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Bhatia’s cancer team designed nanoparticles that quickly zero in on a tumor, then call in a swarm of drug-delivering nanoparticles to the site.
She returned to MIT in 2005, moving with her family back to the Boston suburb where she grew up. Her Laboratory for Multiscale Regenerative Therapies is located on the sunny fourth floor of MIT’s new Koch Institute for Integrative Cancer Research. From her office, she can gesture toward many of the area labs her team is collaborating with to explore liver biology, cancer therapy, stem cells, and infectious disease. “Multiscale” means the group is working with both nanotechnologies and microtechnologies. Because of their small size, nanoparticles, so tiny that about 1,000 of them could fit across a human hair, behave differently than larger particles, and Bhatia’s team is exploiting their unique electromagnetic properties in its cancer research. The microtechnologies, such as the tools they use to produce their artificial livers, are still tiny but about 1,000 times larger than nanoparticles.
Bhatia has a strong instinct for matching her group’s interdisciplinary strengths to some of the most troublesome clinical problems. As a graduate student, she was so fascinated with the medical courses required for her Health Sciences and Technology program that she kept taking “just one more course,” until finally she decided to complete a medical degree. Now, as an “accidental doc,” she speaks fluently with clinicians about the challenges their patients face and the limitations of current technology.
In deciding what research to pursue and how to go about it, Bhatia is guided by a clear objective. “Sangeeta has always been someone who wanted to make an impact, to leave the world better than she found it,” says Christopher Chen, a graduate school classmate of Bhatia’s who is now a bioengineer at the University of Pennsylvania. They have remained close friends, and Bhatia calls him her “science buddy,” scheduling regular phone calls to consult about the rewards, frustrations, and nitty-gritty details of running a lab.
Chen recalls that during the clinical portion of their graduate training, he and Bhatia had a shared goal: to record each day in their notebooks “one really good idea” inspired by their interactions with patients. Although Bhatia was deeply into liver research by that time, “her ideas weren’t just about the liver,” Chen says. “They were about infectious disease, how to improve a surgical technique … all kinds of things. I think she would have made an impact no matter where she landed.”
A Supportive Environment—for the Liver
Bhatia’s enthusiasm for her work is obvious as she speaks animatedly about the wonder of the liver, the organ she learned to love as a graduate student in the lab of tissue engineer Mehmet Toner at Massachusetts General Hospital. The pinkish-brown triangle carries out more than 500 functions in the human body, including removing toxins, generating energy, storing vitamins and minerals, and helping to regulate fats and sugars in the bloodstream. Before her graduate work, researchers faced challenges growing hepatocytes, the cells responsible for most of these functions, in the laboratory. Removed from a complete liver, the cells promptly died. In Toner’s lab, Bhatia found a way to stabilize them by mimicking the liver’s architecture.
In the body, hepatocytes are sandwiched between two layers of extracellular matrix and receive support from neighboring cells called stroma. Hepatocytes and stroma do not establish this structure on their own when placed in a dish, so Bhatia used microfabrication techniques to pattern tiny circular spots of collagen, a component of the extracellular matrix, onto the surface of a culture dish. She let hepatocytes establish themselves on the collagen dots and then added stromal cells. The cells thrived.
Our cells often work in near lockstep with each other. During development, a variety of cells come together in a specific arrangement to create complex organs such as the liver. By fabricating an encapsulated, 3-dimensional matrix of live endothelial (purple) and hepatocyte (teal) cells, as seen in this magnified snapshot, Sangeeta Bhatia can study how spatial relationships and organization impact cell behavior and, ultimately, liver function. In the long term, Bhatia hopes to build engineered tissues useful for organ repair or replacement.
Credit: Bhatia lab
Image: Reprinted with permission from MacMillan Publishers, Ltd: Nature Materials (10:545-552), copyright 2011.