Shailesh K. Shahi, PhD
Postdoctoral Research Scholar
Department of Pathology
1080 Medical Laboratories
500 Newton Road
University of Iowa
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
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
2006-2010: Senior Research Fellow of Indian Council of Agricultural Research (ICAR), New Delhi, India
2010-2014: Senior Research Fellow of Indian Council of Medical Research (ICMR), New Delhi, India
2014-2015: Assistant Professor at S.M.W. College, Mahatma Gandhi Kashi Vidyapith University, UP, India: Directed bench top research
2015-current: Postdoctoral Research Scholar, Mangalam’s Laboratory, University of Iowa, Iowa City, IA, USA
- 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)
- 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 Report. 20, 1-9, DOI. http://dx.doi.org/10.1016/j.celrep.2017.07.031.
- 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.
- Freedman SN, Shahi SK, and Mangalam AK (2017). The Gut Feeling: Breaking Down the Role of Gut Microbiome in Multiple Sclerosis. Neurotherapeutics, DOI. 10.1007/s13311-017-0588-x.
- Shahi SK and Kumar A. (2016). Isolation and genetic analysis of multidrug resistant bacteria from diabetic foot ulcers. Frontiers in Microbiology. 6:1464. doi: 10.3389/fmicb.2015.01464.
- 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. Journal of Microbiology and Biotechnology. 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.
- 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. Journal of Molecular Modelling. 19: 973-983. doi: 10.1007/s00894-012-1635-5.
- 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. African Journal of Microbiology Research. 7: 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. The Journal of 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.
- Shahi SK, Rai AK, Tyagi MB, Sinha RP, Kumar A. (2011) Rhizosphere of rice plants harbor bacteria with multiple plant growth promoting features. African Journal of Biotechnology. 10: 8296-8305.
- Singh SK, Gupta K, Tiwari S, Shahi SK, Kumar S, Gupta SK, Kumar A. (2009) Analysis of aerobic bacterial diversity in diabetic foot infections. The International Journal of Lower Extremity Wounds. 8: 203-208. doi: 10.1177/1534734609353080.
- 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, Chandary 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.