The research of Guojun Bu, Ph.D., is centered on understanding why a specific allele of the apolipoprotein E gene (e4) represents a strong risk factor for Alzheimer's disease. Dr. Bu's Neurobiology of Alzheimer's Disease Laboratory focuses on dissecting the biological and pathological functions of the apolipoprotein E gene (APOE) and APOE receptors with particular emphasis on their roles in the pathogenesis of Alzheimer's disease and related dementias.
Dr. Bu collaborates with Mayo Clinic's Center for Regenerative Medicine to collect skin biopsies from patients with various neurological disorders, some with rare gene mutations or risk gene alleles. The resulting fibroblasts are banked and used for reprogramming into induced pluripotent stem cells (iPSCs) that can be further differentiated into a myriad of central nervous system cell types. These human cells are an important and unique way in which the Dr. Bu's lab is studying the cellular mechanisms of brain disorders, addressing human relevance and developing future replacement therapy.
Dr. Bu and his colleagues collaborate with several labs within the Department of Neuroscience on Mayo Clinic's campus in Jacksonville, Florida, and within Mayo Clinic's Alzheimer's Disease Research Center, which spans both Mayo Clinic's Rochester and Jacksonville campuses, and for which Dr. Bu is an associate director. Dr. Bu also collaborates with numerous labs around the world and helps with training next-generation scientists at the undergraduate, graduate and postdoctoral levels.
- APOE receptors and amyloid-beta (Abeta) clearance. Dr. Bu's lab is focused on investigating the complex mechanisms underlying isoform-dependent effects of APOE in normal central nervous system functions and Abeta clearance and cognition during aging and in Alzheimer's disease.
- Cerebral insulin and wingless-related integration site ( Wnt) signaling. Dr. Bu's lab has demonstrated that impairment of the Wnt/low-density lipoprotein receptor related protein 6 (LRP6) pathway elevated Abeta production and exacerbated amyloidogenesis. This pathway plays an essential role in regulating synaptic integrity and functions even in the absence of amyloid pathology. Additionally, Dr. Bu's lab has demonstrated that low-density lipoprotein receptor related protein 1 (LRP1) interacts with the insulin receptor beta subunit in the brain and regulates insulin signaling and glucose uptake. Since a loss of LRP1 expression is seen in Alzheimer's disease, this pivotal study provides novel insights into insulin resistance in Alzheimer's disease.
- Cerebrovascular risk factors for Alzheimer's disease. Studies in Dr. Bu's lab attempt to define the cerebrovascular effects of APOE isoforms and to explore the potential of APOE-targeted therapies for Alzheimer's disease.
- Triggering receptor expressed on myeloid cells 2 (TREM2) and innate immunity. Mutations in the triggering receptor expressed on TREM2 have been identified as risk factors for late-onset Alzheimer's disease. Work in the Dr. Bu's lab seeks to clarify the functional consequence of impaired APOE binding via the Alzheimer's disease-associated TREM2-R47H mutation and the role TREM2-mediated neuroinflammatory events play in the neurodegenerative process.
- Sex-dependent differences in Alzheimer's disease and cerebrovascular diseases. The results from a recent study conducted by Dr. Bu's lab indicate that sex and APOE genotype differentially influence the presence and severity of cerebral amyloid angiopathy in Alzheimer's disease, likely by affecting interaction and aggregation of Abeta 40 and APOE.
- Collaborative studies. Work in Dr. Bu's lab also includes close collaborations with neurologists and neuropathologists at Mayo Clinic. In collaboration with Dennis W. Dickson, M.D., and Ronald C. Petersen, M.D., Ph.D., Dr. Bu conducts studies that have strong implications in deciphering disease mechanisms and in the design of mechanism-based therapies. Such work also exemplifies the power of collaboration and team-based science.
Significance to patient care
The ultimate goal of Dr. Bu's work is to develop novel methods to diagnose and treat Alzheimer's disease.
- Recipient, Award for Medical Research in Alzheimer's Disease, MetLife Foundation, 2016
- Recipient, Mayo Clinic Investigator of the Year Award, 2015
- Recipient, Zenith Fellows Award, Alzheimer's Association, 2008