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Naseer Sangwan Laboratory

❮Microbial Sciences in Health Naseer Sangwan Laboratory
  • Naseer Sangwan Laboratory
  • Principal Investigator
  • Research
    Overview Microbiota-Driven Tuft Cell Expansion in Early-Onset Colorectal Cancer Intratumoral Microbiome Profiling in Young-Onset Gastrointestinal Cancers Host-Microbe Metabolic Interactions and Chemoresistance in Malignancies
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Principal Investigator

Naseer Sangwan Headshot

Naseer Sangwan, PhD

Associate Staff
Core Director
Email: [email protected]
Location: Cleveland Clinic Main Campus

Research

Our research program investigates host–microbiome interaction frameworks that govern gastrointestinal disease, focusing on the biological drivers of early-onset colorectal cancer. By integrating single-cell multi-omics, patient-derived colonic organoids and gnotobiotic animal models, we delineate how gut microbiota-driven epithelial cell expansion promotes precancerous adenoma formation. Ultimately, we aim to translate these mechanistic insights into predictive clinical biomarkers to improve early detection in colorectal cancer.


Biography

Dr. Naseer Sangwan is an Associate Staff researcher at Cleveland Clinic Research. He serves as an Assistant Professor of Molecular Medicine at Cleveland Clinic Lerner College of Medicine of Case Western Reserve University and is a member of the Case Comprehensive Cancer Center. Additionally, he directs the Microbial Sequencing and Analytics Core within the Department of Shared Laboratory Resources. Dr. Sangwan’s area of expertise is broadly centered on systems microbiology, multi-omics bioinformatics and understanding host–microbiome interactions at the intestinal epithelial barrier. 

Dr. Sangwan earned his Bachelor of Science in Zoology, Master of Science in Molecular Zoology, and PhD in Molecular Microbiology from the University of Delhi. His doctoral research examined the physiology, metabolic biochemistry and metagenomics of microbial communities in extreme environments, as well as predator–prey dynamics in predatory bacteria. He subsequently completed postdoctoral fellowship training at Argonne National Laboratory and the University of Chicago, where he developed computational workflows for large-scale multi-omics data integration and metagenomic population genome reconstruction across diverse human disease states. 

His current work combines experimental microbiology, single-cell multi-omics, metabolomics and advanced computational biology to define how gut microbial signals influence chronic inflammation, epithelial cell fate and gastrointestinal cancer progression. A major focus of his laboratory is investigating host–microbiome interactions in early-onset colorectal cancer (eoCRC) and addressing racial health disparities. Supported by a prestigious NCI R37 MERIT Award, his research investigates how gut microbiota-driven Tuft-2 cell expansion promotes neoplastic adenoma development in early-onset colorectal cancer among US residents, while also characterizing distinct intratumoral microbiome signatures in young-onset gastrointestinal malignancies. 

Over the course of his career, Dr. Sangwan has published more than 100 peer-reviewed manuscripts and has authored three patents on host–microbe interactions. Competitive federal funding from the National Institutes of Health supports his research program, leadership of core facility infrastructure and collaborative initiatives, including multiple awards from the National Cancer Institute. 


Education & Professional Highlights

Education 

Research Associate- Argonne National Laboratory  

Molecular Microbiology   

Chicago, IL, USA   

2019  

 

Postdoctoral Fellowship-University of Chicago Molecular Microbiology  

Molecular Microbiology   

Chicago, IL, USA   

2017 

 

Postdoctoral Fellowship-Argonne National Laboratory  

Molecular Microbiology   

Chicago, IL, USA  

 2016  

 

Doctor of Philosophy-University of Delhi   

Molecular Microbiology    

New Delhi, India   

2010  

 

Bachelor of Science –University of Delhi, Zoology   

Molecular Zoology   

New Delhi, India   

2008 

  

Professional Appointments  

Associate Staff   

Cleveland Clinic Research   

Microbial Sciences in Health  

Cleveland, OH, USA.  

2024-Present  

 

Associate Staff   

Cleveland Clinic Research   

Shared Laboratory Resources (SLR)  

Cleveland, OH, USA.  

2024 – Present  

 

Associate Staff   

Cleveland Clinic Research   

Department of Heart, Blood and Kidney Research   

Cleveland, OH, USA.  

2024 – Present  

 

Assistant Professor  

Cleveland Clinic Lerner College of Medicine (CCLCM) Molecular Medicine   

Cleveland, OH, USA.  

2019 – Present  

 

Assistant Staff  

Cleveland Clinic Lerner Research Institute  

Shared Laboratory Resources (SLR)  

Cleveland, OH, USA.  

2024  

 

Assistant Staff  

Cleveland Clinic Lerner Research Institute   

Cardiovascular & Metabolic Sciences   

Cleveland, OH, USA 2019.  

2024 

 

Honors and Recognition  

NCI R37 Method to Extend Research in Time (MERIT) Award, National Cancer Institute / NIH (2026 – 2031).  

Reviewer, Digestive and Nutrition Physiology and Diseases (DNPD) Study Section, National Cancer Institute (NCI) (2026).  

Reviewer, Cancer Therapeutics (R21)-TCO-81 Study Section, National Cancer Institute (NCI) (2025 – 2026).  

Career Development Award, Cleveland Clinic Research, Cleveland Clinic (2024 – 2025).  

Associate, Early Investigator Advancement Program (EIAP), NCI/NIH (2023 – 2026).  

Associate Editor, Frontiers in Microbiome (2020 – 2026)  

Associate Editor, mSystems Journal, American Society for Microbiology (2026).  

Best Poster Award, 23rd Annual Charles B. Huggins Research Symposium, University of Chicago (2016).  

Postdoctoral Fellowship, Argonne National Laboratory / University of Chicago (2015 – 2017).  

Senior Research Fellowship (SRF), Council of Scientific & Industrial Research (CSIR), India (2012 – 2015).  

1st Prize in Oral Presentation, 53rd Annual Conference of the Association of Microbiologists of India (AMI) (2012).  

Junior Research Fellowship (JRF), Council of Scientific & Industrial Research (CSIR), India (2010 – 2012)  

  

Professional Memberships  

American Association for Cancer Research (AACR) – Member (2020 – Present)  

Ancillary Studies Committee, Liver Cirrhosis Network (LCN), NIH – Member (2020 – 2026)  

American Society for Microbiology (ASM) – Member (2015 – Present)  

Association of Microbiologists of India (AMI) – Member (2015 – Present) 

Research

Research

Overview

Our research program investigates host–microbiome interaction frameworks at the intestinal epithelial barrier to define the molecular mechanisms by which gut microbial signals drive gastrointestinal disease, chronic inflammation and cancer progression. A primary focus of the laboratory centers on unraveling how gut microbial dysbiosis alters epithelial cell fates along the normal-to-adenoma-to-carcinoma continuum in early-onset colorectal cancer (eoCRC). To achieve this, our group integrates single-cell multi-omics (scRNA-seq and scATAC-seq), high-throughput metagenomics, mass spectrometry metabolomics, patient-derived colonic organoid (PDCO) cultures and gnotobiotic animal models. 

A core mission of the lab is translating these mechanistic insights into predictive clinical biomarkers and targeted interception strategies for colorectal cancer. Supported by an NCI R37 MERIT Award, our group investigates how gut microbiota-driven expansion of Tuft-2 cells accelerates neoplastic adenoma formation in early-onset CRC patient cohorts. In addition, Dr. Sangwan directs the Microbial Sequencing and Analytics Core at Cleveland Clinic, leading multi-disciplinary projects that analyze complex host-microbe crosstalk across oncology, hepatology and metabolic disease. 

Microbiota-Driven Tuft Cell Expansion in Early-Onset Colorectal Cancer

This program investigates how specific gut microbial signals and metabolites—such as succinate produced by enriched bacterial taxa like Prevotella—trigger Tuft-2 cell hyperplasia in the colonic epithelium. Using fecal microbiota transplantation (FMT) in gnotobiotic and Apc/Min mouse models alongside patient-derived colonic organoids (PDCOs), we delineate how Tuft-2 cell expansion activates oncogenic signaling cascades (including the JAK-STAT pathway) to accelerate aggressive adenoma development in high-risk early-onset CRC patient populations. 

Intratumoral Microbiome Profiling in Young-Onset Gastrointestinal Cancers

This project applies deep metagenomic sequencing, multi-omics data integration, and machine learning to characterize distinct intratumoral and tissue-associated microbial signatures in early-onset versus average-onset colorectal cancer and pancreatic adenocarcinoma. By mapping localized host–microbiome interactions within tumor microenvironments, this work aims to identify microbial biomarkers and understand how intra-tissue bacteria modulate disease progression and clinical outcomes. 

Host-Microbe Metabolic Interactions and Chemoresistance in Malignancies

In collaboration with multidisciplinary oncology teams, this research area investigates how gut microbial metabolites and dietary interactions influence systemic inflammation, metabolic dysregulation, and therapeutic response in solid tumors, including ovarian and gastrointestinal cancers. Using liquid chromatography-mass spectrometry (LC-MS) metabolomics and microbial co-culture systems, we seek to uncover actionable metabolic pathways that mediate drug resistance and can be targeted for therapeutic interception. 

Our Team

Our Team

Publications

Selected Publications

2026

Kumar, M., Son, R., Preston, S. M., Glowacki, R. W. P., Carr, K. M., Kim, J., Ma, J. Z., Ahern, P., Claesen, J., Sangwan, N., Rieder, F., Nemet, I. (2026). The role of gut microbes in production of aromatic carboxaldehydes. Gut Microbes, 18(1). https://doi.org/10.1080/19490976.2026.2632979

Ponti, A. K., Gatesman, T., Hatem, S.,... Sangwan, N., et al. (2026) SQOR regulates H2S detoxification and lipid metabolism to maintain glioblastoma metabolic fitness. Research Square.  https://doi.org/10.21203/rs.3.rs-11077727/v1?

Arjunan, S., Pemberton, I., Li, X. S., Sangwan, N., et al. (2026) Gut microbial trimethylamine N-oxide generation promotes risk of atrial fibrillation via muscarinic receptor–mediated autonomic dysfunction. The Journal of Clinical Investigation, 136(17). https://www.jci.org/articles/view/201684

Gupta, N., Raymond, M., Hagen, L., Nunn, T., Huang, E., Nagy, L., & Sangwan, N. (2026). Regulation of Microbial and Metabolic Balance in the Gut by B Cells 2309411. The Journal of Immunology : Official Journal of the American Association of Immunologists, 215(Supplement_1). https://doi.org/10.1093/jimmun/vkag141.1540

Salazar, V., Espenschied, S., Fernandez, A., Karell, P., Sangwan, N., & Stappenbeck, T. (2026). 0689 The skin microbiota drives cutaneous immune checkpoint inhibitor toxicity in genetically susceptible mice. The Journal of Investigative Dermatology., 146(8). https://doi.org/10.1016/j.jid.2026.06.720

Carr, K. M., Kim, J., Shin, J., Bacik, K. A., Hong, J., Krukovets, I., Strauch, C. M., Sangwan, N., Cherepanova, O. A., Nemet, I. (2026). Phenylacetic acid, a gut microbially produced metabolite, reduces atherosclerosis burden and impacts host lipid homeostasis. Jounal of the American Heart Association, 15(14). https://doi.org/10.1161/JAHA.125.047044

Bellar, A., Sangwan, N., Miller, A., Kumar, A., Jaramilla, T., Mishra, S., Kannan, P., Attaway, A., Mishra, L., Welch, N., Dasarathy, S. (2026). Volunary wheel running modulates murine gut microbiome during hyperammonemic stress. Microbiology Spectrum. https://doi.org/10.1128/spectrum.03194-25

DiDonato, J. A., Weeks, T. L., Gupta, N., Mallela, D. P., Buffa, J. A., Wang, Z., Li, X. S., Anderson, J. T., Fu, X., Sangwan, N., Nemet, I., Cameron, S. J., & Hazen, S. L. (2026). Targeted Inhibition of Gut Microbial Trimethylamine N -Oxide Production Fosters Regression of CKD Phenotypes. Journal of the American Society of Nephrology https://doi.org/10.1681/ASN.0000001171

Zhevlakova, I., Molokotina, I., Burrows, A. C., Horak III, A. J., Sangwan, N., Brown, J. M., Podrez E. A., Byzova, T. V. (2026) Journal of Investigative Dermatology. https://doi.org/10.1016/j.jid.2026.06.1288 

Aggarwal, A., Josyula, V. P. V., Wang, N., Yang, M., Shim, Y. J., Kennedy, Q. P., Samuel, R., Sangwan, N., Guntupalli, S., Godwin, M., Park, H. E., Ali, M., Jennings, C., Rajasekar, B., Scalise, A., Sloan, A. R., Lathia, J. D., Grondolsky, J., Schumacher, S. M., & Stauffer, S. (2026). Olfactory Receptor Activation Reduces Platelet Reactivity and Arterial Thrombosis Through Actin Cytoskeleton Remodeling. Circulation : Journal of the American Heart Association., 153(23), 1827–1844. https://doi.org/10.1161/CIRCULATIONAHA.125.078927

Hausman, B. S., Kaple, C. E., Cadnum, J. L., Memic, S., Sangwan, N., Donskey, C. J. (2026). PloS One, 21(6). https://doi.org/10.1371/journal.pone.0350031

Aggarwal, A., Park, H., Fendrikova Mahlay, N., Guntupalli, S., Din Abdul Jabbar, M. A., Godwin, M., Manning, E., Scalise, A., Pascual, C., Ali, M., Shi, W., MacNamara, S., Rayz, V., Abroe, H., Arking, D., Sangwan, N., Kim, E., Chabaklo, K., Chen, R., & Svensson, L. (2026). Abstract Or131: Mechanisms of Thrombosis in Fibromuscular Dysplasia. Arteriosclerosis, Thrombosis, and Vascular Biology., 46(Suppl_1). https://doi.org/10.1161/atvb.46.suppl_1.Or131

Daff, K., Han, Y., Feng, Z., Upadhyay, M., Sivampeta, V., Rajasekaran, A., Sangwan, N., Cresci, G. AM. (2026) Role of L-Arginine in the Gut-Liver Axis of Female Mice: Mediating Ethanol's Alterations in Hepatic Steatosis and Oxidative Stress. Antioxidants, 15(5), 537. https://doi.org/10.3390/antiox15050537

Liu, C.-C., Grencewicz, D., Chakravarthy, K., Li, L., Liepold, R., Wolf, M., Marcho, L. M., Sangwan, N., Tzeng, A., Hoyd, R., Jhawar, S. R., Grobmyer, S. R., Al-Hilli, Z., Sciallis, A. P., Spakowicz, D., Ni, Y., & Eng, C. (2026). Breast tumor microbiome regulates anti-tumor immunity and T cell-associated metabolites. Scientific Reports., 16(1). https://doi.org/10.1038/s41598-026-48719-5

Salazar, V., Espenschied, S. T., Fernandez, A. P., Karell, P. E., Sangwan, N., Stappenbeck, T. S. (2026) The skin microbiota drives cutaneous immune checkpoint inhibitor toxicity in genetically susceptible mice. Cell Host & Microbe, 34(4), 588-599. e6. https://doi.org/10.1016/j.chom.2026.03.008

S. Dutta, K.K. Mahen, W.J. Massey, V. Varadharajan, A.C. Burrows, A.J. Horak, M. Mrdjen, N. Mouannes, D. Orabi, L.J. Osborn, T. Grubb, R.C. Hohe, R. Banerjee, V. Uppin, D. Laungani, G.E. Hamilton, X. Ye, N. Sangwan, M. Dwidar, A.M. Hajjar, B. Willard, M. Martin, E. Guetschow, P. Westcott, M.R. McMullen, L.E. Nagy, Z. Wang, S.L. Hazen, & J.M. Brown (2026) Gut microbe–derived N-acyl serinol lipids shape host postprandial metabolic homeostasis. Proceedings of the National Academy of Sciences, 123(12), e2517314123. https://doi.org/10.1073/pnas.2517314123

Brown, J. M., Mouannes, N., Burrows, A.,... Sangwan, N., Walker, M., Spite, M., Cheng, F. (2026) Multi-Omic Analysis of Dietary Fatty Acid-Microbe-Host Interactions Reveal Metaorganismal Lipid Metabolic Crosstalk Impacting Cardiometabolic Disease. https://doi.org/10.21203/rs.3.rs-9013531/v1

McCourt, B., Lemr, K., Chakrabarti, S., Woidke, E., Ramaiah, S., Singh, V., Sangwan, N., Brown, J. M., Cominelli, F., Rodriguez-Palacios, A., & Burberry, A. (n.d.). C9orf72 in myeloid cells prevents an inflammatory response to microbial glycogen. Cell Reports., 45(2). https://doi.org/10.1016/j.celrep.2025.116906

Overstreet, A.-M. C., Burge, M., Anderson, B., Zhu, X., Tao, Y., Cham, C. M., Michaud, B., Horam, S., Sangwan, N., Dwidar, M., Liu, X., Santos, A., Srivastava, V., Finney, C., Goins, C. M., Dai, Z., Koff, B. B., Stauffer, S. R., Leone, V. A., & Messer, J. S. (2026). HMGB1 functions as a critical mediator of host defense at the gut mucosal barrier. Cell Host & Microbe., 34(2), 230-244.e13. https://doi.org/10.1016/j.chom.2026.01.008

 

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