Sutapa ray, ph.d.
Assistant Professor, Division of Hematology/Oncology | University of Nebraska Medical Center
The overall goal of my research is to understand how alterations in signal transduction pathways contribute to childhood cancer development and pathogenesis. Particularly, we focus on:
(1) Elucidating the role of dysregulated IL-6/JAK/STAT3 signaling pathway in pediatric cancers and its cooperation with other oncogenic events in cancer progression
(2) Development of novel targeted treatment strategies in pediatric cancers
(3) Regulation of the immune checkpoint molecules expression in pediatric brain cancer
Research Grants
2019-2021
Targeting Cyclin-dependent kinase 9 (CDK9) in Medulloblastoma.
$100,000
Update from Dr. Ray | March 2024 | In Team Jack grant, we proposed the hypothesis that aberrant expression of CDK9 and STAT3 in MB induces enhanced transcription of oncogenic targets, leading to MB pathogenesis. Therefore, targeting both CDK9 and STAT3 function with small molecule inhibitors (TP1287 and WP1066 respectively) will significantly decrease MB tumor growth in an orthotopic mouse model. For this purpose, we worked successfully on sub-cutaneous MB model in vivo and showed that combination of both inhibitors significantly reduced MB tumor growth and our IHC data with MYC, Ki67 and caspases3 antibodies showed attenuation of proliferation markers and induction of apoptotic cell death marker respectively. Our next step was to determine the efficacy of the inhibitors on the orthotopic mouse model of MB. As mentioned previously we do not have appropriate trained personnel in comparative medicine dept. to give us the training of intracranial surgery in mice to develop tumor in the cerebellum. So, our newly developed core facility (Director, Dr. Mahapatra) has hired a technician to gain training with orthotopic implantation of tumor. My student and I will take help of the core facility to accomplish Aim 2 of Team Jack grant. Meanwhile we are also working with CDK9 PROTAC and generated substantial amount of in vitro data as proposed in Aim 1 with small molecule inhibitor. We also have a plan to determine the efficacy of CDK9 PROTAC in orthotopic MB model in vivo.
September 2024 – September 2026
Role of Coactivator-Associated Arginine Methyltransferase 1 (CARM1) in Pediatric Brain Cancer Medulloblastoma
$350,262
The studies using cell culture/PDX mouse models should provide evidence in support of the hypothesis that targeting the CARM1-STAT3 axis is a viable therapeutic strategy for MYC-driven MB tumors. The expectation is to see significant anti-MB efficacies of the inhibitor when combined, in reducing tumor burden and increasing survival of mice. They expect to see significant anti-MB efficacies of the inhibitor when combined, in reducing tumor burden and increasing survival of mice. High CARM1 expression in human MB tumors is correlated with poor overall survival: The aberrant expression of CARM1 has been associated with a variety of cancers7. However, its expression and function in brain cancers including MB have not been reported. They performed survival analyses with respect to CARM1 expression, using 612 MB samples from the Cavalli (763 samples) dataset. Their survival analyses showed that high A 10X levels of CARM1 expression is significantly correlated with poor survival of MB patients (Fig.1), suggesting that CARM1 expression is not simply deregulated in MB but is also a poor prognostic marker.