Anti-Cancer Technologies Program

3D cell culture platforms for tumor engineering, biomarker discovery and drug assaying

We are developing 3-dimensional (3D) cell culture matrices of tunable physical and biochemical properties, akin to that of native tissue so that experimental manipulations can occur in a physiological context. Since these models can realistically represent the metastatic condition, they could be used to understand the role of cellular and non-cellular components of tissue microenvironment in cancer progression. This might help elucidate cell-cell and cell-stroma crosstalk pathways active during disease progression which could be potential therapeutic targets.

Eventually, we hope to fine tune these culture systems to function as reproducible drug screening platforms to help design more effective therapeutics. Further, these matrices could be tweaked to support growth of primary tumor cells which could then be used to assay therapy response or predict metastatic potential.

We are working with breast cancer as a model to develop these culture systems since it is the most common malignancy in women worldwide. In India, 5-year survival rates for breast cancer remain less than 50%. Moreover, certain conditions like Triple Negative and Metastatic Breast Cancer are unmet clinical needs, with limited treatment options.

Nanotechnology platforms for cancer therapeutics

The advancement of nanotechnology offers a new dimension to tumor-targeting strategies. We are interested in developing smart delivery system for anticancer drugs, i.e. multifunctional nanoplatforms comprising biocompatible polymers, anticancer drug and cancer specific ligands that can efficiently resolve the in vivo stability versus intracellular drug release problem, as well as stealth versus tumor cell uptake issues. This involves, but is not limited to, fabrication of polymeric nanoparticles, effective drug encapsulation, controlled drug release, functionalization with cancer cell specific ligands (surface modification) for specific targeting and to achieve enhanced therapeutic efficacy of drugs without systemic toxicity. This work is being done in collaboration with the Nanomedicine research group.

RNAi-based platforms for targeted therapy

Broad spectrum and standard therapeutic agents fail to target leukemia initiating cells (LIC). It is now believed that relapse originates from LIC-containing minimal residual disease (MRD) and the frequency of relapse correlates with the burden of LIC resistant to conventional chemotherapy. Therefore, targeted therapies that eradicate LIC and complement current regimens are needed. miRNA have recently been shown to play a role in malignant transformation and leukemia. We would like to identify miRNA that have been deregulated in different subtypes of leukemia, understand how miRNA trigger LIC-mediated MRD following chemotherapy and ultimately develop systems for effective delivery of RNAi therapeutics.

Tissue-engineered platforms for biomedical applications

Mesenchymal Stem Cells (MSC) are multi-potent stromal cells that can differentiate into a variety of cell types and thus help maintain tissue homeostasis following injury or inflammation. We are interested in engineering culture environments that will allow us to modulate this pluripotency of MSC and direct their differentiation, enabling clinical use of such `Tissue Engineered Constructs’.

 Silk fibroin hydrogels

Silk fibroin hydrogels

 Silk fibroin electrospun scaffolds

Silk fibroin electrospun scaffolds

 Breast Cancer Cells cultured on 3D scaffolds

Breast Cancer Cells cultured on 3D scaffolds

People

Dr. Aditya Chaubey, Ph.D.
aditya.chaubey@ms-mf.org

Dr. Aditya Chaubey is the Chief Scientific Officer of Mazumdar Shaw Center for Translational Research and heads the  Anti-Cancer Technologies Program lab. He received his Ph.D. in Bioengineering from Clemson University. His doctoral work involved understanding how biomaterial scaffolds can be used to modulate the differentiation of stem cells. His subsequent work at Cincinnati Children’s Hospital Medical Center elucidated the role of hematopoietic stem cells in myeloid differentiation and the role of microRNA in Acute Myeloid Leukemia (AML). His long-term interest in applying engineering principles to biology led him to the Biomedical Engineering Program at University of Cincinnati, where he worked in the area of orthopedic tissue engineering to develop novel methods to modulate microRNA in skeletal biology. He is currently the Chief Scientific Officer of Mazumdar Shaw Center for Translational Research and heads the Anti-Cancer Technologies Program lab. He is a member of the American Society of Haematology (ASH), Orthopaedic Research Society (ORS), Sigma Xi and Tissue Engineering & Regenerative Medicine International Society (TERMIS) and a reviewer for journals like PLoS One, Journal of Cell Transplantation and Journal of Orthopaedics and Traumatology.

Anuradha D.Arya, Ph.D
Research Scientist
anuradha.arya@ms-mf.org

Anuradha has done B.Sc., M.Sc., Ph.D. (Biosciences), Mangalore University and has Post Doc experience at University of Southampton, UK.

Research Interest:

3D cell culture platforms, breast cancer chemoresistance and cancer stem cells.

Avinash Arvind Rasalkar, M.Sc
Research Scientist
avinash.rasalkar@ms-mf.org

Avinash has done B.Sc. Microbiology, Jai-Hind College, Dhule, M.Sc. Biotechnology (North Maharashtra University, Jalgaon, Maharashtra) and Ph.D. (thesis submitted for Dr. Human Biology: awaiting award) University of Ulm, Germany.

Research Interest:

  • Application of advanced molecular biology, cell biology & genetics to probe disease pathogenesis
  • Mechanisms of normal and malignant hematopoiesis
  • Mechanisms of leukemic stem cell biology and its implications in prognostics relevance and therapeutic target discovery
  • Genetics & Evolution

Pradipta Ranjan Rauta, Ph.D
Research Scientist
pradiptha.ranjan@ms-mf.org

Pradipta has done his M.Sc., Orissa University of Agriculture and Technology, Bhubaneshwar and Ph.D. in National Institute of Technology, Rourkela

Research Interest:

  • Nanotechnology in cancer therapeutics

Pavan Hallur, Msc.
Senior Research Fellow
pavan.hallur@ms-mf.org

Pavan has done his B.Sc., M.Sc. from Bangalore University. His previous research experience includes 2 years at Indian Institute of Science, Bangalore.

Research Interest:

  • Biomimetic 3D cell culture platforms, cancer metastasis, Nanotechnology in cancer therapeutics.

Muralidhara Nagarjuna,MDS.
Research Fellow
murali.nagarjuna@ms-mf.org

Dr. Murali has done his MDS., Oral and Maxillofacial Surgery. He is currenty working on Welcome DBT ClinicalFellowship in Cranio-Maxillofacial Surgery.

Research Interest:

  • Mesenchymal Stem Cells, Biomaterials for bone regeneration.

Alice Hepsiba,M.Tech.
Junior Research Fellow
alice.hepsiba@ms-mf.org

Alice has done her B.E., M.Tech from M.S.Ramaiah Institute of Technology, Bangalore.

Research Interest:

  • Breast Cancer, miRNA, photochemicals

Alumni

Publications

  • Arya, A.D., Hallur, P.H., Karkisaval,A.G., Gudipati,A., Rajendiran, S., Dhavale, V., Ramachandran, B., Jayaprakash, A., Gundiah, N., Chaubey, A. (2016) Gelatin Methacrylate Hydrogels are Biomimetic Matrices for Modeling Breast Cancer Invasion and Chemoresistance In Vitro. ACS Applied Materials and Interfaces. DOI: 10.1021/acsami.6b06309
  • Velu CS#, Chaubey A#, Phelan JD, Horman SR, Wunderlich M, Guzman ML, Jegga AG, Zeleznik-Le NJ, Chen J, Mulloy JC, Cancelas JA, Jordan CT, Aronow BJ, Marcucci G, Bhat B, Gebelein B, Grimes HL. Therapeutic antagonists of microRNAs deplete leukemia-initiating cell activity. The Journal of Clinical Investigation. 124(1):222-236, 2014. # Equal contribution
  • Chaubey A*, Grawe B, Meganck JA, Dyment N, Inzana J, Jiang X, Connolley C, Goldstein S, Kenter K, Awad H, Rowe D, Butler DL. Structural and biomechanical responses of osseous healing: a novel murine nonunion model. Journal of Orthopaedics and Traumatalogy, August 30, 2013. *Corresponding Author
  • Horman SR, Velu CS, Chaubey A, Bourdeau T, Zhu J, Paul WE, Gebelein B, Grimes HL. Gfi1 integrates progenitor versus granulocytic transcriptional programming. Blood. 28;113(22):5466-75, 2009.
  • Popovic R, Riesbeck LE, Velu CS, Chaubey A, Zhang J, Achille NJ, Erfurth FE, Eaton K, Lu J, Grimes HL, Chen J, Rowley JD, Zeleznik-Le NJ. 2009. Regulation of mir-196b by MLL and its overexpression by MLL fusions contributes to immortalization. Blood. 2;113(14):3314-22, 2009.
  • Chaubey A, Ross KJ, Leadbetter MR. Gomillion CT, Burg KJL. Characterization of the Differentiation and Leptin Secretion Profile of Adult Stem Cells on Patterned Polylactide Films. Journal of Biomaterials Science, Polymer Edition. 20(7):1163-1177, 2009.
  • Chaubey A, Burg KJL. Extracellular Matrix Components as Modulators of Adult Stem Cell Differentiation in an Adipose System. Journal of Bioactive and Compatible Polymers. 23(1):20-37, 2008.
  • Chaubey A., Ross KJ, Leadbetter RM, Burg KJL. Surface patterning: Tool to Modulate Stem Cell Differentiation in an Adipose System. Journal of Biomedical Materials Research. 84(1):70-8, 2008.