Blood Program

Program Leader: Daniel G. Tenen, M.D., Professor, Medicine, Harvard Medical School and Professor, Hematology/Oncology, Beth Israel Deaconess Medical Center

The blood system has the highest rate of self-renewal of all the organs in the body. Researchers in the HSCI Blood Program investigate how blood stem cells manage this process. The knowledge they gain has implications across the board for stem-cell and regenerative medicine.

To regenerate damaged tissue, the blood’s “self-renewal” mechanism must be turned on. But to stop blood cancers like leukemia and lymphoma from growing, it must be turned off.

Researchers in the HSCI Blood Program explore:

  • how genes influence blood stem-cell self-renewal – both “on” and “off”
  • whether different tissue types share similar stem-cell regulators
  • whether it’s possible to screen for chemical compounds to control self-renewal.

To do this, they use genetic screens, bioinformatics, mouse models of disease, and comparative cell analyses.

What we have achieved so far

HSCI Blood Program researchers have achieved some major milestones:

  • In their work to improve adult cord-blood transplants, they identified a compound that activates blood stem cells in zebrafish – a compound that has passed Phase I clinical trials.
  • Program researchers also discovered an epigenetic process that occurs during recovery from irradiation and chemotherapy. These findings could hasten the search for drugs that enhance self-renewal during bone marrow transplantation.
  • They found differences in the timing of such epigenetic changes in the formation of healthy versus leukaemia cells, which points to the potential of using DNA methylation inhibitors to control leukaemia.
  • They engineered a therapeutic molecule that blocks SALL4, a protein involved in about one-third of cancers, in mice. This discovery has implications for the treatment of liver cancers and leukemias.
  • They identified a potential new strategy for treating acute myeloid leukemia that has progressed to clinical trials and includes re-purposing an existing drug.
  • In work initially supported by GSK and now taken forward by startup company Magenta, HSCI scientists discovered drugs that improve the process of donating stem cells for bone marrow transplantationby enhancing peripheral blood mobilization, making conditioning non-toxic, and improving the productivity of the stem cell niche in the bone marrow.

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