Sarah K. Bergren

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A key issue in cancer biology is whether oncogenic transformation of different cell types of origin within an adult tissue gives rise to distinct tumor subtypes that differ in their prognosis and/or treatment response. We now show that initiation of prostate tumors in basal or luminal epithelial cells in mouse models results in tumors with distinct(More)
Mutations of the lipid phosphatase FIG4 that regulates PI(3,5)P(2) are responsible for the recessive peripheral-nerve disorder CMT4J. We now describe nonsynonymous variants of FIG4 in 2% (9/473) of patients with amyotrophic lateral sclerosis (ALS) and primary lateral sclerosis (PLS). Heterozygosity for a deleterious allele of FIG4 appears to be a risk(More)
The identification of cell types of origin for cancer has important implications for tumor stratification and personalized treatment. For prostate cancer, the cell of origin has been intensively studied, but it has remained unclear whether basal or luminal epithelial cells, or both, represent cells of origin under physiological conditions in vivo. Here, we(More)
The intrinsic ability to exhibit self-organizing morphogenetic properties in ex vivo culture may represent a general property of tissue stem cells. Here we show that single luminal stem/progenitor cells can generate prostate organoids in a three-dimensional culture system in the absence of stroma. Organoids generated from CARNs (castration-resistant(More)
We originally isolated Scnm1 as a disease modifier gene that is required for efficient in vivo splicing of a mutant splice donor site in the sodium channel Scn8a. It was previously unclear whether the modifier effect on splicing was direct or indirect. We now report evidence that sodium channel modifier 1 (SCNM1) has a direct role in splicing. SCNM1 protein(More)
Mutations in the voltage-gated sodium channels SCN1A and SCN2A are responsible for several types of human epilepsy. Variable expressivity among family members is a common feature of these inherited epilepsies, suggesting that genetic modifiers may influence the clinical manifestation of epilepsy. The transgenic mouse model Scn2a Q54 has an epilepsy(More)
A mutation in the voltage-gated sodium-channel Scn2a results in moderate epilepsy in transgenic Scn2a(Q54) mice maintained on a C57BL/6J strain background. The onset of progressive epilepsy begins in adults with short-duration partial seizures that originate in the hippocampus. The underlying abnormality is an increase in persistent sodium current in(More)
Mutations in voltage-gated sodium channels are associated with several types of human epilepsy. Variable expressivity and penetrance are common features of inherited epilepsy caused by sodium channel mutations, suggesting that genetic modifiers may influence clinical severity. The mouse model Scn2a Q54 has an epilepsy phenotype due to a mutation in Scn2a(More)
The auxiliary spliceosomal protein SCNM1 contributes to recognition of nonconsensus splice donor sites. SCNM1 was first identified as a modifier of the severity of a sodium channelopathy in the mouse. The most severely affected strain, C57BL/6J, carries the variant allele SCNM1R187X, which is defective in splicing the mutated donor site in the Scn8a(medJ)(More)
Membrane-bound phosphoinositides are signaling molecules that play a key role in vesicle trafficking in eukaryotic cells (Di Paolo and De Camilli, 2006). Proteins that bind specific phosphoinositides mediate interactions between membrane-bounded compartments whose identity is partially encoded by cytoplasmic phospholipid tags. Little is known about the(More)