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.
Bert Vogelstein, MD, and Kenneth Kinzler, PhD, are codirectors of the Ludwig Center at the Sidney Kimmel Comprehensive Cancer Center of the Johns Hopkins University School of Medicine. Vogelstein and Kinzler demonstrated that colorectal cancer results from the sequential accumulation of mutations in oncogenes and tumor suppressor genes, establishing a paradigm for modern cancer genomics. Additionally, they discovered the tumor suppressors APC and TP53; they were the first to perform exomic sequencing in tumors; and they developed digital PCR. In an interview with JCI’s Editor-at-Large Ushma Neill, Vogelstein and Kinzler reflect on their career trajectories and past discoveries and discuss their goals as scientists.