Swapna Asuthkar PhD | Directory

About the Asuthkar Lab

Swapna Asuthkar’s lab is focused on investigating the molecular mechanisms of cancer progression and identifying novel targets for therapeutic intervention. Her research primarily involves the use of molecular biology, biochemistry and biophysics techniques to study the underlying mechanisms of cancer, with a focus on cancer signaling pathways that are involved in migration, invasion and metastasis.

Her lab also focuses on understanding the protein-protein interactions that drive cancer progression, and how these interactions can be targeted to inhibit cancer growth. The lab also investigates the combination of chemotherapy and radiotherapy to target these mechanisms and develop new therapeutic strategies for cancer treatment.

Overall, the goal of her research is to better understand the molecular mechanisms of cancer and identify new targets for drug development, with the ultimate goal of improving patient outcomes and enhancing cancer treatment.

Exploring the Role of Immune Checkpoint Molecules in Cancer Progression and Metastasis

B7-H3, also known as CD276, is an immune checkpoint protein that has been shown to be overexpressed in a variety of human cancers, including medulloblastoma and lung cancer. Studies have linked high levels of B7-H3 with poor prognosis. Our lab, is dedicated to understanding the role of this protein in cancer progression and identifying new strategies for treatment.

Our lab is focused on investigating the role of the immune checkpoint molecule B7-H3 in cancer progression and metastasis. Our research has shown that B7-H3 plays a significant role in host cell interaction, cancer progression, angiogenesis, and metastasis. We have found that high levels of B7-H3 expression correlate with the activation of the PI3K/Akt signaling pathway, which promotes cancer cell proliferation, survival, and angiogenesis. Additionally, we have investigated the role of B7-H3 in medulloblastoma progression and found that high B7-H3 expression is associated with a higher risk of recurrence and poorer overall survival. Furthermore, B7-H3 plays a critical role in the regulation of the tumor microenvironment by promoting the recruitment and activation of immune cells that contribute to tumor growth, progression, and metastasis. Our research also showed that B7-H3 is expressed in exosomes, which do not require receptors for cell-cell contact, indicating its role in cancer may be more significant than previously thought.

Our lab aims to further understand the regulatory factors that affect B7-H3 expression and determine its oncogenic properties in order to develop new treatments for cancer patients. Targeting B7-H3 through immune checkpoint inhibition may be a promising strategy for treating medulloblastoma and other cancers. We are committed to advancing our understanding of this important protein and developing new treatments to improve the prognosis for cancer patients.

Uncovering the Epigenetic Secrets of Medulloblastoma: Targeting Key Protein Markers for Improved Treatment Outcomes

The research focus of Asuthkar’s lab is the identification of key epigenetic markers that contribute to the development and progression of Group 3 medulloblastoma (MB) using next-generation sequencing data. The goal is to understand how these markers contribute to the disease and develop targeted therapies that can improve treatment outcomes, especially in cases where radiation therapy (RT) is ineffective due to the development of radioresistance (RR). The lab has identified specific epigenetic markers, such as SMYD3 and EZH2, that can sensitize cancer cells to radiation therapy and promote the development of MB by increasing the expression of cell cycle proteins. Targeting these markers, like SMYD3, with small molecule inhibitors could be a promising strategy for treating this type of cancer. The lab’s research aims to improve the quality of life and survival of cancer patients by identifying key protein markers and developing targeted therapies against them, with a specific focus on Group 3 medulloblastoma, a highly aggressive brain cancer with limited treatment options. The lab is also actively investigating the use of epigenetic modifiers as adjuvants to standard cancer therapies to combat RR.

Unlocking the Secrets of TRPM8: A Potential Key to Prostate Cancer Treatment and Beyond

The seminal findings of Asuthkar’s lab research include identifying that the Transient receptor potential melastatin 8 (TRPM8) is a tumor suppressor and a key element of the orphan pathway for non-genomic testosterone actions. TRPM8 is a cold-sensing and Ca2+ permeable channel protein. Oscillations in intracellular Ca2+ levels stimulate cell proliferation and survival while sustained cytosolic Ca2+ concentrations promote apoptosis. Asuthkar’s long-term goal is to achieve therapeutic benefit by inhibiting the desensitization mechanism of TRPM8 channel activation in prostate cancer, subsequently causing apoptotic cell death. In light of these observations, her studies support a strategy for rescuing plasma membrane levels of TRPM8 as a new therapeutic application for prostate cancer. The research also suggests that TRPM8 is a rapid testosterone signaling receptor with implications in the regulation of dimorphic sexual and social behaviors, meaning that TRPM8 plays a role in the regulation of behaviors that are unique to males and females, such as sexual behavior and social interactions. However, it’s important to note that these findings are based on laboratory studies, and their applicability to human patients is still unknown. Further studies and clinical trials are needed to confirm these findings and to determine the potential use of TRPM8 as a therapeutic target for prostate cancer, as well as to determine the extent of TRPM8’s role in regulating dimorphic sexual and social behaviors.

Selected Publications

1. Guda MR, Tsung AJ, Asuthkar S, Velpula KK. Galectin-1 activates carbonic anhydrase IX and modulates glioma metabolism. Cell Death Dis. 2022 Jun 30;13(6):574.
2. Katherine Shishido, Alexis Reinders, and Asuthkar S*. Epigenetic regulation of radioresistance: insights from preclinical and clinical studies. Expert Opin Investig Drugs 2022 Dec 25;1-17.
3. Asuthkar S,* Sujatha Venkataraman, Janardhan Avilala, Katherine Shishido, Rajeev Vibhakar, Bethany Veo, Ian J. Purvis, Maheedhara R. Guda 1 and Kiran K. Velpula. SMYD3 Promotes Cell Cycle Progression by Inducing CyclinD3 Transcription and Stabilizing the Cyclin D1 Protein in Medulloblastoma. Cancers 2022 Mar 25;14(7):1673.
4. John L Caniglia, Anvesh Jalasutram, Asuthkar S, Joseph Sahagun, Simon Park, Aditya Ravindra, Andrew J Tsung, Maheedhara R Guda, Kiran K Velpula. Beyond glucose: alternative sources of energy in glioblastoma. Theranostics. 2021 Jan 1;11(5):2048-2057.
5. Purvis IJ, Avilala J, Nguyen D, Tsung AJ, Velpula KK, Asuthkar S*. B7-H3 in medulloblastoma-derived exosomes; a novel tumorigenic role. Int. J. Mol. Sci. 2020, 21(19), 7050.
6. Purvis IJ, Avilala J, Guda MR, Venkataraman S, Vibhakar R, Alexandrov I, Tsung AJ, Velpula KK, Asuthkar S*. Role of MYC-miR-29-B7-H3 in medulloblastoma growth and angiogenesis. J Clin Med. 2019 Aug; 8(8): 1158.
7. Asuthkar S*, Kiran Kumar Velpula, Pia A. Elustondo, Lusine Demirkhanyan, and Zakharian Eleonora. TRPM8 channel as a novel molecular target in androgen-regulated prostate cancer cells. Oncotarget. 2015 Jul 10; 6(19):17221-36.
8. Asuthkar S, Elustondo, P, Demirkhanyan, L, Baskaran, P, Kiran Kumar Velpula, Thyagarajan, B, Pavlov, E, and Zakharian, E. The TRPM8 protein is testosterone Receptor. Part I. Biochemical evidence for direct TRPM8-testosterone interactions. J Biol Chem. 2015. Jan 30; 290(5):2659-69.
9. Asuthkar S, Demirkhanyan, L, Elustondo, P, Sun, X, Krishnan V, Baskaran, P, Kiran Kumar Velpula, Thyagarajan, B, Pavlov, E, and Zakharian, E. 2015. The TRPM8 protein is testosterone Receptor. Part II. Functional evidence for an ionotrophic effect of testosterone on TRPM8. J Biol Chem. Jan 30; 290(5):2670-88.
10. Asuthkar S*, Velpula, KK., Gondi, CS., Nalla, AK., Gogineni VR., Rao, JS. MMP-9 mediates Syndecan-1 shedding and angiogenesis via epigenetic silencing of miR-494 in medulloblastoma cells. Oncogene. 2014. Apr 10; 33(15):1922-33.
11. Asuthkar S, Gogineni VR, Rao JS, Velpula KK. Nuclear Translocation of Hand-1 Acts as a Molecular Switch to Regulate Vascular Radiosensitivity in Medulloblastoma Tumors: The Protein uPAR is a Cytoplasmic Sequestration Factor for Hand-1. Mol Cancer Ther. 2014.May; 13(5):1309-22.
12. Asuthkar S, Stepanova V, Lebedeva T, Holterman AL, Estes N, Cines DB, Rao JS, Gondi CS. Multifunctional roles of Urokinase Plasminogen Activator (uPA) in Cancer Stemness and in Chemo-resistance of Pancreatic Cancer. Mol Biol Cell. 2013. Sep; 24(17):2620-32.
13. Velpula KK, Bhasin A, Asuthkar S, Tsung, A.J. 2013. Combined targeting of PDK1 and EGFR triggers regression of glioblastoma by reversing the Warburg effect. Cancer Res. Dec 15; 73(24):7277-89.
14. Asuthkar S, Gondi, CS, Nalla, AK. Velpula, KK, Gorantla, B, Rao, JS. Irradiation-induced uPAR promotes stemness via Wnt/β-catenin signaling in medulloblastoma cells. J Biol Chem. 2012, Jun 8; 287 (24):20576-89.
15. Asuthkar S, Rao, J.S. and Gondi, C.S. Drugs in preclinical and early-stage clinical development for pancreatic cancer. Expert Opin Investig Drugs. 2012, Feb; 21(2):143-52.
16. Asuthkar S, Nalla, A.K., Gondi, C.S., Dinh, D.H., and Rao, J.S. Gadd45a sensitizes medulloblastoma cells to irradiation and suppresses MMP-9 mediated EMT Meena Gujrati, Sanjeeva Mohanam, and Jasti S. Rao. Neuro-Oncology, 2011, October 13 (10):1059-1073.

Complete list of published work in my bibliography: https://pubmed.ncbi.nlm.nih.gov/?term=asuthkar+

Special Competencies and Interests

• Cell biology: Cell lines/primary cell culture, cell growth curve, angiogenesis in vitro/in vivo, cell adhesion and chemotactic migration assay, cell apoptosis and differentiation assays, immunofluorescent double/triple staining, cell sorting by FACS, transfection, cancer stem cells, protein extraction and purification.
• Immuno-biology: role of Immune checkpoints the tumor-microenvironment, Enzyme linked immunosorbent assay (ELISA), ELISPOT, microscopic agglutination test (MAT), serotyping, immunochemical analysis of human serum and its fractions, immunoprecipitation, immunoelectrophoresis, immunocytochemistry, immunohistochemistry, flow cytometry, LC/MS/MS analysis.
• Microbiolgy: aseptic and sterile techniques, bacterial staining, plating methods (streak, spread, pour, replica), cell transformation, enumeration and identification of bacteria, use of biological safety cabinets, media and buffer preparation, plaque assay.
• Epigenetics: CpG island analysis, bisulphite modification and sequencing, MSP and USP analysis, Histone modifiers; methylases and acetylases.
• Tumor biology: Animal models (intracranial, subcutaneous and tail vein injections), tumorigenicity, live cell imaging, animal dissection, chemo and radiotherapy, cell proliferation (clonogenic, FACS and MTT assay), apoptosis (TUNEL, apoptotic DNA fragmentation analysis and mitochondrial apoptosis detection), tumor cell adhesion, invasion, migration, angiogenesis wound repair and metastasis, Multidrug Resistance Direct Dye Efflux Assays, CSC sphere formation, Chemotaxis.
• Microscopy: Light microscopy, fluorescent; confocal microscopy, transmission electron microscopy.
• Protein/Molecular biology: Data mining. RNA seq analysis, DNA recombination, plasmid/retroviral plasmid construction, sub-cloning, sequencing, stable/transient transfections, site-directed mutagenesis, siRNA, PCR, RT-PCR, ChIP, in situ hybridization, DNA and RNA isolation, Southern and Northern blotting, EMSA, DNA and protein arrays, transcription factor (TF) binding site prediction, TF-TF/TF-DNA interactions, sub cellular fractionation, culture filtrate fractionation, fibrin and gelatin zymography, ubiquitination, LC/MS/MS analysis.
• miRNA methods: miRNAs and antago-miRNAs, expression profiling, quantification and target identification, 3’ UTR reporter assay, stem-loop PCR.
• Exosome research: Exosome isolations, quantification and analysis.
• Pathology: Histological and pathological diagnosis, techniques for sample/section preparation and H&E staining, immunohistological double/triple staining.
• Biophysics: Calcium Imaging, planar lipid-bilayers.