BERKELEY STEM CELL CENTER IN THE RAIN

By Don C. Reed

It was raining as I walked across the UC Berkeley campus: not a flooding downpour, like the one which made Gene Kelly throw back his head in the MGM classic “SINGIN’ IN THE RAIN”, but still enough to bring a smile from a water-loving person.

“Go past Sather Gate a quarter mile,” a helpful student said, “cross the wooden bridge, turn right, left, then right again–”

And there it was, the Li Ka Shing Center for Biomedical and Health Sciences: strongly built, five stories high: and with two levels for stem cell research.

The Center was one of twelve established by Proposition 71, the $3 billion citizen initiative of 2004—the California Institute for Regenerative Medicine (CIRM).

What a bargain! All applying colleges had to come up with at least 20% of the grant in matching funds, more if possible.

CIRM contributed a grant of $20 million dollars, matched by a $40 million donation from the great Hong Kong philanthropist Li Ka-shing, and additional funding from the Gordon and Betty Moore Foundation, the Wayne and Gladys Valley Foundation, the Ann and Gordon Getty Foundation, and more—new money for California.

https://www.berkeley.edu/news/media/releases/2008/05/07_cirmgrant.shtml

Total CIRM costs for all twelve facilities? $272 million.

But when the matching grants were added in, that $272 million was leveraged to $1.1 billion

https://www.cirm.ca.gov/our-progress/video/cirm-major-facilities-speed-stem-cell-science-and-create-jobs

To be eligible, every center had to have a stem cell program with one, two, or three components:  basic science (hunting for discoveries), translational (developing new products or therapies), and/or clinical trials (testing them on people).

UC Berkeley is focused on basic and translational science.

“Basic research is where the magic is,” said Lily Mirels, cheerful administrator of the program, shaking my hand, “Basic is…the desire to understand nature, to discover underlying principles… Without these discoveries, there is nothing to translate”…no therapies to help people.

For instance, UCB Professor Jennifer Doudna needed laboratory space to work on an incredible discovery: CRISPR/Cas9, a form of genome editing.

What does that mean, to edit a genome?  Imagine a house blueprint on your computer screen.  If you don’t like part of it, you can cut and paste, altering its design; changing the blueprint alters the house.

Similarly, the body’s blueprint (DNA) may have flawed genes, mutations like the one which causes sickle cell disease.

Sickle cell anemia damages the blood cells, warping and stiffening them, until they block the capillaries, and bring pain like broken glass inside the veins.

But if we altered the genes, we might modify the body’s blueprint, and remove the sickle cell mutation.

Stem cell stories that caught our eye: new CRISPR fix for sickle cell disease, saving saliva stem cells, jumping genes in iPSCs and lung stem cells.

Li Ka-shing liked that idea so much, he contributed another $10 million to develop the Innovative Genomics Initiative (IGI) inside the Berkeley’s CIRM Center of Excellence.

“Today,” said Dr. Mirels, “The IGI is using genome editing to fight sickle cell disease.”  In a cooperative effort with UCSF Benioff Children’s Hospital Oakland, scientists including CIRM scholar Mark DeWitt, IGI Scientific Director Jacob Corn, and Mark Walters, Director of the Blood and Marrow Transplant Program, are working to save children from lives of pain.

David Schaffer, Director of the Berkeley Stem Cell Center began his career at the kitchen table.

“My father was a professor of biochemistry,” he said in a phone interview. “My mother was a physician. So it was natural to discuss medical research at dinnertime, and I always wanted a career developing knowledge and improving people’s health.”

“The Berkeley Stem Cell Center was actually begun in 2004 by Randy Schekman, who later won the Nobel Prize,” said Dr. Schaffer. But the nascent program needed laboratory space and sophisticated equipment, and the CIRM major facilities grant made this possible.

The new stem cell program encouraged collaboration. For example, CIRM’s support brought the groups of David Schaffer and Steven Conolly together to fight Parkinson’s disease. Their approach is to develop the nerve cells needed to replace those destroyed by the disease, transplant them into the brain, and monitor them using a process called Magnetic Particle Imaging (MPI).

Dr. Schaffer is working on real-life problems like spinal cord injury, Alzheimer’s, and Parkinson’s disease; studying ways to grow, protect and transplant stem cells for therapies. A CIRM scholar, Maroof Adil, brings the strengths of youth to the Parkinson’s effort as well.

CIRM Scholar Spotlight: Berkeley’s Maroof Adil on stem cell transplants for Parkinson’s disease

What is happening? First, a change in the “media” (stuff the stem cells are grown in), so that it is liquid sometimes, and jello-like at other times, for ease of administration. Liquid, for instance, is easier to inject.

Second, a new way to look inside a body.  The Conolly lab is engineering ever more powerful MPI machines to track transplanted stem cells, regardless of their location.

A practical note: former pre-doctoral CIRM scholar Patrick Goodwill, who with Dr. Conolly was “instrumental in developing MPI,” is now Chief Technical Officer at Magnetic Insight, a startup company based on this work.

https://www.magneticinsight.com

 

Such cooperation brings the world ever closer to stem cell-based cures.

Professor Xavier Darzacq received a CIRM Research Leadership Award to move his laboratory to UC Berkeley from Paris, France, leveraged by funding from the Siebel Stem Cell Institute.

Advancing work begun by the Nobel prize-winner Eric Betzig, Dr. Darzacq is building microscopes so powerful that they can follow a single molecule within a living cell—like following one ant in a colony of billions.

Using such incredible microscopes, Darzacq and his collaborator Robert Tjian are studying how gene regulation works, how the genes are turned on and off in living stem cells.  The Darzacq lab uses these microscopes to understand the factors that control wound healing and tissue regeneration.

How does “Call me Xavier” Darzacq feel about the California stem cell program?

“I was talking to the mechanic working on my car,” he said,  “and I asked him, did he know about the stem cell program California began with Prop 71?”

“When he said he vaguely remembered a controversial proposition, I told him that he should be so proud, because it has now become a statewide enterprise to cure diseases using stem cells. It creates work and business in California and provides hope for patients. It must feel good to realize that your vote made it possible.”

As Dr. Mirels walked me out, I looked back at the beautiful building. Something about the shape of it tugged at my consciousness. And then it occurred to me.

The Li Ka Shing Center had the outline of a tugboat: those work horses of the sea which rescue larger ships, pulling them to safety through the storm.

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