A5029939895- Microbial Metabolic Engineering and Bioproduction
- Celiac Disease Research and Management
- Microbial Metabolites in Food Biotechnology
- Gene Regulatory Network Analysis
- Biofuel production and bioconversion
- Digestive system and related health
- Helicobacter pylori-related gastroenterology studies
- Process Optimization and Integration
- Gut microbiota and health
- Bioinformatics and Genomic Networks
- Enzyme Catalysis and Immobilization
- Bacterial Genetics and Biotechnology
- Nutrition, Genetics, and Disease
- Advanced Control Systems Optimization
- Evolution and Genetic Dynamics
- Microbial Community Ecology and Physiology
- RNA and protein synthesis mechanisms
- Viral Infectious Diseases and Gene Expression in Insects
- Optimization and Variational Analysis
- Optimization and Mathematical Programming
- Cell Image Analysis Techniques
- Experimental Behavioral Economics Studies
- Nutrition and Health in Aging
- Renal and related cancers
- Cerebrovascular and genetic disorders
Harvard University
2020-2025
Massachusetts General Hospital
2020-2025
Boston University
2014-2022
MaineGeneral Medical Center
2020-2021
Lemuel Shattuck Hospital
2021
Pennsylvania State University
2010-2014
Microorganisms rarely live isolated in their natural environments but rather function consolidated and socializing communities. Despite the growing availability of high-throughput sequencing metagenomic data, we still know very little about metabolic contributions individual microbial players within an ecological niche extent directionality interactions among them. This calls for development efficient modeling frameworks to shed light on less understood aspects metabolism Here, introduce...
Most microbial communities change with time in response to changes and/or perturbations environmental conditions. Temporal variations interspecies metabolic interactions within these can significantly affect their structure and function. Here, we introduce d-OptCom, an extension of the OptCom procedure, for dynamic modeling communities. It enables capturing temporal dynamics biomass concentration community members extracellular shared metabolites, while integrating species- community-level...
Significance The incidence of chronic inflammatory autoimmune conditions, such as celiac disease (CD), is increasing at an alarming rate. CD the only condition for which trigger, gluten, known. However, its etiology and pathogenesis remain incompletely defined recent studies suggest other environmental stimuli may play a key role in pathogenesis. Here, we prospectively examine trajectory gut microbiota starting 18 mo before onset 10 infants who developed did not. We identified alterations...
Abstract Metabolite exchanges in microbial communities give rise to ecological interactions that govern ecosystem diversity and stability. It is unclear, however, how the of these varies across metabolites organisms. Here we address this question by integrating genome-scale models metabolism with evolutionary game theory. Specifically, use fitness values estimated metabolic infer evolutionarily stable multi-species “games”. We first validate our approach using a well-characterized yeast...
Computational strain design protocols aim at the system-wide identification of intervention strategies for enhanced production biochemicals in microorganisms. Existing approaches relying solely on stoichiometry and rudimentary constraint-based regulation overlook effects metabolite concentrations substrate-level enzyme while identifying metabolic interventions. In this paper, we introduce k-OptForce, which integrates available kinetic descriptions steps with stoichiometric models to sharpen...
Abstract Background Celiac disease (CD) is an autoimmune digestive disorder that occurs in genetically susceptible individuals response to ingesting gluten, a protein found wheat, rye, and barley. Research shows genetic predisposition exposure gluten are necessary but not sufficient trigger the development of CD. This suggests other environmental stimuli early life, e.g., cesarean section delivery antibiotics or formula feeding, may also play key role CD pathogenesis through yet unknown...
Computational modeling of microbial communities using GEnome-scale Models (GEMs) metabolism is a new frontier in systems biology. Here, we discuss recent developments this area ranging from high-throughput GEMs reconstruction pipelines to approaches for under steady-state and simulating temporal, evolutionary, spatiotemporal dynamics communities. We categorize these based on flux balance analysis or elementary mode mixed-bag compartmentalized their scope applications scalability large-scale...
Celiac disease (CeD) is an autoimmune condition characterized by aberrant immune response triggered the ingestion of gluten, which damages epithelial cells lining small intestine. Small intestinal (sIECs) play key roles in enzymatic digestion and absorption nutrients, maintaining gut barrier integrity, regulating response. Chronic inflammation tissue damage associated with CeD disrupt intricate network metabolic processes sIECs that support these functions, impairing their ability to perform...
Saccharomyces cerevisiae is the first eukaryotic organism for which a multi-compartment genome-scale metabolic model was constructed. Since then sequence of improved reconstructions yeast has been introduced. These models have extensively used to elucidate organizational principles metabolism and drive strain engineering strategies targeted overproductions. They also served as starting point benchmark reconstruction other organisms. In spite successive improvements in details described...
Abstract Background and aims We have identified a decreased abundance of microbial species known to potential anti-inflammatory, protective effect in subjects that developed Celiac Disease (CeD) compared those who did not. aim confirm the role one these species, namely Bacteroides vulgatus , mechanistically establish bacterial bioproducts on gluten-dependent changes human gut epithelial functions. Methods identified, isolated, cultivated, sequenced unique novel strain (20220303-A2) B. found...
Expression of the serine protease HtrA1 is decreased or abrogated in a variety human primary cancers, and higher levels expression are directly related to better response chemotherapeutics. However, precise mechanisms leading down regulation during malignant transformation unclear. To investigate gene breast cancer, we characterized tissues seven epithelial cell lines, including two non-tumorigenic lines. In tissues, was prominent normal ductal glands. DCIS invasive greatly reduced lost...
Metabolic Syndrome (MetS) is a cluster of metabolic disorders that substantially increases the risk chronic diseases. Diet plays crucial role in MetS progression, yet mechanistic understanding its impact on remains elusive. To address this gap, we conducted rigorous silico diet intervention study by leveraging organ-resolved sex-specific whole-body models metabolism. These were utilized to computationally evaluate effect 12 diverse dietary regimens key biomarkers—glucose, triacylglycerol,...
The intestinal microbiome may trigger celiac disease (CD) in individuals with a genetic disposition when exposed to dietary gluten. Research demonstrates that nutrition during infancy is crucial the engraftment. Very few studies date have focused on breast milk composition of subjects history CD gluten-free diet. Here, we utilize multi-omics approach shotgun metagenomics analyze integrated metabolome profiling 36 subjects, 20 diet and 16 healthy controls. These analyses identified...
The ensemble modeling (EM) approach has shown promise in capturing kinetic and regulatory effects the of metabolic networks. Efficacy EM procedure relies on identification model parameterizations that adequately describe all observed phenotypes upon perturbation. In this study, we propose an optimization-based algorithm for systematic genetic/enzyme perturbations to maximally reduce number models retained after each round screening. key premise here is design will scatter predicted...
Abstract Celiac Disease (CeD) is an autoimmune condition characterized by aberrant immune response triggered the ingestion of gluten, which damages epithelial cells lining small intestine. Small intestinal (sIECs) play a key role in various metabolic processes, including enzymatic digestion and absorption nutrients. Although nutritional malabsorption widely recognized CeD, underlying disrupted processes remain largely undefined. To address this knowledge gap, we constructed personalized...
Introducing heterologous pathways into host cells constitutes a promising strategy for synthesizing nonstandard amino acids (nsAAs) to enable the production of proteins with expanded chemistries. However, this has proven challenging, as expression can disrupt cellular homeostasis cell. Here, we sought optimize nsAA para-aminophenylalanine (pAF) in Escherichia coli. First, incorporated pAF biosynthesis pathway genome-scale model E. coli metabolism and computationally identified metabolic...