Dr. Hyung JinAhn

Dr. Hyung Jin Ahn received his PhD from Baylor College of Medicine studying novel transcription factors associated with long-term memory consolidation under the guidance of Dr. David Sweatt. In order to pursue translational aspects of cognitive dysfunction, he joined the Laboratory of Neurobiology & Genetics at The Rockefeller University. His research in the lab of Sydney Strickland at Rockefeller, focused on investigating the mechanisms and therapy of Alzheimer’s disease (AD), with an emphasis on cerebrovascular dysfunction. Increasing evidence suggests that cerebrovascular dysfunction is one of the pathological hallmarks of AD. Many AD patients suffer from cerebral micro infarcts and a damaged cerebral vasculature, and a majority of patients with dementia present with both AD and vascular pathologies. However, the mechanism underlying the vascular contribution in AD is unclear. Based on this idea, Dr. Ahn and colleagues investigated vascular factors contributing to AD and found that fibrinogen, a primary protein component of blood clots, is a strong cerebrovascular risk factor in AD as it specifically binds to beta-amyloid (Aβ), alters blood clot structure, and delays clot degradation, potentially leading to the neuronal cell death observed in AD an related disorders. He was able to show that depletion of fibrinogen pharmacologically or genetically reduces the cognitive impairment in AD mouse models. He also found that the interaction betweenβ-amyloid (Aβ) and fibrinogen can be blocked by novel inhibitors; these novel drug candidates have shown promise as a therapy for AD in in vitro and in vivo functional assays. These works were published in prestigious journals including Neuron, Proceedings of the National Academy of Science (USA) and Journal of Experimental Medicine. He currently has three independent funded research projects. In the first project, he aims to understand the molecular mechanism underlying increased vascular Aβ deposits and cerebrovascular abnormalities in hereditary cerebral amyloid angiopathy. He recently received a R01 grant from NINDS for this project. In the second project, he is developing optical techniques which would allow for the investigation of neurovascular coupling deficits in freely behaving AD mice. Using this new fiber optic technique, he will investigate the molecular basis of neurovascular dysfunction in AD. Preliminary studies for this project have been funded by a pilot grant from the National Center for Advancing Translational Sciences (NCATS, NIH) through the Clinical and Translational Science Award program at The Rockefeller University. HIs third project involves the improvement of pharmacological profile of Aβ-fibrinogen interaction inhibitors using medicinal chemistry approaches and the development of novel Aβ-fibrinogen interaction-inhibiting therapeutic antibodies. This project is done in collaboration with Takeda Pharmaceutical Company. For this work, he received a grant from the Alzheimer’s Drug Discovery Foundation and additional support from the Tri-Institutional Therapeutics Discovery Institute. At Rutgers, his lab continues studies that examine the crosstalk between the cerebrovascular system and the nervous system in AD. To identify novel molecular targets and biomarkers underlying cerebrovascular deficits in AD, he is investigating cerebrovascular dysfunction and blood-brain barrier damage in rodent AD models and postmortem specimens of AD patients using various biochemical and histochemical techniques, in vivo fiber optic spectroscopy, in vivo two photon imaging, RI, and 3D Immunostaining combined with iDISCO tissue clearing method.