Browsing by Author "Axelrad, Marni E."

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    The seventh international RASopathies symposium: Pathways to a cure-expanding knowledge, enhancing research, and therapeutic discovery
    (Wiley, 2022) Kontaridis, Maria I.; Roberts, Amy E.; Schill, Lisa; Schoyer, Lisa; Stronach, Beth; Andelfinger, Gregor; Aoki, Yoko; Axelrad, Marni E.; Bakker, Annette; Bennett, Anton M.; Broniscer, Alberto; Castel, Pau; Chang, Caitlin A.; Cyganek, Lukas; Das, Tirtha K.; den Hertog, Jeroen; Galperin, Emilia; Garg, Shruti; Gelb, Bruce D.; Gordon, Kristiana; Green, Tamar; Gripp, Karen W.; Itkin, Maxim; Kiuru, Maija; Korf, Bruce R.; Livingstone, Jeff R.; López-Juárez, Alejandro; Magoulas, Pilar L.; Mansour, Sahar; Milner, Theresa; Parker, Elisabeth; Pierpont, Elizabeth I.; Plouffe, Kevin; Rauen, Katherine A.; Shankar, Suma P.; Smith, Shane B.; Stevenson, David A.; Tartaglia, Marco; Van, Richard; Wagner, Morgan E.; Ware, Stephanie M.; Zenker, Martin; Pediatrics, School of Medicine
    RASopathies are a group of genetic disorders that are caused by genes that affect the canonical Ras/mitogen‐activated protein kinase (MAPK) signaling pathway. Despite tremendous progress in understanding the molecular consequences of these genetic anomalies, little movement has been made in translating these findings to the clinic. This year, the seventh International RASopathies Symposium focused on expanding the research knowledge that we have gained over the years to enhance new discoveries in the field, ones that we hope can lead to effective therapeutic treatments. Indeed, for the first time, research efforts are finally being translated to the clinic, with compassionate use of Ras/MAPK pathway inhibitors for the treatment of RASopathies. This biannual meeting, organized by the RASopathies Network, brought together basic scientists, clinicians, clinician scientists, patients, advocates, and their families, as well as representatives from pharmaceutical companies and the National Institutes of Health. A history of RASopathy gene discovery, identification of new disease genes, and the latest research, both at the bench and in the clinic, were discussed.
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    Verbal Memory Functioning in Adolescents and Young Adults with Costello Syndrome: Evidence for Relative Preservation in Recognition Memory
    (Wiley, 2013) Schwartz, David D.; Katzenstein, Jennifer M.; Hopkins, Elisabeth; Stabley, Deborah L.; Sol-Church, Katia; Gripp, Karen W.; Axelrad, Marni E.; Neurology, School of Medicine
    Costello syndrome (CS) is a rare genetic disorder caused by germline mutations in the HRAS proto-oncogene which belongs to the family of syndromes called rasopathies. HRAS plays a key role in synaptic long-term potentiation (LTP) and memory formation. Prior research has found impaired recall memory in CS despite enhancement in LTP that would predict memory preservation. Based on findings in other rasopathies, we hypothesized that the memory deficit in CS would be specific to recall, and that recognition memory would show relative preservation. Memory was tested using word-list learning and story memory tasks with both recall and recognition trials, a design that allowed us to examine these processes separately. Participants were 11 adolescents and young adults with molecularly confirmed CS, all of whom fell in the mild to moderate range of intellectual disability. Results indicated a clear dissociation between verbal recall, which was impaired (M = 69 ± 14), and recognition memory, which was relatively intact (M = 86 ± 14). Story recognition was highly correlated with listening comprehension (r = 0.986), which also fell in the low-average range (M = 80 ± 12.9). Performance on other measures of linguistic ability and academic skills was impaired. The findings suggest relatively preserved recognition memory that also provides some support for verbal comprehension. This is the first report of relatively normal performance in a cognitive domain in CS. Further research is needed to better understand the mechanisms by which altered RAS-MAPK signaling affects neuronal plasticity and memory processes in the brain.