Presidential Award goes to UCSF high school internship program hosting CIRM-supported students

Last summer CIRM sponsored high school students to carry out stem cell research at five California universities in association with existing high school internship programs at those schools. Yesterday we learned that President Obama likes our choice of partner programs — the UCSF program that included six CIRM-supported students received the Presidential Award for Excellence in Science, Mathematics, and Engineering Mentoring. That award to the Science & Health Education Partnership (SEP) High School Internship Program comes with a $25,000 grant.

The SEP program is focused on drawing students from disadvantaged backgrounds and giving them experiences that will help them succeed in college. In a press release, UCSF described their students:

The program works closely with San Francisco high school science teachers to identify students from disadvantaged backgrounds with significant potential. For example, the majority of high school interns come from families where neither parent has completed college. The education outcomes of students who participate in the internship program far exceed that of their peers - 92 percent matriculate to college, 76 percent complete Bachelor's degrees in the sciences, and 87 percent pursue post-baccalaureate degrees.

Congratulations to the UCSF team, and to the outstanding students who have gone through the program.

CIRM science officer Mani Vessal led the high school internship program for CIRM. The awards—called Creativity Awards—encourage participants to carry out research in an additional field unrelated to stem cell research. He said:

It really does foster creativity to have a mulitlinear approach to learning as opposed to just a single dimensional one. We're hoping to get the next generation of stem cell scientists who can think outside the box.

This short video features Ben Koo, the Academic Coordinator for the SEP program, and Creativity Award students from the UCSF and other programs talking about their research projects.
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After last summer's success, CIRM is expanding our Creativity Awards program for next summer. The request for applications just got posted to our website.

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UCSF stem cell building: generating therapies and making news

The new UCSF stem cell building has made the news again. The September 19 issue of The New Yorker, architecture critic Paul Goldberger features UCSF’s Ray and Dagmar Dolby Regeneration Medicine as one of three new science buildings in the United States “crafted with the specific intention of fostering interaction and connections, as a means of generating ideas.”

A press release from UCSF says:

Constructed on what Goldberger called an “eye-poppingly impossible site,” the building is home to some 300 scientists studying the earliest stages of cell and tissue development, with the goal of understanding and developing cell-based treatment strategies for such diseases as heart disease, diabetes, epilepsy, multiple sclerosis, Parkinson’s disease, Lou Gehrig’s disease, spinal cord injury and cancer.

This is one of the buildings CIRM partially funded back in 2008, when the agency realized that a critical component of generating new therapies was providing scientists with a place to work. CIRM's investment of $271 million leveraged $560 million from private donors and $322 million in commitments from the institutions themselves. UCSF has this to say about funding for the building:

The $123 million building was paid for with state and private funds. In 2006, Ray and Dagmar Dolby contributed $16 million to launch the university’s fundraising campaign for the facility. In 2007, UCSF received a highly competitive $34.9 million grant from California Institute for Regenerative Medicine (CIRM). In 2008, UCSF received a $25 million grant from The Eli and Edythe Broad Foundation.  Last winter, UCSF received an additional $20 million donation from the Dolbys. The university has $12 million left to raise.

When Eli and Edythe Broad made their donation to UCSF CIRM made this video about our hopes for the stem cell buildings:


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CIRM grantee Robert Blelloch wins ISSCR Outstanding Young Investigator Award

CIRM grantee Robert Blelloch of the University of California, San Francisco won the 2011 Outstanding Young Investigator Award from the International Society for Stem Cell Research. The society's annual meeting is taking place now in Toronto.

Blelloch presented his research June 15 at 6pm and will participate in a press briefing at noon June 16. His work focuses on the role of small molecules called microRNAs and their role in stem cell biology and cancer.

Jennifer O'Brien described Blelloch's work in a press release from UCSF:

During the last few years, Blelloch’s team has reported several key findings. In 2008, they reported that microRNAs promote self renewal of embryonic stem cells in mice (Nature Genetics, 2008). In 2009, they showed that when those same microRNAs were inserted into adult cells the cells de-differentiated back into embryonic stem cells (Nature Biotechnology, 2009). In 2010, they inserted a microRNA into embryonic stem cells and promoted differentiation, but determined that the microRNA had to compete with microRNAs that promote embryonic stem cell self-renewal (Nature, 2010). This year, his laboratory has been looking at microRNAs as a potential tool to systematically dissect the molecular pathways that regulate cell fate transitions, including dedifferentiation of adult cells to create induced pluripotent stem cells (Nature Biotechnology, 2011).

“People have come to realize microRNAs are remarkably powerful,” said Blelloch, associate professor in the Departments of Urology, Obstetrics, Gynecology and Reproductive Sciences and Pathology and a member of the Helen Diller Family Comprehensive Cancer Center.

Using microRNAs for therapeutic purposes has great potential , he said. “They could be used either to induce adult cells to de-differentiate to embryonic stem cells, which could be expanded, manipulated and returned to a patient, or to promote differentiation of embryonic stem cells to produce tissues that would remain integrated in the body once re-introduced.” They also could be used to target cancers, and they attract interest from biotechnology companies.

Blelloch has a SEED Award and a New Faculty II Award, both looking at the role of microRNAs in embryonic stem cell biology. Not to blow our own horn, but CIRM does know how to pick high quality research. Last year Stanford's Joanna Wysocka won the same award. She has a SEED Award and a New Faculty I Award from CIRM.

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CIRM grantee Alvarez-Buylla wins 2011 Prince of Asturias Award for neural stem cell research

Arturo Alvarex-Buylla, PhD

CIRM grantee and UCSF professor Arturo Alvarez-Buylla, PhD, won the prestigious 2011 Prince of Asturias Award for Technical and Scientific Research for his work with neural stem cells. He is credited with first discovering the regenerative cells in the brains of mammals, work that laid the groundwork for a number of CIRM grants and clinical trials based on neural stem cells.

In their announcement about the award UCSF quotes Arnold Kriegstein, MD, PhD, director of the Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research at UCSF.

“Arturo’s contribution to the field of adult stem cell science has been tremendous. He has helped lay the foundation for our understanding of the role and behavior of neural stem cells in the adult brain, which could lead to new strategies for treating brain damage and diseases.”

In the announcement, Jennifer O'Brien describes the work that earned Alvarez-Buylla his recognition:

Alvarez-Buylla, specifically, was recognized for identifying neural stem cells in the brains of mammals, and for his ongoing research on their behavior – and potential therapeutic use – in treating diseases. He is exploring their possible role in the development of the most common type of brain tumor, the glioma, and their potential use in regenerating brain tissue damaged by injury or degenerative diseases. More generally, he is studying the way in which adult neural stem cells behave and function – their development into young neurons, the migration of these neurons from their site of birth to their final destinations, and their function in the adult brain.

Alvarez-Buylla has a CIRM Early Translational II Award to develop a cell-based therapy to inhibit the hyperactive neural circuits in people with epilepsy. In his public summary for the award he writes:

In 20-30% of these patients, seizures are unresponsive to drugs, requiring invasive surgical resection of brain regions with aberrant activity. The candidate cells we propose to develop can inhibit hyperactive neural circuits after implantation into the damaged brain. As such, these cells could provide an effective treatment not just for epilepsy, but also for a variety of other neurological conditions like Parkinson's, traumatic brain injury, and spasticity after spinal cord injury.

It's great to see CIRM grantees honored for the incredible advances they've in medicine and human health.

A.A.

Eradicate cancer stem cells, eradicate drug-resistant leukema

Markus Müschen/UCSF

CIRM grantees at the University of California San Francisco have found the protein certain leukemia cells use to evade chemotherapy. A press release from UCSF says:

Doctors who treat children with the most common form of childhood cancer – acute lymphoblastic leukemia – are often baffled at how bulk cancer cells die from chemotherapy whereas the rare stem cells in cancer survive their best efforts and the most powerful modern cancer drugs. Months after a seemingly successful treatment, the cancer stem cells re-initiate the disease, which is then more resistant to treatment than before.

It turns out the resistant cancer stem cells make a protein called BCL6, which protects them from the effects of chemotherapy. In a Nature paper published today, the team tested an experimental drug called RI-BPI, which attacks cells that make BCL6. Combined with the drug Gleevac, which is very effective at destroying the non-BCL6 cells, the experimental drug could effectively cure mice with drug resistant leukemia. In the release, CIRM grantee and senior author Markus Müschen said:

“We believe this discovery is of immediate relevance to patient care.”

In the work reported in this paper, the team used a molecule to block BCL6 that, though effective for small scale use, would be difficult to mass produce. Müschen has a CIRM Early Translational II Award to develop a drug that is similarly effective at destroying drug-resistant leukemia cells but that would be easier to mass produce for widespread use.

We have more information about cancer stem cells on our website:

• Leukemia information
• Cancer stem cell video

Nature, May 18, 2011
CIRM Funding: Markus Müschen (TR2-01816)

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.

Top four list: why embryonic stem cells are critical

Yesterday CIRM grantee Bruce Conklin gave his top four reasons why embryonic stem cells are so valuable and why federal funding for the work needs to be able to continue. Conklin, who is Senior Investigator Gladstone Institute of Cardiovascular Disease and professor at UCSF, studies heart rhythm defects by creating iPS cells from people genetically predisposed to have those defects, then maturing those into heart cells in a dish. This gives him a way of studying the rhythm defect in the lab, and allows him to test drugs that might correct the arrhythmia. (You can see his New Cell Lines Award research summary here.)

Conklin says he’d never be able to carry out his iPS work without advances made with embryonic stem cells. Here’s his list:

1) Scientists have genetically engineered embryonic stem cells that are widely used for studying specific processes in the lab. “Obviously, we can remake those cells lines using iPS cells but it’s a huge waste of time,” he said. Instead of making progress toward developing new therapies or finding new drugs, labs would have to spend years redoing work they’ve already done.

2) Embryonic stem cells are farther along clinically than iPS cells or the new directly reprogrammed cells. “The first clinical trials of pluripotent cells will be embryonic stem cells. Ten years from now we’ll probably see a mix of embryonic and iPS cells,” he predicted. Adult cells are good for many things, he said, but aren’t as flexible as pluripotent embryonic or iPS cells.

3) Embryonic stem cells reproduce the steps taken by nature. “The idea is that nature knows something we don’t, because we don’t know very much,” Conklin said. Studying embryonic stem cells as they go down the path toward a specific cell type, like a skin cell or a neuron or a pancreatic islet cell, can give us clues about what might be going wrong in diseases afflicting those cell types.

4) Some diseases seem to begin at the earliest stages of development. “If we are going to understand human development we have to know how the process happens naturally,” he said. Only by studying embryonic stem cells can we understand genetic diseases that strike at the earliest stage, or what’s called epigenetic changes that can alter the way genes function.

Conklin seemed optimistic about the future of iPS and direct reprogramming, but pointed out that even Jamie Thomson, who was part of one of the two teams that first created iPS cells, has predicted that iPS cell research would be five years ahead of where it is now if embryonic stem cell research weren’t slowed under the Bush funding regulations.

The CIRM Governing Board recently passed a resolution that “strongly encourages federal policy that supports all forms of stem cell research for the millions of Americans who suffer from disease and injury and strongly supports criminalizing human reproductive cloning.” You can read Resolution 2010-01 here, which supports both the DeGette and Spector legislation “or any successor legislation that embodies the policies advanced in President Obama’s Executive Order 13505 and the National Institutes of Health July 7, 2009 guidelines on hESC research.”

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Nobel prize winner Stanley Prusiner calls for Alzheimer's disease funding

Nobel Prize winner Stanley Prusiner was one of the authors on a letter to the New York Times on October 27 advocating that congress pass legislation that “would raise the annual federal investment in Alzheimer’s research to $2 billion, and require that the president designate an official whose sole job would be to develop and execute a strategy against Alzheimer’s.”

Prusiner, who is director of the Institute for Neurodegenerative Diseases at UCSF, along with retired U.S. Supreme Court Justice Sandra Day O'Connor and gerontologist/psychologist Ken Dychtwald, wrote:

As things stand today, for each penny the National Institutes of Health spends on Alzheimer’s research, we spend more than $3.50 on caring for people with the condition. This explains why the financial cost of not conducting adequate research is so high. The United States spends $172 billion a year to care for people with Alzheimer’s. By 2020 the cumulative price tag, in current dollars, will be $2 trillion, and by 2050, $20 trillion.

If we could simply postpone the onset of Alzheimer’s disease by five years, a large share of nursing home beds in the United States would empty. And if we could eliminate it, as Jonas Salk wiped out polio with his vaccine, we would greatly expand the potential of all Americans to live long, healthy and productive lives — and save trillions of dollars doing it.

Their letter came days after CIRM board member Leeza Gibbons joined California’s First Lady Maria Shriver in her first March on Alzheimer’s at the California Women’s Conference. Gibbons founded Leeza's Place to provide support for caregivers of people with Alzheimer's disease and other disorders. The march raised a quarter of a million dollars for Alzheimer’s research.

During Alzheimer’s disease awareness month here are some numbers to keep in mind, from the NYT letter:

Starting on Jan. 1, our 79-million-strong baby boom generation will be turning 65 at the rate of one every eight seconds. That means more than 10,000 people per day, or more than four million per year, for the next 19 years facing an increased risk of Alzheimer’s. Although the symptoms of this disease and other forms of dementia seldom appear before middle age, the likelihood of their appearance doubles every five years after age 65. Among people over 85 (the fastest-growing segment of the American population), dementia afflicts one in two. It is estimated that 13.5 million Americans will be stricken with Alzheimer’s by 2050 — up from five million today.

CIRM has a Alzheimer's disease fact sheet about stem cell therapies for Alzheimer’s disease, and a list of all awards addressing Alzheimer’s disease funded by CIRM. One of those grantees, Frank LaFerla, is in this video about a discovery he made as part of the CIRM-funded research.




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The University of California enters stem cell funding battle

The University of California has now entered the stem cell funding legal fracas, filing a motion to participate in the pending lawsuit. In a statement, the UC Office of the President said they are the first institution to seek to intervene in the lawsuit:

The recent U.S. District Court preliminary injunction blocking federally funded human embryonic stem cell (hESC) research threatens ongoing potential life-saving research and undermines the time-honored system of peer-reviewed science.

CIRM funds stem cell research projects at all ten UC system campuses (you can look up those awards on our online funding chart). In their blog, Nature breaks down the impact of the funding battle on just two of the UC schools:

The University of California, Los Angeles receives a total of 16 NIH grants from nine different NIH institutes involving work on human embryonic stem cells; those grants are worth a total of $8.7 million and provide full-time support for 46.5 researchers and staff. The University of California, San Diego, meanwhile, receives 14 NIH grants from five NIH institutes for human embryonic stem cell work, worth $7 million and employing 17.17 researchers and staff.

CIRM grantee at UC San Francisco Arnold Kriegstein wrote a statement in support of the motion. Kriegstein is director of the Eli and Edythe Broad Center for Regeneration Medicine and Stem Cell Research at UC San Francisco. In his statement, he says that although much of the human embryonic stem cell research taking place in California is funded by CIRM, the injunction has an impact that is disproportionate to the amount of funding received.

"The preliminary injunction has an impact on dozens of researchers and students, affecting programs across the UC campuses and across departments... Any loss of funding for the federal [human embryonic stem cell] projects will result in a loss of hours for these employees."

Kriegstein specifically cites a training program that includes 88 PhD and MD students being trained at UCSF, and which has had its funding discontinued due to the preliminary injnuction issued Aug. 23.

The court has ordered both the plaintiffs and defendants in the case to file a response to the UC motion by Thursday, September 23.

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Resting stem cells are cancer-prone

CIRM grantees at University of California, San Francisco, have published a Cell Stem Cell paper explaining why blood-forming stem cells accumulate cancer-causing mutations with age. Basically, they found that inactivity is genetically risky for the cells.

The blood-forming stem cells exist in the bone marrow where they divide periodically to form new cells of the blood system, including red blood cells, immune cells and platelets. When the cells are actively dividing they use a highly effective mechanism for repairing any damage to their DNA. The danger comes during the down-time. When the cells -- also called hematopoietic stem cells -- aren't dividing they use a less rigorous method for repairing DNA damage, which can be caused by radiation, drugs, or regular wear and tear.

In a press release from UCSF, the lead author Emmanuelle Passegué said:

“Our results demonstrate that quiescence is a double-edged sword, protecting hematopoetic stem cells from cellular stress but rendering them intrinsically vulnerable to mutagenesis following DNA damage.”

Passegue is associate professor of medicine (division of hematology/oncology) and a member of the Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research. She also received a CIRM New Faculty II Award, which funded this work.

A review that accompanies the paper says:

Because many hematopoietic disorders that stem from DNA damage accrual arise during aging, these results also stress the importance of examining DNA damage response and damage accrual during ontogeny and aging.

Cell Stem Cell, August 6, 2010
CIRM funding: Mary Mohrin (T1-00002); Emmanuelle Passegué (RN2-00934-1)

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Shinya Yamanaka receives Kyoto prize for reprogramming skin cells

Last week, while stem cell researchers from around the world congregated in San Francisco for their annual meeting, stem cell pioneer Shinya Yamanaka won the Kyoto Prize for Advanced Technology. This award in generally considered to be a precursor to a Nobel Prize.

A press release from UCSF said:

Yamanaka received the prize for his discovery of a method of reprogramming adult skin cells to become embryonic-like stem cells. The discovery has opened up the field of stem cell research and dramatically changed the field of cell biology. He also is affiliated with and has a research lab at Kyoto University.

Yamanaka has a lab at the Gladstone Institute of Cardiovascular Disease in San Francisco, which is affiliated with UCSF. He does not have CIRM funding, but the Institute does have shared lab space funded by CIRM for carrying out stem cell research.

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Between Mice and Men, a New Type of Stem Cell

Humans and other non-human primates stand out from their fellow mammals in many ways, but notably by having one particularly oversized area of the brain. This area, the outer subventricular zone (OSVZ) feeds migrating neurons to the neocortex the seat of sensory perception, spatial reasoning, conscious thought and language. Scientists always assumed the OSVZ must have its own source of stem cells if, in the developing brain, it is supplying neurons for such a broadly vital area of the human brain. They have now found them.

Arnold Kriegstein’s team at UCSF used discarded fetal tissue to monitor cellular activity at various stages of development using a new labeling and tracking technique. They found the OSVZ to be a hub of cell proliferation. The newly found stem cell type goes through asymmetrical division producing a copy of itself and a daughter cell that is further along the path to becoming a neuron. That cell then goes through many rounds of symmetrical division producing many copies that can all then go on to become the desired neuronal cells needed in the neocortex.

A press release issued by UCSF on May 24 noted that the understanding provided by this model could shed light on many developmental brain diseases such as autism and schizophrenia. Kreigstein is quoted saying this understanding is critical:

“If we’re going to understand how these disorders develop, we have to better understand how the human and primate cerebral cortex develops.”

Understanding this developmental pathway will also inform efforts to direct neural stem cells to become the replacement cells of choice for various therapies.

D.G.

Nature, March 25 2010
CIRM Funding: Arnold Kriegstein (RC1-00346-1), Jan Lui (T1-00002)

Protein required to maintain full potential of stem cells

Researchers at the University of California, San Francisco have pinpointed a protein that is critical for maintaining a stem cell’s full potential to self-renew and to differentiate. Stem cells lacking the protein were impaired in their ability to divide and make identical copies of themselves, called self-renewal. These cells also lost their capacity to differentiate into key cell types, such as cardiac muscle. The protein, Chd1, acts to keep chromosome strands loosely wound, which permits widespread gene activation in the cell’s nucleus. Previous studies hypothesized that this open chromosome structure is necessary in stem cells to maintain their potential to specialize into any cell type. Additional results in this study demonstrate that Chd1 is required for efficient reprogramming of adult cells, such as skin cells, back into a pluripotent state. These new insights into Chd1 function may lead to safer, more efficient methods for growing up large numbers of embryonic stem cells and deriving specific cell types, both critical steps for successful stem cell therapeutic strategies.

Nature, July 8, 2009 (online publication)
CIRM funding: Rupa Sridharan (T1-00002), Kathrin Plath (RN1-00564-1), Miguel Ramalho-Santos (RS1-00434-1)

Related Information: press release, University of California, San Francisco

Genetic molecule enables safer method for creating iPS cells

Researchers at the University of California, San Francisco have designed a safer technique for reprogramming adult cells into a state that resembles embryonic stem cells. This method takes advantage of genetic molecules called microRNAs, which regulate the activity of genes. The original 2007 method for creating reprogrammed cells, called induced pluripotent stem (iPS) cells, relied on inserting four genes, some potentially tumor-causing, into the DNA of an adult cell such as a skin cell. Since then, researchers have whittled the number of genes down to two, and in one case generated iPS cells with only chemicals. However, the process is often inefficient. In this study, the researchers substituted one of the four genes with a microRNA molecule and obtained iPS cells at high efficiency. The researchers suggest microRNAs could replace other genes or improve the efficiency of chemical means of creating iPS cells. In addition, understanding how microRNAs function in reprogramming could lead to new therapeutic strategies for blocking reprogramming in cancer stem cells.



Nature Biotechnology, April 12, 2009
CIRM funding: Robert Blelloch (RS1-00161)

Related Information: Press release, University of California, San Francisco

Genetic Factors Found to Speed Embryonic Stem Cell Division

Researchers at UC, San Francisco developed a novel way of finding out the role of DNA-relatives called microRNA. These molecules are known to turn genes on and off and appear to regulate whether embryonic stem cells remain as stem cells or develop into mature cell types, but learning which genes are controlled by each microRNA has been a challenge. Using this screen, the researchers found 14 microRNAs that speed up cell division; of those, five are commonly found in human embryonic stem cells. It turns out these microRNAs deactivate genes that slow the cell cycle, essentially releasing the brakes on cell division. Identifying the role of these and other microRNAs could help researchers understand how to hold embryonic stem cells in their immature state, guide how those cells mature, or even develop treatments for cancer.

Nature Genetics: November 2, 2008
CIRM funding: Yangming Wang (T1-00002)

Related Information: Press release, UCSF Institute for Regeneration Medicine, Blelloch bio

Genes Identified as Unique to Specialized Colon Cells

Researchers at University of California, San Francisco found nearly a thousand genes that are expressed differently in different parts of the colon. The colon is constantly renewed via its own stem cells and understanding how these genes are expressed differently as the cells specialize will help understand what happens when this goes wrong as in colon cancer.

Proceedings of the National Academy of Sciences: September 25, 2007
CIRM-funded author: Cynthia Kosinski (T1-00002)

Related Information: UCSF Institute for Regeneration Medicine

Proteins Found that Guide Neuron Migration in Brain

Researchers at UC, San Francisco discovered that membrane proteins that form cell to cell connections also have an important role in controlling how neurons migrate in the brain. Understanding neuronal migration is a critical aspect of cell therapy in the nervous system, as replacement cells will need to be directed to their appropriate site of action. This research project is also an example of how funding work in one field moves along work in another. The membrane proteins highlighted in this report had previously been identified in some cancers, and these new observations in neurons provide rationale for targeting them in cancer therapy.

Nature: August 23, 2007
CIRM funding: Laura Elias (T1-00002)

Related Information: Press release, UCSF Institute for Regeneration Medicine

Genes Found that Characterize Embryonic Stem Cells

Researchers at UC, San Francisco identified a group of genes that are active in embryonic stem cells but not in more differentiated cells. They also developed a technique to find DNA regions that could be important for activating these genes, and identified a factor that directs the production of proteins from genes that contain these regulatory DNA regions. These studies will greatly inform research efforts that rely on maintaining a stem cell's ability to proliferate and to generate the many different cell types in a human body.

PLoS Genetics: August 2007
CIRM funding: Marcia Grskovic (T1-00002)

Related Information: UCSF Institute for Regeneration Medicine

Genetic Factors Found to Regulate Embryonic Stem Cell Maturation

Researchers at UC, San Francisco identified a molecule that regulates differentiation of embryonic stem cells. In some cases, small molecules of the genetic material RNA have the ability to turn genes on and off rather than carrying out the normal RNA function of coding for proteins. These small RNAs, called micro RNA or miRNA, are thought to be one way the cell regulates genes that control how stem cells differentiate into mature cell types. In this study, the researchers created genetically altered mouse embryonic stem cells that lack the miRNA DGCR8. These cells did not respond properly to signals that would normally cause stem cells to differentiate into mature cell types. Even after the cells began differentiating they continued making proteins that are normally only found in embryonic stem cells. This work shows that miRNAs are key molecules to target for controlling ES cell differentiation, which is essential for developing safe protocols for stem cell-based therapies.

Nature Genetics: March, 2007
CIRM funding: Yanging Wang (T1-00002)

Related Information: UCSF Institute for Regeneration Medicine

Neural Stem Cell Repair Mechanism in the Brain Revealed

Researchers at UC, San Francisco found that proteins involved in the generation of neurons early in development also help neural stem cells produce neurons after birth. Furthermore, the researchers identified a self-repair mechanism in the brain that relies on these neural stem cells. Understanding how endogenous neural stem cells repair and remodel a mature brain is critical to successful stem cell therapy.

Cell: December 15, 2006
CIRM-funded author: Chay Kuo (T1-00002)

Related Information: Press release, UCSF Institute for Regeneration Medicine