Vasu Lab

Chenthamarakshan Vasu, Ph.D.
Professor, Microbiology & Immunology

Education and Training

1997: PhD, Nagpur University, India
1997-1999: Post-Doctoral Fellow, University Malaya, Malaysia
1999-2004: Post-Doctoral Fellow, University of Illinois at Chicago, USA

Contact Info
vasu@musc.edu
Tel: 843-792-1032
Office: BSB 214B

Research Interests

1. Gut microbiota-host interaction in autoimmunity. This project is focused on understanding how gut microbial communities are contributing to autoimmune disease progression and suppression in genetically susceptible individuals and animal models. Gut microbiota-TLR interactions in the context of intestinal immune and epithelial cell function and gut integrity are being studied in both systemic lupus erythematosus and type 1 diabetes. Microbial community interactions (mutualism and competition) which are critical to the structure and function of a healthy gut microbiota are being studied in the context of these diseases. This project employs human samples, and a series of knockout and germ-free mouse models in autoimmune-prone backgrounds. “Microbiota- and immune cell- humanized” mouse models are also being employed to understand the interactions between human immune system and gut microbiota. Therapeutic value of gut evidence-based microbiota manipulation approaches is also being studied.
2. Engineering immune and adult stem cells for autoimmune therapy. This project is focused on engineering immune cells to achieve long-lasting antigen specific immune tolerance for treating autoimmune diseases. Dendritic cells (DCs) that are engineered to express T cell checkpoint receptor selective ligands as well as immune regulatory cytokines are being employed to induce autoantigen specific regulatory T cells and immune tolerance for suppressing autoimmunity in type 1 diabetes and lupus. The lab is also engineering adult stem cells such as mesenchymal stromal/stem cells (MSCs) to be used as delivery vehicles of growth factors, peptide hormones, and cytokines for achieving tissue-repair and restoration of function in the autoimmune target organs. Combination engineered DC and MSC therapy is also being employed to achieve concurrent autoimmune suppression and islet cell regeneration/tissue repair simultaneously.
3. Cellular mechanisms of vesicular transport, tumorigenesis, viral propagation. Vesicular transport plays a critical role in various cellular functions. Defects in this function can lead to malignancies and inflammation. Cellular vesicular transport pathway is also exploited by microbial pathogens including virus for their intracellular propagation and dissemination. Our project studies the fundamental cellular regulatory mechanisms of vesicular transport in the context of cell surface receptor homeostasis and tumor prevention. In addition, we are investigating how vesicular transport and these regulatory mechanisms impact, exosome release, and viral entry and egress. Novel peptide and small molecule based therapeutic approaches targeting the vesicular transport pathway are also being explored to prevent cancer and inhibit viral propagation.
4. Identification and therapeutic manipulation of microbial metabolites of dietary polysaccharides.  Fermentation of non-digestible, complex dietary polysaccharides by distal gut microbes can enhance and maintain beneficial microbes in the distal gut and generate immune regulatory metabolites. Therefore, identification and functional characterization of microbial metabolites from complex dietary polysaccharide degradation could lead to the development of precision -nutrition and -medicine approaches to prevent and treat immune-mediated disorders. Our studies are expected to identify novel microbial metabolites of candidate complex dietary polysaccharide degradation and functionally characterize them for the ability to enhance gut and systemic immune regulation to prevent and treat autoimmune and inflammatory conditions such as lupus, type 1 diabetes, and colitis.

Recent Publications / Additional Publications:

Gudi R, Kamen D, Vasu C. Fecal immunoglobulin A (IgA) and its subclasses in systemic lupus erythematosus patients are nuclear antigen reactive and this feature correlates with gut permeability marker levels. Clin Immunol. 2022 Sep;242:109107. doi: 10.1016/j.clim.2022.109107. Epub 2022 Aug 29. PMID: 36049603.

Helke KL, Gudi RR, Vasu C, Delaney JR. Combination of Autophagy Selective Therapeutics With Doxil: An Assessment of Pathological Toxicity. Front Toxicol. 2022 Jun 29;4:937150. doi: 10.3389/ftox.2022.937150. PMID: 35846434; PMCID: PMC9276957.

 

Gudi RR, Perez N, Karumuthil-Melethil S, Li G, Vasu C. Activation of T cell checkpoint pathways during β-cell antigen presentation by engineered dendritic cells promotes protection from type 1 diabetes. Immunology. 2022 Jul;166(3):341-356. doi: 10.1111/imm.13476. Epub 2022 Apr 22. PMID: 35404483; PMCID: PMC9233138.

 

Gaudreau MC, Gudi RR, Li G, Johnson BM, Vasu C. Gastrin producing syngeneic mesenchymal stem cells protect non-obese diabetic mice from type 1 diabetes. Autoimmunity. 2021 Dec 9;:1-14. doi: 10.1080/08916934.2021.2012165. [Epub ahead of print] PubMed PMID: 34882054.

Taylor HB, Vasu C. Impact of Prebiotic β-glucan Treatment at Juvenile Age on the Gut Microbiota Composition and the Eventual Type 1 Diabetes Onset in Non-obese Diabetic Mice. Front Nutr. 2021;8:769341. doi: 10.3389/fnut.2021.769341. eCollection 2021. PubMed PMID: 34805251; PubMed Central PMCID: PMC8595985.

Gudi R, Palanisamy V, Vasu C. Centrosomal P4.1-associated protein (CPAP) positively regulates endocytic vesicular transport and lysosome targeting of EGFR. Sci Rep. 2021 Jun 16;11(1):12689. doi: 10.1038/s41598-021-91818-8. PubMed PMID: 34135376; PubMed Central PMCID: PMC8209166.

Gudi RR, Janakiraman H, Howe PH, Palanisamy V, Vasu C. Loss of CPAP causes sustained EGFR signaling and epithelial-mesenchymal transition in oral cancer. Oncotarget. 2021 Apr 13;12(8):807-822. doi: 10.18632/oncotarget.27932. eCollection 2021 Apr 13. PMID: 33889303.

Sun W, Gudi RR, Johnson BM, Vasu C. Abundance and nuclear antigen reactivity of intestinal and fecal Immunoglobulin A in lupus-prone mice at younger ages correlate with the onset of eventual systemic autoimmunity. Sci Rep. 2020 Aug 31;10(1):14258. doi: 10.1038/s41598-020-71272-8. PubMed PMID: 32868790; PubMed Central PMCID: PMC7458927.

Taylor HB, Gudi R, Brown R, Vasu C. Dynamics of Structural and Functional Changes in Gut Microbiota during Treatment with a Microalgal β-Glucan, Paramylon and the Impact on Gut Inflammation. Nutrients. 2020 Jul 23;12(8). doi: 10.3390/nu12082193. PubMed PMID: 32717991; PubMed Central PMCID: PMC7468787.

Gudi R, Suber J, Brown R, Johnson BM, Vasu C.Pretreatment with Yeast-Derived Complex Dietary Polysaccharides Suppresses Gut Inflammation, Alters the Microbiota Composition, and Increases Immune Regulatory Short-Chain Fatty Acid Production in C57BL/6 Mice. J Nutr. 2020 May 1;150(5):1291-1302. doi: 10.1093/jn/nxz328. PubMed PMID: 31879786; PubMed Central PMCID: PMC7198290.

Johnson BM, Gaudreau MC, Gudi R, Brown R, Gilkeson G, Vasu C. Gut microbiota differently contributes to intestinal immune phenotype and systemic autoimmune progression in female and male lupus-prone mice J Autoimmun. 2020 Mar;108:102420. doi: 10.1016/j.jaut.2020.102420. Epub 2020 Feb 2. PubMed PMID: 32019684; PubMed Central PMCID: PMC7204266.

Sofi MH, Johnson BM, Gudi RR, Jolly A, Gaudreau MC, Vasu C. Polysaccharide A-Dependent Opposing Effects of Mucosal and Systemic Exposures to Human Gut Commensal Bacteroides fragilis in Type 1 Diabetes. Diabetes. 2019 Oct;68(10):1975-1989. doi: 10.2337/db19-0211. Epub 2019 Jul 16. PubMed PMID: 31311801; PubMed Central PMCID: PMC6754247.

Gudi RR, Karumuthil-Melethil S, Perez N, Li G, Vasu C. Engineered Dendritic Cell-Directed Concurrent Activation of Multiple T cell Inhibitory Pathways Induces Robust Immune Tolerance. Sci Rep. 2019 Aug 19;9(1):12065. doi: 10.1038/s41598-019-48464-y. PubMed PMID: 31427630; PubMed Central PMCID: PMC6700167.

Funding

R01AI138511 (NIAID), 3R01AI138511-02S1(NIA) & 3R01A138511-02S2 (ODS)
Vasu (PI)
11/06/2018 - 10/31/2023
Role of microbiota-TLR7/8 Interaction in systemic lupus erythematosus

NIH/NIDCR: R01DE030331-01A1 Vasu/Gudi (multi-PI)
Vasu (Contact-PI)
09/01/2022-06/30/2027
ESCRT-dependent novel regulatory mechanism of EMT and tumorigenesis in oral cancer

The Leona M. and Harry B. Helmsley Charitable Trust. Grant# 2306-06097
Vasu (PI)
12/01/2022-9/30/2025
Engineered dendritic cell-based robust antigen specific therapy for type 1 diabetes