Sengupta Laboratory at
Harvard Medical School and MIT 

Current projects
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;
3. Developing next generation therapeutics, including nanomedicines, that can modulate the tumor stromal contexture, including the immune cells.

That being said, we love exciting and hard problems that will have an impact on patient's lives, and hence often take up projects that are beyond the scope of the above projects. This could range from mathematical simulations of biological events (for example, we have used mathematical models to design optimal combiation therapy), design of computational algorithms, to design and testing of novel antibiotics that retard the development of resistance. We provide students and fellows the freedom to explore beyonds boundaries set by grants.

Our laboratory is fully equipped with most chemistry (such as hoods, analytical and prep HPLCs with multiple detectors, FTIR, nanozetasizer, rotavaps, uv-vis spectrophotometer, fluorimeter, etc), biology (PCR/RT-PCR, Gel-Doc system, deconvolution microscopes, cell culture facility, ultracentrifuge, plate reader, in vivo studies, etc) resources. We also have access to core facilities at MIT and Harvard (we are members of Harvard Nanoscience Center and Dana Farber Cancer Institute)   

  

Electron micrograph of a metastatic cancer cell (EPI) invading a layer of endothelial cells (ENDO) below. We demonstrated,for the first time, that the cancer cell forms nanoconduits (arrow) with the endothelial cell, and through these conduits injects miRNA that transforms the recicipent endothelial cells. This is an example of a fundamental project in the lab (Connor Y et al, Nature Comm. 2015).   

FUNDAMENTAL BIOLOGY

ENGINEERING APPROACH

CLINICAL TRANSLATION

Once we define a question, we approach the solution with an engineering mind-set. Problems are broken down into small solvable steps building upto the final story. Often we design tools to probe the biological question. For example, in a Nature paper, we developed the first layer-by-layer nanoparticle to target two distinct compartments of a tumor, the stroma and the parenchyma. On the path to development, we also developed a 3D-coculture system that allowed us to test combination therapy.
Our research emphasizes a mechanistic understanding of biological phenomenon. We reduce clinial challenges to basic biology questions, and then ask the why and how questions. Observational findings need to be underpinned by an explanation. We use both in vitro and in vivo systems to probe the question. The question holds primacy and not techniques.

Both our problems as well as solutions are geared towards the clinics. We typically define problems based on unmet medical challenges emerging fromthe clinics, and the solutions fromthe bench are translated backtothe clinics. Mutiple start ups have evolved around the technology developed in the lab.