Robert Blelloch, MD, PhD

Research Interests

Stem Cell Differentiation and Cancer

Stem cells exist both in the developing embryo and in many organs of the adult. Differentiation of stem cells is tightly regulated so that as they become increasingly specialized, they lose the potential to revert or transform into other cell types. This regulation is very important both to maintain organ function and to avoid the possibility of uncontrolled cell growth, the basis of cancer. Very little is known about the mechanisms that control and lock-in cell differentiation. We now know that under exceptional circumstances, it is possible to reverse a fully differentiated adult cell into early embryonic cell, which is capable of producing all the tissues of the adult. This amazing feat is the result of somatic cell nuclear transfer where a differentiated nucleus is transferred into an immature female egg. The egg is then able to reprogram the differentiated nucleus into an embryonic nucleus that is then able to direct development of an entirely new organism.

We have used somatic cell nuclear transfer in mice to determine whether this method of de-differentiating adult cells could also alter the deadly potential of tumor cells. Amazingly, we did succeed at temporarily reverting the tumor into embryonic stem cells that could differentiate into normal tissues. However, eventually the tumors reformed, suggesting that the reprogrammed nucleus remained unstable. We are now following up this work by determining the normal molecular factors involved in inhibiting an adult cell’s ability to revert or transform into less differentiated or entirely different cell types. We are very interested in understanding how the deregulation of these factors leads to cancer and can be, at least temporarily, reprogrammed by the process of somatic cell nuclear transfer.

Furthermore, to understand the link between stem cells and cancer, we are using mouse models to determine whether stem cells are the origin of tumors. Recent studies have shown that only a small number of cells within a tumor can propagate the tumor and that these cells express markers similar to those found on normal adult stem cells. However, it remains unknown whether these tumor stem cells result from the de-differentiation of terminally differentiated cells or the transformation of stem cells directly. We are developing genetic screens that will directly address this question. We expect to identify genes that cause tumors by blocking the differentiation of stem cells. Identification of these genes should lead to drug targets that will act on the most deadly and currently drug-resistant population of cells within a tumor.

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