Hashimoto Laboratory

SIRT1 Activation and Intracranial Aneurysm Biology

Our laboratory investigates the role of Sirtuin-1 (SIRT1), an NAD⁺-dependent regulator of vascular inflammation and remodeling, in the progression and stability of intracranial aneurysms. Because SIRT1 regulates several inflammatory pathways implicated in aneurysm formation and rupture, we are testing the hypothesis that activating SIRT1 promotes aneurysm stability and reduces the risk of rupture.

We employ a combination of genetic models—including overexpression and cell-type-specific knockouts—and pharmacological approaches to compare the effects of SIRT1 inhibition versus activation. Ongoing work evaluates how SIRT1 influences vascular inflammation, extracellular matrix integrity, and maladaptive remodeling within the aneurysm wall.

Redox-Active Porphyrins for Stroke and Hemorrhage

Oxidative stress is a major driver of secondary brain injury following ischemic stroke and subarachnoid hemorrhage. In collaboration with the Tovmasyan Laboratory, we are advancing novel redox-active metalloporphyrins engineered for high superoxide dismutase–mimetic activity, low systemic toxicity, and strong preclinical efficacy.

Our goal is to determine whether these next-generation compounds improve neurological outcomes by enhancing superoxide dismutation, reducing peroxynitrite-mediated cellular damage, and restoring redox balance in the brain and cerebrovasculature. Studies are underway in mouse models of ischemic stroke and subarachnoid hemorrhage, with endpoints including neurological recovery, lesion burden, blood–brain barrier integrity, and oxidative and inflammatory biomarkers.