Matthew Blurton-Jones, PhD



Sunil Gandhi, PhD




Drs. Matthew Blurton-Jones and Sunil Gandhi were 2017 WAM Research Grant recipients. Women have a significantly increased risk of developing Alzheimer’s Disease (AD), yet the underlying biological reasons for this remains unknown. A team of UC Irvine scientists led by Drs. Matt Blurton-Jones and Sunil Gandhi were funded by WAM to determine whether a small but important cell type called Microglia could play a role in this sex difference. Microglia are the immune cell of the brain and recent genetic studies have implicated these cells in both the development and progression of AD. But human microglia differ considerably from mouse microglia, so the UCI team needed to develop a new approach to study female and male human microglia and how they respond to AD pathology. To achieve this goal the team developed a new ‘chimeric’ model which involves the transplantation of human microglia into specialized mice. Using this approach, the researchers were able to detect important differences in the expression of key genes by male and female microglia that likely underlie important differential responses to AD pathology. For example, they found that female microglia tend to exhibit a heightened ‘Interferon-responsive’ genetic signature. This altered gene expression is in turn associated with a heightened and potentially detrimental inflammatory response. While the UCI team continues to pursue this promising research, they are excited that the initial support provided by WAM allowed them to successfully compete for a multimillion-dollar ‘Brain Initiative Grant’ funded by the National Institute of Health and to publish some of their initial findings in an influential scientific journal (Hasselmann et. al., Neuron, 2019).


More about Dr. Matthew Blurton-Jones

Dr. Matt Blurton-Jones is a professor in the Department of Neurobiology and Behavior at the University of California, Irvine and director of the UCI ADRC iPS cell core and the UCI Stem Cell CRISPR core. Dr. Blurton-Jones earned his PhD in Neurosciences at UC San Diego and then pursued postdoctoral studies at UC Irvine in the labs of Dr. Carl Cotman and Dr. Frank LaFerla.  His current research utilizes human induced pluripotent stem (iPS) cells and chimeric mouse models to examine the underlying molecular mechanisms that drive the development and progression of Alzheimer’s disease (AD). His earlier studies were among the first to show that neural stem cells can improve cognitive and motor function in transgenic models of neurodegeneration by elevating levels of brain-derived neurotrophic factor (BDNF) and enhancing plasticity. His lab also demonstrated that the adaptive immune system restrains the development of AD pathology by modulating microglial activation states. More recently, his group developed one of the leading approaches to differentiate patient-derived iPS cells into microglia (Abud et. al., Neuron, 2017) and generated chimeric models to study human microglial function in vivo (Hasselmann et. al., Neuron, 2019). Ongoing work in the Blurton-Jones lab is now combining iPS cells, CRISPR gene editing, and chimeric modeling to examine the impact of AD-associated genes and the intrinsic and extrinsic effects of sex on human microglial function (McQuade et al., Nat Comm, 2020).


More about Dr. Sunil Gandhi

Dr. Sunil Gandhi is an Associate Professor in the Department of Neurobiology and Behavior at the University of California, Irvine and is the co-director of the Center for the Neurobiology of Learning and Memory. Dr. Gandhi obtained his PhD in Neurosciences at UC San Diego and then pursued postdoctoral studies at Stanford University in the laboratory of Dr. Michael Stryker.  Dr. Gandhi has focused his scientific career on developing cell transplantation technology to tap the brain’s latent capacity to rewire itself.  With the support of a New Innovator Award from the Office of the NIH Director, a Searle Scholars Award, among other awards, his group has pioneered the use of embryonic inhibitory neuron transplantation to rewire the postnatal visual system.  His lab discovered that transplanted inhibitory neurons restore normal visual acuity to visually impaired mice. In addition, Dr. Gandhi has developed new methods for whole brain visualization using brain clearing and light sheet microscopy. His group worked with Zeiss Microscopy to adapt their light sheet microscope to accommodate brains cleared using high refractive index solutions. This collaboration has produced optimized hardware for the rapid imaging of cleared tissue at higher resolution and greater speed than rivaling commercial systems. To disseminate these technologies to the neuroscience community, he co-founded a BRAIN Initiative supported startup company Translucence Biosystems. In recent years, with colleagues at UCI, he has combined his lab’s expertise in cell transplantation and advanced brain imaging to develop a new cell therapeutic platform for brain disease.