Laura Tipton

Bio: Laura Tipton is an academic researcher from New York University. The author has contributed to research in topics: Microbiome & Lung microbiome. The author has an hindex of 10, co-authored 18 publications receiving 605 citations. Previous affiliations of Laura Tipton include Chaminade University of Honolulu & University of Hawaii at Manoa.

Salicylate (Salsalate) in Patients With Type 2 Diabetes: A Randomized Trial

Abstract: Salicylate is one of the oldest drugs in clinical practice, with documented use of relevant plant extracts for treating pain and inflammation dating back at least 3500 years (1). Nevertheless, its medicinal properties and mechanisms of action remain incompletely understood. Chemically pure forms were introduced during the 19th century (2, 3), but by the century’s end, salicylate had been acetylated by chemists to yield aspirin, which became the most used—and most marketed—drug in history (1, 4). The mechanism of aspirin is well-established; the acetyl group covalently modifies a serine at the active site of the cyclooxygenase (COX) enzymes (5), making it the prototypic nonsteroidal anti-inflammatory drug (NSAID). Salicylate lacks an acetyl group and, thus, must have a different mechanism of action. Neither salicylate nor prodrugs, including salsalate or trilisate, which are marketed for pain, have been tested for efficacy and safety under what regulatory agencies now consider to be current standard practice in clinical trials. Interest in salicylate was renewed after suggestions that it lowers blood glucose in type 2 diabetes mellitus (T2DM) (6). Results from proof-of-principle studies using salsalate in patients with T2DM demonstrated reduced blood glucose, triglyceride, free fatty acid, and C-reactive protein concentrations; improved glucose utilization during euglycemic hyperinsulinemic clamp (defined as the glucose infusion rate required to maintain euglycemia at steady state during insulin infusion); and increased circulating insulin and adiponectin levels (7). The National Institutes of Health–sponsored TINSAL-T2D (Targeting Inflammation Using Salsalate in Type 2 Diabetes) trials determine whether this generic and inexpensive drug is safe, tolerated, and efficacious in diabetes. Stage 1, a dose-ranging study, was reported (8); stage 2 of TINSAL-T2D is a larger study to assess the magnitude and durability of glycemic efficacy over 1 year, tolerability, and an array of safety variables relevant to patients with diabetes.

Fungi stabilize connectivity in the lung and skin microbial ecosystems

Abstract: No microbe exists in isolation, and few live in environments with only members of their own kingdom or domain. As microbiome studies become increasingly more interested in the interactions between microbes than in cataloging which microbes are present, the variety of microbes in the community should be considered. However, the majority of ecological interaction networks for microbiomes built to date have included only bacteria. Joint association inference across multiple domains of life, e.g., fungal communities (the mycobiome) and bacterial communities, has remained largely elusive. Here, we present a novel extension of the SParse InversE Covariance estimation for Ecological ASsociation Inference (SPIEC-EASI) framework that allows statistical inference of cross-domain associations from targeted amplicon sequencing data. For human lung and skin micro- and mycobiomes, we show that cross-domain networks exhibit higher connectivity, increased network stability, and similar topological re-organization patterns compared to single-domain networks. We also validate in vitro a small number of cross-domain interactions predicted by the skin association network. For the human lung and skin micro- and mycobiomes, our findings suggest that fungi play a stabilizing role in ecological network organization. Our study suggests that computational efforts to infer association networks that include all forms of microbial life, paired with large-scale culture-based association validation experiments, will help formulate concrete hypotheses about the underlying biological mechanisms of species interactions and, ultimately, help understand microbial communities as a whole.

Topographic Diversity of the Respiratory Tract Mycobiome and Alteration in HIV and Lung Disease

Abstract: Rationale: Microbiome studies typically focus on bacteria, but fungal species are common in many body sites and can have profound effects on the host. Wide gaps exist in the understanding of the fungal microbiome (mycobiome) and its relationship to lung disease.Objectives: To characterize the mycobiome at different respiratory tract levels in persons with and without HIV infection and in HIV-infected individuals with chronic obstructive pulmonary disease (COPD).Methods: Oral washes (OW), induced sputa (IS), and bronchoalveolar lavages (BAL) were collected from 56 participants. We performed 18S and internal transcribed spacer sequencing and used the neutral model to identify fungal species that are likely residents of the lung. We used ubiquity–ubiquity plots, random forest, logistic regression, and metastats to compare fungal communities by HIV status and presence of COPD.Measurements and Main Results: Mycobiomes of OW, IS, and BAL shared common organisms, but each also had distinct members. Candida was d...

Correlation of the lung microbiota with metabolic profiles in bronchoalveolar lavage fluid in HIV infection

Abstract: While 16S ribosomal RNA (rRNA) sequencing has been used to characterize the lung’s bacterial microbiota in human immunodeficiency virus (HIV)-infected individuals, taxonomic studies provide limited information on bacterial function and impact on the host. Metabolic profiles can provide functional information on host-microbe interactions in the lungs. We investigated the relationship between the respiratory microbiota and metabolic profiles in the bronchoalveolar lavage fluid of HIV-infected and HIV-uninfected outpatients. Targeted sequencing of the 16S rRNA gene was used to analyze the bacterial community structure and liquid chromatography-high-resolution mass spectrometry was used to detect features in bronchoalveolar lavage fluid. Global integration of all metabolic features with microbial species was done using sparse partial least squares regression. Thirty-nine HIV-infected subjects and 20 HIV-uninfected controls without acute respiratory symptoms were enrolled. Twelve mass-to-charge ratio (m/z) features from C18 analysis were significantly different between HIV-infected individuals and controls (false discovery rate (FDR) = 0.2); another 79 features were identified by network analysis. Further metabolite analysis demonstrated that four features were significantly overrepresented in the bronchoalveolar lavage (BAL) fluid of HIV-infected individuals compared to HIV-uninfected, including cystine, two complex carbohydrates, and 3,5-dibromo-l-tyrosine. There were 231 m/z features significantly associated with peripheral blood CD4 cell counts identified using sparse partial least squares regression (sPLS) at a variable importance on projection (VIP) threshold of 2. Twenty-five percent of these 91 m/z features were associated with various microbial species. Bacteria from families Caulobacteraceae, Staphylococcaceae, Nocardioidaceae, and genus Streptococcus were associated with the greatest number of features. Glycerophospholipid and lineolate pathways correlated with these bacteria. In bronchoalveolar lavage fluid, specific metabolic profiles correlated with bacterial organisms known to play a role in the pathogenesis of pneumonia in HIV-infected individuals. These findings suggest that microbial communities and their interactions with the host may have functional metabolic impact in the lung.

The lung mycobiome in the next-generation sequencing era

Abstract: The fungi that reside in the human lungs represent an understudied, but medically relevant comm-unity. From the few studies published on the lung mycobiome, we find that there are fungi in both the healthy and diseased respiratory tract, that these fungi vary widely between individuals, and that there is a trend toward lower fungal diversity among individuals with disease. This review discusses the few studies of the lung mycobiome and details the challenges that accompany lung mycobiome studies. These challenges include sample collection and processing, sequence amplification and processing, and a history of multiple names for species. Some challenges may never be solved, but others can be solved with more data and additional studies of the lung mycobiome.

The Theory of Island Biogeography

Abstract: Preface to the Princeton Landmarks in Biology Edition vii Preface xi Symbols Used xiii 1. The Importance of Islands 3 2. Area and Number of Speicies 8 3. Further Explanations of the Area-Diversity Pattern 19 4. The Strategy of Colonization 68 5. Invasibility and the Variable Niche 94 6. Stepping Stones and Biotic Exchange 123 7. Evolutionary Changes Following Colonization 145 8. Prospect 181 Glossary 185 References 193 Index 201

Inflammation, metaflammation and immunometabolic disorders

Abstract: Proper regulation and management of energy, substrate diversity and quantity, as well as macromolecular synthesis and breakdown processes, are fundamental to cellular and organismal survival and are paramount to health. Cellular and multicellular organization are defended by the immune response, a robust and critical system through which self is distinguished from non-self, pathogenic signals are recognized and eliminated, and tissue homeostasis is safeguarded. Many layers of evolutionarily conserved interactions occur between immune response and metabolism. Proper maintenance of this delicate balance is crucial for health and has important implications for many pathological states such as obesity, diabetes, and other chronic non-communicable diseases.

Mechanisms of Insulin Action and Insulin Resistance

Abstract: The 1921 discovery of insulin was a Big Bang from which a vast and expanding universe of research into insulin action and resistance has issued. In the intervening century, some discoveries have ma...

Immunity to Fungal Infections

Abstract: Fungal diseases represent an important paradigm in immunology, as they can result from either a lack of recognition by the immune system or overactivation of the inflammatory response. Research in this field is entering an exciting period of transition from studying the molecular and cellular bases of fungal virulence to determining the cellular and molecular mechanisms that maintain immune homeostasis with fungi. The fine line between these two research areas is central to our understanding of tissue homeostasis and its possible breakdown in fungal infections and diseases. Recent insights into immune responses to fungi suggest that functionally distinct mechanisms have evolved to achieve optimal host-fungus interactions in mammals.