Professor and Chair, Department of Neurodegenerative Diseases; Director, Division of Stem Cell Biology Research

Yanhong Shi, Ph.D, is the Chair of the Department of Neurodegenerative Diseases, Herbert Horvitz Endowed Professor in Neuroscience, and Director of the Division of Stem Cell Biology Research at the Beckman Research Institute of City of Hope. Dr. Shi is also a beneficiary of the Christopher Family Endowed Innovation Fund for Alzheimer’s Disease Research in Honor of Vineta Christopher, and an elected fellow of the American Institute for Medical and Biological Engineering (AIMBE).Dr. Shi has a longstanding interest in the induced pluripotent stem cell (iPSC) technology and its applications in disease modeling, drug discovery, and cell therapy. The Shi laboratory has pioneered innovative human iPSC-based models of Alzheimer’s disease (listen to a podcast here) and other neurological diseases (see here). Dr. Shi was a scientific organizer of the Keystone Symposia “iPSCs: A Decade of Progress and Beyond,” a landmark conference that set the trends for the next decade of iPSC technology-based research (see Shi et al. 2017). The Shi laboratory has also developed cGMP-compatible manufacturing processes for human iPSC derivation, differentiation, and genetic engineering, and has demonstrated robust disease-modifying effects of human iPSC-derived neural progenitor cells as a cell therapy for Canavan disease in preclinical studies (highlighted here).Dr. Shi also aims to understand the molecular mechanisms that govern brain cancer progression with a focus on glioblastoma and RNA modifications. The Shi laboratory was among the first to demonstrate a therapeutically actionable dysregulation of RNA modifications in glioblastoma (Cui et al. 2017, Cui et al. 2021), thus uncovering a novel approach to treat brain cancer. Together with other experts in the field, Dr. Shi is also part of the inaugural 2023 NSAS Summit workshops “Exploring the Brain Epitranscriptome” focused on RNA modifications in brain development and diseases to promote research into brain epitranscriptomics and facilitate RNA modification-targeted therapeutic development (see Lee et al., 2023).View Dr. Yanhong Shi full profile

Yanhong Shi, Ph.D.

Professor and Chair, Department of Neurodegenerative Diseases; Director, Division of Stem Cell Biology Research

Yanhong Shi, Ph.D, is the Chair of the Department of Neurodegenerative Diseases, Herbert Horvitz Endowed Professor in Neuroscience, and Director of the Division of Stem Cell Biology Research at the Beckman Research Institute of City of Hope. Dr. Shi is also a beneficiary of the Christopher Family Endowed Innovation Fund for Alzheimer’s Disease Research in Honor of Vineta Christopher, and an elected fellow of the American Institute for Medical and Biological Engineering (AIMBE).

Dr. Shi has a longstanding interest in the induced pluripotent stem cell (iPSC) technology and its applications in disease modeling, drug discovery, and cell therapy. The Shi laboratory has pioneered innovative human iPSC-based models of Alzheimer’s disease (listen to a podcast here) and other neurological diseases (see here). Dr. Shi was a scientific organizer of the Keystone Symposia “iPSCs: A Decade of Progress and Beyond,” a landmark conference that set the trends for the next decade of iPSC technology-based research (see Shi et al. 2017). The Shi laboratory has also developed cGMP-compatible manufacturing processes for human iPSC derivation, differentiation, and genetic engineering, and has demonstrated robust disease-modifying effects of human iPSC-derived neural progenitor cells as a cell therapy for Canavan disease in preclinical studies (highlighted here).

Dr. Shi also aims to understand the molecular mechanisms that govern brain cancer progression with a focus on glioblastoma and RNA modifications. The Shi laboratory was among the first to demonstrate a therapeutically actionable dysregulation of RNA modifications in glioblastoma (Cui et al. 2017, Cui et al. 2021), thus uncovering a novel approach to treat brain cancer. Together with other experts in the field, Dr. Shi is also part of the inaugural 2023 NSAS Summit workshops “Exploring the Brain Epitranscriptome” focused on RNA modifications in brain development and diseases to promote research into brain epitranscriptomics and facilitate RNA modification-targeted therapeutic development (see Lee et al., 2023).

View Dr. Yanhong Shi full profile

Chun-Wei (David) Chen, Ph.D.

Associate Professor, Department of Systems Biology; Department of Neurodegenerative Diseases

Dr. Chen’s research program focuses on novel opportunities for advanced cancer therapies, and target identification and therapeutic development for neurological disorders such as Alzheimer’s disease (in collaboration with Dr. Shi), by understanding how genetic/epigenetic regulators and their networks control gene expression, the epigenetic landscape, and genome integrity under normal and disease conditions. Dr. Chen has more than 10 years of research experience in high-throughput genetic screens and epigenetic mechanisms and has pioneered single-cell CRISPR gene tiling pipelines “sc-Tiling” (Yang et al. 2021, Nat Commun*) and “CRISPR-TICA,” the CRISPR-Tiling Instructed Computer-Aided pipeline (Mattson et al. Nat Struct Mol Biol*, accepted 2023-10), for structural/functional genomics and therapeutics discovery (*corresponding). Dr. Chen’s research program is funded by several NIH (R37 MERIT, R01s, K99/R00) and foundation (ASH Scholar, ALSF Innovation) awards. View Dr. Chun-Wei (David) Chen full profile

Qi Cui, Ph.D.

Assistant Research Professor, Department of Neurodegenerative Diseases

Dr. Cui’s research is focused on cancer stem cells of glioblastoma, the most aggressive type of brain cancer. Dr. Cui aims to understand how cancer stem cells can be targeted therapeutically and eradicated to prevent glioblastoma progression and recurrence. During his graduate studies, Dr. Cui made a pioneering discovery that glioblastoma stem cells exhibited a dysregulated landscape of N6-methyladenosine, a chemical modification that decorates RNA molecules (see Cui et al., 2017). More recently, Dr. Cui has found that another RNA modification, pseudouridine, is also aberrantly installed in glioblastoma stem cells (see Cui et al. 2021). Importantly, Dr. Cui has shown that both N6-methyladenosine and pseudouridine modifications can be modulated therapeutically to specifically eliminate glioblastoma stem cells, thus offering a new way to treat brain cancer. Dr. Cui is also involved in the development of age-relevant glial cellular models for neurodegenerative diseases, such as Alzheimer’s disease, using directly reprogrammed cells.

Matthew Huentelman, Ph.D.

Professor and Director, Neurogenomics Division at TGEN Scientific Director, TGEN’s Center for Rare Childhood Disorders; Professor, Department of Neurodegenerative Diseases at City of Hope

Dr. Huentelman’s research interests center around the investigation of the “-omics” (genomics, transcriptomics, and proteomics) of neurological traits and disease. His laboratory’s overarching goal is to leverage findings in these disciplines to better understand, diagnose, and treat human diseases of the nervous system.Dr. Huentelman completed his doctoral work at the University of Florida’s Department of Physiology and Functional Genomics at the McKnight Brain Institute where he investigated the application of gene therapy in the study and prevention of hypertension. His undergraduate degree is in Biochemistry from Ohio University’s Department of Chemistry and Biochemistry at Clippinger Laboratories. His career includes visiting researcher stints in Moscow, Russia at the MV Lomonosov Moscow State University “Biology Faculty” and in the United Kingdom within the University of Bristol’s Department of Physiology.Alzheimer’s Disease | There are over six million Alzheimer's disease patients in the United States alone. The disease exerts a wide-ranging and significant personal, social, and economic toll that is only predicted to increase as the population continues to live longer. The Huentelman lab examines Alzheimer’s disease with the use of next generation DNA and RNA sequencing and cultured brain organoids. They are interested in helping to identify an individual’s personal risk for developing the disease as early as possible in life as well as identifying new drug targets and developing new drugs.Aging | Like other physiological developmental stages, our individual response to the process of aging differs dramatically from person to person. Importantly, the natural process of aging takes place over many decades and therefore our lifestyle choices, demographic factors, and medical conditions may play a major role in how each one of us ages. The Huentelman lab is using genomics and transcriptomics to better understand why some individuals exhibit better cognitive aging when compared to others. The hope is that through the better understanding of these differences they may someday be able to develop therapeutics that could enable a larger portion of the population to exhibit better cognitive aging. Conceptually they believe that this will require a true personalization of the approach to brain aging, something that they refer to as “Precision Aging”.Cognition | Our individual differences in brain performance remain of great interest to the field of Neuroscience. Dr. Huentelman’s group leverages their innovative web-based approach to study the drivers of these individual differences in brain performance via their study site at https://mindcrowd.org. The overarching goal of this research is to utilize this new information to improve brain performance in all humans with the hope of enabling a greater number of individuals to avoid diseases of cognition or to decrease their severity.Rare Disease | The genetic dissection of rare human disease is uniquely powered by our ability to sequence the entire human genome and interpret the results with increasing clarity. The Huentelman laboratory utilizes this approach to tackle rare diseases in children - via TGen’s Center for Rare Childhood Disorders - as well as in adults. The greatest successes in this area come from the study of the entire nuclear family, therefore, Dr. Huentelman’s group typically focuses on the study of diseases that strike at a time in life when the affected patient and parent’s DNA can be studied together.View Dr. Matthew Huentelman full profile

Matthew Huentelman, Ph.D.

Professor and Director, Neurogenomics Division at TGEN Scientific Director, TGEN’s Center for Rare Childhood Disorders; Professor, Department of Neurodegenerative Diseases at City of Hope

Dr. Huentelman’s research interests center around the investigation of the “-omics” (genomics, transcriptomics, and proteomics) of neurological traits and disease. His laboratory’s overarching goal is to leverage findings in these disciplines to better understand, diagnose, and treat human diseases of the nervous system.

Dr. Huentelman completed his doctoral work at the University of Florida’s Department of Physiology and Functional Genomics at the McKnight Brain Institute where he investigated the application of gene therapy in the study and prevention of hypertension. His undergraduate degree is in Biochemistry from Ohio University’s Department of Chemistry and Biochemistry at Clippinger Laboratories. His career includes visiting researcher stints in Moscow, Russia at the MV Lomonosov Moscow State University “Biology Faculty” and in the United Kingdom within the University of Bristol’s Department of Physiology.

Alzheimer’s Disease | There are over six million Alzheimer's disease patients in the United States alone. The disease exerts a wide-ranging and significant personal, social, and economic toll that is only predicted to increase as the population continues to live longer. The Huentelman lab examines Alzheimer’s disease with the use of next generation DNA and RNA sequencing and cultured brain organoids. They are interested in helping to identify an individual’s personal risk for developing the disease as early as possible in life as well as identifying new drug targets and developing new drugs.

Aging | Like other physiological developmental stages, our individual response to the process of aging differs dramatically from person to person. Importantly, the natural process of aging takes place over many decades and therefore our lifestyle choices, demographic factors, and medical conditions may play a major role in how each one of us ages. The Huentelman lab is using genomics and transcriptomics to better understand why some individuals exhibit better cognitive aging when compared to others. The hope is that through the better understanding of these differences they may someday be able to develop therapeutics that could enable a larger portion of the population to exhibit better cognitive aging. Conceptually they believe that this will require a true personalization of the approach to brain aging, something that they refer to as “Precision Aging”.

Cognition | Our individual differences in brain performance remain of great interest to the field of Neuroscience. Dr. Huentelman’s group leverages their innovative web-based approach to study the drivers of these individual differences in brain performance via their study site at https://mindcrowd.org. The overarching goal of this research is to utilize this new information to improve brain performance in all humans with the hope of enabling a greater number of individuals to avoid diseases of cognition or to decrease their severity.

Rare Disease | The genetic dissection of rare human disease is uniquely powered by our ability to sequence the entire human genome and interpret the results with increasing clarity. The Huentelman laboratory utilizes this approach to tackle rare diseases in children - via TGen’s Center for Rare Childhood Disorders - as well as in adults. The greatest successes in this area come from the study of the entire nuclear family, therefore, Dr. Huentelman’s group typically focuses on the study of diseases that strike at a time in life when the affected patient and parent’s DNA can be studied together.

View Dr. Matthew Huentelman full profile

Zhenqing (Crystal) Liu, Ph.D.

Staff Scientist, Department of Neurodegenerative Diseases

Dr. Liu research interest is functional studies of glial cells using human induced pluripotent stem cell (hiPSCs) models and defining the roles of these glial cells in neurodegenerative diseases such as Alzheimer’s disease.