In Review: Rare and Neglected Diseases Symposium 2022

Author: CRND

April 26th, 2022: Rare Tumors


On April 26th, the 2022 Notre Dame Rare and Neglected Diseases Symposium hosted its fourth session which began with a focus on von Hippel-Lindau (VHL) disease, a rare tumor syndrome that affects 1 in 36,000 live births. Boler Family Foundation has supported a multi-group project at CRND to study the mechanism and translational opportunities of VHL disease. Three researchers in CRND and one patient advocate gave talks about VHL disease in the session.

Professor Zach Schafer presented the research where Dr. Jianping He in the lab characterized the non-conventional cell death process ferroptosis in kidney cancer cells. This study on VHL-deficient kidney cancer is important, because kidney cancer represents the most malignant form of VHL disease and finding new cell death mechanisms may provide new therapeutic opportunities.

Professor Xin Lu summarized three publications on VHL disease from his lab, which addressed challenges about VHL disease from different angles. In the first study, Dr. Lu’s team identified a dramatically downregulated mitochondrial gene, UQCRH, in VHL-deficient kidney cancer and discovered that loss of UQCRH expression promotes mitochondrial dysfunction and the tumor-specific metabolism phenotype (“Warburg effect”). Restoring UQCRH expression decelerated kidney tumor growth in animal models, which has clinical implications. In the second study, Xuechun Wang in the Lu lab used a multi-omics approach to identify two new client proteins (NFKB2, TGFBI) for the VHL complex that tags client proteins for degradation. These two new targets expand the mechanistic understanding on how VHL loss can cause a wide range of malignant features. The third study was through collaboration between the Lu lab and the Haldar Lab, where a synonymous VHL mutation was found to lead to pathogenic familial hemangioblastoma through dysregulating the splicing of VHL mRNA. Following Lu’s talk, Sean Murphy, a fourth-year graduate student from the Lu lab, presented his to-be-published work on the antitumor effect of special diets on kidney cancer. Based on Murphy’s study, kidney cancer may be controlled through the change of diet, which is an appealing alternative to the generally toxic anti-cancer therapies.

Last but not least, a patient with his family affected by the VHL disease gave a talk about how his family has dealt with VHL disease, including the diagnosis, surgery treatment, disease monitoring, onset of retinal hemangioblastoma in two young children, and collaboration of the family with labs at CRND to develop fibroblast cell lines from skin biopsies for research purposes.  Overall, the VHL disease session illustrated the concerted efforts from researchers and patient family to discover new insight and therapeutic potentials for VHL disease.

The session ended with a panel featuring the parents of children with rare diseases including Neurofibromatosis 1 (NF1), a disorder resulting in the widespread formation of tumors throughout the body, neurodevelopment disorders including Rett Syndrome and Fragile X Syndrome, and an ultra-rare connective tissue disorder Shprintzen-Goldberg Syndrome (SGS). Common threads between the panelists included the challenges in diagnosis and treatment. The range of symptoms presented by patients with NF1 can vary greatly, such that one may present aggressive tumors in the brain while another show primarily bone deformation.  Rett Syndrome and Fragile X syndrome are both neurological and developmental disorders, although in Rett babies seem to develop normally for the first six to eighteen months and then lose their skills.  In SGS the first year of life is a critical period and subsequent management requires complex and well timed surgeries. It is one of several diseases caused by genetic mutations in the TGF-β pathway and has benefited from the study of related disorders. The families also shared their incredible satisfaction when their children reach key milestones despite these difficulties. The session concluded with how important it was for researchers to learn from patients with the ultimate goal of working together to help patients


Thanks to all of the presenters, panelists, and audience members for helping to make the session on Rare Tumor Biology & Rare Diseases in Our Community at the 2022 Notre Dame Rare and Neglected Diseases Symposium a success!