Biology subjects

Willis, K. A.

Publications and source records attributed to Willis, K. A..

7 recordsLinked to original sources

bioRxiv2025

A thirty-year trend of increasing clinical orientation at the National Institutes of Health

It is widely recognized that funding for biomedical research supports the development of major medical advances. However, little systematic effort has been made to determine whether a link exists between the types of funding opportunities that are available to scientists and progress towards new treatments in the clinic. To better understand this relationship, we analyzed the funding opportunities offered by the National Institutes of Health (NIH) over a span of thirty-two years, together with the resulting portfolio of applications and awards. We found NIH funding opportunity announcements became more numerous and increasingly clinically oriented over that span, following a trend that parallels the increasing clinical and translational orientation of both NIH grant applications and NIH-funded publications. Surprisingly, this increase appears to be independent of the representation of clinician-scientists in the NIH workforce.

scientific communication and education↗

bioRxiv2025

Prediction of transformative breakthroughs in biomedical research

The ability to predict scientific breakthroughs at scale would accelerate the pace of discovery and improve the efficiency of research investments. Recent advances in artificial intelligence, graph theory, and computing power have provided new ways to pursue this elusive goal. We have identified a common signature within co-citation networks that accurately predicts the occurrence of breakthroughs in medical research, on average more than 5 years in advance of the subsequent publication(s) that announced the discovery. A combination of features produces these diagnostic signals: a burst of papers exploring a novel scientific concept, an unusually high number of very influential papers in specialty journals, and low topical cohesion of the associated content. We analyzed two different periods separated by 20 years to show that the kinetics of breakthrough formation are conserved, suggesting that our approach can be used to predict which topics will produce future transformative discoveries. Significance statementScientific breakthroughs are rare, as is contemporaneous recognition of their initial expression. Faster, more efficient identification of topics likely to produce future breakthroughs would speed scientific and technological progress. We introduce an AI/ML-detected signature in co-citation networks that recognizes such topics up to twelve years before the breakthrough itself occurs. Our findings illustrate how a better understanding of the scientific process may lead to greater scientific returns.

scientific communication and education↗

bioRxiv2023

Antimicrobial peptides modulate pulmonary inflammation by altering the intestinal microbiota

Mammalian mucosal barriers secrete antimicrobial peptides (AMPs) as critical host-derived regulators of the microbiota. However, mechanisms that support homeostasis of the microbiota in response to inflammatory stimuli such as supraphysiologic oxygen remain unclear. Here, we show that neonatal mice breathing supraphysiologic oxygen or direct exposure of intestinal organoids to supraphysiologic oxygen suppress the intestinal expression of AMPs and alters the composition of the intestinal microbiota. Oral supplementation of the prototypical AMP lysozyme to hyperoxia exposed neonatal mice reduced hyperoxia-induced alterations in their microbiota and was associated with decreased lung injury. Our results identify a gut-lung axis driven by intestinal AMP expression and mediated by the intestinal microbiota that is linked to lung injury. Together, these data support that intestinal AMPs modulate lung injury and repair. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=185 SRC="FIGDIR/small/529700v2_ufig1.gif" ALT="Figure 1"> View larger version (66K): org.highwire.dtl.DTLVardef@800123org.highwire.dtl.DTLVardef@1caac5forg.highwire.dtl.DTLVardef@faa875org.highwire.dtl.DTLVardef@49c4e9_HPS_FORMAT_FIGEXP M_FIG C_FIG In BriefUsing a combination of murine models and organoids, Abdelgawad and Nicola et al. find that suppression of antimicrobial peptide release by the neonatal intestine in response to supra-physiological oxygen influences the progression of lung injury likely via modulation of the ileal microbiota. HighlightsO_LISupraphysiologic oxygen exposure alters intestinal antimicrobial peptides (AMPs). C_LIO_LIIntestinal AMP expression has an inverse relationship with the severity of lung injury. C_LIO_LIAMP-driven alterations in the intestinal microbiota form a gut-lung axis that modulates lung injury. C_LIO_LIAMPs may mediate a gut-lung axis that modulates lung injury. C_LI

microbiology↗

bioRxiv2022

Dietary Lipid Oxidization Products Alter Growth, Adiposity and Gut Microbial Ecology in Prepubertal Porcine Model

Elevated levels of dietary fats in westernized diets, associated with increased risk of obesity and other chronic diseases, are increasingly consumed by children in the United States. Cooking practices such as high heat frying and increased use of oxidizable sources of fats have introduced high levels of lipid oxidation products (LOPs) into these diets. The effects of these highly reactive dietary compounds on human biology are largely unstudied, especially in the gut where these compounds are likely present at higher concentrations. Given that the gut microbiome can be influenced by dietary components and then in turn have a systemic impact, we investigated the effects of consuming LOPs on gut bacterial and fungal communities and on growth and body composition during the prepubertal period in a porcine model. The presence of LOPs in the high fat diet reduced growth and body fat gain in the model. The gut microbiome was uniquely altered by both high fat and the presence of LOPs, with notable changes in the abundances of Turicibacterales, Spriochaetales, RF39, Lactobacillales and Erysipelotrichales. The mycobiome was dominated by Kazachstania, a porcine specific yeast, which was only minimally influenced by the dietary regimen. Application of machine learning identified dietary fat and LOPs as strong predictors of body fat. The genus Methanobrevibacter was the key microbial predictor of body fat. This study highlights the need for further studies on the biological effects of LOPs which have become ubiquitous in human, livestock and pet diets in developed countries.

physiology↗

bioRxiv2021

The effect of mentee and mentor gender on scientific productivity of applicants for NIH training fellowships

Several studies have suggested that women in science are less productive than men, and that this gap contributes to their under-representation in the ranks of senior researchers. However, few studies have examined the role of mentoring, and in particular mentor gender, on the productivity of female scientists early in their careers. Such efforts are limited by the difficulties of unambiguously linking mentees to their mentors and measuring the research productivity resulting from those relationships. Here we use our novel author disambiguation solution to investigate the role of self-identified gender in mentorship of 12,932 trainees who either successfully or unsuccessfully applied to the National Institutes of Health for research fellowships between fiscal years 2011 and 2017, applying a multi-dimensional framework to assess productivity. We found that, after normalizing for the funding level of mentors, the productivity of female and male mentees is indistinguishable; it is also independent of the gender of the mentor, other than in measures of clinical impact, where women mentored by women outperform other mentee-mentor dyads.

scientific communication and education↗

bioRxiv2020

The gut mycobiome of healthy mice is shaped by the environment and shapes metabolic outcomes in response to diet

ObjectiveAs an active interface between the host and their diet, the gut bacteriome influences host metabolic adaptation. However, the contribution of gut fungi to host metabolic outcomes is not yet understood. Therefore, we aimed to determine if host metabolic response to an ultraprocessed diet reflects gut fungal community composition. DesignWe compared jejunal fungi and bacteria from 72 healthy mice with the same genetic background but different starting mycobiomes before and after 8 weeks on an ultra-processed or standardized diet using 16S and internal transcribed spacer region 2 ribosomal RNA sequencing. We measured host body composition using magnetic resonance imaging, examined changes in metabolically active host tissues and quantified serum metabolic biomarkers. ResultsGut fungal communities are highly variable between mice, differing by vendor, age and sex. After exposure to an ultra-processed diet for 8 weeks, persistent differences in fungal community composition strongly associate with differential deposition of body mass in male mice compared to mice on standardized diet. Fat deposition in the liver, genomic adaptation of metabolically active tissues and serum metabolic biomarkers are correlated with alterations in fungal diversity and community composition. Variation in fungi from the genera Thermomyces and Saccharomyces most strongly associate with increased weight gain. ConclusionsIn the gut of healthy mice, host-microbe metabolic interactions strongly reflect variability in fungal communities. Our results confirm the importance of luminal fungal communities to host metabolic adaptation to dietary exposure. Gut fungal communities may represent a therapeutic target for the prevention and treatment of metabolic disease. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=169 SRC="FIGDIR/small/158287v1_ufig1.gif" ALT="Figure 1"> View larger version (40K): org.highwire.dtl.DTLVardef@1d80579org.highwire.dtl.DTLVardef@14f5729org.highwire.dtl.DTLVardef@1e379bcorg.highwire.dtl.DTLVardef@14d2ab6_HPS_FORMAT_FIGEXP M_FIG C_FIG In BriefO_LIWhat is already known about this subject? Gut bacterial communities have evolved to influence the metabolic outcomes of the host in mammals. Evidence from across the lifespan suggests that differences in composition of these communities is associated with energy consumption. However, gut microbial communities, while often equated to bacteria, are diverse, multi-kingdom ecologies and limited information is available for the role of other kingdoms of life, such as fungi. C_LIO_LIWhat are the new findings? Gut fungal communities, collectively termed the mycobiome, are less diverse and abundant than bacterial communities in the gastrointestinal tract. This study identifies the considerable influence of the environment and dietary exposure on the composition of jejunal fungal communities in healthy mice with the same genetic background. After exposure to processed diet, differences in fungal community composition in male mice were strongly correlated with persistent differences body composition and markers of metabolic tone. C_LIO_LIHow might it impact on clinical practice in the foreseeable future? These results verify that the baseline metabolic tone of health mice strongly reflects the ecological complexity of the gastrointestinal mycobiome. Variation in the composition of gut fungal communities is likely an underappreciated source of experimental and clinical variability in metabolic studies. Gastrointestinal fungi are likely a target for prevention and treatment of metabolic disease. C_LI

microbiology↗

bioRxiv2019

Fungi form interkingdom microbial communities in the primordial human gut that develop with gestational age

Fungal and bacterial commensal organisms play a complex role in the health of the human host. Expansion of commensal ecology after birth is a critical period in human immune development. However, the initial fungal colonization of the primordial gut remains undescribed. To investigate primordial fungal ecology, we performed amplicon sequencing and culture-based techniques of first-pass meconium, which forms in the fetal intestine prior to birth, from a prospective observational cohort of term-born and preterm newborns. Here, we describe fungal ecologies in the primordial gut that develop complexity with advancing gestational age at birth. Our findings suggest homeostasis of fungal commensals may represent an important aspect of human biology present even before birth. Unlike bacterial communities which gradually develop complexity, the domination of the fungal communities of some preterm infants by Saccromycetes, specifically Candida, may suggest a pathologic association with preterm birth.

microbiology↗