Shailesh K. Shahi, PhD
Associate of Pathology
Department of Pathology
University of Iowa
25 S. Grand Avenue, 1080 Medical Laboratories
Iowa City, IA 52242-1109
BSc, Biology, Magadh University, India
MSc, Biotechnology, Banaras Hindu University, India
PhD, Biotechnology, Banaras Hindu University, India
Multiple Sclerosis (MS) is a chronic inflammatory and demyelinating disease of the central nervous system of presumed autoimmune origin. Both genetic and environmental factors are associated with predisposition to MS. Among genetic factors, HLA class II genes show the strongest association. Although a number of environmental factors (Epstein-Barr virus, smoking, vitamin-D, and ultra violet light) are linked to MS susceptibility, none of them has shown significant association in epidemiological studies. Recent reports indicate that trillions of bacteria residing on our gut might play an important role in maintaining a healthy state, and significant changes in the composition of microbial flora (dysbiosis) might be a risk factor for autoimmune diseases such as MS. Based on these data, we are testing the hypothesis that i) Perturbation of gut microbial flora might be the missing environmental factor responsible for predisposition to MS; ii) MS patients have a gut dysbiosis with an increase in inflammation inducing microbial flora; and iii) restoration of MS patients’ gut flora by transfer of specific gut bacteria or a mixture of gut bacteria capable of inducing an anti-inflammatory environment might be used as a potential therapeutic agent.
Dr. Mangalam’s lab has utilized a novel HLA transgenic mouse model of MS (experimental autoimmune encephalomyelitis- EAE) to show that intestinal microflora plays an important role in the health of the host, and a single gut bacteria (Prevotella histicola) can have a drastic impact on host immunity. We will utilize HLA class II transgenic as well as wild type mice to better understand the mechanism by which gut bacteria modulate systemic immune responses to suppress inflammatory diseases such as MS. We will be also performing studies to identify important commensal bacterial species by mining our resident microbes and their metabolites to find new therapies for MS. On completion of the study we may be able to better understand the functional activity of the human gut microbiome and possibly provide a new strategy for MS treatment.
In a related project I am deciphering the mechanism of obesity induced inflammation in multiple sclerosis utilizing human leucocyte antigen (HLA) class-II transgenic mice. As obesity and gut microbiota are two major players in regulating host immune response, a better understanding of the mechanism through which these factors modulate host regulatory and pro-inflammatory immune response will help in developing better treatment options for MS. A number of studies have suggested that obesity/elevated body mass index (BMI) in early adulthood or in individual with genetically elevated BMI is associated with higher risk of MS. The exact mechanism through which obesity might predispose to MS or accelerate the disease onset is not well understood. Our preliminary data indicate that a possible conversion of Treg cells in to pro-inflammatory Trogue cells. Understanding the mechanism of obesity induced inflammation in the setting of animal model of MS and identification of pathogenic gut bacteria induced by obesity which are responsible for modulation of local mucosal as well as systemic immune response might help in filling that knowledge gap.
Fellowships & Positions Held
June 2021-Current: Associate in Pathology (Junior Faculty), University of Iowa, Iowa City, IA, USA
Sept. 2020-June 2021: Assistant Research Scientist, Mangalam’s Laboratory, University of Iowa, Iowa City, IA, USA
2015-2020: Postdoctoral Research Scholar, Mangalam’s Laboratory, University of Iowa, Iowa City, IA, USA
2014-2015: Assistant Professor at S.M.W. College, Mahatma Gandhi Kashi Vidyapith University, UP, India: Directed bench top research
2010-2014: Senior Research Fellow of Indian Council of Medical Research (ICMR), New Delhi, India
2006-2010: Senior Research Fellow of Indian Council of Agricultural Research (ICAR), New Delhi, India
2004-2006: Department of Biotechnology Studentship for Pursuing Master’s Degree in Biotechnology, Granted by Ministry of Science and Technology Government of India, New Delhi
- Podium Presentation and Trainee Abstract Award, American Association of Immunology Meeting, Virtual Immunology, USA. (2021)
- American Association of Immunology Trainee Abstract Award recipients for “Immunology- 2020 Conference” Honolulu, Hawaii. May 08-12 (2020).
- American Association of Immunology Trainee Abstract Award recipients for Immunology- 2019, Conference held in San Diego, California. May 09-14 (2019).
- American Association of Immunology Trainee Abstract Award recipient for Immunology- 2018, Conference held in Austin, TX, USA. May 04-08 (2018)
- Americas Committee for Treatment and Research in Multiple Sclerosis Educational (ACTRIMS) Travel Award recipient for ACTRIMS Forum 2018 Conference held in San Diego, California from February 1-3 (2018)
- American Association of Immunology Trainee Abstract Award recipient for Immunology- 2017, Conference held in Washington, D.C., USA (2017)
- National Multiple Sclerosis Society’s Travel Award recipients for Autumn Immunology Conference held in Chicago, USA (2016)
- Young Scientist Award (Research Grant) by Department of Science Technology, Government of India, New Delhi (2014)
- 2nd Best Paper Award in 9th Annual National Conference of Diabetic foot Society of India, Bangalore, India (2010)
- Best Paper Award (Microbial Diversity in Diabetic foot Infection) in National Conference at SBSPGI, Dehradun, India (2007)
Shahi SK*, Ghimire S, Lehman P, and Mangalam AK* (2022). Obesity induced gut dysbiosis contribute to disease severity in the animal model of multiple sclerosis. Frontier in Immunology. DOI: 10.3389/fimmu.2022.966417. (*Co-corresponding author)
Ghimire S, Cady NM., Lehman P, Peterson SR, Shahi SK, Rashid F, Giri S, and Mangalam AK (2022). Dietary Isoflavones Alter Gut Microbiota and Lipopolysaccharide Biosynthesis to Reduce Inflammation, Gut Microbes, 14:1, DOI: 10.1080/19490976.2022.2127446
Sugiura A, Andrejeva G, Voss K, Heintzman DR, Xu X, Madden MZ, Ye X, Beier KL, Chowdhury NU, Wolf MM, Young AC, Greenwood DL, Sewell AE, Shahi SK, Freedman SN, Cameron AM, Foerch P, Bourne T, Garcia-Canaveras JC, Karijolich J, Newcomb DC, Mangalam AK, Rabinowitz JD, Rathmell JC (2022). MTHFD2 is a metabolic checkpoint controlling effector and regulatory T cell fate and function. Immunity. 2022 Jan 11;55(1):65-81.e9. doi: 10.1016/j.immuni.2021.10.011. Epub 2021 Nov 11. PMID: 34767747
Aggarwal N, Deerhake ME, DiPalma D, Shahi SK, Gaggioli MR, Mangalam AK, Shinohara ML (2021). Secreted osteopontin from CD4+ T cells limits acute graft-versus-host disease. Cell Reports. 2021 Dec 28;37(13):110170. doi: 10.1016/j.celrep.2021. 110170. PMID: 34965439
Yadav M, Ali Soham, Shrode RL, Shahi SK, Jensen SN, Hoang J, Cassidy S, Olalde H, Guseva N, Paullus M, Cherwin C, Wang K, Cho T, Kamholz J, and Mangalam AK. (2022). Multiple sclerosis patients have an altered gut mycobiome and increased fungal to bacterial richness. LPoS ONE 17(4): e0264556. https://doi.org/10.1371/journal.pone.0264556. PMID: 35472144
Abu El Haija M, Ye Y, Chu Y, Herz H, Linden B, Shahi SK, Zarei K, Mangalam AK, Mcelroy SJ, Mokadem M (2021). Toll-like receptor 4 and myeloid differentiation factor 88 are required for gastric bypass-induced metabolic effects. Surg Obes Relat Dis. 2021 Dec;17(12):1996-2006. doi: 10.1016/j.soard.2021.07.019. PMID: 34462225
Shahi SK, Ali S, Jaime CM, Guseva NV, Mangalam AK (2021). HLA Class II Polymorphisms Modulate Gut Microbiota and Experimental Autoimmune Encephalomyelitis Phenotype. Immunohorizons. 2021 Aug 11;5(8):627-646. doi: 10.4049/immunohorizons.2100024. PMID: 34380664
Chau J, Yadav M, Liu B, Furqan M, Dai Q, Shahi S, Gupta A, Mercer KN, Eastman E, Hejleh TA, Chan C, Weiner GJ, Cherwin C, Lee STM, Zhong C, Mangalam A, Zhang J (2021). Prospective correlation between the patient microbiome with response to and development of immune-mediated adverse effects to immunotherapy in lung cancer. BMC Cancer. 2021 Jul 13;21(1):808. doi: 10.1186/s12885-021-08530-z. PMID: 34256732
Jensen SN, Cady NM, Shahi SK, Peterson SR, Gupta A, Gibson-Corley KN, Mangalam AK. (2021). Isoflavone diet ameliorates experimental autoimmune encephalomyelitis through modulation of gut bacteria depleted in patients with multiple sclerosis. Science Advances. 2021 Jul;7(28). doi: 10.1126/sciadv.abd4595. PMID: 34244137
Shahi SK, Freedman SN, Murra AC, Gibson-Corley KN, Karandikar NJ, Tang N, Gua H, Zhang J, Murray JA, Mangalam AK (2020). Human commensal Prevotella histicola ameliorates disease as effectively as interferon-beta in the experimental autoimmune encephalomyelitis. Frontiers in Immunology, 11:578648. doi: 10.3389/fimmu.2020.578648. PMID: 33362764
Ye Y, Abu El Haija M, Morgan DA, Guo D, Song Y, Frank A, Tian L, Riedl RA, Burnett CML, Gao Z, Zhu Z, Shahi SK, Zarei K, Couvelard A, Poté N, Ribeiro-Parenti L, Bado A, Noureddine L, Bellizzi A, Kievit P, Mangalam AK, Zingman LV, Le Gall M, Grobe JL, Kaplan LM, Clegg D, Rahmouni K, Mokadem M. (2020). Endocannabinoid Receptor-1 and Sympathetic Nervous System Mediate the Beneficial Metabolic Effects of Gastric Bypass. Cell Reports. 2020 Oct 27;33(4):108270. doi: 10.1016/j.celrep.2020.108270. PMID: 33113371
Shahi SK, Freedman SN, Dahl R, Karandikar NJ, Mangalam AK (2019). Scoring disease in an animal model of multiple sclerosis using a novel infrared-based automated activity-monitoring system. Scientific Reports. 9(1):19194. doi: 10.1038/s41598-019-55713-7. PMID: 31844134
Shahi SK, Zarei K, Guseva NV, Mangalam AK. (2019) Microbiota Analysis Using Two-Step PCR and Next-Generation 16S rRNA Gene Sequencing. The Journal of Visualized Experiments. (152). doi: 10.3791/59980. PMID: 31680682
Shahi SK, Freedman SN, Murra AC, Zarei K, Sompallae R, Gibson-Corley KN, Karandikar NJ, Murray JA, Mangalam AK (2019). Prevotella histicola, A Human Gut Commensal, Is as Potent as COPAXONE in an Animal Model of Multiple Sclerosis. Frontiers in Immunology 2019 Mar 22; 10:462. doi: 10.3389/fimmu.2019.00462. PMID: 30984162
Mangalam AK, Shahi SK, Luckey D, Karau M, Marietta E, Luo N, Choung SR Ju J, Sompallae R, Gibson-Corler K, Patel R, Rodriguez M, Chella D, Taneja V, and Murray J (2017). Human Gut-derived Commensal Bacteria Suppress Central Nervous System Inflammatory and Demyelinating Disease. Cell Reports. 20, 1-9, DOI. http://dx.doi.org/10.1016/j.celrep.2017.07.031 PMID: 28793252
Shahi SK, Freedman SN, and Mangalam AK (2017). Gut Microbiome in Multiple Sclerosis: The Players Involved and the Roles They Play. Gut Microbes, 1-9, DOI. 10.1080/19490976.2017.1349041 PMID: 28696139
Freedman SN, Shahi SK, and Mangalam AK (2018). The Gut Feeling: Breaking Down the Role of Gut Microbiome in Multiple Sclerosis. Neurotherapeutics, DOI. 10.1007/s13311-017-0588-x PMID: 29204955
Shahi SK and Kumar A. (2016). Isolation and genetic analysis of multidrug resistant bacteria from diabetic foot ulcers. Front in Microbiology. 6:1464. doi: 10.3389/fmicb.2015.01464. PMID: 26779134
Singh G, Babele P, Shahi SK, Sinha RP, Tyagi MB, Kumar A (2014). Synthesis of silver nanoparticles using cell extracts of a nitrogen-fixing cyanobacterium Anabaena doliolum and screening of their biocidal effects. J Microbiol Biotechnol. 24:1354-1367. doi.org/10.4014/jmb.1405.05003.
Shahi SK, Singh VK, Kumar A (2013). Detection of Escherichia coli and associated β-lactamases genes from diabetic foot ulcers by multiplex PCR and molecular modelling and docking of SHV-1, TEM-1, and OXA-1 β-lactamases with clindamycin and piperacillin-tazobactam. PLoS ONE 8(7): e68234. doi: 10.1371/journal.pone.0068234. PMID: 23861873
Shahi SK, Singh VK, Kumar A, Kumar S, Singh SK, Gupta SK. (2013) Interaction of dihydrofolate reductase and aminoglycoside adenyltransferase enzyme from Klebsiella pneumoniae strain DF12SA with clindamycin: a molecular modelling and docking study. J Molecular Modelling. 19: 973-983. doi: 10.1007/s00894-012-1635-5. PMID: 23097003
Shahi SK, Kumar A, Gupta SK, Singh SK (2013). Occurrence of multiple antibiotic resistance phenotype and class 1 integron in bacteria isolated from diabetic foot ulcers. Afr. J. Microbiol. Res: 5424-5432.
Shahi SK, Kumar A, Kumar S, Singh SK, Gupta SK, Singh TB (2012). Prevalence of diabetic foot ulcer and associated risk factors in diabetic patients from north India. J Diabetic Foot Complications. 3: 83-91.
Aherrao N, Shahi SK, Dwivedi A, Kumar A, Gupta SK, Singh SK (2012). PCR detection of anaerobic infection in diabetic foot wounds and effect of metronidazole therapy on treatment outcome. Wounds. 24: 283-288. PMID: 25876052
Shahi SK, Rai AK, Tyagi MB, Sinha RP, Kumar A. (2011) Rhizosphere of rice plants harbor bacteria with multiple plant growth promoting features. Afr. J. Biotechnol. 10: 8296-8305.
Singh SK, Gupta K, Tiwari S, Shahi SK, Kumar S, Gupta SK, Kumar A. (2009) Detecting aerobic bacterial diversity in patients with diabetic foot wounds using ERIC-PCR: a preliminary communication. Int. J. Low. Extrem. Wounds. 8: 203-208. doi: 10.1177/1534734609353080 PMID: 1993418
- Shahi SK, Yadav Meeta, Ghimire S, Mangalam AK (2022). Role of the gut microbiome in multiple sclerosis. International Review of Neurobiology. ISBN 0074-7742. https://doi.org/10.1016/bs.irn.2022.06.001
- Shahi SK, Rai AK, Tyagi MB, Sinha RP, Kumar A. (2013). Isolation and characterization of plant growth promoting rhizobacteria from rice crops of eastern Uttar Pradesh. In Microbial Resources for Crop Improvement (Eds. Chakraborty B, Chakraborty U.) Satish Serial Publishing House, New Delhi, India, ISBN 9789381226391. p no.85-100.
- Chaturvedy V, Kumar S, Shahi SK, Tyagi MB, Kumar A. (2012). Sodium dodecyl sulfate (SDS): Applications, toxicity, and biodegradation. In Plant Genome; Conservation, Manipulation, and diversity (Eds. Roy BK, Chaudhary BR, Sinha RP). Narosa Publishing House Pvt. Ltd. New Delhi, ISBN 978-81-8487-133-5, p no. 113-126.
- Kumar S, Shahi SK, Kumar A, Dixit VK. (2011). The Enigma of Helicobacter pylori Infection and Gastrointestinal Diseases. In Current Topics in Biotechnology and Microbiology (Eds. Dhingra HK, Jha PN, Chandary PB). LAP Lambert Academic Publishing AG & Co. KG, Dudweller Landstr, Germany, ISBN 978-3-8443-2975-9, p no. 237-267.