State-of-the-Art Science and Architecture combine for a World-Class Downtown

Erin Rhoades is a professional city planner and lifelong Berkeley resident. Ms. Rhoades' planning interests are focused on infill development and sustainability. Erin is a founding Board member of Livable Berkeley and the Board Chair.

The Li Ka Shing Center for Biomedical and Health Sciences/
University of California, Berkeley

 

The Li Ka Shing Center for Biomedical and Health Sciences, dedicated last week, stands at the nexus of downtown Berkeley and the University of California, Berkeley campus. The center is symbolic of a vision, not just for UC Berkeley, but the community as a whole. This building is the eighth of twelve stem cell research facilities funded in part by CIRM to open its doors (read more about CIRM's major facilities).

From the standpoint of design, the building incorporates a range of environmental features. The materials and energy efficiency are state-of-the-art, including a living roof. Architecturally, the center incorporates contemporary design and finish into a space surrounded by structures of historic significance and natural green space.

These design features are thoroughly consistent with the Downtown Area Plan's (DAP) goals for LEED Gold or equivalent development with outwardly visible sustainable design features that display innovation in green architecture in the context of a downtown with a predominanlty historic character.

Robert Birgeneau,
Chancellor of UC Berkeley,
at the dedication ceremony

Inside, the center will be home to student scientists at every level of education working to tackle emerging and neglected diseases of national and international significance. The flexible and open design will facilitate collaboration among these teams.

The $257 million facility, which received $20 million from CIRM, was financed through an innovative public private partnership involving state bond funds, individual donors and foundations. This model of combining public investment with private funds serves to leverage tax dollars and accelerate benefits to taxpayers.

Innovative funding approaches, like those used to construct the Li Ka Shing Center and the other CIRM major facilities, will be required in Berkeley to achieve the magnitude of investment necessary for high-density infill development and at the same time to accomplish the affordable housing component, community benefits and streetscaping called for in the DAP.

The combination of creating state-of-the-art development, supporting the knowledge (“imagined in California”) economy through public / private financing is an important model for the City of Berkeley. As we move into the 21st century, Berkeley should build on these success stories and support development that builds on this innovative model.

Development in downtown Berkeley should look for ways to showcase the best thinking in progressive environmental design and urban culture. Buildings like the Li Ka Shing Center and the David Brower Center, including their programmatic functions, exemplify Livable Berkeley's advocacy for a "world class" downtown. Our hope is that the Downtown Area Plan will result in the next building that defines Berkeley not for where it's been, but where it's going.

Erin Rhoades

Rolling back the clock on muscle disease, aging

Last week CIRM grantees at University of California Berkeley published a follow-up to some of my favorite stem cell research. I'm speaking personally here as a runner who is getting older and would like to turn my race recovery back to what it was in my youth.

Irina Conboy started investigating the slow response of aging muscle stem cells as a postdoctoral fellow in the lab of Thomas Rando at Stanford University (I've written about that work here). What they found is that older muscles in mice don't respond very effectively to muscle damage. But, and this is a big but, if those older mice have younger blood, the muscle stem cells work just fine. Strange, but true.

Since that discovery, Conboy and her lab at Berkeley has been piecing together the story of how and why the younger blood refreshes those old and tired muscle stem cells. In their latest work, which was published in the journal Chemistry & Biology, they show a way using a short-term dose of chemicals to roll back the clock on mature muscle and return it to an earlier state.

A press release from UC Berkeley says:

Building new muscle to replace old or damaged tissue is the routine job of muscle stem cells, or satellite cells. Stationed along the perimeter of adult muscle tissue, they wait for a signal to grow, divide and fuse into new muscle fibers when there’s damage to repair.

But that repair process gets worn out in people with Duchenne muscular dystrophy, a genetic condition in which muscles degenerate because of a defective structural protein and subsequent exhaustion of muscle stem cells. Muscle repair also becomes incapacitated with advancing age.

The group hopes that by turning back the clock, they can return the muscle to a state where it is better able to repair damage. The press release goes on to say:

The researchers say the next steps include testing the process on human muscle tissue and screening for other molecular compounds that could help de-differentiate mature tissue.

“This approach won’t work for all degenerative diseases,” said Conboy. “It might work for some diseases or conditions where we can start with differentiated tissue, such as neurons or liver cells. But patients with type I diabetes, for instance, lack the pancreatic beta-islet cells to produce insulin, so there is no functional differentiated tissue to start with. Our approach is not a replacement for pluripotent cells, but it’s an additional tool in the arsenal of stem cell therapies.”

The group is a long way from marketing the next race recovery beverage. They still have to show that the technique works in human muscle and that those more youthful cells are better able to repair damage.

CIRM Funding: Irina Conboy (RN1-00532-1)
Chemistry & Biology, September 23, 2011


A.A.

On stem cells, aging and hopes for spryer golden years

Last week my three year old scraped up the entire left side of his face. Today, there's barely a trace of the injury. That's the glory of three year old skin, or more precisely, the glory of three year old stem cells.

Erin Allday at the San Francisco Chronicle had a story last week about the issue of aging stem cells featuring several CIRM grantees who are, like me, curious about why stem cells heal damage more slowly as we age. Her story includes Thomas Rando of Stanford University, whose work I wrote about several years ago. What I found fascinating then, and what still isn't understood, is why a stem cell grows less able to repair damage over time. Rando and his former postdoctoral fellow Irina Conboy (now at University of California, Berkeley) have found that in older muscle, the stem cells are still able to respond, but the signals themselves may not be as strong. The stem cells are there, they just don't hear damaged muscle's cry for help.

Allday quotes Rando, who is director of the Glenn Laboratories for the Biology of Aging at Stanford:

“I don’t necessarily see it as a way of reversing Alzheimer’s or making people live to 200 years old, but there’s this dormant potential that can be unleashed that can profoundly affect the way stem cells repair tissues.”

Allday also quotes Irina Conboy, who spoke at last week's annual meeting of the International Society for Stem Cell Research in Toronto:

Like physicists trying to find the unified theory of everything, we’re trying to find the unified theory of all these bad things that happen with aging. I think they all stem from a lack of stem cell responses.

Conboy has a New Faculty Award from CIRM to learn more about how stem cells age.

Nobody is arguing that studying stem cells will uncover the fountain of youth (at least, CIRM scientists aren't). Instead, CIRM President Alan Trounson said that by understanding how and why our body's stem cells age scientists could learn how to keep those stem cells more lively during a person's golden years. We wouldn't live longer, maybe, but as long as we're alive it would be nice to heal more effectively or resist disease. Just having bones heal more quickly could significantly reduce health care costs for the elderly.

“With aging, there are a lot of systems that start to become less efficient or break down or be more inclined to diseases. We may work out ways to provide stem cells that would enable people to remain vigorous.”

Remaining vigorous sounds pretty good to me, even if I don't ever again heal with the speed of a three year old.

A.A.

New UCSF stem cell building -- a beautiful setting for discovering new therapies

Today the University of California, San Francisco is unveiling their brand new CIRM-funded stem cell building. It’s not the largest of the 12 new buildings CIRM has funded throughout the state, but it sure is pretty with its labs perched along the Parnassus campus hillside. Like all of the new buildings, CIRM’s investment in this one required a substantial investment on the part of UCSF and inspired gifts from private donors. The Eli and Edythe Broad Foundation gave to the tune of $25 million, and two gifts from Ray and Dagmar Dolby were worth a total of $36 million.

These leveraged funds at UCSF and other facilities around the state helped create 25,000 jobs and $200 million in tax revenue for the state — an achievement CIRM is especially proud of during these dark financial times.

Now that the building has created jobs, we’re looking forward to seeing the cures and the resulting biotech investment. A story about the new Ray and Dagmar Dolby Regeneration Medicine Building in the San Francisco Chronicle quotes CIRM president Alan Trounson:

"These buildings have galvanized an area (of medical research) that had an enormous amount of potential, but scientists were being careful about entering the field. Business is really taking off in California, whereas in other parts of the country, it's a struggle."

A hallmark of the stem cell buildings CIRM has funded is that they encourage collaboration and consolidate resources. I was talking to David Shaffer at UC Berkeley while filming this video about CIRM's major facilities and he highlighted the importance of having everything in one place. Scientists in his lab must sometimes walk samples across campus to access technologies. Those hours spent readying samples for transport and walking around campus can be better spent doing the research that leads to cures.

At UCSF, scientists who might once have needed shuttles to attend colleague’s seminars can now wander down the hall. Technologies are in one place, meetings are centralized and we hope ideas can flow as freely as the wide open workspaces.

To date, Davis, UC Irvine, UC Berkeley, UCLA, Stanford and USC have all opened their facilities. The remaining five are under construction and all but one is expected to open its doors this year.

- A.A.

Mighty mice point to stem cell therapy for muscle diseases and aging

The L.A. Times gave it’s rodent of the week designation to a mighty mouse produced by University of Colorado, Boulder researchers.

The group transplanted muscle stem cells from healthy mice into mice with damaged muscles. Not only did the muscle stem cells spring to action, repairing the damaged muscle, but they maintained the mouse in its newly bulked up state for its entire two-year lifespan.

The Telegraph quotes lead author Bradley Olwin as saying:

"We found that the transplanted stem cells are permanently altered and reduce the ageing of the transplanted muscle, maintaining strength and mass."

"With further research we may one day be able to greatly resist the loss of muscle mass, size and strength in humans that accompanies ageing, as well as chronic degenerative diseases like muscular dystrophy."

In their story, the L.A. Times points out that the stem cells came from young mice and were implanted into similarly young mice. Other research by CIRM grantee Irina Conby at University of California, Berkeley has found that the environment in older mice somehow inhibits muscle stem cells from repairing damaged muscle (here's a blog entry on her work). Likewise, bathing muscle stem cells from older mice in the blood of young mice seems to rejuvenate the cell’s ability to repair tissue.

The issue of aging and environment is an important one when looking at transplantation of adult stem cells. Where the cells are implanted could play an important role in how well the cells repair damage. (You can read more about aging and stem cells in this story from Stanford University.)

As a runner prone to muscle damage and whose clock is relentlessly ticking, I'll be watching for researchers to figure out what it is that allows the transplanted stem cells to flourish and prevent aging in mice. And I can only hope the answer is not that I have to remain young for my muscle stem cells to thrive.

A.A.

Growing space for California stem cell research

On left and right, Berkeley Stem Cell Center co-directors
David Schaffer and Randy Shekman, and center,
Mary West, manager of the new lab. (Photo by Jan Ambrosini)

Berkeley is the most recent institution to open new stem cell space funded by CIRM. Their CIRM-funded stem cell facility, which had its opening Oct. 5, is also a core facility for QB3, a bay area biotech incubator. David Shaffer, co-director of the Berkeley Stem Cell Center, said of the facility:

“The new facility will serve as a central resource to greatly enhance stem cell research amongst Berkeley and QB3 investigators, as well as collaborators at Lawrence Berkeley National Lab and Children’s Hospital Oakland Research Institute.”

To date, University of California campuses at Irvine and Davis have both opened their new stem call buildings amidst much fanfare. By the end of October, UCLA, University of Southern California, and Stanford will all have cut their respective ribbons.

These buildings are, to a one, beautiful, gleaming, well equipped centers for cutting edge research. But they are more than that. They are also a safe haven for stem cell research, protected from the ups and downs of federal funding. CIRM first dreamed up and approved funding for these stem cell buildings when President Bush was in office and most stem cell research had to occur in isolation from the microscopes, the pipettes, the refrigerators, the reagents, and the latex gloves most labs purchase with their NIH funds. The research had to take place in space and on lab benches supported only through private or state dollars.

That space was hard to come by, making the early days of stem cell research a considerable challenge. Take Susan Fisher at UCSF who lost her stem cell lines to a power outage while working in a converted dentist office in San Francisco in order to put distance between her cells and federal dollars. (Here's a video about Fisher's experience)

In the past year President Obama opened up federal funding for more stem cell research, but now recent events put that funding back in question. During this time of uncertainty, it’s reassuring to know that so many institutions in California have space where their work toward new therapies can continue uninterrupted by political turmoil.




A.A.

Geron to begin stem cell trial for spinal cord injury

Hans Keirstead, UC Irvine

The FDA has lifted a clinical hold that has been in place since 2008 on Menlo Park, CA-based Geron's proposed trial for spinal cord injury. The multi-center phase I trial will be the world's first trial of a therapy based on embryonic stem cells.

In a press release, the company's president and CEO, Thomas Okarma, said:

"Our goals for the application of GRNOPC1 in subacute spinal cord injury are unchanged - to achieve restoration of spinal cord function by the injection of hESC-derived oligodendrocyte progenitor cells directly into the lesion site of the patient's injured spinal cord."

Alan Trouson, CIRM President, said:

“This is an important milestone for the whole field to have an embryonic stem cell therapeutic in clinical trials. We are looking with hope and expectation that the transplant will be safe and effective.”

The trial is based on work by CIRM grantee Hans Keirstead at UC Irvine. Prior to CIRM funding, his team matured embryonic stem cells into a form of neuronal cell called oligodendrocytes. When injected into rats with spinal cord injury, those cells protected the remaining spinal cord neurons and allowed the rats to walk.

In their press release, Geron described the reasons for the clinical hold:

The clinical hold was placed following results from a single preclinical animal study in which Geron observed a higher frequency of small cysts within the injury site in the spinal cord of animals injected with GRNOPC1 than had previously been noted in numerous foregoing studies.

In follow up work, Geron was able to prove to the FDA the safety of their stem cell product. The work directly leading to this clinical trial took place prior to the passage of proposition 71 to create CIRM. CIRM has funded follow-up work by Keirstead and others to improve on this potential therapy and expand the application of these cells to other diseases.

Here is Hans Keirstead discussing the long path from basic research to this clinical trial:





A.A.

Old muscle stem cells experimentally returned to youth

Researchers at the University of California, Berkeley have found molecular pathways that human muscle stem cells rely on to repair damaged muscle. These pathways are active in younger people but less active in older people, explaining why muscles repair more slowly with age. The group found that younger volunteers had double the number of regenerative muscle stem cells in their thigh muscles compared to older volunteers. After two weeks in a leg cast, both groups began exercise routines to rebuild muscle. During this phase, the older volunteers had four times fewer muscle stem cells and rebuilt muscle more slowly. The researchers said that the poor response wasn’t the fault of the older stem cells. Instead, signals in the aging muscle and blood locked the stem cells in an inactive state. From their work in mice, the researchers knew that proteins present in the muscle surrounding the stem cells helped these cells respond to distress signals from the injured tissue. In the human cells, they found a protein called MAPK that interprets these distress signals and triggers the muscle stem cells to begin the repair process. Young people have high levels of MAPK and older people have low levels of MAPK, providing one explanation for the older volunteers’ poor response to exercise. In a lab dish, the group found that by artificially blocking MAPK in young muscle stem cells they could make young cells respond like older cells in a matter of days. The reverse was also true. Amplifying MAPK in older muscle stem cells in a lab dish rejuvenated the older cells. This work is an important step in verifying results from mouse stem cell aging studies in humans. The researchers hope their work could lead to therapies for muscle diseases and help older people to remain active, build stronger muscles and recover from injury.

EMBO Molecular Medicine: September 30, 2009
CIRM funding: Irina Conboy (RN1-00532-1), Morgan Carlson (T1-00007)

Related Information: Press Release, University of California, Berkeley

A.A.

Aging Muscles Inhibit Stem Cells, Prevent Repair

Researchers at UC, Berkeley identified a signaling molecule that interferes with the ability of older skeletal muscle to regenerate. After injury, adult skeletal muscle regenerates by activating muscle stem cells that fuse with the existing muscle cells to repair the damage. This ability to regenerate diminishes with age, not because of a decline in the number of resident stem cells, but because stem cells in the older muscle don’t respond when damage occurs. It turns out that older muscles release molecules that actively inhibit the resident stem cells. In this study, the team identified one of those molecules and showed that interfering with that molecule’s function restores the ability of muscle in older mice to regenerate after injury. This research illustrates the potential for recruiting adult resident stem cells in tissue repair.

Nature: June 15, 2008.
CIRM funding: Morgan Carlson (T1-00007)

Related Information: Press release, Berkeley Stem Cell Center