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Tackett, A.

Publications and source records attributed to Tackett, A..

2 recordsLinked to original sources

Farm exposure is associated with human breast milk immune profile and microbiome

Prenatal and early life farm exposure, and breastfeeding, are associated with protection from allergic diseases. We hypothesize that farm exposure influences the human breast milk microbiome and immune proteins. The immune protein profiles and microbial communities of 152 human breast milk samples were compared among three maternal farm exposure groups (traditional agrarian, farm, and non-farm) in rural Wisconsin to identify signatures associated with farm status and atopic disease. We found significant differences between farm groups for 23 immune proteins (p-adj<0.05), microbiome diversity (p=2.2E-05), and microbiome richness (p=8.0e-06). Traditional agrarian human breast milk had the highest immune protein levels and microbiome diversity and richness, followed by farm and non-farm human breast milk. Furthermore, Gram-positive bacterial species correlated with IL-23 mediated signaling events (p-adj<1.0E-05). These data suggest that increased farm exposures promotes human breast milk that is more microbially-diverse and rich in immune-associated proteins, ultimately influencing immune development in the infant.

microbiology↗

YY1 cistrome analysis uncovers an essential requirement of the YY1:BRD4-PFKP regulatory axis for promoting tumorigenesis of castration-resistant prostate cancer

Castration-resistant prostate cancer (CRPC) is a terminal disease, demanding a better understanding of its pathogenesis. Targeted therapy needs to be developed for CRPC due to its heterogeneity and resistance to current treatments. Here, through cistrome study of YY1, a transcription factor significantly overexpressed during prostate cancer progression, we identify a YY1-PFKP axis to be essential for CRPC tumorigenesis. Depletion of YY1 in independent CRPC models dramatically reduced tumor cell growth in vitro and delayed oncogenic progression in vivo. Importantly, YY1 functions as a master regulator of prostate tumor metabolism including the Warburg effect and mitochondria respiration. Loss-of-function and rescue studies further reveals a mechanistic underpinning in which YY1 directly binds and trans-activates PFKP, a gene encoding the rate-limiting enzyme for glycolysis, significantly contributing to the YY1-enforced oncogenic phenotypes such as enhanced tumor cell glycolysis and malignant growth. Additionally, a vast majority of gene-regulatory element in advanced prostate cancer cells are bound by YY1, lending a support for its role as a master regulator of prostate cancer progression. YY1 interactome studies point to bromodomain-containing coactivators in prostate cancer, which act as functional partners of YY1 to potentiate YY1-related target gene activation. Altogether, this study unveils an unexplored YY1:BRD4-PFKP oncogenic axis operating in advanced prostate cancer with implications for therapy.

cancer biology↗