Shirley Yan’s research is geared toward unraveling the cellular and molecular basis of neurodegeneration and devising therapeutic strategies to hamper the processes that cause neuronal death. Yan’s Lab was the first to identify the specific cellular targets (RAGE, receptor for advanced glycation end product; ABAD, amyloid binding alcohol dehydrogenase, and cyclophilin D) of amyloid-beta peptide (Aβ) and to find evidence of Aβ-mediated neuronal stress. We have developed a novel transgenic mouse model relevant to the pathogenesis of neurodegenerative diseases including Alzheimer disease (AD), multiple sclerosis, and Parkinson disease. Through analyses of genetically manipulated AD-type mouse models, we have elucidated new insights into cellular and molecular mechanisms underlying the pathogenesis of AD. All of our findings indicate that cell surface RAGE and intracellular proteins such as ABAD or cyclophilin D service as cellular co-factors for promoting Aß-mediated neuronal toxicity relevant to Alzheimer’s disease. In the future, we may blockade these targeted proteins as a novel therapeutic approach in the treatment of Alzheimer’s disease.
Mitochondrial dysfunction is a hallmark of AD. Following up on their studies, Yan and her research team were the first to find that Aβ progressively accumulates in the mitochondria of brains from AD patients and transgenic AD-type mouse model. Accumulation of Aβ in mitochondria was associated with mitochondrial dysfunction. The interaction of mitochondrial Aβ with its binding protein exaggerates mitochondrial and synaptic dysfunction. These studies provide new insights into mechanisms of Aβ-mediated mitochondrial toxicity causing neuronal damage relevant to AD and open new avenues for the treatment of AD. Recently, Yan’s group has provided substantial evidence of mitochondrial abnormalities directly linked to synaptic dysfunction. These studies have been highlighted in globally leading journals including Nature, Nature Medicine, Science, and PNAS. Yan’s research has been supported by the grant from the National Institutes of Health and other foundations since 1995. Yan’s research clearly advances our understanding of mechanisms through which Aβ induces cellular stress. Her work could lead to new therapeutic strategies for AD.
Yan also has expertise in cellular and molecular mechanisms of ischemia-induced cardiac and cerebral injury, autoimmune disease such as EAE (experimental autoimmune encephalomyelitis) animal model relevant to multiple sclerosis, and Parkinson disease. Recently, we are working on a project related to tumor pathogenesis. She has been a keynote speaker at multiple international professional scientific meetings. She is an active member of multiple scientific review committees for neurodegenerative disease of the National Institutes of Health (NIH), VA merit grant, Alzheimer Association, and other foundation grants. Yan’s laboratory has been collaborating with research scientists from Japan, Germany, Italy, and England, in addition to the United States.