Videos
Atherosclerosis is a hardening of the arterial wall as the result of cholesterol accumulation. Macrophages deposit LDL-derived cholesterols via pinocytotis; therefore, preventing macrophage-mediated lipid deposition has potential to limit disease progression. In this episode, Takuro Miyazaki and colleagues reveal that elevation of calpain-6 in macrophages promotes atherogenic functions by disrupting CWC22/EJC/Rac1 signaling. Moreover, loss of calpain-6 in murine models was atheroprotective, suggesting that targeting this pathway has therapeutic potential for atherosclerosis.
Some patients with diabetes develop diabetic kidney disease (DKD), which can progress to a loss of renal function. High levels of TNF are predictive of disease and organ damage; however, it is not clear how elevated TNF promotes injury. In this episode, Alessia Fornoni reveals that TNF promotes free cholesterol–dependent podocyte apoptosis via an NFATc1/ ABCA1-dependent mechanism. The results of this study indicate that agents targeting cholesterol efflux should be further explored for treating proteinuric kidney diseases.
During sepsis, there is a progression from a hyperactive immune response to an immunosuppressive state that is characterized by macrophage reprogramming. However, the factors that drive this macrophage response are not well defined. In this episode, Dimitrios Balomenos and Gorjana Rackov discuss their recent study, which shows that p21 is instrumental in macrophage switching from a pro-inflammatory to an immunosuppressive state during sepsis. The results of this study reveal that p21 regulates the balance between p50-p50 and p65-p50 NF-κB during sepsis and provides a potential therapeutic target for this complex condition.
Laurie Glimcher is a world-class immunologist who discovered the master transcription factors that direct immune cells to commit and activate. She has also discovered a key anabolic bone pathway and become an expert on ER stress and lipoprotein production. Most recently, Glimcher discovered a critical signaling pathway in both tumor cells and host immune responses. All the while, she’s acted as an academic leader, at Harvard School of Public Health and as dean of Weill Cornell Medical School, and she is about to take the reins of the Dana-Farber Cancer Institute as President and CEO.
Psoriasis is a chronic inflammatory disease that is characterized by the presence of pruritic skin lesions. Aberrant interactions between the epithelia and immune system underlie the disease; however, the pathways that promote psoriasis are poorly understood. In this episode, Peter Marinkovich and Mårten Winge discuss their work, which shows that hyperactivation of RAC1 in the skin drives pathogenic interactions between the epidermis and the immune system in psoriasis. The results of this work suggest that RAC1 is a potential therapeutic target for this disease.
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