Bridging the gap: training scientists to speak everyday English

Getting a start in your chosen career is never easy. Without experience it’s hard to get a job. And without a job you can’t get experience. That’s why the CIRM Bridges program was created, to help give undergraduate and Master’s level students a chance to get the experience they need to start a career in stem cell research.

Last week our governing Board approved a new round of funding for this program, ensuring it will continue for another 5 years.

But we are not looking to train just any student; we are looking to recruit and retain students who reflect the diversity of California, students who might not otherwise have a chance to work in a world-class stem cell research facility.

Want to know what that kind of student looks like? What kind of work they do? Well, the Bridges program at City College of San Francisco recently got its latest group of Bridges students to record an “elevator pitch”; that’s a short video where they explain what they do and why it’s important, in language anyone can understand.

They do a great job of talking about their research in a way that’s engaging and informative; no easy matter when you are discussing things as complex as using stem cells to test whether everyday chemicals can have a toxic impact on the developing brain, or finding ways to turn off the chromosome that causes Down’s syndrome.

Regular readers of the CIRM blog know we are huge supporters of anything that encourages scientists to be better communicators. We feel that anyone who gets public funding for their work has an obligation to be able to explain that work in words the public can understand. This is not just about being responsive, there’s also a certain amount of self-interest here. The better the public understands the work that scientists do, and how that might impact their health, the more they’ll support that work.

That’s why one of the new elements we have added to the Bridges program is a requirement for the students to engage in community outreach and education. We want them to be actively involved in educating diverse communities around California about the importance of stem cell research and the potential benefits for everyone.

We have also added a requirement for the students to be directly engaged with patients. Too often in the past students studied solely in the lab, learning the skills they’ll need for a career in science. But we want them to also understand whom these skills will ultimately benefit; people battling deadly diseases and disorders. The best way to do that is for the students to meet these people face-to-face, at a bone marrow drive or at a health fair for example.

When you have seen the face of someone in need, when you know their story, you are more motivated to find a way to help them. The research, even if it is at a basic level, is no longer about an abstract idea, it’s about someone you know, someone you have met.

Even the early worm gets old: study unlocks a key to aging

A new study poses the question, ‘When does aging really begin?’ One glance in the mirror every morning is enough for me to know that regardless of where it begins I know where it’s going. And it’s not pretty.

But enough about me. Getting back to the question about aging, two researchers at Northwestern University have uncovered some clues that may give us a deeper understanding of aging and longevity, and even lead to new ways of improving quality of life as we get older.

The researchers were focused on C. elegans, a transparent roundworm. They initially thought that aging was a gradual process: that it began slowly and then picked up pace as the animal got older. Instead they found that in C. elegans aging begins just as soon as the animal reaches reproductive maturity. It hits its peak of fertility, and it is all downhill from there.

The researchers say that once C. elegans has finished producing eggs and sperm – ensuring its line will continue – a genetic switch is thrown by germline stem cells. This flipped switch begins the aging process by turning off the ‘heat shock response’; that’s a mechanism the body uses to protect cells from conditions that would normally pose a threat or even be deadly.

In a news release Richard Morimoto, the senior author of the study, says that without that protective mechanism in place the aging process begins:

C. elegans has told us that aging is not a continuum of various events, which a lot of people thought it was. In a system where we can actually do the experiments, we discover a switch that is very precise for aging. All these stress pathways that insure robustness of tissue function are essential for life, so it was unexpected that a genetic switch is literally thrown eight hours into adulthood, leading to the simultaneous repression of the heat shock response and other cell stress responses.”

You read that right. In the case of poor old C. elegans the aging process begins just eight hours into adulthood. Of course the lifespan of the worm is only about 3 weeks so it’s not surprising the aging process kicks in quite so quickly.

To further test their findings the researchers carried out an experiment where they blocked the genetic switch from flipping, and the worm’s protective mechanisms remained strong.

Now, taking findings from something as small as a worm and trying to extrapolate them to larger animals is never easy. Nonetheless understanding what triggers aging in C. elegans could help us figure out if a similar process was taking place at the cellular level in people.

Morimoto says that knowledge might help us develop ways to improve our cellular quality of life and delay the onset of many of the diseases of aging:

“Wouldn’t it be better for society if people could be healthy and productive for a longer period during their lifetime? I am very interested in keeping the quality control systems optimal as long as we can, and now we have a target. Our findings suggest there should be a way to turn this genetic switch back on and protect our aging cells by increasing their ability to resist stress.”

The study is published in the journal Molecular Cell.

Sonic Hedgehog provides pathway to fight blood cancers

Dr. Catriona Jamieson: Photo courtesy Moores Cancer Center, UCSD

Dr. Catriona Jamieson:
Photo courtesy Moores Cancer Center, UCSD

For a lot of people Sonic Hedgehog is a video game. But for stem cell researcher Dr. Catriona Jamieson it is a signaling pathway in the body that offers a way to tackle and defeat some deadly blood cancers.

Dr. Jamieson – a researcher at the University of California, San Diego (UCSD) – has a paper published online today in The Lancet Haematology that highlights the safety and dosing levels for a new drug to treat a variety of blood cancers. CIRM funding helped Dr. Jamieson develop this work.

The drug targets cancer stem cells, the kind of cell that is believed to be able to lie dormant and evade anti-cancer therapies before springing back into action, causing a recurrence of the cancer. The drug coaxes the cancer stem cells out of their hiding space in the bone marrow and gets them to move into the blood stream where they can be destroyed by chemotherapy.

In a news release Dr. Jamieson says the drug – known by the catchy name of PF-04449913 – uses the sonic Hedgehog signaling pathway, an important regulator of the way we develop, to attack the cancer:

“This drug gets that unwanted house guest to leave and never come back. It’s a significant step forward in treating people with refractory or resistant myeloid leukemia, myelodysplastic syndrome and myelofibrosis. It’s a bonus that the drug can be administered as easily as an aspirin, in a single, daily oral tablet.”

The goal of this first-in-human study was to test the drug for safety; so 47 adults with blood and marrow cancer were given daily doses of the drug for up to 28 days. Those who were able to tolerate the dosage, without experiencing any serious side effects, were then given a higher dose for the next 28 days. Those who experienced problems were taken off the therapy.

Of the 47 people who started the trial in 2010, 28 experienced side effects. However, only three of those were severe. The drug showed signs of clinical activity – meaning it seemed to have an impact on the disease – in 23 people, almost half of those enrolled in the study.

Because of that initial promise it is now being tested in five different Phase 2 clinical trials. Dr. Jamieson says three of those trials are at UCSD:

“Our hope is that this drug will enable more effective treatment to begin earlier and that with earlier intervention, we can alter the course of disease and remove the need for, or improve the chances of success with, bone marrow transplantation. It’s all about reducing the burden of disease by intervening early.”

Improving process drives progress in stem cell research

shutterstock_212888935Process is not a sexy word. No one gets excited thinking about improving a process. Yet behind every great idea, behind every truly effective program is someone who figured out a way to improve the process, to make that idea not just work, but work better.

It’s not glamorous. Sometimes it’s not even pretty. But it is essential.

Yesterday in Oakland our governing Board approved two new concepts to improve our process, to help us fund research in a way that is faster, smarter and ultimately helps us better meet our mission of accelerating the development of stem cell therapies for patients with unmet medical needs.

The new concepts are for Discovery – the earliest stage of research – and the Translational phase, a critical step in moving promising therapies out of the lab and toward clinical trials where they can be tested in people.

In a news release C. Randal Mills, Ph.D., CIRM’s President and CEO, said that these additions built on the work started when the agency launched CIRM 2.0 in January for the clinical phase of research:

“What makes this approach different is that under CIRM 2.0 we are creating a pathway for research, from Discovery to Translational and Clinical, so that if a scientist is successful with their research at one level they are able to move that ahead into the next phase. We are not interested in research just for its own sake. We are interested in research that is going to help us help patients.”

In the Discovery program, for example, we will now be able to offer financial incentives to encourage researchers who successfully complete their work to move it along into the Translational phase – either themselves or by finding a scientific partner willing to take it up and move it forward.

This does a number of things. First it helps create a pipeline for the most promising projects so ideas that in the past might have stopped once the initial study ended now have a chance to move forward. Obviously our hope is that this forward movement will ultimately lead to a clinical trial. That won’t happen with every research program we fund but this approach will certainly increase the possibility that it might.

There’s another advantage too. By scheduling the Discovery and Translational awards more regularly we are creating a grant system that has more predictability, making it easier for researchers to know when they can apply for funding.

We estimate that each year there will be up to 50 Discovery awards worth a total of $53 million; 12 Translation awards worth a total of $40 million; and 12 clinical awards worth around $100 million. That’s a total of more than $190 million every year for research.

This has an important advantage for the stem cell agency too. We have close to $1 billion left in the bank so we want to make sure we spend it as wisely as we can.

As Jonathan Thomas, Ph.D. J.D, the Chair of our Board, said, having this kind of plan helps us better plan our financial future;

“Knowing how often these programs are going to be offered, and how much money is likely to be awarded means the Board has more information to work with in making decisions on where best to allocate our funding.”

The Board also renewed funding for both the Bridges and SPARK (formerly Creativity) programs. These are educational and training programs aimed at developing the next generation of stem cell scientists. The Bridges students are undergraduate or Master’s level students. The SPARK students are all still in high school. Many in both groups come from poor or low-income communities. This program gives them a chance to work in a world-class stem cell research facility and to think about a career in science, something that for many might have been unthinkable without Bridges or SPARK.

Process isn’t pretty. But for the students who can now think about becoming a scientist, for the researchers who can plan new studies, and for the patients who can now envision a potential therapy getting into clinical trials, that process can make all the difference.

Moving Beyond Current CIRM Funding

Delivering on CIRM’s mission of “accelerating stem cell treatments to patients with unmet medical needs” requires the participation of multiple stakeholders to span the research, development, and commercialization phases of bringing a new product to market. In this post, I am pleased to highlight two recent examples of CIRM-funded projects moving beyond their period of CIRM funding by establishing partnerships with industry and investors to further develop the underlying CIRM-funded technology.

In 2000, Dr. Jill Helms, an academic investigator at Stanford University, received a $6.5 million grant from CIRM under an Early Translational award. The title of Dr. Helms’ project was Enhancing Healing via Wnt-Protein Mediated Activation of Endogenous Stem Cells,” and the goal of the award was to develop a novel, protein-based therapeutic platform to accelerate and enhance tissue regeneration through activation of adult stem cells. The five-year award achieved many critical milestones along the way, including the initiation of two preclinical studies aimed at demonstrating the effectiveness of a protein called L-WNT3A to improve the success of spinal fusion surgery and to treat a degradative bone disease called osteonecrosis, both of which represent unmet medical needs.

Helms_bonegraft

Through CIRM funding, Dr. Jill Helms’ team was able to demonstrate that treatment with a protein called L-Wnt3a regenerates and promotes bone formation in animals models (Figs D,F: untreated; Figs E,G: Wnt3a treated). (image credit: Leucht et al. J Bone Joint Surg Am. 2013;95:1278-88)

Dr. Helms’ work attracted considerable interest from the investor community during the lifespan of her grant, and during the final year of her award Dr. Helms’ WNT3A technology platform was successfully spun out of Stanford into a newly created company called Ankasa Regenerative Therapeutics. Ankasa was established with the financial support of Avalon Ventures – a La Jolla based life sciences venture capital firm, Correlation Ventures – an analytics driven venture capital firm, and Heraeus Medical – a diversified global medical device company based in Germany with over $1 billion of annual revenue. Ankasa has raised an initial $8.5 million in the first round of the total $17 million Series A financing to continue the development of the previously CIRM-funded technology.

Moving Radially Branched Deployment_Neurosurgery_Lim

Dr. Daniel Lim’s CIRM-funded BranchPoint Device allows neurosurgeons to deliver cell based therapies to multiple areas of the brain with just one needle penetration.  (image credit: Silvestrini et al. Stereotact Funct Neurosurg 2013;91:92–103)

The second recent example comes from a CIRM Tools & Technology grant to Dr. Daniel Lim, a neurosurgeon at UCSF. Dr. Lim was awarded a $1.8 million grant to develop a more efficient device for transplanting stem cells into the brain, titled Development and Preclinical Testing of New Devices for Cell Transplantation to the Brain.” Dr. Lim successfully developed a platform technology that enables Radially Branched Deployment (RBD) of cells to multiple target locations at variable radial distances and depths along the initial brain penetration tract with real-time interventional magnetic resonance image (iMRI) guidance. This technology is a huge leap forward over the conventional and crude syringe and needle device that are typically used to inject living cells into the brain.

Dr. Lim’s work attracted the attention of Accurexa, a publicly traded medical device company that licensed the CIRM-funded technology from UCSF. Under the guidance of Accurexa, a 510(k) application was submitted to the FDA for the newly coined “BranchPoint Device.” In June of this year, Accurexa successfully raised $2.5 million in equity financing to continue the development and for commercialization of the BranchPoint Device.

Overall, there remains a lack of industry pull for early stage stem cell technologies, however, both Drs. Helms and Lim’s stories represent successful examples of CIRM providing public dollars for early stage research with the resulting potentially life-saving applications attracting interest from investors and companies. These new investors will further fund and develop the technologies well beyond current CIRM funding and, assuming they are successful, deliver them to patients with unmet medical needs.

Partnering with Big Pharma to benefit patients

Our mission at CIRM is to accelerate the development of stem cell therapies for patients with unmet medical needs. One way we have been doing that is funding promising research to help it get through what’s called the “Valley of Death.” This is the time between a product or project showing promise and the time it shows that it actually works.

Many times the big pharmaceutical companies or deep pocketed investors, whose support is needed to cover the cost of clinical trials, don’t want to get involved until they see solid proof that this approach works. However, without that support the researchers can’t do the early stage clinical trials to get that proof.

The stem cell agency has been helping get these projects through this Catch 22 of medical research, giving them the support they need to get through the Valley of Death and emerge on the other side where Big Pharma is waiting, ready to take them from there.

We saw more evidence that Big Pharma is increasingly happy doing that this week with the news that the University of California, San Diego, is teaming up with GSK to develop a new approach to treating blood cancers.

Dr. Catriona Jamieson: Photo courtesy Moores Cancer Center, UCSD

Dr. Catriona Jamieson:
Photo courtesy Moores Cancer Center, UCSD

Dr. Catriona Jamieson is leading the UCSD team through her research that aims at killing the cancer stem cells that help tumors survive chemotherapy and other therapies, and then spread throughout the body again. This is work that we have helped fund.

In a story in The San Diego Union Tribune, reporter Brad Fikes says this is a big step forward:

“London-based GSK’s involvement marks a maturation of this aspect of Jamieson’s research from basic science to the early stages of discovering a drug candidate. Accelerating such research is a core purpose of CIRM, founded in 2004 to advance stem cell technology into disease therapies and diagnostics.”

The stem cell agency’s President and CEO, Dr. C. Randal Mills, is also quoted in the piece saying:

“This is great news for Dr. Jamieson and UCSD, but most importantly it is great news for patients. Academic-industry partnerships such as this bring to bear the considerable resources necessary to meaningfully confront healthcare’s biggest challenges. We have been strong supporters of Dr. Jamieson’s work for many years and I think this partnership not only reflects the progress that she has made, but just as importantly it reflects how the field as a whole has progressed.”

As the piece points out, academic researchers are very good at the science but are not always as good at turning the results of the research into a marketable product. That’s where having an industry partner helps. The companies have the experience turning promising therapies into approved treatments.

As Scott Lippman, director of the Moores Cancer Center at UCSD, said of the partnership:

“This is a wonderful example of academia-industry collaboration to accelerate drug development and clinical impact… and opens the door for cancer stem cell targeting from a completely new angle.”

With the cost of carrying out medical research and clinical trials rising it’s hard for scientists with limited funding to go it alone. That’s why these partnerships, with CIRM and industry, are so important. Working together we make it possible to speed up the development and testing of therapies, and get them to patients as quickly as possible.

Share your voice, shape our future

shutterstock_201440705There is power in a single voice. I am always reminded of that whenever I meet a patient advocate and hear them talk about the need for treatments and cures – and not just for their particular disease but for everyone.

The passion and commitment they display in advocating for more research funding reflects the fact that everyday, they live with the consequences of the lack of effective therapies. So as we at CIRM, think about the stem cell agency’s future and are putting together a new Strategic Plan to help shape the direction we take, it only makes sense for us to turn to the patient advocate community for their thoughts and ideas on what that future should look like.

That’s why we are setting up three meetings in the next ten days in San Diego, Los Angeles and San Francisco to give our patient advocates a chance to let us know what they think, in person.

We have already sent our key stakeholders a survey to get their thoughts on the general direction for the Strategic Plan, but there is a big difference between ticking a box and having a conversation. These upcoming meetings are a chance to talk together, to explore ideas and really flesh out the details of what this Strategic Plan could be and should be.

Our President and CEO, Dr. C. Randal Mills wants each of those meetings to be an opportunity to hear, first hand, what people would like to see as we enter our second decade. We have close to one billion dollars left to invest in research so there’s a lot at stake and this is a great chance for patient advocates to help shape our next five years.

Every voice counts, so join us and make sure that yours is heard.

The events are:

San Diego, Monday, July 13th at noon at Sanford Consortium for Regenerative Medicine, 2880 Torrey Pines Scenic Drive, La Jolla, CA 92037

Los Angeles: Tuesday, July 14th at noon at Eli and Edythe Broad CIRM Center for Regenerative Medicine and Stem Cell Research at USC, 1425 San Pablo Street, 1st floor conf. room Los Angeles, CA 90033

San Francisco: Wednesday, July 15th at noon at CIRM, 210 King Street (3rd floor), San Francisco, CA 94107

There will be parking at each event and a light lunch will be served.

We hope to see you at one of them and if you do plan on coming please RSVP to info@cirm.ca.gov

And of course please feel free to share this invitation to anyone you think might be interested in having their voice heard. We all have a stake in this.

Creative partnerships that promote progress

Lewis and Clark: great partnerships can change the world

Lewis and Clark: great partnerships can change the world

Having a good partner can turn something good into something truly memorable. Where would Laurel be without Hardy, Lewis without Clark, Butch Cassidy without the Sundance Kid. That’s why the stem cell agency has partnerships on a number of different levels as part of our mission of accelerating the development of stem cell cures to patients with unmet medical needs.

Our latest partnership is with RegMedNet which, in its own words, “provides a unique and unparalleled platform for the regenerative medicine community to share insights, discuss the latest research, and help move the field forward.” With a goal like that why would we not want to support them?

Like us RegMedNet believes that regenerative medicine is going to completely change the way we treat disease, even the way we think about disease. They also believe that progress of the kind we all want is only going to come by bringing together all the key players from the researchers and manufacturers, to the government regulators and, of course, the patient advocates. Each has a vital role to play in moving the field forward and RegMedNet reflects that in both the content it posts online and in the contributors, who represent institutions and companies worldwide.

One of the most important elements in any partnership is understanding, and RegMedNet does a great job of trying to raise awareness about the field, the challenges we all face, and the progress being made. Bringing together so many different perspectives in one spot really helps create a much deeper understanding of regenerative medicine as a whole.

In a few short years regenerative medicine has gone from a relatively small field to a global industry. Our hope is that creating partnerships with like-minded groups around the world, is going to help it get even bigger and, even better.

New tech tool speeds up stem cell research

It’s hard to do a good job if you don’t have the right tools. Now researchers have access to a great new tool that could really help them accelerate their work, a tool its developers say “will revolutionize the way cell biologists develop” stem cell models to test in the lab.

Fluidigm's Castillo system

Fluidigm’s Callisto system

The device is called Callisto™. It was created by Fluidigm thanks to two grants from CIRM. The goal was to develop a device that would allow researchers more control and precision in the ways that they could turn stem cells into different kinds of cell. This is often a long, labor-intensive process requiring round-the-clock maintenance of the cells to get them to make the desired transformation.

Callisto changes that. The device has 32 chambers, giving researchers more control over the conditions that cells are stored in, even allowing them to create different environmental conditions for different groups of cells. All with much less human intervention.

Lila Collins, Ph.D., the CIRM Science Officer who has worked closely with Fluidigm on this project over the years, says this system has some big advantages over the past:

“Creating the optimal conditions for reprogramming, stem cell culture and stem cells has historically been a tedious and manually laborious task. This system allows a user to more efficiently test a variety of cellular stimuli at various times without having to stay tied to the bench. Once the chip is set up in the instrument, the user can go off and do other things.”

Having a machine that is faster and easier to use is not the only advantage Callisto offers, it also gives researchers the ability to systematically and simultaneously test different combinations of factors, to see which ones are most effective at changing stem cells into different kinds of cell. And once they know which combinations work best they can use Callisto to reproduce them time after time. That consistency means researchers in different parts of the world can create cells under exactly the same conditions, so that results from one study will more readily support and reflect results from another.

In a news release about Callisto,  Fluidigm’s President and CEO Gajus Worthington, says this could be tremendously useful in developing new therapies:

“Fluidigm aims to enable important research that would otherwise be impractical. The Callisto system incorporates some of our finest microfluidic technology to date, and will allow researchers to quickly and easily create complex cell culture environments. This in turn can help reveal how stems cells make fate decisions. Callisto makes challenging applications, such as cellular reprogramming and analysis, more accessible to a wide range of scientists. We believe this will move biological discovery forward significantly.”

And as Collins points out, Callisto doesn’t just do this on a bulk level, working with millions of cells at a time, the way the current methods do:

“Using a bulk method it’s possible that one might miss an important event in the mixture. The technology in this system allows the user to stimulate and study individual cells. In this way, one could measure changes in small sub-populations and find ways to increase or decrease them.”

Having the right tools doesn’t always mean you are going to succeed, but it certainly makes it a lot easier.

How one strong ARM can create a community

I spent the last two days at the annual Washington meeting of the Alliance for Regenerative Medicine (ARM), the advocacy organization that CIRM became a founding member of in 2009. Having been CIRM’s representative at that first organizing meeting it has been a pleasure to see the organization mature into an effective advocacy group for our field. It has lived up to its goal of creating a community where all the stakeholders in the field, from academic and industry leaders to patient advocates and investors, can come together in a coordinated front.

ARM and CIRM share the goal of accelerating the development of regenerative therapies to patients with unmet medical needs. The organization also dovetails well with our effort to inform the public about the great hope in the field. To quote ARM’s website: “ARM also works to increase public understanding of the field and its potential to transform human healthcare.”

But that transformation can be fostered or impeded by actions in our nation’s capital, both regulatory and legislative, the main thrust of the past two days’ activities.

While the iconic Capitol building is the most recognized footprint of our Congress, it is the House and Senate office buildings that ring three sides of the Capitol where most of the work gets done, like in the Rayburn building, which houses the office of Dianna DeGette, the Colorado congresswoman and champion of regenerative medicine.

While the iconic Capitol building is the most recognized footprint of our Congress, it is the House and Senate office buildings that ring three sides of the Capitol where most of the work gets done, like in the Rayburn building, which houses the office of Dianna DeGette, the Colorado congresswoman and champion of regenerative medicine.

ARM members presented three specific proposals for advancing the field to members of congress and their staffs. These would:

  • Create a center of excellence to develop technical and process standards for regenerative medicine. Not very sexy on the surface, but agreement in advance on what regulators will accept in creating a new product can shave months or years off the development of needed therapies.
  • Create a special pathway within the Food and Drug Administration—much like the one created for orphan diseases—for “Qualified Regenerative Medicine Products (QRMPs). These products would have shown potential to change the course of a disease with currently unmet medical needs and the FDA would be required to meet with their sponsors to discuss expedited review of the product.
  • Advocate for the adoption of a national regenerative medicine strategy that includes federal agency coordination, support for research and regulatory reform to create a clear and predictable pathway that enables quick approval of safe and effective products. To accomplish that ARM has promoted the establishment of a Regenerative Medicine Coordinating Council within the U.S. Department of Health & Human Services.
Jamie Goldfarb with her son Kai and husband Jeff. Photo courtesy Melanoma Research Alliance

Jamie Goldfarb with her son Kai and husband Jeff.
Photo courtesy Melanoma Research Alliance

Jamie Goldfarb, who beat back melanoma with the help of a cell-based immune therapy, made a clear and passionate case for the urgency of making it easier to get these therapies to patients at the ARM member dinner Tuesday night:

“Enhanced awareness for the power of regenerative medicine means a world of difference. It means less suffering, less pain, less fear, less expense, less hardship, less loss. It also means more hope, more determination, more love, more strength for individuals and for society as a whole. Every person in this room and those organizations you represent are improving lives.”

Don Gibbons