Sengupta Laboratory at
Harvard Medical School and MIT 

Laboratory for Nanomedicine

In the lab we push the boundaries in medical research keeping clinical translation in focus

Our laboratory is located within the rich ecosystem of Department of Medicine, Brigham and Women's Hospital, a teaching hospital of the Harvard Medical School, and the Harvard-MIT Division of HST. Our research is unique in that we address medical problems with an engineering appproach.  
We focus primarily on cancer, with the goal of doing research that can be translated to the clinics. Our solutions are therefore simple. At a fundamental level, we are currently working on three different themes: 1. The early events of metastasis; 2. Understanding the mechanisms (such as phenotypic plasticity) that allow cancer cells to tolerate chemotherapy; and 3. Developing next generation therapeutics, including nanomedicines, that can modulate the tumor stromal contexture, including the immune cells. We also provide students and fellows the freedom to explore beyonds these boundaries. We love exciting and hard problems that will have an impact on patient's lives. 
Vineeth joins Oxford University for a PhD in cancer biology on a CRUK fellowship.
We view problems from a different perspective. For example, while testing anticancer drugs on cancer cell viability we noticed that the beautiful dose response curves rarely reached zero even at very high concentrations. Instead of getting excited about the large percentages of cells that were getting killed by treatment, we were intrigued by why a fraction of cells were still viable at that lethal concentration. This led us to collaborate with mathematicians to understand that cancer cells can switch phenotype to a stem-like state. This phenotypic cell state transition allowed the cancer cells to tolerate chemotherapy. We engineered chimeric nanoparticles that could target these phenotypic states.  
Research Highlights

Nanoscale conduits in metastatic hijack

Nanoscience and Immunooncology 

Why does cancer therapy fail?

Funded by a Breakthrough Grant from the US DoD BCRP program, we are exploring the early events in metastasis. For example, we recently demonstrated a novel mechanism communication between metastatic cancer cells and enothelium lining vasculature, where the cancer cells connect with endothelial cells via nanoscale tubes (arrow in picture above), and can transfer miRNAs to the endothelium via these conduits. We are now exploring the mechanisms that drive these nanotubes in an attempt to perturb this communication. (Connor Y et al. Nature Communication, 2015) 

Cancer immunotherapy is the emerging paradigm.  Current approaches are limited by a reliance on T cells and the lack of tools to study outcomes. We are In the laboratory, we are exploring the use of nanotechnology to expand immunotherapy beyond T cells. In a recent PNAS paper, we reported the first nano theranostic that allows the imaging of an immunotherapy in action in real-time. We are also studying combination therapies that can be enabled using nanotechnology. We also developed the first computational algorithm to design nanomedicines.  (Kulkarni et al, PNAS, 2016; Kulkarni et al. ACS Nano 2016,a,b). In a recent study, we designed bifunctional therapeutics that activated macrophages against cancer cells (Kulkarni et al, Nature BME, 2018).
Some bacteria, called 'persisters' are known to survive antibiotics  without mutating. Cancer cells also exhibit a  similar 'persister' behaviour. We study this behaviour, exploring contribution of phenotypic plasticity, tumor heterogeneity, and metabolic states leading tp tolerance. Such behaviour can limit the power of genetic-based precision medicine. We are therefore working on engineering tumor organoid systems for functional testing of drugs. We recently demonstrated that merging an organoid system with machine learning can be used to predict chemotherapy outcomes. (Majumder et al, Nature Comm. 2015; Goldman et al, Nature Comm, 2015)