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 D.Arya completed her BSc. (CBZ) and M.Sc.(Biosciences) from Mangalore University, Mangalore. She received her Ph.D. in Biosciences, under a CSIR fellowship from Mangalore University. She has post-doctoral research experience from the University of Southampton, UK.

.

Research Interest:

3D culture platforms, cancer chemoresistance, organoid cultures, precision medicine.

Dr. Shivaprasad Manchineella, Ph.D
Research Scientist
shivaprasad@ms-mf.org

Dr. Shivaprasad Manchineella received his M.Sc. in Organic Chemistry from Osmania University (2010), and Ph.D. in Chemical Sciences from Jawaharlal Nehru Centre for Advanced Scientific Research (JNCASR) Bengaluru, India (2016).

Research Interest:

    • Peptide Chemistry, Hydrogels, Biomaterials, Tissue Engineering, Engineered Disease Models.

.

Dr. Ritu Raj, Ph.D
Research Scientist
rituraj@ms-mf.org

Dr. Ritu Raj has done M.Sc. in Nanoscience and Nanotechnology from National Center of Nanoscience and Nanotechnology, University of Madras, Chennai. He has Ph.D. in Life science from National Institute of Technology, Rourkela, for work on fluorescent nanoparticles for cancer theranostics. He has also been to Instituto Superior Tecnico (IST), Lisbon, Portugal, to carry out part of Ph.D. work, which was sponsored by ERASMUS MUNDUS Experts Sustain exchange program.

Research Interest:

  •        Nanocarriers based biosensors for circulating tumor cells
    •    Nanoparticle-assisted targeted drug delivery for cancer therapy
    •   Development of nanofibers for biomedical applications
    •   Formulation of Magnetic-nano platform as contrast agents for magnetic resonance imaging (MRI) and magnetic hyperthermia for solid tumors.

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.

Krishna Kumar
Research Fellow
KrishnaKumar@ms-mf.org

  • A perspicacious researcher with 10 years of rich research experience in drug discovery, cancer biology, stem cell engineering and neuroscience. Self driven, adroit with capabilities to achieve professional and organisational objectives. He is proficient in cell biology, drug screening, glial organoids and animal handling. Has intense knowledge of developmental biology, molecular mechanism and signalling pathways. A team player and implements interdisciplinary, transversal projects in collaborative environment
    .

    Research Interest:

    • Screening of phytochemicals for potential anti-cancer studies.
      Organoid culture, 3D culture system
      Regenerative medicine to address neurodegeneration.
  • Alice Hepsiba
    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

    KISHORE A.K,MRes.
    Junior Research Fellow
    Kishore.ak@ms-mf.org

    Kishore has done MSc in biochemistry from Bangalore University (2015) and Master of Research in cancer biology from the University of Dundee (United Kingdom, 2017). Project assistant at Indian Institute of Science to work on 3D culturing of breast cancer cells and lectin staining of developing limbs and wings of chick embryo is a great add on to his research experience.

    Research Interest:

    Culturing of primary breast cancer cells using 3D culture system.
    Understanding of metabolomics of breast cancer cells in a co-culture system.
    Efficacy of drugs in microfluidic microenvironment.
    Curious to understand mTORC1 regulation in response to different drug combinations in 3D culture systems.

    Manjunath E.V,B.Sc., M.Sc.
    Junior Research Fellow
    manjunatha.ev@ms-mf.org

    Manjunatha E V has done his B.Sc., M.Sc, from Mangalore University.

    Research Interest:

      • 3D Spheroid culture of primary breast cancer cells and personalised medicine.

     Priyanka Yolmo

  • Junior research fellow
    Priyanka.yolmo@ms-mf.org

  • Priyanka has done her B.Tech in Genetic Engineering from SRM Institute of Science and Technology, Kattankalathur Campus, Chennai.

    Research Interest:

  • Cancer Biology, 3D cell culture, Genetics.
  • 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.