CIRM Creativity Program: Interns Document their Experiences, One Photo at a Time

This summer we’re sponsoring high school interns in stem cell labs throughout California as part of our annual Creativity Program. We asked those students to share their experiences through blog posts, videos and on Instagram.

Today, we take a look at some of the top Instagram photos from our students. Want to take a peak at the rest? Search for the #CIRMCreativityLab hashtag on your Instagram app!

Megan Handley, a Creativity student in the Denise Montell lab at UCSB, snapped this image of a Drosophila ovariole(egg string) taken in fluorescence microscopy. The blue is DAPI(stains nucleus, and the green is anti-HTs(stains membranes).

Megan Handley, a Creativity student in the Denise Montell lab at UCSB, snapped this image of a Drosophila ovariole(egg string) taken in fluorescence microscopy. The blue is DAPI(stains nucleus, and the green is anti-HTs(stains membranes). [Credit: Megan Handley]

Students from the City of Hope practice their routine for the group video

Students from the City of Hope practice their routine for the group video[Credit: Grace Lo]

Emma Cruisenberry, an intern in the Rothman Lab at UCSB, snapped these two photos C. elegans—the top under normal conditions, versus C. elegans expressing the GFP marker under UV light in the intestinal cells. [Credit: Emma Cruisenberry]

Emma Cruisenberry, an intern in the Rothman Lab at UCSB, snapped these two photos C. elegans—the top under normal conditions, versus C. elegans expressing the GFP marker under UV light in the intestinal cells. [Credit: Emma Cruisenberry]

Research points to another path toward giving diabetics the insulin-producing cells they need

Type 1 diabetes is such a life-changing illness that scores of teams around the world are looking for ways to replace the insulin-producing pancreatic cells that are destroyed in the disease.

Many of these researchers use stem cells of various types to try to generate large quantities of insulin producing cells that could be transplanted. But a few are trying to directly reprogram other pancreas cells into desired beta cells. Often called transdifferentiation, this process could be a great shortcut to getting the needed cells.


Fred Levine and his CIRM-funded colleagues at the Sanford-Burnham Medical Research Institute in La Jolla have succeeded in causing this identity change using a single peptide, which you can think of as a very small protein. The islet cells in our pancreas contain beta cells and alpha cells in close proximity. When a diabetic’s immune system destroys the insulin-producing beta cells it does not harm the alpha cells, so they are a ready supply of cells that could be reprogrammed that are already in the right location. Levine’s team did this with the peptide caerulein. In a press release Levine noted:

“We have found a promising technique for type 1 diabetics to restore the body’s ability to produce insulin. By introducing caerulein to the pancreas we were able to generate new beta cells—the cells that produce insulin—potentially freeing patients from daily doses of insulin to manage their blood-sugar levels.”

Injecting the peptide worked in both a mouse model of diabetes and in human pancreas tissue from cadavers. But it also caused enough inflammation of the pancreas that the team is now tracking down the molecular target where the peptide does its magic. With that knowledge they hope to develop a more specific drug without the side effect.

Levine is well aware that a second step would be needed to protect any new beta cells they create from immune system attack. In a video that the institute produced a collaborator talked about preliminary work to prevent this immune rejection [starting at 2:45 into the video]. She is trying to super charge the type of immune cell called T-regulatory cells that are responsible for maintaining a balanced immune response.

The team published their work online in Cell Death and Disease, July 31.

Don Gibbons

Blood Test Reveals Alzheimer’s Disease Risk, CIRM-Funded Study Finds

Could a simple blood test predict your risk for one day developing Alzheimer's disease?

Could a simple blood test predict your risk for developing one day developing Alzheimer’s disease?

By the time someone begins to experience the clinical symptoms of Alzheimer’s disease, the damage has already been done. An accumulation of toxic proteins is causing brain cells to whither and die, taking with them a lifetime of precious memories.

But what if we had a definitive test that could predict one’s risk of developing Alzheimer’s, even before the onset of symptoms? Could we use it to develop an early-detection method and—even more importantly—a way to slow or halt the disease before it is too late?

While this may seem closer to fiction than reality, scientists from the Western University of Health Sciences are reporting that they’ve done just that: a simple blood test that can accurately predict one’s Alzheimer’s risk—up to ten years before symptoms begin to develop.

Reporting in the latest issue of Translational Psychiatry, senior author Dr. Doug Ethell and his research team describe their ingenious method of tracking the earliest stages of Alzheimer’s via a simple blood test.

Their test, called the CD4see assay, tracks the body’s early immune response to toxic proteins—called amyloid beta proteins—that accumulate and form harmful plaques in the brains of Alzheimer’s patients.

Ethell has long been studying how a class of immune cells, called T cells, responds to the buildup of amyloid beta. Previously, he showed that these so-called amyloid beta-specific T cells could actually counter the cognitive decline seen in Alzheimer’s. So, lower amyloid T cell levels should correlate with symptoms. As he explained in an interview:

“If our mouse studies were correct, then there should be fewer of those cells in Alzheimer’s patients. Translating those studies from mouse to man was going to take a big effort—characterizing the small proportion of T cells that respond to amyloid-beta from the millions of other kinds of T cell would require technology that didn’t exist yet.”

So Ethell turned to stem cells. With support from CIRM, Ethell and his team took human embryonic stem cells (hESCs) and developed a type of immune system cell called dendritic cells. These cells stimulated the growth of amyloid-beta T cells—effectively bringing them out of hiding and allowing the researchers to locate and count them.

“Everyone showed a decrease in these T cells as they aged, but the decline occurred earliest in women with the apoE4 gene (the single greatest genetic risk factor for Alzheimer’s), often right around the same time as menopause,” explained Ethell. “When our raw data was pasted on foam boards all over my office it seemed to us that older women had lower responses than men, and when the data was finally plotted the dramatic decline around menopause was clear.”

Interestingly, this observation seems to correlate with the fact that Alzheimer’s is more prevalent in women than in men.

Ethell and his team propose that the CD4see assay could soon be used to measure amyloid-beta-specific T cells against one’s age, sex and whether they carry apoE4. This could then be used to calculate the individual’s risk for developing Alzheimer’s symptoms in the future.

This assay could also prove helpful when looking to test new therapeutic strategies that treat early-stage Alzheimer’s—something that has proven difficult without a reliable early detection method.

“Alzheimer’s disease is a puzzle and every bit of knowledge adds a new piece,” added Ethell. “We now view Alzheimer’s disease very differently than we did even just a few years ago.”

Bridging the gap: helping create a new generation of stem cell scientists

Inspiration comes in many different shapes and sizes, but when you see it there is no mistaking it. And when you meet and talk to the students in our Bridges program you find inspiration in each and every one of them.

The program is designed to train the next generation of stem cell scientists, bridging (hence the name) the gap between undergraduate and Master’s level training in research. But it’s so much more than just a recruiting and training program because one of the goals of Bridges is to find students who are often overlooked for opportunities like this: students who may be the first in their family to go to college, who don’t come from a wealthy family or fancy school. These students seize the opportunity with both hands and their sense of delight at being given a chance, and enthusiasm for the work is exciting and infectious.

We held our annual Bridges Trainee Meeting in Burlingame this week, a chance for all the students in the program to come together, listen to lectures from world-class stem cell researchers, and show their posters describing the work they have done over the past year.

At first many of them seem a little shy but once you ask them about their experiences their enthusiasm simply bubbles over. Shayda Kianfar graduated from Berkeley City College and is now studying at the University of California, Berkeley. She says she was accepted into the program even though she had no prior lab experience:

“This has given me an amazing experience. To be surrounded by so many incredible people, to have great mentors is life changing. You learn so many new skills and it opens your eyes. I hadn’t thought about stem cell work before but now I would love to do this. It’s so exciting.”

Kevin Martinez talks to fellow Bridges student David James

Kevin Martinez talks to fellow Bridges student David James

Kevin Martinez graduated from San Francisco State University and says getting a chance to work with extraordinary researchers like Thea Tlsty, Ph.D., at the University of California, San Francisco, was incredible. Kevin got to work with Tlsty and her team on their discovery that certain rare cells extracted from adult breast tissue can be instructed to become different types of cells – a discovery that could have important potential for regenerative medicine.

He says what surprised him most of all was how much independence they gave him, he wasn’t treated like a student but like a colleague:

“They trained me and gave me the experience and opportunity to do amazing work. This is great training for a career either in academia or industry because they teach you how to do research independently, but to also work as part of a team.”

Eleanor Kim, spent her year at City of Hope near Los Angeles. She focused on leukemia stem cells (LCS), testing different medications to see if they could be effective at preventing recurrence of the leukemia or the speed with which it spreads.

Bridges student Eleanor Kim

Bridges student Eleanor Kim

Eleanor was a pre-med student who hadn’t really thought about research until she found out about the Bridges program. Now she’s set her sights on becoming an MD/PhD:

“This got me much more interested in the biology of cancers, what is driving them, what controls them. I want to be able to talk to my patients about what is happening to them but also to be able to do research that might be able to help them.”

Eleanor says she also learned a valuable lesson about the need for a good night’s sleep:

“I learned that you have to work hard but that you also can’t work to the point where you are sleep deprived. This is such detail-oriented work that being sleepy can lead to mistakes and one mistake can set you back days.”

Each Bridges student has their own story; each brings their own unique perspective to their work and to the field. You can hear some of our students talk about how important this opportunity was for them, and how it has changed them in so many ways.

kevin mccormack

CIRM Creativity Student Long Nguyen Learns First-Hand about the Value of Scientific Research

This summer we’re sponsoring high school interns in stem cell labs throughout California as part of our annual Creativity Program. We asked those students to share their experiences through blog posts and videos.

Today, we hear from Long Nguyen, who has been busy at Stanford University’s Beckman Center for Molecular and Genetic Medicine.

Summer Reflections

Long Nguyen

It’s been a real pleasure spending the past eight weeks here at Stanford University. When I first walked into Beckman Center on June 9th, I did not know what to expect. There was a crowd of students all waiting, just as I was. I got my lab coat, my notebooks, and my bag. Frankly, I was anxious beyond imagination. At the time, I was still wondering to myself: “How did I get into this program? It’s inexplicable.” Those thoughts vanished as I stepped out of that room three hours later and headed to my workplace. I was confident and ready to start the new experience.

The beloved hood upon which I daringly cultured my cells!

The beloved hood upon which I daringly cultured my cells!

Learning about stem cells has made me more passionate about scientific research. I am glad to have been given this opportunity. Up to this point, I had only been exposed to textbooks upon textbooks—a dull methodology, as many may agree. The only hands-on experience I ever had were agarose gel electrophoresis and transformation of bacteria with an insulin-GFP reporter complex.

My experience here, however, has given me a strong foundation beyond the scope of these. Initially, I could not open a conical tube with one hand, and my pipetting was absolutely horrendous. I could not calculate simple dilutions for my working solutions. I even made the mistake of vacuum-aspirating over half of my cells during the second week. As time progressed, my culturing of stem cells improved considerably and I made few, if no, mistakes. I learned the background, the methodology, and the purpose of my work. These little details proved more important than they seemed, as they gave me a much clearer understanding of my work. Looking back, despite many, many errors, I learned to appreciate the value of science.

An interesting moment before a media change.

An interesting moment before a media change.

Prior to my experience, I had known little about stem cells: they were mentioned briefly in a page of my AP Biology textbook. I only knew that they differentiated into specific cell types to repair the body; there was no mention of iPSCs in the slightest. My knowledge of stem cells now is much more extensive. Regenerative medicine, wound healing, disease treatments—all that can be possible with stem cell research surprised me, to say the least. I have no doubts that this developing field will be a major game changer in the coming decades. The research is definitely something to respect. Being a part of ongoing research made me more aware of the problems that scientists, especially those in medicine, face in their attempts to do something, whether it be to cure scleroderma, to repair damaged neural connections, or to screen drugs with iPSC-derived cells. One thing is for sure: what I do now and what I expose myself to will be critical once I start planning for my future. Thanks go to Stanford’s faculty, SIMR 2014, CIRM, my peers, and my family, all of whom have supported me in my work.

My dear cells!

My dear cells!

Stem Cell Stories that Caught our Eye: Multiple Sclerosis, Parkinson’s and Reducing the Risk of Causing Tumors

Here are some stem cell stories that caught our eye this past week. Some are groundbreaking science, others are of personal interest to us, and still others are just fun.

Cell therapy for Parkinson’s advancing to the clinic. A decade-long moratorium on the transplant of fetal nerve tissue into Parkinson’s patient will end in two months when the first patients in a large global trial will receive the cells. BioScience Technology did a detailed overview on the causes for the moratorium and the optimism about the time being right to try again. The publication also talks about what most people in the field believe will be the long-term solution: moving from scarce fetal tissue to nerve cells grown from readily available embryonic stem cells. The author’s jumping off point was a pair of presentations at the International Society for Stem Cell Research in June, which we wrote about at the time. But the BioScience piece provides more background on the mixed results of earlier studies and references to recent journal publications showing long term—as much as 20 year—benefit for some of those patients.

It goes on to describe multiple reasons why, once the benefit is confirmed with fetal cells, moving to stem cells might be the better way to go. Not only are they more readily available, they can be purified in the lab as they are matured into the desired type of early-stage nerve cell. Researchers believe that some of the side effects seen in the early fetal trials stemmed from the transplants containing a second type of cell that caused jerking movements known as dyskinesias. One stem cell trial is expected to start in 2017, which we discussed in June.

Immunity persists through a special set of stem cells. Our immune system involves so many players and so much cell-to-cell interaction that there are significant gaps in our understanding of how it all works. One of those is how we can have long-term immunity to certain pathogens. The T-cells responsible for destroying invading bugs remember encountering specific ones, but they only live for a few years, generally estimated at five to 15. The blood-forming stem cells that are capable of generating all our immune cells would not have memory of specific invaders so could not be responsible for the long term immunity.

Now, an international team from Germany and from the Hutchison Center in Washington has isolated a subset of so-called “memory T-cells” that have stem cell properties. They can renew themselves and they can generate diverse offspring cells. Researchers have assumed cells like this must exist, but could not confirm it until they had some of the latest gee-wiz technologies that allow us to study single cells over time. ScienceDaily carried a story derived from a press release from the university in Munich and it discusses the long-term potential benefits from this finding, most notably for immune therapies in cancer. The team published their work in the journal Immunity.

Method may reduce the risk of stem cells causing tumors. When teams think about transplanting cells derived from pluripotent stem cells, either embryonic or iPS cells, they have to be concerned about causing tumors. While they will have tried to mature all the cells into a specific desired adult tissue, there may be a few pluripotent stem cells still in the mix that can cause tumors. A team at the Mayo Clinic seems to have developed a way to prevent any remaining stem cells in transplants derived from iPS cells from forming tumors. They treated the cells with a drug that blocks an enzyme needed for the stem cells to proliferate. Bio-Medicine ran a press release from the journal that published the finding, Stem Cells and Development. Unfortunately, that release lacks sufficient detail to know exactly what they did and its full impact. But it is nice to know that someone is developing some options of ways to begin to address this potential roadblock.

Multiple sclerosis just got easier to study. While we often talk about the power of iPS type stem cells to model disease, we probably devote too few electrons to the fact that the process is not easy and often takes a very long time. Taking a skin sample from a patient, reprogramming it to be an iPS cell, and then maturing those into the adult tissue that can mimic the disease in a dish takes months. It varies a bit depending on the type of adult tissue you want, but the nerve tissue that can mimic multiple sclerosis (MS) takes more than six months to create. So a team at the New York Stem Cell Foundation has been working on ways to speed up that process for MS. They now report that they have cut the time in half. This should make it much easier for more teams to jump into the effort of looking for cures for the disease. ScienceCodex ran the foundations press release.

Spiderman Sets the Tone for Stem Cell Agency Board Meeting

I don’t often think about Spiderman at meetings of our governing Board – no, really I don’t – but yesterday was an exception. Not that I was daydreaming, rather I was listening to our new President & CEO C. Randal Mills, Ph.D., talk about his determination to set a very specific tone in leading the agency.

shutterstock_109433912

Randy had just explained to the Board that he had asked the agency’s General Counsel to draw up an agreement stating he – Randy, not the lawyer – will not accept a job with any company funded by CIRM for at least one year following his departure from the agency. In addition he will also refuse to accept gifts or travel payments from any company, institution or individual who receives agency funding.

In a news release we issued following the Board meeting he explained his reasons for making this commitment:

“I want the people of California to know that my sole interest in being at CIRM is to help advance stem cell treatments to patients who are in need. I will do so with a full commitment to transparency and by never compromising the integrity of our mission nor our trust to the taxpayers of California.”

And that’s where Spiderman comes in. As any fan of the movie or comic books can tell you one of the things Spiderman says a lot is “With great power comes great responsibility.”

In making his commitment Randy wanted to send a very clear and very strong message that he understands what his role as the President involves, and that it’s important for him to demonstrate that through his actions.

Board member and patient advocate, Sherry Lansing, echoed that saying:

“We take even the possibility of a perception of a conflict of interest very seriously and are determined to do whatever is necessary to ensure that we protect the reputation of the agency and the work that we do. We fully support Dr. Mills in the way he is handling this issue.”

Randy decided to make that commitment after his predecessor, Dr. Alan Trounson joined the Board of Stem Cells Inc., a company that we awarded more than $19 million to develop a therapy for Alzheimer’s disease. While there is nothing illegal about Dr. Trounson’s actions the news did cause a bit of a stir with a few commentators saying this was a dark mark against the agency – even though there is nothing we could have done to stop it because we did not know it was happening.

Randy is not asking anyone else to make the same commitment he has made, but he says it was important for him to do so. His role as President & CEO carries great responsibility and he says he wants to show that he takes it very seriously and will lead by example.

I rather think Spiderman would approve.

Kevin McCormack

July ICOC Board Meeting Now Beginning

The July ICOC Boarding Meeting is now beginning in San Francisco.

The complete agenda can be found here.

For those not able to attend, feel free to dial in:

Dial In (800) 230-1085
Confirmation Number: 331407

Audio Cast:
Web Meeting Address: https://www.webmeeting.att.com
* Meeting Number(s): (511)468-6455
* HOST CODE: 697745
* PARTICIPANT CODE: 249234

WebEx Link:
Go to https://cirm.webex.com/cirm/onstage/g.php?MTID=eb948a1127913f44c7cdffcedc0fa510a
Click “Join Now”.

We will be providing a summary of the meeting’s highlights after the meeting—so stay tuned!

Making stem cells feel like they are growing in the right neighborhood may be key to success

An adage in real estate says that the most important thing is neighborhood, neighborhood, neighborhood. Researchers are learning that the same may be true for stem cell therapies. If you want to mature stem cells into the right adult tissue and get them to behave the way you want, you better pay attention to the environment where they are grown in the lab—before they are transplanted into people.

Two journal articles posted online this month provide good reasons to head the realtors’ advice. CIRM-grantee Shyni Varghese at the University of California, San Diego, provides an elegantly simple example. When trying to turn embryonic stem cells into bone researchers often embed them inside a hydrogel scaffold. This helps them to stay put when transplanted. But researcjers generally rely on chemical or genetic signals to get the stem cells to mature into bone. This results in a mixed population of bone cells and fat cells because both those cell types branch from the same maturation pathway.

Varghese’s team altered the scaffold to make it seem more like the neighboring bone cells the maturing stem cells would encounter in normal bone. They mineralized it with calcium and phosphate. And when they did, they got pure bone cells in the lab dish. What’s more, when they implanted those “tissues” into animals, they formed densely calcified bone—the hard kind we want. The team published the work in the Journal of Materials Chemistry online July 4.

A review article in the journal BioResearch provided a good overview of ways various groups have tried to precondition stem cells in the lab so that they will survive after transplant. One of the biggest stumbling blocks in the field remains the difficulty of getting stem cells to survive in the patient, whether those are humans or little mouse patients. It turns out from the research cited in this review that turning the lab growth environment into something more closely resembling the environment in the patient improves survival.

Stem cell researchers need their version of the Google mapping bike to reveal the natural neighborhoods where the cells would grow.

Stem cell researchers need their version of the Google mapping bike to reveal the natural neighborhoods where the cells would grow.

They looked at several aspects of typical lab cell cultures that don’t mimic real tissue. Sites of injury where stem cells are needed often are also sites of lowered oxygen levels, inflammation and a disruption of the normal cell-to-cell contact that helps guides cell behavior. They found that adjusting each of those in the lab resulted in cells that were more likely to survive after transplant.

Most notably, when they grew cells in aggregates that restored cell-to-cell contact—restored the sense of neighborhood—cell survival improved significantly. Genetic Engineering & Biotechnology News wrote a brief summary of the work.

Don Gibbons

The Fatal Flip: How Nerve Cells go from Healthy to Cancerous

Every gene in the human genome has a job to do. One such gene, called Merlin, prevents cells from dividing out of control and forming into tumors. A so-called ‘tumor suppressor,’ Merlin has proven to be essential to maintaining healthy cell division. Scientists knew that without Merlin, nerve cells grew uncontrollably, often leading to tumors and a type of inherited cancer called neurofibromatosis type 2 (NF2).

Scientists have uncovered the mechanism whereby an absence of the gene called Merlin causes normal nerve cells to turn rogue.

Scientists have uncovered the mechanism whereby an absence of the gene called Merlin causes normal nerve cells to turn rogue.

Now, scientists have uncovered the mechanism that causes an absence of Merlin to transform nerve cells into rogue, tumor-producing cells—helping shed new light on how the smallest genetic shifts—even in just one gene—can have an impact on the normal pattern of growth and development of cells.

Reporting in the latest issue of Cancer Cell, a joint team from the Sloan-Kettering Institute for Cancer Research and Plymouth University Peninsula Schools of Medicine and Dentistry have found that without Merlin a chemical pathway, called the Hippo pathway, switches on. This, in turn, spurs tumor cell growth in nerve cells.

Professor Dr. Oliver Hanemann of Plymouth University and one of the study’s senior authors, explained in a July 22 news release:

“We have known for some time that the loss of the tumor suppressor Merlin resulted in the development of nervous system tumors, and we have come tantalizingly close to understanding how this occurs.”

This research advance is especially important in the case of NF2, a condition for which there are limited treatment options. Current treatments usually involve a combination of surgery and radiation, but rarely is the cancer fully eradicated.

“By understanding the mechanism [of Merlin], we can use this knowledge to develop effective drug therapies—in some cases adapting existing drugs—to treat patients for whom current therapies are limited and potentially devastating.”

Stem cell biology has also proven essential when shining a light on or explaining the complexities surrounding cancer’s underlying mechanisms, including the notion of cancer stem cells—a concept that has gained increasing support in recent years. To learn more about how CIRM-funded scientists are harnessing stem cells to understand—and develop treatments for—cancer, check out our 2009 Spotlight on Cancer Stem Cells as well as our Brain Tumor fact sheet.