Debabrata (Dev) Mukhopadhyay, Ph.D., has a broad background in tumor microenvironment with training and expertise in angiogenesis, cancer, cardiovascular diseases and diabetes. Dr. Mukhopadhyay and his team are using pancreatic and renal cancer disease models to examine how tumors develop and particularly how they induce the angiogenic response that is essential for their survival.
Vascular permeability factor (VPF), also known as vascular endothelial growth factor (VEGF), has been implicated in the new vessel development found in most tumors. Although the mechanism of these complex processes remains unclear, Dr. Mukhopadhyay and his team are investigating the importance of VPF-VEGF as well as its signaling pathways to elucidate the mechanisms by which VPF-VEGF function in a variety of tumor models.
Moreover, Dr. Mukhopadhyay and his team are stuying the role of other angiogenic-related factors in tumor angiogenesis and metastasis, such as vascular endothelial growth factor C (VEGFC), vascular endothelial growth factor D (VEGFD) and phosphatidylinositol glycan anchor biosynthesis class F protein (PIGF).
Additional research interests include stellate cell biology, new drug delivery systems and nanotechnology, and incorporating the use gold nanoparticles and other bioconjugates as messengers to deliver reagents capable of manipulating the angiogenic response in vivo.
- Defining various signaling pathways of VEGF receptors. VEGF induces vascular permeability in ischemic diseases and cancer leading to many pathophysiological consequences. Dr. Mukhopadhyay and his team are developing models to quantitatively assess the cumulative contributions of the involved receptors — such as neuropilin 1, other VEGF receptors and transduction molecules — which has led to zebra fish and mouse models. The development of these models will assist in identifying genetic regulators of vascular permeability and may subsequently translate into therapeutic targets for the treatment of cancer, heart disease and other disorders.
- Defining the regulation of renal cancer. Novel therapeutics for renal cell carcinoma (RCC) are urgently needed as tumors eventually progress after current first line treatments. Diverse factors contributing to RCC progression and chemoresistance have been linked to nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB). Dr. Mukhopadhyay is investigating involvement and signaling pathways of factors such as glycogen synthase kinase-3 beta (GSK-3b). Other areas of focus in RCC are exosomes and their link with the von Hippel-Lindau tumor suppressor, E3 ubiquitin ligase tumor suppressor gene. Exosomes are known to have specific functions, such as intercellular signaling, so understanding their role in RCC and other disease settings may potentially lead to the identification of new biomarkers and the development of more-effective therapies.
- Understanding the regulatory role of GAIP-interacting protein, C terminus (GIPC) and its downstream molecules in pancreatic cancer. Dr. Mukhopadhyay and his team are developing novel peptide-based therapeutic strategies to block GIPC, via its PDZ domain, in pancreatic cancer. With the use of in vitro studies and mouse models, the most promising peptides were found to downregulate epidermal growth factor receptor (EGFR) and insulin-like growth factor receptor (IGF-1R) expression by disrupting cytosolic protein interactions. IGF-1R and EGFR are known to overexpress in many cancers. Their activation induces signaling cascades that lead to cell migration and proliferation. With further side-chain modifications of these peptides, the hope is to develop more-efficient probes to target GIPC and other PDZ-bearing proteins and modulate tumor progression from a therapeutic standpoint.
Significance to patient care
Current clinical challenges related to Dr. Mukhopadhyay's research include the difficulty of early cancer detection, effective therapies for nonresponsive diseases and identification of new therapeutic targets. The goal of this translational research is to develop therapies and methodologies tailored to the individual patient, supporting the concept of individualized medicine. This includes designing effective therapies appropriate for the patient's specific disease target signature as well as screening methodologies for earlier disease detection.