The research of Na Zhao, M.D., Ph.D., is focused on understanding the physiological and pathological functions of apolipoprotein E (APOE) and triggering receptor expressed on myeloid cells 2 (TREM2) in aging and aging-related diseases and disorders. Specifically, Dr. Zhao's Neurobiology of Alzheimer Related Dementias Laboratory focuses on dissecting the molecular and cellular mechanisms underpinning the pathogenesis of Alzheimer's Disease (AD) and related dementias such as Lewy body dementia (LBD) with a particular highlight on the roles of APOE and microglial function through TREM2.
Using techniques spanning biochemistry, cell biology, animal modeling and induced pluripotent stem cell (iPSC) culturing modeling, Dr. Zhao's lab aims to conduct translational research to find targeted therapeutic strategies for these devastating neurodegenerative diseases.
- APOE in LBD. LBD is one of the most common forms of progressive dementia after AD. APOE4 allele, the strongest genetic risk factor for late-onset AD, is also the most replicated genetic risk factor for LBD wherein the causal mechanism remains unclear. Dr. Zhao's lab is working to elucidate the pathomechanisms of APOE4 in LBD, with the aim of identifying strategies to target APOE4 and its related pathways for LBD treatment.
- APOE in tauopathies and TDP-43 proteinopathies. Dr. Zhao has previously reported that APOE2 allele increases tau pathology in mouse models bearing TauP301L mutation and in the human postmortem brains from primary tauopathies such as progressive supranuclear palsy and corticobasal degeneration. This finding indicates that while protective against AD, APOE2 is not benign with respect to the risk of developing other neurodegenerative diseases. Therefore, Dr. Zhao's lab is currently investigating the underlying mechanisms of the three APOE isoforms in modifying the pathogenesis of tauopathies and TDP-43 proteinopathies.
- TREM2 in AD and related dementias. This work, in collaboration with Guojun Bu, Ph.D., and colleagues in his Neurobiology of Alzheimer's Disease Laboratory, is to understand the molecular etiology of AD by studying the strong genetic risk factor TREM2, which modulates microglial functions and immune responses in the brain. Using in vivo transgenic disease models, in vitro iPSC cellular models and postmortem human brains, Dr. Zhao aims to collectively address the dynamic effects of TREM2-mediated molecular pathways in AD and related dementias to both explore disease mechanisms and inform potential treatment strategies.
Significance to patient care
The ultimate goal of Dr. Zhao's work is to gain a deep perspective into disease mechanisms in AD and related disorders to discover targeted therapeutics to treat them.