Pascal Gagneux | University of California, San Diego (original) (raw)

Papers by Pascal Gagneux

Proceedings of the National Academy of Sciences of the United States of America, Sep 28, 2021

Membrane-associated mucins protect epithelial cell surfaces against pathogenic threats by serving... more Membrane-associated mucins protect epithelial cell surfaces against pathogenic threats by serving as nonproductive decoys that capture infectious agents and clear them from the cell surface and by erecting a physical barrier that restricts their access to target receptors on host cells. However, the mechanisms through which mucins function are still poorly defined because of a limited repertoire of tools available for tailoring their structure and composition in living cells with molecular precision. Using synthetic glycopolymer mimetics of mucins, we modeled the mucosal glycocalyx on red blood cells (RBCs) and evaluated its influence on lectin (SNA) and virus (H1N1) adhesion to endogenous sialic acid receptors. The glycocalyx inhibited the rate of SNA and H1N1 adhesion in a size- and density-dependent manner, consistent with the current view of mucins as providing a protective shield against pathogens. Counterintuitively, increasing the density of the mucin mimetics enhanced the retention of bound lectins and viruses. Careful characterization of SNA behavior at the RBC surface using a range of biophysical and imaging techniques revealed lectin-induced crowding and reorganization of the glycocalyx with concomitant enhancement in lectin clustering, presumably through the formation of a more extensive glycan receptor patch at the cell membrane. Our findings indicate that glycan-targeting pathogens may exploit the biophysical and biomechanical properties of mucins to overcome the mucosal glycocalyx barrier.

Genome Biology and Evolution, Jun 18, 2020

Physiological Reviews, Jan 5, 2023

Anthropogeny is a classic term encompassing transdisciplinary investigations of the origins of th... more Anthropogeny is a classic term encompassing transdisciplinary investigations of the origins of the human species. Comparative anthropogeny is a systematic comparison of humans and other living nonhuman hominids (so-called “great apes”), aiming to identify distinctly human features in health and disease, with the overall goal of explaining human origins. We begin with a historical perspective, briefly describing how the field progressed from the earliest evolutionary insights to the current emphasis on in-depth molecular and genomic investigations of “human-specific” biology and an increased appreciation for cultural impacts on human biology. While many such genetic differences between humans and other hominids have been revealed over the last two decades, this information remains insufficient to explain the most distinctive phenotypic traits distinguishing humans from other living hominids. Here we undertake a complementary approach of “comparative physiological anthropogeny,” along the lines of the preclinical medical curriculum, i.e., beginning with anatomy and considering each physiological system and in each case considering genetic and molecular components that are relevant. What is ultimately needed is a systematic comparative approach at all levels from molecular to physiological to sociocultural, building networks of related information, drawing inferences, and generating testable hypotheses. The concluding section will touch on distinctive considerations in the study of human evolution, including the importance of gene-culture interactions.

Journal of Evolutionary Biology, May 1, 1991

Journal of Heredity, May 1, 2004

F&S reports, Jun 1, 2021

Objective To examine the changes in AMH levels longitudinally over time and their relationship wi... more Objective To examine the changes in AMH levels longitudinally over time and their relationship with both body composition, particularly abdominal adiposity, and milestones of pubertal development in female children. Design Secondary analysis of a prospective, longitudinal study. Setting University affiliated research center and laboratories. Patient(s) Eighty-nine females were examined between 1990 and 2015 to study child growth and development. Intervention(s) Demographic, anthropometric, growth, and pubertal milestone data with serum samples stored and subsequently analyzed for AMH. Main Outcome Measure(s) Longitudinal change in AMH and predicted AMH levels based on body composition, age, and pubertal milestones including, pubarche, thelarche, and menarche. Result(s) Natural log-transformed AMH (AMHlog) levels appeared to have a nonlinear relationship with age, decreasing between 10 and 14 years of age, increasing until 16 years. A mixed effect linear model demonstrated that increased abdominal adiposity (waist/height ratio, WHtR) was significantly associated with the predicted increased AMHlog levels (β=1.37). As females progressed through the Tanner stages, the model predicted decreasing AMHlog values when adjusting for age and WHtR. Conclusion(s) Declining AMH levels during puberty may not be reflective of diminished ovarian reserve as observed in adults, but may suggest a permissive role of AMH in the activation of the hypothalamic-pituitary-ovarian axis.

Trends in Ecology and Evolution, Nov 1, 2004

Chem, Dec 1, 2021

ABSTRACTInfluenza A viruses (IAVs) exploit host glycans in airway epithelial mucosa to gain entry... more ABSTRACTInfluenza A viruses (IAVs) exploit host glycans in airway epithelial mucosa to gain entry and initiate infection. Rapid detection of changes in IAV specificity towards host glycan classes can provide early indication of virus transmissibility and infection potential. IAVs use hemagglutinins (HA) to bind sialic acids linked to larger glycan structures and a switch in HA specificity from α2,3-to α2,6-linked sialoglycans is considered a prerequisite for viral transmission from birds to humans. While the changes in HA structure associated with the evolution of binding phenotype have been mapped, the influence of glycan receptor presentation on IAV specificity remains obscured. Here, we describe a glycan array platform which uses synthetic mimetics of mucin glycoproteins to model how receptor presentation in the mucinous glycocalyx, including glycan type and valency of the glycoconjugates and their surface density, impact IAV binding. We found that H1N1 virus produced in embryonated chicken eggs, which recognizes both receptor types, exclusively engaged mucin-mimetics carrying α2,3-linked sialic acids in their soluble form. The virus was able utilize both receptor structures when the probes were immobilized on the array; however, increasing density in the mucin-mimetic brush diminished viral adhesion. Propagation in mammalian cells produced a change in receptor pattern recognition by the virus, without altering its HA affinity, toward improved binding of α2,6-sialylated mucin mimetics and reduced sensitivity to surface crowding of the probes. Application of a support vector machine (SVM) learning algorithm as part of the glycan array binding analysis efficiently characterized this shift in binding preference and may prove useful to study the evolution of viral responses to a new host.

Journal of Biological Chemistry, Nov 1, 2003

F&S Reports

Perspectives in Biology and Medicine, 2019

Reactome - a curated knowledgebase of biological pathways, 2010

Journal of the Royal Society Interface, Jul 24, 2007

Nature, 1997

1. Nature. 1997 May 22;387(6631):358-9. Furtive mating in female chimpanzees. Gagneux P, Woodruff... more 1. Nature. 1997 May 22;387(6631):358-9. Furtive mating in female chimpanzees. Gagneux P, Woodruff DS, Boesch C. Retraction in Nature. 2001 Nov 29;414(6863):508. PMID: 9163418 [PubMed - indexed for MEDLINE]. Publication Types: Letter; Retracted Publication. ...