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Olfactory stimulus acquisition is perfectly synchronized with inhalation, which tunes neuronal ensembles for incoming information. Because olfaction is an ancient sensory system that provided a template for brain evolution, we hypothesized that this link persisted, and therefore sniffs may tune the brain for acquisition of non-olfactory information as well. To test this, we measured nasal airflow and electroencephalography during various non-olfactory cognitive tasks. We observed that participants spontaneously inhale at non-olfactory cognitive task onset, and that such inhalations shift brain functional network architecture. Concentrating on visuospatial perception, we observed that inhalation drove increased task-related brain activity in specific task-related brain regions, and resulted in improved performance accuracy in the visuospatial task. Thus, mental processes with no link to olfaction are nevertheless phase-locked with sniffing, consistent with the notion of an olfaction-based template in the evolution of human brain function.

The tumor microenvironment (TME) has gained increasing attention in the last few years, yet the exact mechanism by which the TME is reprogrammed to promote tumor phenotypes is not very clear. We have recently found that Heat shock factor 1 (HSF1) transcriptionally reprograms cancer associate fibroblasts (CAFs) in the TME towards a protumorigenic phenotype. HSF1 is a transcription factor that activates 3 different transcriptional programs in 3 different states of the cell - heat-shock, cancer cell and CAF. In this work I explore the hypothesis that a disparate DNA methylation or histone modification landscape results in differential access of HSF1 to the DNA, and leads to different transcriptional programs between cancer cells, CAFs and heat-shocked cells, by using bisulfite sequencing for establish a methylome profile of each cell states and Preform ChIP-seq with HSF1 antibodies in each type of cells to obtain the binding pattern of this TF in the different cells types/states. This work will provide a much-needed understanding on the epigenetic map of CAFs in the TME, which is currently lacking.

Type I interferons (IFN-1) are best known for their role in innate immunity, but they are also involved in immunomodulation, proliferation, cancer surveillance, and the regulation of the adaptive immune response. How does the interaction of a cytokine with its receptors promote such diverse activities? To answer this question, I generated knockout (KO) HeLa cell lines and learned how these KOs affect different activities. The deletion of either STAT1 or STAT2 alone reduced, but did not eliminate IFN-1 induced activities. Conversely, the deletion of both completely abrogated any IFN-1 activity. So did the double STAT2-IRF1 KO, and a knockdown of IRF9 on background of STAT1 KO, suggesting the GAS pathway and the STAT2-IRF9 dimer as complimentary pathways to STAT1-STAT2. Interestingly, deletion of any of the mentioned components had no effect on the phosporylation of any of the other STATs including STAT3 and STAT6. To directly asses the importance of STAT3 in the system, I generates its KO, which had no effect on IFN-1 activation. Those evidence suggest that IFN-1 induced signaling goes only through STAT1 and STAT2, although not both are required.