J Wang*, EM Wissink*, NB Watson*, NL Smith, A Grimson, & BD Rudd. 2016. Fetal and adult progenitors give rise to unique populations of CD8+ T cells. Blood, 128: 3073-3082. PDF
Unlike adult mice, the CD8+ T cells in neonatal mice do not form long-term memory cells during infection. Here, we discovered that these differences are because the neonatal and adult cells are generated from different stem cell niches.
EM Wissink, EA Fogarty, & A Grimson. 2016. High-throughput discovery of post-transcriptional cis-regulatory elements. BMC Genomics, 17: 177. PDF
The fate of an mRNA is dictated by sequences in its untranslated regions (UTRs). Here, I used a cell-based fluorescence screen to measure the impact that thousands of sequences had on a reporter gene’s fate.
EM Wissink*, NL Smith*, R Spektor, BD Rudd, & A Grimson. 2015. MicroRNAs and their targets are differentially regulated in adult and neonatal mouse CD8+ T cells. Genetics, 201: 1017-30. PDF
Because miRNAs are developmentally regulated and needed for CD8+ T cells to respond to infections, we found ones that could underlie differences in young animals’ immune responses. Many miRNAs are differentially expressed before infection, but adults and neonates have very similar expression during infection, suggesting pre-infection differences alter how animals respond. We’re especially in miR-29 and miR-130, because their target genes also have global differences in gene expression.
NL Smith*, EM Wissink*, A Grimson, & BD Rudd. 2015. miR-150 regulates differentiation and cytolytic effector function in CD8+ T cells. Scientific Reports, 5: 16399. PDF
Here, we explored the role of a highly expressed miRNA, miR-150 in CD8+ T cells. CD8+ T cells lacking miR-150 proliferate less than wild-type cells, and they are deficient at differentiating into the effector cells that kill infected cells. I found that miR-150 is highly abundant, and I analyzed gene expression differences between the wild-type and knock-out cells, finding that knock-out cells have lower expression of genes needed for the cell cycle and cell killing. Instead, they have increased expression of transcription factors associated with memory cells.
NL Smith, E Wissink, J Wang, JF Pinello, MP Davenport, A Grimson, & BD Rudd. 2014. Rapid proliferation and differentiation impairs the development of memory CD8+ T cells in early life. Journal of Immunology, 193: 177-84. PDF
In this paper, we wanted to better understand why young mice have deficient adaptive immune systems. We found that these mice have intrinsic differences in their cytotoxic T lymphocytes which prevent them from forming memory CD8+ T cells that can fight the same infection in the future. Their cells instead preferentially make effector cells which fight the infection. I found gene expression differences between adult and young mice that mirror the phenotypic differences we observed — young mice produce more the genes needed for killing pathogens and less of the genes needed for surviving beyond the infection.
RN Saha, EM Wissink, ER Bailey, M Zhao, DC Fargo, J Hwang, KR Daigle, JD Fenn, K Adelman, & SM Dudek. 2011. Rapid activity-induced transcription of arc and other IEGs relies on poised RNA polymerase II. Nature Neuroscience 14: 848–856. PDF
We found that many genes needed for long-term memory formation use a form of transcriptional regulation called polymerase stalling. The polymerase begins transcribing a new mRNA, then stalls until a signal from the cell allows the polymerase to continue. In this way, new mRNAs can be made rapidly when needed.
JP Adams, RA Robinson, ED Hudgins, EM Wissink, & SM Dudek. 2009. NMDA receptor-independent control of transcription factors and gene expression. NeuroReport 20: 1429-33. PDF
We showed that signals traveling from neuronal dendrites to the cell body can do so even when NMDA receptors are blocked, indicating that other mechanisms are responsible for inducing transcription.