UC Berkeley research spurs hope for those with bone deformities

UC Berkeley/Courtesy

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Creating hope for those with bone deformities, UC Berkeley professor Michael Rape and his laboratory team discovered a link between stem cell and calcium development in bone formation and growth in findings published Thursday in the journal Cell.

With help from Nobel Prize-winning UC Berkeley professor Randy Schekman’s lab, Rape found the protein interaction that changes stem cells into a cell type for craniofacial bone development. According to Achim Werner, a postdoctoral research fellow at UC Berkeley, this fundamental research could be beneficial to help develop regenerative medicine for people that have bone formation problems like Treacher Collins syndrome, or TCS, a genetic disease that inhibits bone growth.

Originally, Rape’s research focused on stem cells as a whole because he wanted to find important stem cell processes.

“Stem cells are great (because) they produce any cell type in your body,” Rape said. “If you can coax stem cells to make any cell type, you can make a cell type in a specific disease.”

Through his research, he began to focus on ubiquitin, a molecule that controls protein activity within stem cells and how it drives cells to move enzyme vesicles that contain specific packages. Known as the ubiquitin pathway, this process adds ubiquitin to the protein code on the vesicle, causing a larger ubiquitin chain that allows for larger “cargos” including collagen, the blueprint for bone formation.

“The role of my lab was to help visualize these vesicles of binding proteins and show that they have collagen in them,” Schekman said. “My lab over many years discovered the molecular transport. … We are now pursuing a parallel investigation writing a paper on further characterization on these giant vesicles and how they perform.”

If the ubiquitin pathway for craniofacial development does not fully form, diseases like TCS could develop.

Rape stated that an enzyme, CUL3, regulates the amount of ubiquitin added to TCOF1 — a protein that regulates the formation of neural crest cells that can develop into bones. Patients with TCS lack one copy of the TCOF1 protein so the CUL3 enzyme cannot create enough neural crest cells for craniofacial development.

This fundamental understanding can also help clarify other nongenetic disorders like Fetal Alcohol Syndrome, which affects the calcium homeostasis in fetal development and therefore interferes with bone formation, according to Rape.

Francis Smith, a TCS patient who has undergone more than 20 reconstructive surgeries and a TCS researcher at the University of Colorado, Denver, spent a day with Rape to film an in-person interview that will be used to increase public awareness of craniofacial anomalies.

“TCS patients have the same challenges, goals, and desires as everyone else,” Smith said in an email. “Behind the apparent defects of the face, there is a sharp mind and a heart. … There is much work to be done in public awareness, education, and changing social attitudes.”

According to Rape, meeting Smith was “incredibly inspiring.” Science is often thought of in very “abstract” ways but seeing somebody with this health-related issue is a reminder that scientific research is conducted for an important reason, Rape said.

In addition, Rape states that his research reinforces the importance of having enough milk to strengthen the calcium as “the instructive signal” and the “building block of the bone.”

Further research, however, must be done before regenerative medicine using stem cells or cell replacement can be implemented. The community’s response has been “very positive,” Rape noted.

“(I) don’t want to speculate when it will happen,” Rape said. “(There is) lot of potential in this work. … Getting into a molecular understanding (of the process) gets people very excited about this.”

Contact Gibson Chu at [email protected] and follow him on Twitter at @thegibsonchu.