Scientist E: Institute of Life Sciences (2019 onwards)
Scientist D: Institute of Life Sciences (2015 onwards)
Ramalingaswami Fellow: Institute of Life Sciences, (2012-2015)
Post-Doctoral Fellow: VCU Medical Center, Richmond, VA
Research Fellow: Institute of Molecular and Cell Biology, Singapore
Ph.D. Department Biotechnology, IIT Kharagpur, India
Fellowships and Awards
Ramalingaswami Fellow
DST-INSPIRE Faculty
Department of Defense Prostate Cancer Training Award
Senior Research Fellowship, Council of scientific and industrial research, New Delhi
Junior Research Fellowship, Indian council of agricultural research, New Delhi.
Recognitions
Recognized as Ph.D. Guide of : Manipal University, KIIT
Gene Therapy for Cancer
Broad research activities
Systemic and targeted gene therapy for cancer, targeting anti-apoptotic Bcl-2 family members for effective therapy of oral squamous carcinomas.
Developing an effective systemic and targeted gene therapy for cancer
A major challenge for effective gene therapy is the ability to specifically deliver the therapeutic directly into diseased tissue without exposure to the immune system, particularly with a systemic approach in an immune competent animal model. Progress in gene therapy has been hampered by concerns over the safety and practicality of viral vectors, particularly for intravenous delivery, and the inefficiency of currently available non-viral transfection techniques. We will explore novel targeted-delivery approaches to develop a site-specific delivery and henceforth therapy in immune competent transgenic mouse cancer model. These approaches of systemic gene delivery will facilitate development of efficient, selective and non-toxic modes for gene therapy using therapeutically beneficial genes that offer significant potential to translate into a Phase I/II clinical trial. For therapeutic arms we will explore the tumor suppressor activity of 1) human melanoma differentiation gene-7/Interleukin-24 (mda-7/IL-24) and 2) Suppressor of AP-1 regulated by IFN (SARI) in oral squamous cacinomas. mda-7/IL-24 shows ubiquitous anti tumor effect, its mode of action involves preferential induction of apoptosis in cancer cells while exerting no discernible toxic effects toward normal cells by eliciting unique potent “antitumor bystander activity” as a consequence of autocrine secretion. Similarly, forced expression of SARI resulted in tumor-selective growth inhibition and induction of apoptosis in prostate cancer, malignant glioma and metastatic melanoma cells. Although the precise molecular mechanism by which SARI induces tumor-suppressing activity requires further clarification, preliminary studies revealed that forced expression of SARI resulted in inhibition of DNA binding of activator protein (AP-1) complexes and, consequently, it selectively inhibited AP-1-dependent gene expression. Targeting anti-apoptotic Bcl-2 gene family for effective therapy of Oral squamous carcinomas: Despite intensive investigation, oral cancer remains formidable clinical challenges resulting in high frequencies of morbidity and mortality. Reprogramming tumor cells to undergo programmed cell death (apoptosis) represents a promising and powerful strategy for treating both local and metastatic disease. Ways of achieving this objective involve the selective down regulation of dysregulated oncogenes and/or expression/activation of apoptosis-inducing genes or their products in tumor cells. For example the role of Bcl-2 family members is critical for onset and progression of cancer. Dysregulation of Bcl-2 family members including myeloid cell leukemia-1 (Mcl-1) is often implicated in the acquisition of resistance to apoptosis in malignant cell lines. Mcl-1 plays a pivotal role in cancer cell survival, including that of oral cancer cells, suggesting involvement of this gene in oral squamous carcinogenesis. Over expression of Mcl-1 protects cells from apoptosis induced by a variety of stress-promoting agents. Considering the fact that Mcl-1 is over expressed in the majority of oral cancers, we hypothesize that selectively targeting Mcl-1 alone or in combination with other conventional anti cancer drugs or potential tumor suppressors might provide an effective therapeutic for this metastatic disease.
Publications (best 15)
Maji S, Shriwas O, Samal SK, Priyadarshini M, Rath R, Panda S, Das Majumdar SK, Muduly DK, Dash R*: STAT3- and GSK3beta-mediated Mcl-1 regulation modulates TPF resistance in oral squamous cell carcinoma. Carcinogenesis 2018 (in press).
Maji S, Panda S, Samal SK, Shriwas O, Rath R, Pellecchia M, Emdad L, Das SK, Fisher PB, Dash R*. 2018. Bcl-2 Antiapoptotic Family Proteins and Chemoresistance in Cancer. Adv Cancer Res 137: 37-75
Maji S, Samal SK, Pattanaik L, Panda S, Quinn BA, Das SK, Sarkar D, Pellecchia M, Fisher PB, Dash R*. 2015. Mcl-1 is an important therapeutic target for oral squamous cell carcinomas. Oncotarget 6: 16623-37.
Samal SK, Routray S, Veeramachaneni GK, Dash R*, Botlagunta M*. 2015. Ketorolac salt is a newly discovered DDX3 inhibitor to treat oral cancer. Scientific Reports 5: 9982.
Samantara AK, Maji S, Ghosh A, Bag B, Dash R*, Jena BK* (2016). Good’s Buffer Derived Highly Emissive Carbon Quantum Dots:Excellent Biocompatible Anticancer Drug Carrier, Journal of Materials Chem B.
Dash R, Bhoopathi P, Das SK, Sarkar S, Emdad L, Dasgupta S, Sarkar D, Fisher PB. 2014. Novel mechanism of MDA-7/IL-24 cancer-specific apoptosis through SARI induction. Cancer Res 74:563-574
Dash R, Azab B, Quinn BA, Shen X, Wang XY, Das SK, Rahmani M, Wei J, Hedvat M, Dent P, Dmitriev IP, Curiel DT, Grant S, Wu B, Stebbins JL, Pellecchia M, Reed JC, Sarkar D, Fisher PB. 2011 Apogossypol derivative BI-97C1 (Sabutoclax) targeting Mcl-1 sensitizes prostate cancer cells to mda-7/IL-24-mediated toxicity. Proc Natl Acad Sci U S A 108: 8785-90.
Dash R, Azab B, Shen XN, Sokhi UK, Sarkar S, Su ZZ, Wang XY, Claudio PP, Dent P, Dmitriev IP, Curiel DT, Grant S, Sarkar D, Fisher PB. 2011. Developing an effective gene therapy for prostate cancer: New technologies with potential to translate from the laboratory into the clinic. Discov Med 11: 46-56.
Dash R, Richards JE, Su ZZ, Bhutia SK, Azab B, Rahmani M, Dasmahapatra G, Yacoub A, Dent P, Dmitriev IP, Curiel DT, Grant S, Pellecchia M, Reed JC, Sarkar D, Fisher PB. 2010. Mechanism by which Mcl-1 regulates cancer-specific apoptosis triggered by mda-7/IL-24, an IL-10-related cytokine. Cancer Res 70: 5034-45.
Dash R, Su ZZ, Lee SG, Azab B, Boukerche H, Sarkar D, Fisher PB. 2010. Inhibition of AP-1 by SARI negatively regulates transformation progression mediated by CCN1. Oncogene 29: 4412-23.
Dash R, Dmitriev I, Su ZZ, Bhutia SK, Azab B, Vozhilla N, Yacoub A, Dent P, Curiel DT, Sarkar D, Fisher PB. 2010. Enhanced delivery of mda-7/IL-24 using a serotype chimeric adenovirus (Ad.5/3) improves therapeutic efficacy in low CAR prostate cancer cells. Cancer Gene Ther 17: 447-56.
Dash R, Bhutia SK, Azab B, Su ZZ, Quinn BA, Kegelmen TP, Das SK, Kim K, Lee SG, Park MA, Yacoub A, Rahmani M, Emdad L, Dmitriev IP, Wang XY, Sarkar D, Grant S, Dent P, Curiel DT, Fisher PB. 2010. mda-7/IL-24: a unique member of the IL-10 gene family promoting cancer-targeted toxicity. Cytokine Growth Factor Rev 21: 381-9.
Quinn BA, Dash R, Sarkar S, Azab B, Bhoopathi P, Das SK, Emdad L, Wei J, Pellecchia M, Sarkar D, Fisher PB. 2015. Pancreatic Cancer Combination Therapy Using a BH3 Mimetic and a Synthetic Tetracycline. Cancer Res 75: 2305-1.
Kumar A, Samal SK, Dash R, Ojha U. 2014. Polyacryloyl hydrazide based injectable & stimuli responsive hydrogels with tunable properties. Journal of Materials Chemistry B 2: 7429-7439.
Tormo D, Checinska A, Alonso-Curbelo D, Perez-Guijarro E, Canon E, Riveiro-Falkenbach E, Calvo TG, Larribere L, Megias D, Mulero F, Piris MA, Dash R, Barral PM, Rodriguez-Peralto JL, Ortiz-Romero P, Tuting T, Fisher PB, Soengas MS. 2009. Targeted activation of innate immunity for therapeutic induction of autophagy and apoptosis in melanoma cells. Cancer Cell 16: 103-14.
Dash R, Acharya C, Bindu PC, Kundu SC. 2008. Antioxidant potential of silk protein sericin against hydrogen peroxide-induced oxidative stress in skin fibroblasts. BMB Rep 41: 236-41.
Dash R, Mandal M, Ghosh SK, Kundu SC. 2008. Silk sericin protein of tropical tasar silkworm inhibits UVB-induced apoptosis in human skin keratinocytes. Mol Cell Biochem 311: 111-9.
Gene Therapy for Cancer
Dr. Swati Chauhan, DST-WOSA
Mr. Omprakash Shriwas, UGC-JRF
Project: Role of glucose metabolism in Oral Squamous Cell Carcinoma (OSCC)
Miss Laxmipriya Pattanaik (Lab Technician)
Miss. Manashi Priyadarshini (Institutional JRF )
Project: Gene Therapy for OSCC
Mr. P. Srinath (DBT-JRF)
Project: Understanding the mechanism of chemoresistance in OSCC
Miss. Pallavi Mohapatra (CSIR-JRF)
Project: Role of glucose metabolism in Oral Squamous Cell Carcinoma
Miss. Tanushree Mahapatra (CSIR-JRF)
Mr. Sibasish Mohanty (CSIR-JRF)
Abhilipsha Mishra (Project Assistant)
Alumni:
PhD
1) Dr. Santanu Maji, Phd, Currently post doc fellow at VCU medical center, Richmond, Virginia
2) Dr. Sabindra K Samal: Currently Assistant Professor: BJB autonomous college, Bhubaneswar, Odisha
RA/Post-doc/Woman Scientist
Dr. Neera Singh
Gene Therapy for Cancer
DBT sponsored project entitled ‘Investigating the potential tumor suppressive activity of SARI (Suppressor of AP-1 regulated by interferon) in Oral Squamous Cell Carcinomas’ for 3 years (2015-2018).
DST-SERB sponsored project entitled “Restoring cell death in chemoresistant oral squamous cell carcinomas (OSCC) for 3 years (2016-2019)