Dr. Aisan Farhadi Gharehgheshlaghi is a postdoctoral research scholar in the Department of Neurology at Washington University School of Medicine in St. Louis. Dr. Gharehgheshlaghi received a Ph.D. in Developmental Biology from the Royan Institute in 2022. The doctoral research investigated tau hyperphosphorylation and dysfunction leading to Alzheimer’s disease (AD) in the context of diabetes mellitus (DM). Because DM is a major risk factor for AD but its underlying mechanisms remain unclear, this work focused on identifying molecular links between the two conditions. The research demonstrated that DM was associated with a cis tau conformation phosphorylated at threonine 231 (cis pT231-tau), which induces neuronal stress caused by diabetes both in vitro and in a mouse model of DM. Dr. Gharehgheshlaghi observed that cis pT231-tau accumulated in specific brain regions and neuronal populations of diabetic mice before the onset of overt pathology, suggesting that it could serve as an early marker of phosphorylated tau in DM.
In 2022, Dr. Gharehgheshlaghi joined the laboratory of Dr. Gilbert Gallardo at Washington University in St. Louis for postdoctoral training. Now, Dr. Gharehgheshlaghi focuses on developing engineered targeted protein degradation strategies by designing chimeric receptors to eliminate pathological proteins and neuroinflammatory cytokines in AD. By combining these novel degradation strategies with adeno-associated virus (AAV) gene therapy, Dr. Gharehgheshlaghi aims to develop a long-term therapeutic strategy for AD.