Biology subjects

Lohman, B. K.

Publications and source records attributed to Lohman, B. K..

4 recordsLinked to original sources

bioRxiv2022

Senescence-Induced Immune Remodeling Facilitates Metastatic Adrenal Cancer in a Sex-Dimorphic Manner

Aging is a carcinogen that markedly increases cancer risk, yet we have limited mechanistic understanding of cancer initiation in aged cells. Here, we demonstrate induction of the hallmark aging process cellular senescence, triggered by loss of Wnt inhibitor ZNRF3, remodels the tissue microenvironment and ultimately permits metastatic adrenal cancer. Detailed characterization reveals a striking sexual dimorphism. Males exhibit earlier senescence activation and a greater innate immune response. This results in high myeloid cell accumulation and lower incidence of malignancy. Conversely, females present a dampened immune response and are more prone to metastatic cancer. Senescence-recruited myeloid cells become increasingly depleted with advanced tumor progression, which is recapitulated in patients where a low myeloid signature is associated with worse outcome. Collectively, our study reveals a novel role for myeloid cells in restraining adrenal cancer progression with significant prognostic value, and provides a model for interrogating pleiotropic effects of cellular senescence in cancer. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=67 SRC="FIGDIR/small/488426v1_ufig1.gif" ALT="Figure 1"> View larger version (21K): org.highwire.dtl.DTLVardef@bddf22org.highwire.dtl.DTLVardef@18434a3org.highwire.dtl.DTLVardef@9bc772org.highwire.dtl.DTLVardef@1430fbb_HPS_FORMAT_FIGEXP M_FIG Graphical abstract created with BioRender.com C_FIG

cancer biology↗

bioRxiv2021

Evolution of a costly immunity to cestode parasites is a pyrrhic victory

Parasites impose fitness costs on their hosts. Biologists therefore tend to assume that natural selection favors infection-resistant hosts. Yet, when the immune response itself is costly, theory suggests selection may instead favor loss of resistance. Immune costs are rarely documented in nature, and there are few examples of adaptive loss of resistance. Here, we show that when marine threespine stickleback colonized freshwater lakes they gained resistance to the freshwater-associated tapeworm, Schistocephalus solidus. Extensive peritoneal fibrosis and inflammation contribute to suppression of cestode growth and viability, but also impose a substantial cost of reduced fecundity. Combining genetic mapping and population genomics, we find that the immune differences between tolerant and resistant populations arise from opposing selection in both populations acting, respectively, to reduce and increase resistance consistent with divergent optimization. One Sentence SummaryRecently-evolved freshwater populations of stickleback frequently evolve increased resistance to tapeworms, involving extensive fibrosis that suppresses parasite growth; because this fibrosis greatly reduces fish fecundity, in some freshwater populations selection has favored an infection-tolerant strategy with fibrosis suppression.

evolutionary biology↗

bioRxiv2018

SV-plaudit: A cloud-based framework for manually curating thousands of structural variants

SV-plaudit is a framework for rapidly curating structural variant (SVs) predictions. For each SV, we generate an image that visualizes the coverage and alignment signals from a set of samples. Images are uploaded to our cloud framework where users assess the quality of each image using a client-side web application. Reports can then be generated as a tab-delimited file or annotated VCF. As a proof of principle, nine researchers collaborated for one hour to evaluate 1,350 SVs each. We anticipate that SV-plaudit will become a standard step in variant calling pipelines and the crowd-sourced curation of other biological results.\n\nCode available at https://github.com/jbelyeu/SV-plaudit\n\nDemonstration video available at https://www.youtube.com/watch?v=ono8kHMKxDs

bioinformatics↗

bioRxiv2017

The role of gene expression in the recent evolution of resistance in a model host parasite system

Damage by parasites is a perpetual challenge for hosts, often leading to the evolution of elaborate mechanisms of avoidance, immunity, or tolerance. Host resistance can evolve via changes in immune protein coding and/or expression. Heritable population differences in gene expression following infection can reveal mechanisms of immune evolution. We compared gene expression in infected and uninfected threespine stickleback (Gasterosteus aculeatus) from two natural populations that differ in their resistance to a native cestode parasite, Schistocephalus solidus. Genes in both the innate and adaptive immune system were differentially expressed as a function of host population, infection status, and their interaction. These genes were enriched for loci controlling immune functions that we independently verified differ between host populations, or in response to infection. For instance, populations differ strongly in reactive oxygen (ROS) production, and we observed corresponding differences in expression of ROS-affecting loci. Differentially expressed genes also were involved in fibroblast activation, B-cell activation, and leukocyte trafficking. Coexpression network analysis identified two distinct immune processes contributing to stickleback resistance; several modules of genes are correlated with parasite survival while a different set of modules are correlated with suppression of cestode growth. Comparison of networks between populations showed resistant fish have a dynamic expression profile while susceptible fish are static. In summary, recent evolutionary divergence between two vertebrate populations has generated population-specific gene expression responses to parasite infection, which reveal a few immune modules likely to separately affect cestode establishment, and growth.

evolutionary biology↗