Grants - V Scholar Grants - Massachusetts - 2020

Sahand Hormoz, Ph.D.

Abeloff V Scholar * (Three-way Tie for Top Rank)

Funded by the Constellation Gold Network Distributors

The human body generates hundreds of billions of new blood cells every day to replace old and dying cells. These new cells come from stems cells that live in the bone marrow. Sometimes the genetic material inside one of the stem cells is altered in a way that changes its behavior. The altered stem cells produce too many blood cells and slowly take over the bone marrow. In the clinic, we diagnose this as a type of blood cancer (called myeloproliferative neoplasm or MPN). Intriguingly, the same genetic alteration in different patients can result in very different forms of the disease. The disease outcome is just as unpredictable. Some patients show no symptoms for decades whereas others rapidly deteriorate. To understand this disease, for each patient, we would like to know where and when the disease originated and how the cancer cells expanded over decades. To answer these questions, we have developed technologies that allow us to measure molecular profiles of individual cells. To reconstruct the history of the disease, we will use the genomes of individual cancer cells in the same way that the evolutionary history of species is reconstructed from their presentday genomes. Our preliminary work has shown that cancer first occurs decades before diagnosis. Finally, to test therapies, we will engineer mice in which individual cells record their lineage histories in their own DNA. Together, our measurement will provide the most comprehensive molecular history of how cancers originate and progress in individual patients.