Amber Todd

YPEL3, a p53-Regulated Gene that Induces Cellular Senescence

Cellular senescence, the limited ability of cultured normal cells to divide, can result from cellular damage triggered through oncogene activation (premature senescence) or the loss of telomeres following successive rounds of DNA replication (replicative senescence). Although both processes require a functional p53 signaling pathway, relevant downstream p53 targets have been difficult to identify. Discovery of senescence activators is important because induction of tumor cell senescence may represent a therapeutic approach for the treatment of cancer. In microarray studies in which p53 was reactivated in MCF7 cells, we discovered that Yippee-like-3 (YPEL3), a member of a recently discovered family of putative zinc finger motif coding genes consisting of YPEL1-5, is a p53-regulated gene. YPEL3 expression induced by DNA damage leads to p53 recruitment to a cis-acting DNA response element located near the human YPEL3 promoter. Physiologic induction of YPEL3 results in a substantial decrease in cell viability associated with an increase in cellular senescence. Through the use of RNAi and H-ras induction of cellular senescence, we show that YPEL3 activates cellular senescence downstream of p53. Consistent with its growth suppressive activity, YPEL3 gene expression is repressed in ovarian tumor samples. One mechanism of YPEL3 downregulation in ovarian tumor cell lines seems to be hypermethylation of a CpG island upstream of the YPEL3 promoter. We believe these findings point to YPEL3 being a novel tumor suppressor, which upon induction triggers a permanent growth arrest in human tumor and normal cells.

Validation of the Learning Progression-based Assessment of Modern Genetics in a college context

ABSTRACT Building upon a methodologically diverse research foundation, we adapted and validated the Learning Progression-based Assessment of Modern Genetics (LPA-MG) for college students’ knowledge of the domain. Toward collecting valid learning progression-based measures in a college majors context, we redeveloped and content validated a majority of a previous version of the LPA-MG which was developed for high school students. Using a Rasch model calibrated on 316 students from 2 sections of majors introductory biology, we demonstrate the validity of this version and describe how college students’ ideas of modern genetics are likely to change as the students progress from low to high understanding. We then utilize these findings to build theory around the connections college students at different levels of understanding make within and across the many ideas within the domain.

Why YPEL3 Represents a Novel Tumor Suppressor

Yippee-like 3 (YPEL3) was reported in 2004 as one of five family members of the Yippee protein with conservation in species down to slime molds. While reports of other YPEL family members have surfaced our laboratory was the first to report that YPEL3 is induced by the p53 tumor suppressor. Furthermore we demonstrated that YPEL3 is growth suppressive, triggering cellular senescence in human cell lines and is down-regulated in several human tumors. Studies with mouse YPEL3, originally named small unstable apoptotic protein (SUAP), confirmed that the gene encodes a growth suppressive highly unstable protein. In this review we show that transcriptionally active forms of p73 and p63, family members of p53, can transactivate the human YPEL3 gene. While there are several reported YPEL3 transcripts and potentially 2 protein isoforms, no clear protein structure has been reported. As evidence mounts that YPEL3 is a tumor suppressor gene, studies aimed at understanding its biological function, regulation of gene expression and impact on tumorigenesis will help.

Empirical Validation of a Modern Genetics Progression Web for College Biology Students

ABSTRACT Research in learning progressions (LPs) has been essential towards building understanding of how students’ ideas change over time. There has been little work, however, into how ideas between separate but related constructs within a multi-faceted LP relate. The purpose of this paper is to elaborate on the idea of progression webs to model connections within and between related constructs simultaneously, and to explain and demonstrate the efficacy of path analysis towards validating a hypothesised progression web for understanding of modern genetics. Specifically, we evaluate strength of evidence for a progression web based upon multiple related constructs within a multi-faceted LP describing undergraduate biology students’ understanding of genetics. We then utilise the progression web to generalise theory around how undergraduate students understand relationships between related genetics concepts, and how they use simpler concepts to scaffold those which are more complex.

The Learning Loss Effect in Genetics: What Ideas Do Students Retain or Lose After Instruction?

Modern genetics is a relatively new domain, but it is increasingly important for students to have a firm grasp on the content, because genetic technologies are becoming more commonplace. In a previous study, we used the Learning Progression-based Assessment of Modern Genetics to assess high school students’ knowledge of genetics concepts after an intensive inquiry-based genetics instructional period. Given that this type of intensive inquiry-based instruction is unique, we are now investigating how students’ knowledge of genetics changes after instruction (i.e., learning loss effect). Using a six-measure longitudinal design, we found that students retained significant gains in five of the 12 constructs 18 months after instruction; scores were not significantly different than the pretest in seven of the constructs. Through a nonparametric analysis, we found that students are better able to retain mechanistic explanations in genetics than memorized details. This study uses an learning progression framework that examines what happens to genetics knowledge over an extended period of time after instruction and indicates that classroom time is better spent helping students construct mechanistic explanations of genetic phenomena as opposed to memorizing terminology.