Radhakrishnan Lab
Sidebar
About
The Radhakrishnan Lab investigates the molecular and cellular mechanisms by which truncated O-glycans—particularly the tumor-associated Tn and sialyl-Tn (STn) antigens—drive pancreatic cancer progression, early metastasis, and immune suppression. We also focus on the therapeutic potential of monoclonal antibodies targeting Tn and MUC16 antigens, as well as natural compounds, in preclinical models of pancreatic cancer.
A key area of interest is the role of abnormal glycoforms of MUC16 and insulin-like growth factor binding proteins (IGFBPs) in modulating disease progression and contributing to cancer-associated cachexia, a debilitating muscle-wasting syndrome commonly seen in advanced pancreatic cancer.
Our ultimate goal is to translate these insights into the development of novel antibody-based immunotherapeutics and targeted treatment strategies to combat lethal pancreatic cancer.
We welcome collaborations and inquiries from students, postdocs, and scientists interested in cancer glycobiology, tumor immunology and translational oncology.
Key Research Areas
- Mucin and mucin-glycans mediated pancreatic cancer progression and metastases
- Antibody-based therapeutics (ADC, Bi-specific, and CAR-T)
- Natural product-based therapeutics
- Tumor immunology and tumor microenvironment
- Autocrine and paracrine cell signaling mechanisms
- Preclinical models of pancreatic cancer
- Cachexia in pancreatic cancer
- Translational strategies in oncology
Current Projects
- Altered Glycosylation in Pancreatic Cancer:
Investigating how changes in glycosylation, particularly the expression of Tn and STn antigens, contribute to pancreatic cancer progression, metastasis, and immune suppression within the tumor microenvironment. - Targeted Immunotherapy with Monoclonal Antibodies:
Developing and testing monoclonal antibodies that selectively target cancer-specific glycoforms of mucin (MUC16) and Tn-antigen for use in precision immunotherapy. - Mechanisms of Cachexia:
Exploring how insulin-like growth factor binding proteins (IGFBPs) contribute to cancer-associated cachexia, intending to identify therapeutic strategies to prevent or reverse muscle wasting. - Natural Compounds in Cancer Therapy:
Evaluating the anti-tumor efficacy of bromelain, a proteolytic enzyme derived from pineapple, as a potential complementary therapy in pancreatic cancer.
Team
- Rajith Varman Seshappa Venkatesan
Postdoctoral Fellow
rajithvarman.seshappavenkatesan@louisville.edu
Recent Publications
- Aguilar EN, Sagar S, Murray BR, Rajesh C, Lei EK, Michaud SA, Goodlett DR, Caffrey TC, Grandgenett PM, Swanson B, Brooks TM, Black AR, van Faassen H, Hussack G, Henry KA, Hollingsworth MA, Brooks CL, Radhakrishnan P. Structural Basis for Multivalent MUC16 Recognition and Robust Anti-Pancreatic Cancer Activity of Humanized Antibody AR9.6. Mol Cancer Ther. 2024 Jun 4;23(6):836-853. doi: 10.1158/1535-7163.MCT-23-0868. PubMed PMID: 38394685; PubMed Central PMCID: PMC11660185.
- Muilenburg KM, Isder CC, Radhakrishnan P, Batra SK, Ly QP, Carlson MA, Bouvet M, Hollingsworth MA, Mohs AM. Mucins as contrast agent targets for fluorescence-guided surgery of pancreatic cancer. Cancer Lett. 2023 May 1;561:216150. doi: 10.1016/j.canlet.2023.216150. Epub 2023 Mar 29. Review. PubMed PMID: 36997106; PubMed Central PMCID: PMC10150776.
- Rajesh C, Radhakrishnan P. The (Sialyl) Tn antigen: Contributions to immunosuppression in gastrointestinal cancers. Front Oncol.2022;12:1093496. doi: 10.3389/fonc.2022.1093496. eCollection 2022. Review. PubMed PMID: 36686742; PubMed Central PMCID: PMC9852904.