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个人简介
I completed my PhD from Sanjay Gandhi Postgraduate Institute of Medical Science, Lucknow, India in 2002 and postdoctoral studies from Mayo Clinic. I am currently a faculty in the Department of Pathology at Carver College of Medicine, University of Iowa, Iowa City, IA. I have authored more than 50 peer reviewed papers (till Jan 2022) in reputed journals, 5 book chapters; one patent, serve as expert reviewer for reputed journals and various grant study sections. My research program focuses on understanding role of gut microbiome in human health and disease as well as to find a better cure for human diseases including multiple sclerosis (MS). To achieve these goals, my program has three components: clinical research (identifying linkage between microbiome and microbial pathways linked with disease in people with MS (pwMS)), basic research (utilizing preclinical animal models to understand the mechanism through gut microbiome can protect or predispose to disease), and translational research (test novel therapies in a preclinical model of MS which can be translated into clinic).
We first performed a fecal microbiota profiling study in pwMS and showed that MS patients had depletion of certain bacteria whereas enrichment of others (PMID: 27346372). Using s bed to bench and back to bed method, we identified a human gut commensal "Prevotella" is depleted in pwMS, a finding validated by multiple studies all across the world. As a proof of concept, we isolated Prevotella histicola from healthy individual and observed that it can induce regulatory CD4 T cells as well as suppress disease in experimental autoimmune encephalomyelitis (EAE), an animal model of MS (Cell Reports 2017, PMID: 28793252) but also in animal models of arthritis and type 1 diabetes. We have coined a term Bacteria as drug (BRUG) to differentiate it from probiotics. This BRUG is currently under clinical trial in human and have shown encouraging results in patients with Psoriasis and COVID. We have an ongoing study using biospecimens from pwMS to identify additional microbiome and microbial pathways playing an important role in disease.
The gut microbiota help in maintaining our health by regulating various functions, including: food metabolism, energy homeostasis, maintenance of the intestinal barrier, inhibition of colonization by pathogenic organisms and shaping of both the mucosal and systemic immune responses. Alteration of the gut microbiota and resulting changes in its metabolic network perturb this homeostasis, often leading to intestinal and systemic disorders such as MS. Our microbiome study showed that MS patients have alteration in gut bacteria involved in metabolism of phytoestrogens, fibers/carbohydrates, bile acids and tryptophan. Therefore, multiple projects in the laboratory are investigating the mechanism through which gut bacteria regulate host physiology, e.g. numbers of bacteria responsible for metabolism of phytoestrogens (specifically Prevotella, Parabacteroides, and Adlercreutzia) are depleted in MS patients. We have shown that isoflavone (a type of phytoestrogen) can protect mice from MS like disease and gut bacteria are critical for this protection as protection is lost in the mice treated with broad spectrum antibiotic to deplete the gut microbiota (Science Advances 2021, PMID: 34244137).
As the name suggest that phytoestrogen are compound similar to estrogen, it is possible that phytoestrogen such as isoflavone mediate their disease protective effect through estrogen receptors. However there are two estrogen receptors (ER), ERα or ERβ and it is unknown that which one or both receptors are involved and if yes then which cells (intestinal cells vs immune cells). We are utilizing genetically modified mice and gut bacteria to understand the mechanisms through which phytoestrogen modulate host immunity and inflammation. , specifically the involvement of estrogen re Based on these two observations we are testing the hypothesis that a decrease in microbial flora associated with metabolism of plant lignan and isoflavone might be responsible for pro-inflammatory state and predisposition to disease.
We expect to utilize this bed (patients) to bench (preclinical model) and back to bed (clinical translation (approach) to develop microbiome based novel therapeutic and diagnostic agents for MS which can be translated to other human disease including cancer.
研究兴趣
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Ti-Ara J. Turner,Ashutosh K. Mangalam
Reference Module in Neuroscience and Biobehavioral Psychology (2024)
biorxiv(2024)
Moleculesno. 6729 (2023): 6729-6729
Scientific reportsno. 1 (2023): 526-526
Journal of Immunologyno. 1 (2023): 170.04-170.04
Journal of Immunologyno. 1 (2023): 77.09-77.09
bioRxiv : the preprint server for biology (2023)
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