Professor Xiangmin Xu has been awarded $3.8 million by the National Institute on Aging to conduct an epigenomic analysis of neural circuits in the brain.
By revealing molecular changes that occur during the course of Alzheimer’s disease (AD), the team hopes to identify new therapeutic targets and molecular biomarkers for early detection and better treatment.
The interdisciplinary research team is led by multiple principal investigators, including Xiangmin Xu, PhD, a professor of anatomy and neurobiology and director of the Center for Neural Circuit Mapping at the UCI School of Medicine, and Carl Cotman, PhD, a professor of neurology and founding director of the Institute for Brain Aging and Dementia at the UCI School of Medicine, and Bing Ren, PhD, a professor of cellular and molecular medicine and director of the Center for Epigenomics at the UCSD School of Medicine. The team will study how the epigenome of key cell types in neural circuits shapes hippocampal circuit activity and behaviors during AD progression. The proposed research will involve the use of single cell genomic technologies coupled with functional circuit mapping and behavioral analysis. The study will be conducted using mouse models that mimic the neurodegenerative disease.
“Our goal is to reveal the molecular changes that occur during the course of the disease, that impact learning and memory, and identify a path toward early detection and new drug therapies for Alzheimer’s disease,” said Xu.
Alzheimer’s disease is the most common cause of progressive dementia (memory and cognitive loss) in older adults and a growing major health concern in the U.S. Currently, more than 5.5 million Americans may have dementia caused by AD.
“Currently, there is no cure for Alzheimer’s disease,” said Xu. “And, as millions of people are affected by this debilitating condition, it is increasingly critical that we develop better early diagnostic tools and new treatment strategies to care for them.”
[Xu lab/Lynch lab]
Two projects were funded. A&N Professor Xiangmin Xu, in collaboration with Professor Shaista Malik (Associate Vice Chancellor, College of Health Sciences; Executive Director, Susan Samueli Integrative Health Institute) and Dr. Zhi-Ling Guo (Project Scientist, Department of Medicine and Susan Samueli Integrative Health Institute), received support for their project titled “Using new viral and genetic approaches to study neural mechanisms of acupuncture modulation of cardiovascular function”. The team will use recent viral and genetic techniques developed in the Xu laboratory to examine the neural circuit basis of acupuncture modulation in the mouse model. Findings from the proposed research will address important questions in the field of acupuncture research, which cannot be achieved using conventional anatomical and physiological approaches.
A&N Project Scientist Dr. Linda Palmer in the Lynch lab, in collaboration with Professor of Fine Arts Jesse Jackson, was funded for the proposal, Investigating Exploration and the ‘Aha’. This project uses scientific and artistic tools to investigate exploration, testing specific brain networks as potential substrates for a signal of ‘discovery’ in animals and comparing human discovery patterns in engagement with works of art, expressing multi-level themes of open-ended exploration and the organization of perception.
Both projects are designed to bring together investigators with different expertise to explore novel questions in brain science. Congratulations to both teams!
We are happy to announce that Laura Ewell, PhD will be joining our Department of Anatomy and Neurobiology in May 2021 as a newly hired assistant professor!
Dr. Ewell’s lab will study in vivo and in vitro circuit mechanisms of memory and epilepsy
We are happy to announce that Javier Diaz-Alonso, PhD will be joining our Department of Anatomy and Neurobiology as a newly hired assistant professor!
Dr. Diaz is currently a postdoc at UCSF and will study the molecular organization of the synapse using electrophysiology, imaging and molecular biology in his new lab.
We are happy to announce that Momoko Watanabe, PhD, will be joining our Department , as a new assistant professor jointly appointed with UCI Sue and Bill Gross Stem Cell Research Center starting Aug 1, 2020!
Dr. Watanabe is currently a postdoc at UCLA and will study neurodevelopment using brain organoids derived from human pluripotent stem cells in her new lab.
Professor Xiangmin Xu receives $4.3 million NIH BRAIN Initiative grant
Assistant Professor Kei Igarashi receives three NIH R01 grants
Postdoc Jessica Bolton receives prestigious NIH K99/R00 Pathway to Independence Award
Assistant Professor Kei Igarashi receives the New Vision Award from Donors Cure Foundation for his Alzheimer’s Disease Research
Professor Danielle Piomelli led a research showing that cells involved in allergies also play a key role in survival
Postdoc Tom Nakazono found a possible mechanism for cognitive dysfunction in a mouse model of Alzheimer’s Disease
Graduate student Yanjun Sun uncovers new molecular signaling mechanism for correcting childhood visual disorders
Neuroscientists at University of California, Irvine have discovered a molecular signaling mechanism that translates visual impairments into functional changes in brain circuit connections. The discovery may help to develop novel therapeutic drugs to treat the childhood visual disorder amblyopia and other neurodevelopment disorders. Xiangmin Xu, Todd Holmes and Sunil Gandhi conducted the study, which appears online Sept. 15 in Neuron. Amblyopia is the most common cause of permanent visual defects among children and is often a result of improper brain development due to deprivation during the “critical period” of vision development. In a previous study, Xu helped discover that a specific class of inhibitory neurons (parvalbumin-expressing neurons, or PV neurons) control the critical period of vision development. In this study, Xu and colleagues found that neuregulin-1 (NRG1) molecules modulate the activities of these neurons, thus outlining a new path for treatments that can restore normal vision in children who have had early deficits. As neurodevelopmental disorders such as schizophrenia appear to result from brain developmental defects during defined postnatal windows, the linkage of NRG1 signaling to critical growth periods provides important new insights. Xu said he hopes that therapeutic interventions targeting NRG1 may be exploited to treat cortical neurodevelopmental disorders. Link to study (subscription needed): http://www.cell.com/neuron/fulltext/S0896-6273(16)30526-8.
Dr. Daniele Piomelli − a UC Irvine School of Medicine professor of anatomy and neurobiology − has determined after 25 years of studying the pain-relieving properties of cannabis and its progeny that the substance could be used to treat opioid addiction − which was responsible for the deaths of 19,000 people in 2014 alone.
Neuroscientist Daniele Piomelli, who has studied the connection at the University of California, Irvine, [said]: “There’s every reason to be excited, because clearly the gut and brain are two peas in a pod and they really work together,” Piomelli sees potential in learning more about how the gut and brain communicate. “If we are able to find ways to understand that and to leverage that for therapeutic purposes, that will be key,” he says.
Tallie Baram, professor of pediatrics and anatomy-neurobiology at University of California, Irvine, and her colleagues used a rat model to study how good but disrupted attention from mothers can affect their newborns.
Dr. Julie Lauterborn receives NIH R21 grant to study synaptic defects in Down Syndrome (DS)
Associate Researcher Dr. Julie Lauterborn has received an R21 grant from the Eunice Kennedy Shriver National Institute of Child Health & Human Development to identify disturbances in synaptic proteins in DS. People with DS have mild-to-moderate intellectual disability and are predetermined to develop Alzheimer’s Disease. Dr. Lauterborn and colleague Dr. Christine Gall will test the hypothesis that in DS there are disturbances in Rho GTPase pathway proteins that are essential for synaptic function and plasticity. These studies will evaluate human postmortem tissue using Fluorescent Deconvolution Tomography, developed by UCI professor Dr. Gary Lynch, to define core synaptic defects associated with DS versus those that rise with aging and Alzheimer’s Disease pathology. Studies will also test how well a commonly used mouse model of DS replicates synaptic defects in the human condition. Findings could benefit efforts to devise treatments to improve cognitive function in DS and other intellectual disability disorders.