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Rare Disease Day 2023

Tuesday, February 28, 2023

Check out the work of two of our faculty who work on rare diseases: Dr. Brian Kelch & Dr. Mary Munson.

tweet that reads: Today is #RareDiseaseDay & the research of two of our faculty members is directly related to rare diseases:  @BrianKelch  lab works on PARD, and  @mary_munson4  lab works on SCN. Check the thread   to learn more about our research on these diseases! with pictures of Dr. Brian Kelch and Dr. Mary MunsonRare disease #1: PCNA-associated DNA repair disorder (PARD) is an autosomal recessive neurodegenerative disease. Symptoms can include slower growth, hearing loss, learning difficulties, premature aging, and increased photosensitivity. (image from Baple et al, 2014 showing a scan of a patient brain)The mutations causing this disease impair the ability of the protein PCNA to regulate DNA replication and damage repair. image is a ribbon model of the protein PCNAIn 2016,  @cmduffy88  Brendan Hilbert &  @BrianKelch  found this mutation actually changed the shape of the PCNA protein! This blocked it from interacting with other proteins needed for DNA replication. image is a space-filling model of PCNA surrounded by script resembling elvishIn a recent pre-print article ( @medrxivpreprint ),  @joemagrino0528  Veridiana Munford, Davi Jardim Martins, Brendan Page,  @ChristlGaubitz…characterized another mutation in PCNA that also causes PARD. However, this mutation did not change the shape of PCNA – instead, it made it less stable at higher temperatures.This instability affects the function of PCNA enough to lead to the same disease phenotype. image is from a publication showing cell migration capabilities of patient cellsThe  @BrianKelch  lab’s understanding of how these mutations cause disease might help scientists develop a treatment for this currently uncurable disease and to untangle PCNA’s role in cancer! #RareDiseaseDayRare disease #2: Severe Congenital Neutropenia (SCN).   @Mary_Munson4  lab & Peter Newburger’s lab study one form of this rare disease that occurs in children. They study SCN5 that is linked to mutations in VPS45. image is a ribbon model of the proteinVPS45 is an evolutionarily conserved protein that regulates membrane fusion in the endosomal trafficking pathway (moves proteins and lipids around inside the cell).Severe Congenital Neutropenia occurs when the body has problems producing a type of immune cell called neutrophils. These cells are a type of white blood cell that help eat and destroy harmful invaders like bacteria and fungi. image is an illustration of a neutrophilWithout enough neutrophils, patients’ immune systems are severely dampened. Since this disease is congenital (present at birth), infant patients often develop life-threatening infections before they are 6 months old. In the future, the biochemical, structural and cell biological studies of VPS45 by  @mary_munson4  and colleagues may help scientists design treatments for Severe Congenital Neutropenia 5 that stabilize VPS45 and help it do its job inside neutrophils.To learn more about  @mary_munson4  and  @briankelch  work on #RareDiseaseDay as part of the  @RareDiseaseCure  institute  @UMassChan  , check out our website!

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