Shailesh, K. Shahi, PhD
Education
BSc, Biology, Magadh University, India
MSc, Biotechnology, Banaras Hindu University, India
PhD, Biotechnology, Banaras Hindu University, India
Research Description
Multiple Sclerosis (MS) is a chronic inflammatory and demyelinating disease of the CNS that affects nearly one million Americans (Nelson et. al. 2019). Studies on large samples of individuals with MS show that the combined prevalence of those who are overweight (body mass index-BMI ≥ 25 kg/m²) or obese (BMI ≥ 30 kg/m²) ranges from 50 to 65 percent, indicating that the majority of patients with MS are overweight or obese (Wang et. al. 2024). Epidemiological evidence also confirm that obesity increases the risk and severity of MS (Lutfullin et. al. 2023). A Western diet rich in protein and fat contributes to an increased incidence of obesity (650 million people worldwide and 100 million in the USA), alters the gut microbiota, and increases inflammatory diseases, including MS (Hoffman et. al. 2023). Moreover, obesity reduces the efficacy of standard immunomodulatory therapies in autoimmune diseases, including MS (Huppke et al., 2019; Signoriello et al., 2020). Despite this evidence, the precise mechanisms by which obesity promotes treatment resistance and worsens disease severity remain unknown.
Given the increasing prevalence of overweight and obese individuals and their heightened susceptibility to autoimmune and inflammatory demyelinating diseases, my long-term goal is to uncover the mechanisms that drive MS severity in the context of obesity. By doing so, I aim to develop novel therapeutic interventions tailored to this patient population. My overarching ambition is to establish a cutting-edge translational research laboratory focused on elucidating the mechanistic links between obesity, gut microbiota, and the heightened risk and severity of MS, as well as other inflammatory diseases and cancer.
Additionally, 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 (Shahi et. al., 2019; Shahi et. al., 2020; Mangalam and Shahi et al., 2017). We are utilizing 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.
Fellowships & Positions Held
- July 2023–Current: Junior Faculty (Pathology Instructor), University of Iowa, Iowa City, IA, USA
- June 2021–June 2023: 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
Awards
2007 | Best Paper Award, National Conference, Microbial Diversity: Avenue and Applications, Dehradun, UK, India |
2010 | Award Paper for Diabetic foot Care Specialist 2nd Prize 9th Annual National Conference Diabetic foot Society of India, Bangalore, India |
2014 | Young Scientist Award (Research Grant), Department of Science Technology Government of India, New Delhi, India |
2016 | National Multiple Sclerosis Society’s Travel Award, Autumn Immunology Conference (AIC), Chicago, USA |
2017 | American Association of Immunologists (AAI) Trainee Abstract Award, Washington DC, USA |
2018 | Americas Committee for Treatment and Research in Multiple Sclerosis Educational Travel Award, ACTRIMS Forum, San Diego, California, USA |
2018 | American Association of Immunologists (AAI) Trainee Abstract Award, Austin, TX, USA |
2019 | American Association of Immunologists (AAI) Trainee Abstract Award, San Diego, California, USA |
2020 | American Association of Immunologists (AAI) Trainee Abstract Award, Honolulu, Hawai'I, USA |
2021 | American Association of Immunologists (AAI) Trainee Abstract Award, Virtual annual meeting, USA |
2023 | 2023 AAI Early Career Faculty Travel Award, American Association of Immunology Meeting, Immunology- 2023, Washington, DC. USA |
2024 | 2024 AAI Early Career Faculty Travel Award, American Association of Immunology Meeting, Immunology- 2024, Chicago, Illinois, USA |
Publications
- 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). PMID: 36164343
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- Turner TA, Lehman P, Ghimire S, Shahi SK, and Mangalam A. (2024). Game of microbes: the battle within - gut microbiota and multiple sclerosis. Gut Microbes, 16(1). https://doi.org/10.1080/19490976.2024.2387794. PMID: 39114974
- Hoang J, Gilbertson-White S, Cady N, Yadav M, Shahi S, Aguilar L, Mangalam AK, Cherwin C (2024). Preliminary analysis of gut microbiome and gastrointestinal symptom burden in breast cancer Patients receiving chemotherapy compared to healthy controls. Biol Res Nurs. doi: 10.1177/10998004231205277. PMID: 37830211.
- Lehman PC, Cady N, Ghimire S, Shahi SK, Shrode RL, Lehmler HJ, Mangalam AK (2023). Low-dose glyphosate exposure alters gut microbiota composition and modulates gut homeostasis. Environ Toxicol Pharmacol. 15;100:104149. doi: 10.1016/j.etap.2023. PMID: 37196884.
- 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. PMID: 36179318
- 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
- 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
- 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, 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
- 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: 19934183
- 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.
Intellectual Property
- Intellectual Property (US Patent US20240091279A1) Combination of Phytoestrogen Plus Gut Bacteria as a Treatment for Inflammatory Disease (US patent -US20240091279A1) Date: 2024/3/21.
Book Chapters
- 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.