural progenitor/stem cells
Dr. Lu’s research is aimed at understanding how neural progenitor cells control the balance between proliferation and differentiation in the developing and adult brains. His laboratory is studying the mechanisms that regulate symmetric vs. asymmetric cell division in the embryonic cerebral cortex, as well as the epigenetic mechanisms that specify neural progenitor cell state. His group is also examining how defects in the regulation of asymmetric cell division may contribute to tumorigenesis.
Stem cells in neurogenesis and neurological diseases
Dr. Shi is developing stem cell –based “disease in a dish” platform to model neurological diseases, such as Alzheimer’s disease, schizophrenia and leukodystrophy, and establishing drug discovery pipeline for these diseases. The Shi laboratory is also developing stem cell-based cell therapies for neurological diseases, and creating therapeutic tools for glioblastoma, the most deadly primary brain tumor.
Neurobiology of Development
Dr. Barish investigates electrical and ionic signaling in the developing hippocampus and cortex, and their roles in establishing cell identity during both normal neural maturation and brain tumor progression.
2. Fundamental mechanisms underlying diseases of the human nervous system and development of novel therapeutic approaches to these diseases.
Dr. Aboody oversees a translational research laboratory focused on neural stem cells (NSC) as platforms for targeted delivery of therapeutic agents to invasive and metastatic solid tumors. Ongoing are first in human NSC gene therapy trials for patients with glioblastoma.
Dr. Ikeda studies neurotransmitter-mediated neural degeneration and death in amyotrophic lateral sclerosis (ALS), using the Drosophila neuromuscular synapse as a model system.
Dr. Salvaterra focuses on degenerative diseases, and has developed a new human embryonic stem cell model to study Alzheimer’s-like Abeta42 dependent neurodegeneration. The App gene was edited using TALEN to directly express this proteotoxic peptide and differentiated neurons appear to undergo degeneration as a consequence of dysfunction in the autophagy-endosomal-lysosomal pathway.
Dr. Tomoda (visiting professor, Kyoto University) studies membrane transport and cycling in stress-induced autophagy, and possible connections to diseases including Huntington’s and schizophrenia.
Transcriptional Control of Tumor Cell Dissemination and Metastasis
Dr. Glackin investigates the molecular mechanisms by which the bHLH transcription factor TWIST regulates cellular invasiveness. Understanding these mechanisms has allowed Glackin’s laboratory to develop novel nanoparticle approaches for delivering genetically modified therapeutics that interfere with the function of TWIST to inhibit invasion of tumor cells in many aggressive cancers.