• Ram K. Singh

  • Bhushan Thakur

  • Ajit Dhadve

  • Abhilash Deo

  • Aniketh Bishnu

Ram Kumar Singh

Project Title: Molecular imaging of cancer stem cells (CSCs) during development of chemo resistance in ovarian carcinoma

Cancer Stem Cells, a small population residing within the tumor bulk are inherently chemoresistant in nature and the major cause behind tumor relapse. Previously we have shown modulation in IGF-1R-Akt axis is associated with development of chemoresistance in ovarian cancer cells (Singh et. al., 2014). Currently I am trying to investigate the role of IGF-1R-Akt signaling in Cancer Stem Cell phenotype and function during acquirement of chemoresistance.

Bhushan Thakur

Investigating the mechanistic insight of PIK3CA transcriptional regulation in Chemoresistant Ovarian carcinoma

Chemotherapeutic agents attenuate expression of PIK3CA, a crucial cell survival gene, in p53 dependent manner. This attenuation is abolished in chemoresistant ovarian carcinoma cells which aids the cells to survive against chemotherapeutic agent via escalated PI3K/AKT signalling. My work focuses on investigating the mechanism involved in this differential regulation of PIK3CA in chemoresistant ovarian carcinoma utilizing reporter assays, live cell and in vivo imaging. We find that p53 exerts a unique regulatory mechanism to PIK3CA by altering binding site preference in chemosensitive and in chemoresistant cells. This altered p53 binding is facilitated via various post translational modifications. Currently, I am working on identifying regulator/s of PIK3CA promoter in chemoresistant ovarian carcinoma. Identifying such regulators can be extended in drug discovery research for chemoresistant ovarian carcinoma.

Ajit Dhadve

Project Title: Investigating role of IGF-1R signalling at early stage of chemoresistance in Ovarian Carcinoma.

Majority of human cancers upregulate insulin-like growth factor receptor 1 (IGF1R), a tyrosine kinase receptor, upon chemotherapy or radiotherapy and is predicated to have poor outcome of treatment modality. Resistance to current line of therapy is major cause for failure of treatment and disease recurrence. Signalling through IGF1R has strong proliferative and anti-apoptotic effect, which argues for its importance in tumorigenesis; however understanding the significance of IGF1R upregulation during development of chemoresistance will be important. Recent study from our lab using isogenic models of chemoresistant ovarian cancer cells showed that expression of IGF1R is increased at both transcript and protein level during onset of chemoresistance. In the present study I aim to identify the transcriptional regulators for IGF1R which modulate its expression during course of chemoresistance development and investigate the role of IGF-1R signalling in maintenance of chemoresistance and pathogenesis.

Abhilash Deo

Project title: Role of IGF-1R in ovarian cancer metastasis

Our lab has been working on IGF-1R signalling to understand its role in chemo-resistance. Previous studies from our lab have shown oscillatory expression of IGF-1R across sensitive, early and late chemo-resistant ovarian cancer cells. IGF-1R is also known to promote several processes of metastasis like migration, invasion, angiogenesis etc. Therefore, I am trying to understand the role of IGF-1R in ovarian cancer metastasis using in vitro cell models and in vivo molecular imaging.

Aniketh Bishnu

Understanding the modulation in MAPK/ERK and PI3K/AKT signaling during acquirement of drug resistance

I am presently developing high throughput optical imaging sensors for understanding how the different components of PI3K-AKT and MAPK-ERK signaling pathways interact through the course of acquirement of chemo resistance in ovarian cancer cells. These sensors will be used can be used to understand the dynamicity of protein–protein interaction inside the cancer cells.

Colaborative Projects

  • In collaboration with Prof. D. Bahadur's group (IIT, Mumbai) we have developed pH and thermolablie magnetic mesoporous nanoassemblies and demonstrated their effectiveness towards chemoresistant tumors by real time optical imaging (Pradhan et al, Theranostics, 2016).
  • Comprehension of biophysical properties of chemoresistant cells governed by molecular alteration leading to migration and metastasis of the disease is an active area for drug development. Working together with Dr. Shamik Sen (IIT, Mumbai) we find distinct migratory behaviors between cisplatin and paclitaxel and dual resistant cells. Currently, we are exploring the candidate target molecule/s and pathways responsible for this differential behavior.
  • In collaboration with Prof. Anil K Sood, MD Anderson Cancer Centre, Texas, USA and Dr. Yu Kang, Fudan University, China, we are investigating the role of Notch-3/Jagged-1 signaling in adherence and progression of metastatic ovarian cancer. This proposal is selected for funding by Global Academic Program (GAP) under Sister Institutional Network Foundation in 2015.
  • An in house collaboration with clinicians from Tata memorial Hospital engage us to longitudinally monitor the development of chemoresistance in advanced stage ovarian cancer patients.