BE Seminar: Harnessing Nanoscale Cellular Communication for Designing Next-Generation Therapeutics by Dr. Tanmoy Saha,

Speaker: Dr. Tanmoy Saha, MSc, PhD.

Instructor, Harvard Medical School

Associate Bioengineer, Brigham and Women’s Hospital

Date: 13th March
Time: 2.00 PM
Venue: TCS Smart X Building, Seminar Hall – (G F – 22)

Title: Harnessing Nanoscale Cellular Communication for Designing Next-Generation Therapeutics

Abstract: Aberrant intercellular communication underlies disease progression. For example, cancer cells communicate with neighboring cells to exchange organelles, proteins, metabolites, and ions, which helps them gain survival advantages. He is interested in three different types of communication: (i) transmembrane ionic communication, (ii) extracellular protein-mediated communication, and (iii) intercellular nanoscale physical communication.

Cells maintain an ionic homeostasis with the extracellular environment using ion channels and transporters. He has developed a variety of unimolecular and supramolecular artificial chloride channels (ACT). The ACTs are robust supramolecular architecture made up of small molecules. This helps in a better understanding of ion transport activity and modulating ionic communication in cells. He has performed structure-activity relationships to identify the best ACT. He introduced the first-ever example of ACT, which can induce apoptosis in cancer cells by disrupting ionic homeostasis.

Cancer cells use extracellular proteins, known as immune checkpoints, to send kill-me-not signals to T cells and macrophages. Immunotherapy has made a paradigm shift in cancer treatment by blocking such interactions using monoclonal antibodies. However, more than 70% of cancer patients do not respond to immunotherapy. He has introduced immunoengineered nanotherapeutics that serve as a platform technology to deliver a combination of pharmacological drugs and biologics to cancer cells. This nanotherapeutic can block more than one immune checkpoint and activate both innate and adaptive immunity. This has shown increased therapeutic efficacy in syngeneic lung cancer, which is not responsive to traditional immunotherapy and monotherapies.

Furthermore, they investigated a novel mechanism of immune evasion by cancer cells through nanoscale physical communication. They have used high-resolution electron and optical microscopy to identify the nanoscale communication of the cancer cells with T cells and hijack mitochondria. The transfer of mitochondria metabolically empowers the cancer cells and increases their proliferation, metastasis, and drug resistance. In contrast, the T cell population depletes because of metabolic deactivation. Blocking the nanotube-mediated mitochondria transfer by pharmacological inhibitors has shown potential therapeutic implications in increasing intrinsic T cell immune response and elevating therapeutic efficacy in combination with traditional immunotherapy. Moreover, they have shown elevating the immune response by supercharging T cells with exogenous mitochondria. Hence, a mechanistic understanding of cellular communication and novel therapeutic strategies are critical to offer better therapeutic outcomes in cancer and other chronic diseases.

About the Speaker: Dr. Saha is an entry-level faculty at Harvard Medical School and an Associate Bioengineer at Brigham and Women’s Hospital. He has received PhD from the Indian Institute of Science Education and Research Pune and received the best thesis award from the chemistry department. Dr. Saha’s. major research direction is to develop tools to study cellular communication and introduce novel therapeutic strategies. He has published his research in prestigious journals, including Nature Nanotechnology, Science Advances, J. Am. Chem. Soc., Cell, PNAS, etc. He has received independent research grants from the Department of Defense and Melanoma Research Alliance.