HSCI Science Update: February 2010

February 18, 2010

Tumor Suppressor Genes DOK Lung Cell Growth

Tumor suppressors are genes whose products act to control cell division. Disturbance of tumor suppressor gene function can have serious implications for the development of cancer. HSCI Principal Faculty member Pier Pandolfi and colleagues recently described, the discovery of three lung tumor suppressors. The group identified the downstream of tyrosine kinase (Dok) family members Dok1, Dok2, and Dok3 as lung tumor suppressors that result in lung cancer when mutated in a mouse. The identification of these genes may provide important insights into mechanisms associated with lung cancers and potential drug targets for lung cancer therapies.

Berger, A.H., Niki, M., Morotti, A., Taylor, B.S., Socci, N.D., Viale, A., Brennan, C., Szoke, J., Motoi, N., Rothman, P.B., Teruya-Feldstein, J., Gerald, W.L., Ladanyi, M., Pandolfi, P.P. (2010). Identification of DOK genes as lung tumor suppressors. Nat Genet. 2010 Feb 7 [Epub ahead of print].

Sprouty1 Muscles up to Satellite Cell Regulation

The regulation of quiescence versus proliferation in tissue specific stem cell populations plays an important role in regeneration and repair. In skeletal muscle, stem cells called satellite cells can self-renew and differentiate after they have been transplanted, but their role in repair of existing muscle has been unclear. HSCI Principal Faculty member Andrew Brack and fellow researchers set out to investigate this question and recently reported that satellite cells begin to proliferate after an injury.  Using a technique called lineage tracing, they found that some satellite cells contribute to the repair of injured muscle and others to replenishing the satellite cell pool. Further, they describe how the factor Sprouty1 plays a role in the return to quiescence and the ongoing maintenance of the satellite cell pool. These findings shed light on the process of muscle repair and the role of adult muscle stem cells in this process along with implications for therapeutic interventions.

Shea, K.L., Xiang, W., Laporta, V.S., Licht, J.D., Keller, C., Basson, M.A., Brack, A.S. (2010). Sprouty1 Regulates Reversible Quiescence of a Self-Renewing Adult Muscle Stem Cell Pool during Regeneration. Cell Stem Cell. 6, 117-129.

Cardiomyocyte Cells Just Like Mother (Nature) Used to Make

Engineered cardiac muscle cells made from neonatal rat cardiomyocytes provide a promising model for cardiovascular disease, but are only useful to the extent that they recapitulate function on the level of cardiac tissue in order for them to have in vivo relevance.  HSCI Principal Faculty member Kevin Kit Parker and colleagues recently described a method to measure the contractility of engineered muscle cultured on synthetic polymer thin films in response to electrical or pharmacological stimulation. The results they measured in engineered tissue were comparable to those in non-engineered tissue, suggesting that the engineered tissue may provide a relevant model system for testing the safety and effectiveness of drugs on cardiovascular tissue. The ability to perform these types of studies has important implications for being able to eliminate potentially harmful drugs from consideration before embarking on risky and costly clinical trials.

Alford, P.W., Feinberg, A.W., Sheehy, S.P., Parker, K.K. (2010). Biohybrid thin films for measuring contractility in engineered cardiovascular muscle. Biomaterials. Feb 8. [Epub ahead of print].