Dr. Deborah Deas joins CIRM Board

Deborah Deas has been appointed dean of the UCR School of Medicine

Deborah Deas, MD, MPH, UCR School of Medicine

Dr. Deborah Deas is clearly not someone who opts for the quiet life. If she were, she would have stayed home in Adams Run, the tiny town in rural South Carolina where she was born.

The website, NeighborhoodScout.com describes Adams Run (current population 1,492) as:

“One of the quietest neighborhoods in America. When you are here, you will find it to be very quiet. If quiet and peaceful are your cup of tea, you may have found a great place for you.”

Dr. Deas obviously wasn’t a tea drinker because she packed her bags and went off to college in Charleston. That was the first step on a journey that led the self-described “farmer’s daughter” to become an MD, then an MPH (Masters in Public Health), before assuming a leadership role at the Medical University of South Carolina (MUSC). More recently she headed to California’s Inland Empire where she was named the Dean and CEO for Clinical Affairs of the UC Riverside School of Medicine.

And now we are delighted to add to that list of achievements by announcing she is the newest member of the CIRM Board.

She was appointed to the Board by state Treasurer John Chiang who praised her for her:

“Passion to improve  health for underserved populations and to diversify the health care work force. She is committed to making the benefits of advanced medicine available to all Californians.”

 

In a news release our CIRM Board Chair, Jonathan Thomas, was equally fulsome in his praise and welcome to Dr. Deas.

 “We are delighted to have someone with Dr. Deas’ broad experience and expertise join us at CIRM. Her medical background and her commitment to diversity and inclusion are important qualities to bring to a Board that is striving to deliver stem cell treatments to patients, and to reflect the diversity of California.”

To say that she brings a broad array of skills and experience to the Board is something of an understatement. She is board certified in adult psychiatry, child and adolescent psychiatry and addiction psychiatry, and is widely regarded as a national leader in research into youth binge drinking, adolescent nicotine dependence, marijuana use and panic disorder, and pharmaceutical treatment of pediatric depressive disorder.

As if that wasn’t enough, she has also been named as one of the best doctors in the U.S. by U.S. News & World Report for the last eight years.

But the road to UC Riverside and CIRM hasn’t always been easy. In a first person perspective in Psychiatric News.

she said that at MUSC she was just one of two African Americans among the 500 residents in training:

“It was not uncommon for me to be mistaken by many for a social worker, a secretary, or a ward clerk despite wearing my white coat with Deborah Deas, M.D., written on it. This mistake was even made by some of my M.D. peers. I found that the best response was to ask, “And just why do you think I am a social worker?”

She says the lessons she learned from her parents and grandparents helped sustain her:

“They emphasized the importance of setting goals and keeping your eyes on the prize. Service was important, and the ways that one could serve were numerous. The notion that one should learn from others, as well as teach others, was as common as baked bread. My parents instilled in me that education is the key to a fruitful future and that it is something no one can take away from you.”

Her boss at UC Riverside, the Provost and Executive Vice Chancellor, Paul D’Anieri said Dr. Deas is a great addition to the CIRM Board:

“Deborah is a public servant at heart. Her own values and goals to help underserved patient populations align with the goals of CIRM to revolutionize medicine and bring new, innovative treatments to all patients who can benefit. I am confident that Dr. Deas’ service will have a lasting positive impact for CIRM and for the people of California.”

Dr. Deas ends her article in Psychiatric News saying:

“The farmer’s daughter has come a long way. I have stood on the shoulders of many, pushing forward with an abiding faith that there was nothing that I could not accomplish.”

She has indeed come a long way. We look forward to being a part of the next stage of her journey, and to her joining CIRM and bringing that “abiding faith” to our work.

 

 

Young Minds Shine Bright at the CIRM SPARK Conference

SPARK students take a group photo with CIRM SPARK director Karen Ring.

SPARK students take a group photo with CIRM SPARK director Karen Ring.

Yesterday was one of the most exciting and inspiring days I’ve had at CIRM since I joined the agency one year ago. We hosted the CIRM SPARK conference which brought together fifty-five high school students from across California to present their stem cell research from their summer internships.

The day was a celebration of their accomplishments. But it was also a chance for the students to hear from scientists, patient advocates, and clinicians about the big picture of stem cell research: to develop stem cell treatments and cures for patients with unmet medical needs.

Since taking on the role of the CIRM SPARK director, I’ve been blown away by the passion, dedication, and intelligence that our SPARK interns have shown during their short time in the lab. They’ve mastered techniques and concepts that I only became familiar with during my PhD and postdoctoral research. And even more impressive, they eloquently communicated their research through poster presentations and talks at the level of professional scientists.

During their internships, SPARK students were tasked with documenting their research experiences through blogs and social media. They embraced this challenge with gusto, and we held an awards ceremony to recognize the students who went above and beyond with these challenges.

I’d like to share the winning blogs with our readers. I hope you find them as inspiring and motivating as I do. These students are our future, and I look forward to the day when one of them develops a stem cell treatment that changes the lives of patients. 

Andrew Choi

Andrew Choi

Andrew Choi, Cedars-Sinai SPARK student

Am I crying or is my face uncontrollably sweating right now? I think I am doing both as I write about my unforgettable experiences over the course of the past 6 weeks and finalize my poster.

As I think back, I am very grateful for the takeaways of the research field, acquiring them through scientific journals, lab experiments with my mentor, and both formal and informal discourses. It seems impossible to describe all the episodes and occurrences during the program in this one blog post, but all I can say is that they were all unique and phenomenal in their own respective ways.

Gaining new perspectives and insights and being acquainted with many of the techniques, such as stereology, immunocytochemistry and immunohistochemistry my peers have utilized throughout their careers, proved to me the great impact this program can make on many individuals of the younger generation.

CIRM SPARK not only taught me the goings on behind the bench-to-bedside translational research process, but also morals, work ethics, and effective collaboration with my peers and mentors. My mentor, Gen, reiterated the importance of general ethics. In the process of making my own poster for the program, her words resonate even greater in me. Research, education, and other career paths are driven by proper ethics and will never continue to progress if not made the basic standard.

I am thankful for such amazing institutions: California Institute of Regenerative Medicine (CIRM) and Cedars-Sinai Medical Center for enabling me to venture out into the research career field and network. Working alongside with my fellow seven very brilliant friends, motivated me and made this journey very enjoyable. I am especially thankful my mentor, Gen, for taking the time to provide me with the best possible resources, even with her busy ongoing projects. She encouraged me to be the best that I am.

I believe, actually, I should say, I KNOW Cedars-Sinai’s CIRM SPARK program does a SUPERB and astounding job of cultivating life-long learners and setting exceptional models for the younger generation. I am hoping that many others will partake in this remarkable educational program.

I am overall very blessed to be part of a successful summer program. The end of this program does not mark the end of my passions, but sparks them to even greater heights.

Jamey Guzman

Jamey Guzman

Jamey Guzman, UC Davis SPARK student

When I found out about this opportunity, all I knew was that I had a fiery passion for learning, for that simple rush that comes when the lightbulb sputters on after an unending moment of confusion. I did not know if this passion would translate into the work setting; I sometimes wondered if passion alone would be enough to allow me to understand the advanced concepts at play here. I started at the lab nervous, tentative – was this the place for someone so unsure exactly what she wanted to be ‘when she grew up,’ a date now all too close on the horizon? Was I going to fit in at this lab, with these people who were so smart, so busy, people fighting for their careers and who had no reason to let a 16-year-old anywhere near experiments worth thousands of dollars in cost and time spent?

I could talk for hours about the experiments that I worked to master; about the rush of success upon realizing that the tasks now completed with confidence were ones that I had once thought only to belong to the lofty position of Scientist. I could fill pages and pages with the knowledge I gained, a deep and personal connection to stem cells and cell biology that I will always remember, even if the roads of Fate pull me elsewhere on my journey to a career.

The interns called the experience #CIRMSparkLab in our social media posts, and I find this hashtag so fitting to describe these last few months. While there was, of course, the lab, where we donned our coats and sleeves and gloves and went to work with pipets and flasks…There was also the Lab. #CIRMSparkLab is so much more than an internship; #CIRMSparkLab is an invitation into the worldwide community of learned people, a community that I found to be caring and vibrant, creative and funny – one which for the first time I can fully imagine myself joining “when I grow up.”

#CIRMSparkLab is having mentors who taught me cell culture with unerring patience and kindness. It is our team’s lighthearted banter across the biosafety cabinet; it is the stories shared of career paths, of goals for the present and the future. It is having mentors in the best sense of the word, trusting me, striving to teach and not just explain, giving up hours and hours of time to draw up diagrams that ensured that the concepts made so much sense to me.

#CIRMSparkLab is the sweetest ‘good-morning’ from scientists not even on your team, but who care enough about you to say hi, to ask about your projects, to share a smile. It is the spontaneity and freedom with which knowledge is dispensed: learning random tidbits about the living patterns of beta fish from our lab manager, getting an impromptu lecture about Time and the Planck Constant from our beloved professor as he passes us at lunch. It is getting into a passionate, fully evidence-backed argument about the merits of pouring milk before cereal that pitted our Stem Cell team against our Exosome team: #CIRMSparkLab is finding a community of people with whom my “nerdy” passion for learning does not leave me an oddball, but instead causes me to connect instantly and deeply with people at all ages and walks of life. And it is a community that, following the lead of our magnificent lab director, welcomed ten interns into their lab with open arms at the beginning of this summer, fully cognizant of the fact that we will break beakers, overfill pipet guns, drop gels, bubble up protein concentration assays, and all the while never stop asking, “Why? Why? Why? Is this right? Like this? WHY?”

I cannot make some sweeping statement that I now know at age 16 exactly what I want to do when I grow up. Conversely, to say I learned so much – or I am so grateful – or you have changed my life is simply not enough; words cannot do justice to those sentiments which I hope that all of you know already. But I can say this: I will never forget how I felt when I was at the lab, in the community of scientists. I will take everything I learned here with me as I explore the world of knowledge yet to be obtained, and I will hold in my heart everyone who has helped me this summer. I am truly a better person for having known all of you.

Thank you, #CIRMSparkLab. 

Adriana Millan

Adriana Millan

Adriana Millan, CalTech SPARK student

As children, we all grew up with the companionship of our favorite television shows. We enjoyed sitcoms and other animations throughout our childhood and even as adults, there’s no shame. The goofy and spontaneous skits we enjoyed a laugh over, yet we did not pay much attention to the lessons they attempted to teach us. As a child, these shows play crucial roles in our educational endeavors. We are immediately hooked and tune in for every episode. They spark curiosity, as they allow our imaginations to run wild. For me, that is exactly where my curiosity stemmed and grew for science over the years. A delusional young girl, who had no idea what the reality of science was like.

You expect to enter a lab and run a full day of experimentations. Accidentally mix the wrong chemicals and discover the cure for cancer. Okay, maybe not mix the incorrect chemicals together, I learned that in my safety training class. The reality is that working in a lab was far from what I expected — eye opening. Working alongside my mentor Sarah Frail was one of the best ways I have spent a summer. It was not my ideal summer of sleeping in until noon, but it was worthwhile.

My experience is something that is a part of me now. I talk about it every chance I get, “Mom, can you believe I passaged cells today!” It changed the way I viewed the principles of science. Science is one of the most valuable concepts on this planet, it’s responsible for everything and that’s what I have taken and construed from my mentor. She shared her passion for science with me and that completed my experience. Before when I looked at cells, I did not know exactly what I was supposed to observe. What am I looking at? What is that pink stuff you are adding to the plate?

However, now I feel accomplished. It was a bit of a roller coaster ride, with complications along the way, but I can say that I’m leaving this experience with a new passion. I am not just saying this to please the audience, but to express my gratitude. I would have never even looked into Huntington’s Disease. When I first arrived I was discombobulated. Huntington’s Disease? Now I can proudly say I have a grasp on the complexity of the disease and not embarrass my mentor my calling human cells bacteria – quite embarrassing in fact.  I’m a professional pipette handler, I work well in the hood, I can operate a microscope – not so impressive, I have made possibly hundreds of gels, I have run PCRs, and my cells love me, what else can I ask for.

If you are questioning what career path you are to take and even if it is the slightest chance it may be a course in science, I suggest volunteering in a lab. You will leave with your questioned answered. Is science for me? This is what I am leaving my experience with. Science is for me.

Other SPARK 2016 Awards

Student Speakers: Jingyi (Shelly) Deng (CHORI), Thomas Thach (Stanford)

Poster Presentations: Jerusalem Nerayo (Stanford), Jared Pollard (City of Hope), Alina Shahin (City of Hope), Shuling Zhang (UCSF)

Instagram Photos: Roxanne Ohayon (Stanford), Anna Victoria Serbin (CHORI), Diana Ly (UC Davis)

If you want to see more photos from the CIRM SPARK conference, check out our Instagram page @CIRM_Stemcells or follow the hashtag #CIRMSPARKLab on Instagram and Twitter.

Advancing Stem Cell Research at the CIRM Bridges Conference

Where will stem cell research be in 10 years?

What would you say to patients who wanted stem cell therapies now?

What are the most promising applications for stem cell research?

Why is it important for the government to fund regenerative medicine?

These challenging and thought-provoking questions were posed to a vibrant group of undergraduate and masters-level students at this year’s CIRM Bridges to Stem Cell Research and Therapy conference.

Educating the next generation of stem cell scientists

The Bridges program is one of CIRM’s educational programs that offers students the opportunity to take coursework at California state schools and community colleges and conduct stem cell research at top universities and industry labs. Its goal is to train the next generation of stem cell scientists by giving them access to the training and skills necessary to succeed in this career path.

The Bridges conference is the highlight of the program and the culmination of the students’ achievements. It’s a chance for students to showcase the research projects they’ve been working on for the past year, and also for them to network with other students and scientists.

Bridges students participated in a networking pitch event about stem cell research.

Bridges students participated in a networking pitch event about stem cell research.

CIRM kicked off the conference with a quick and dirty “Stem Cell Pitch” networking event. Students were divided into groups, given one of the four questions above and tasked with developing a thirty second pitch that answered their question. They were only given ten minutes to introduce themselves, discuss the question, and pick a spokesperson, yet when each team’s speaker took the stage, it seemed like they were practiced veterans. Every team had a unique, thoughtful answer that was inspiring to both the students and to the other scientists in the crowd.

Getting to the clinic and into patients

The bulk of the Bridges conference featured student poster presentations and scientific talks by leading academic and industry scientists. The theme of the talks was getting stem cell research into the clinic and into patients with unmet medical needs.

Here are a few highlights and photos from the talks:

On the clinical track for Huntington’s disease

Leslie Thompson, Professor at UC Irvine, spoke about her latest research in Huntington’s disease (HD). She described her work as a “race against time.” HD is a progressive neurodegenerative disorder that’s associated with multiple social and physical problems and currently has no cure. Leslie described how her lab is heading towards the clinic with human embryonic stem cell-derived neural (brain) stem cells that they are transplanting into mouse models of HD. So far, they’ve observed positive effects in HD mice that received human neural stem cell transplants including an improvement in the behavioral and motor defects and a reduction in the accumulation of toxic mutant Huntington protein in their nerve cells.

Leslie Thompson

Leslie Thompson

Leslie noted that because the transplanted stem cells are GMP-grade (meaning their quality is suitable for use in humans), they have a clear path forward to testing their potential disease modifying activity in human clinical trials. But before her team gets to humans, they must take the proper regulatory steps with the US Food and Drug Administration and conduct further experiments to test the safety and proper dosage of their stem cells in other mouse models as well as test other potential GMP-grade stem cell lines.

Gene therapy for SCID babies

Morton Cowan, a pediatric immunologist from UC San Francisco, followed Leslie with a talk about his efforts to get gene therapy for SCID (severe combined immunodeficiency disease) off the bench into the clinic. SCID is also known as bubble-baby disease and put simply, is caused by a lack of a functioning immune system. SCID babies don’t have normal T and B immune cell function and as a result, they generally die of infection or other conditions within their first year of life.

Morton Cowan

Morton Cowan, UCSF

Morton described how the gold standard treatment for SCID, which is hematopoietic or blood stem cell transplantation, is only safe and effective when the patient has an HLA matched sibling donor. Unfortunately, many patients don’t have this option and face life-threatening challenges of transplant rejection (graft-versus host disease). To combat this issue, Morton and his team are using gene therapy to genetically correct the blood stem cells of SCID patients and transplant those cells back into these patients so that they can generate healthy immune cells.

They are currently developing a gene therapy for a particularly hard-to-treat form of SCID that involves deficiency in a protein called Artemis, which is essential for the development of the immune system and for repairing DNA damage in cells. Currently his group is conducting the necessary preclinical work to start a gene therapy clinical trial for children with Artemis-SCID.

Treating spinal cord injury in the clinic

Casey Case, Asterias Biotherapeutics

Casey Case, Asterias Biotherapeutics

Casey Case, Senior VP of Research and Nonclinical Development at Asterias Biotherapeutics, gave an update on the CIRM-funded clinical trial for cervical (neck) spinal cord injury (SCI). They are currently testing the safety of transplanting different doses of their oligodendrocyte progenitor cells (AST-OPC1) in a group of SCI patients. The endpoint for this trial is an improvement in movement greater than two motor levels, which would offer a significant improvement in a patient’s ability to do some things on their own and reduce the cost of their healthcare. You can read more about these results and the ongoing study in our recent blogs (here, here).

Opinion: Scientists should be patient advocates

David Higgins gave the most moving speech of the day. He is a Parkinson’s patient and the Patient Advocate on the CIRM board and he spoke about what patient advocates are and how to become one. David explained how, these days, drug development and patient advocacy is more patient oriented and patients are involved at the center of every decision whether it be questions related to how a drug is developed, what side effects should be tolerated, or what risks are worth taking. He also encouraged the Bridges students to become patient advocates and understand what their needs are by asking them.

David Higgins, Parkinson's advocate and CIRM Board member

David Higgins

“As a scientist or clinician, you need to be an ambassador. You have a job of translating science, which is a foreign language to most people, and you can all effectively communicate to a lay audience without being condescending. It’s important to understand what patients’ needs are, and you’ll only know that if you ask them. Patients have amazing insights into what needs to be done to develop new treatments.”

Bridging the gap between research and patients

The Bridges conference is still ongoing with more poster presentations, a career panel, and scientific talks on discovery and translational stem cell research and commercializing stem cell therapies to all patients in need. It truly is a once in a lifetime opportunity for the Bridges students, many of whom are considering careers in science and regenerative medicine and are taking advantage of the opportunity to talk and network with prominent scientists.

If you’re interested in hearing more about the Bridges conference, follow us on twitter (@CIRMnews, @DrKarenRing, #CIRMBridges2016) and on Instagram (@CIRM_Stemcells).

California high schoolers SPARK interest in stem cell research through social media

I have a job for you today and it’s a fun one. Open your Instagram app on your phone. If you’re not an Instagrammer, don’t worry, you can access the website on your computer.

Do you have it open? OK now type in the hashtag #CIRMSparkLab and click on it.

What you’ll find is around 200 posts of the most inspiring and motivating pictures of stem cell research that I’ve seen. These pictures are from high school students currently participating in the CIRM summer SPARK program, one of our educational programs, which has the goal to train the next generation of stem cell scientists.

The SPARK program offers California high school students an invaluable opportunity to gain hands-on training in regenerative medicine at some of the finest stem cell research institutes in the state. And while they gain valuable research skills, we are challenging them to share their experiences with the general public through blogging and social media.

Communicating science to the public is an important mission of CIRM, and the SPARK students are excelling at this task by posting descriptive photos on Instagram that document their internships. Some of them are fun lab photos, while others are impressive images of data with detailed explanations about their research projects.

Below are a few of my favorite posts so far this summer. I’ve been so inspired by the creativity of these posts that we are now featuring some of them on the @CIRM_Stemcells account. (Yes this is a shameless plug for you to follow us on Instagram!).

City of Hope SPARK program.

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I encourage you all to follow our talented SPARK students this summer as they continue to document their exciting journeys on Instagram. These students are our future and supporting their training and education in stem cell research is an honor for CIRM and a vital step towards achieving our mission of accelerating stem cell treatments to patients with unmet medical needs.

Stay tuned for more blog coverage about SPARK and our other educational program, the Bridges to Stem Cell Research program for undergraduate and master-level students. The annual Bridges conference that brings all the students together to present their research will be held next week, and the SPARK conference is on August 8th both in Berkeley.

Another way to dial back stem cell hype (but not hope): Put a dollar figure on it

In an effort to reign in the hype surrounding stem cell research that has led to a proliferation of unapproved and potentially dangerous stem cell therapies, the International Society for Stem Cell Research (ISSCR) recently released updated guidelines outlining conduct for stem cell researchers that,  for the first time, included communications activities.  At only 1.5 pages in the 37-page document, the statements around communications asked researchers, communications professionals, institutions and the media to be more proactive in combatting stem cell hype by ensuring accuracy and balance in communications activities.

Stock Image

Stock Image

It’s too early to know what the full impact of the guidelines will be, however, the communications recommendations did generate a good deal of interest and some media, at least, have taken steps to address the issue.

Whether directly influenced by the guidelines or not, in the final plenary session of the ISSCR annual meeting last week, Professor Roger Barker, a research-clinician at the University of Cambridge, provided a candid portrayal of some of the challenges of preclinical and early clinical research.

Though he may have poked a small hole in some of the optimism that characterized the four-day conference, in providing a rare glimpse of the real costs of research, Dr. Barker might also have given us a new way to frame research to downplay hype.

Dr. Roger Barker

Dr. Roger Barker

Dr. Barker is one of many researchers across the globe working on a potential cell-based treatment for Parkinson’s Disease. Parkinson’s is a rather straightforward disease to tackle in this way, because its cause is known: the death of cells that produce the chemical dopamine. Even so, the challenges in developing a treatment are many. Apart from the design of a clinical study (which includes, for example, careful selection of the Parkinson’s patients to include; as Barker pointed out, there are two main types of Parkinson progression and one type may respond to a treatment while the other may not. This is a real concern for Barker, who commented that “a lack of rigour in selecting patients has dogged the field for the past 25 years.”), there are several other factors that need to be addressed in the pre-clinical work, such as identifying the best type of cells to use, how to scale them up and make them both GMP-compliant and standardized for reproducibility.

Such work, Barker estimated, costs between £2 and £3 million (or roughly $3-5 million, valued at pre-Brexit currency rates, one would assume). And, having invested so much to this point, you don’t even have something that can be published yet.

Running the actual clinical phase 1 study, with roughly 20 patients, will cost millions more. If it doesn’t work, you’re back to lab and in search of more pre-clinical funding.

But, assuming the study nets the desired results, it’s still only looking at safety, not efficacy. Getting it to phases 2 and 3 costs several orders of magnitude more. Put in this light, the $3 billion USD given to the California Institute for Regenerative Medicine seems like not nearly enough. The Ontario Institute for Regenerative Medicine’s $25 million CAD is nothing at all. Not that we aren’t grateful — we do what we can to maximize impact and make even a small investment worthwhile. Every step counts.

Another point to consider is whether the final therapy will be more cost-effective than existing, approved medical interventions. If it’s not, there is little incentive in pursuing it. This is the notion of headroom that I’ve heard discussed more directly at commercialization-based conferences (and is very well explained here) but is one that will become increasingly relevant to research as more basic and translational work finds its way into the clinic.

Talking about money with regard to health can be seen as tedious and even crass. The three short talks given by patient advocates at the ISSCR meeting served to emphasize this – each outlined personal tragedy connected to illness or disease: congestive heart failure at 11 years of age, four generations of a family with sickle cell disease, retinitis pigmentosa that derailed a young woman’s budding career. You simply can’t put a price on a person’s life, happiness and well-being. Each of these patients, and millions more, have hope that research will find an answer. It’s a lofty goal, one that is sometimes hard to remember in the lab trenches when a grant doesn’t materialize or a negative result sends the work back to ground zero.

And therein lies some of the tension that can easily lead to hype. We do want to fly high. We do want to deliver cures and therapies. We need to be reminded, by interactions with the patient community, of what’s at stake and what we can gain for humanity. The field should and will continue to strive to achieve these goals.

But not without responsibility. And a dose of realism.


This post appears simultaneously on OIRM Expression and appears here with permission by the author Lisa Willemse.

Presentations at ISSCR that caught our eye: Stem cell clinical trials expand as work to improve our understanding of just how they work goes on in parallel

In a special edition of our weekly roundup, here are some highlights from just the first two days of the four-day annual meeting of the International Society for Stem Cell Research

 Seeing stem cells from both sides now. As the biggest gathering of stem cell researchers each year, the annual meeting of the International Society for Stem Cell Research offers a chance to catch up on progress across the complete spectrum of research, from fundamental exploration in the lab to clinical trials. This year’s meeting in San Francisco offers more advances toward the clinic than ever before, but it also shows a cadre of basic researchers struggling to understand what is really going on at the genetic and molecular level with some of the biggest breakthroughs of the past few years. It is a bit like the opening verse of Joni Mitchell’s song “Both Sides Now” in which she laments that even after seeing clouds as beautiful patterns and as blocks to the sun she does not really know clouds at all.

Yamanaka at ISSCR 2016

Nobelist Shinya Yamanaka at the annual ISSCR meeting

Nothing captured that spirit better than the opening talk on the second day by Nobel Prize winner Shinya Yamanaka who maintains labs at Kyoto University in Japan and at the Gladstone institutes here in San Francisco, about a mile from the site of the meeting. This year marks the 10th anniversary of his Nobel-winning discovery that you can use genetic factors to reprogram adult cells into embryonic-like stem cells called iPS cells. Even as his institute is supplying the cells for the first ever clinical trial using iPS, in this case in the blinding disease called macular degeneration, he spent much of his talk discussing his ongoing basic research trying to understand what really goes on in that reprogramming process, and why so many cells are refractory to reprogramming with only a few percent in most experiments becoming stem cells.

Before launching into his ongoing basic research—some of it from a research thread he began to unravel as a postdoc at the Gladstone—he told an enlightening tale of how he had been reprogrammed as a scientist.  He said that he went from a a basic researcher just working in his lab to someone who spent much of their time talking to government officials, bankers and donors. But he noted that like our cells, part of him was refractory to reprogramming and he still liked getting into the lab to do the basic research needed to understand the creation of iPS cells and make it it faster and more efficient, which is critical to any future role for the cells at the other end of the research pipeline—treating patients in need.

 

It takes a neighborhood. As usual much of the basic science revolved around the lab recipes needed to keep stem cells in the stem cell state in the lab, or how to efficiently direct them to become a specific type of adult tissue. On the latter there was also considerable work presented on how to get around the fact that too often the adult cells created from stem cells are not fully mature and function more like those tissues would in the fetus than they should in an adult patient.

Fiona Watt of Kings College London presented her work on studying the one “organ” that is easier to study in humans than mice: the skin hair follicle. In the furry critters the hair follicles are too close together to easily isolate individual ones. With our sparser covering it is easy to study single hair follicles, which serve as the niche that houses skin stem cells until they are needed to replenish or repair our outer barrier. In recent years, when trying to understand how stem cells stay stem cells or decide to mature into specific tissue, researchers have increasingly turned their attention to the niches all over the body that stem cells call home. They are finding that there are many facets to these homes—physical, chemical and genetic—that like any neighborhood, impact how a stem cell grows up.

Watt opened by paying tribute to a pioneer in the field who died this past year, Harvard Med School’s Howard Green, who was always a treat to interview when I was there, and who pioneered single cell analysis in skin four decades ago. Watt’s work tries to break down the various components of the skin stem cell niche in the lab to see how each contributes to cell fate. She looked at the extracellular matrix, the scaffold that holds cells in place, and found a link between the size of the hole in the scaffold and cells remaining stem cells. She also found difference between soft and hard scaffolds. She noted other factors such as the type of cell that lives next door and the oxygen level all impact the cell decisions.

She suggested that these determinants of cell fate are likely consistent across stem cell niches throughout the body and will be critical to more efficiently producing replacement tissues to help patients.

 

Jumping from A to C, skipping B.  Two researchers followed Watt who are trying to develop ways to skip the step of turning adult cells in to iPS-type stem cells and instead convert them directly into the desired tissue needed for repair. Stanford’s Marius Wernig, who cited funding from CIRM and the New York Stem Cell Foundation, reported on his work trying to improve his breakthrough from a few years ago in which he converted skin into nerve with just one genetic factor. He is investigating the underlying structures of our DNA to try to understand why only 20 percent of cells make the desired conversion. He is finding some answers but has more to ferret out.

 

parmar

Malin Parmar

Then Malin Parmar of Sweden’s Lund University went into more detail on the fetal cell and stem cell transplant trials she is working with in Parkinson’s disease that she described at our public symposium earlier in the week. But she closed with work that she thinks could be the ultimate best solution to the disease.  Finding genetic factors that can convert other nerve cells directly into the dopamine-producing nerve cells lost in patients with the disease. She started with Wernig’s recipe and added a genetic factor known to drive cells to become dopamine nerves. She succeeded in turning brain cells called glial cells into dopamine nerves inside the brains of mice and showed they made the needed connections to other brain cells. But the work is still some years from getting to patients.

 

The complexities of the heart.  Yesterday afternoon five researchers presented different ways to figure out how to use stem cells to repair or replace a very complex organ, the heart. Shen Ding from Gladstone, who has pioneered the concept of using chemical instead of genetic factors to reprogram cells, presented his latest work in which he used that technique to grow partially mature heart cells in the lab, transplanted them into mice and saw them mature into tissue that improved heart function in a model of heart attack. He said his next experiments will involve finding a way to deliver the chemicals directly into the damaged heart to try to get the reprogramming done in the living animal.

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Stephanie Protze, of the McEwen Centre for Regenerative Medicine in Toronto, presented work on another component of the heart, the pace maker cells that ensure any new muscle cell beats at the right speed.  She described a recipe to drive stem cells to become pace maker cells, but there was a glitch. They beat at 150 beats per minute, which is the fetal rate not the adult rate. So, once again the field ran into the block of creating only partially mature tissue.

Tamer Mohamed, also of the Gladstone, presented work using chemicals to convert heart scar tissue to functional heart muscle. His work tweaked an earlier recipe that resulted in fewer than one percent of cells converting to a procedure that resulted in 30 percent. In the mouse model he saw improved heart function and reduced scarring.

University of Pittsburgh’s Lei Yang presented work on a very big, long-term goal for the field: producing a complete replacement heart. Like several other teams, his group started with a mouse donor heart and used detergents to wash away the cells so that all that was left was the scaffold of that extracellular matrix mentioned above.  He then seeded the scaffold with heart cells derived from iPS cells and let them mature.  The work resulted in what he called “beating heart constructs.”  Some of the cells beat with needed synchronicity and some did not.

All in all, the meeting exudes measured confidence. The field is clearly making rapid strides toward understanding stem cells well enough to create meaningful therapies.  However, it is ripe for what is called “reverse translation,” which is taking the findings of early clinical trials  that don’t perform quite as well as desired, and going back to  the lab to figure out how to make them better.

Circular RNAs: the Mind-Boggling Dark Matter of the Human Genome

We were just a few hours into the 2016 annual meeting of the International Society for Stem Cell Research (ISSCR) yesterday afternoon and my mind was already blown away. Pier Paolo Pandolfi of the Beth Israel Deaconess Medical Center at Harvard, spoke during the first plenary session about circular RNAs, which he dubbed, “the mind-boggling dark matter of the human genome” because their existence wasn’t confirmed until just four years ago.

To introduce the topic, Pandolfi compared human DNA to that of bacteria. Both species contain stretches of DNA sequence called genes that contain the instructions for making proteins which collectively form our bodies. Each gene is first transcribed into messenger RNA (mRNA) which in turn is translated into a protein.

Iceberg

Our DNA contains 20,000 genes. But that genetic material is just the tip of the iceberg.

But with the ability to sequence all the mRNA transcripts of an organism, or its transcriptome, came a startling fact about how differently our genetic structure is organized compared to bacteria. It turns out that 88% of DNA sequence in bacteria make up genes that code for proteins but only 2% of human DNA sequence directly codes for proteins. So what’s going with the other 98%? Scientist typically call this 98% chunk of the genome “regulatory DNA” because it contains sequences that act as control switches for turning genes on or off. But Pandolfi explained that more recent studies suggest that a whopping 70% of our genome (maybe even 95%) is transcribed into RNA but those RNA molecules just don’t get translated into protein.

 

One type of this “non-coding” RNA which we’ve blogged about plenty of times is called microRNA (miRNA). So far, about 5,000 human miRNAs have been identified compared to the 20,000 messenger RNAs that code for proteins. But by far the most abundant non-coding RNA in our transcriptome is the mysterious circular RNA (circRNA) with at least 100,000 different transcripts. circRNA was first observed as cellular structures in the 1980’s via electronic microscope images. Then in the 1990’s a scientist published DNA sequencing data suggesting the existence of circRNA. But the science community at that time panned the results, discrediting it as merely background noise of the experiments.

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Pier Paolo Pandolfi
Image: Beth Israel Deaconess Medical Center

But four years ago, the circRNAs were directly sequenced and their existence confirmed. The circRNAs are formed when messenger RNA goes through a well-described trimming process of its sequence. Some of the excised pieces of RNA form into the circular RNAs. It would seem that these circRNAs are just throw away debris but Pandolfi’s lab has found evidence that they directly play a role in cellular functions and even cancer.

His team studies a gene called Pokemon which, when genetically “knocked out” or removed from a mouse’s genome, leads to cancer. Now, it turns out this knockout not only removes the Pokemon protein but also a Pokemon circRNA (circPok). When the lab added back just the Pokemon gene, as you might expect, it acted to suppress cancer in the mice. But when just the circPok was added back, stunningly, it increased the formation of cancer in the mice. Given that genetic knockouts are one of the most pervasive techniques in biomedical science, a closer look at circRNAs that may have been overlooked in all of those results is clearly warranted.

Though this finding is somewhat scary in the fact that it’s a whole aspect of our genome that we’ve been unaware of, one fortunate aspect of circRNA is that they all carry a particular sequence which could be used as a target for a new class of drugs.

This data may extend to stem cells as well. We know that microRNAs have critical roles in regulating the maturation of stem cells into specialized cell types. Since circRNAs are thought to act by competing microRNA, it may not be long before we learn about circRNA’s role in stem cell function.

The other speakers at the first plenary session of the ISSCR annual meeting all gave high caliber talks. Luckily, Paul Knoepfler live blogged on two of those presentations. Here are the links:

 

Multi-Talented Stem Cells: The Many Ways to Use Them in the Clinic

CIRM kicked off the 2016 International Society for Stem Cell Research (ISSCR) Conference in San Francisco with a public stem cell event yesterday that brought scientists, patients, patient advocates and members of the general public together to discuss the many ways stem cells are being used in the clinic to develop treatments for patients with unmet medical needs.

Bruce Conklin, Gladstone Institutes & UCSF

Bruce Conklin, Gladstone Institutes & UCSF

Bruce Conklin, an Investigator at the Gladstone Institutes and UCSF Professor, moderated the panel of four scientists and three patient advocates. He immediately captured the audience’s attention by showing a stunning video of human heart cells, beating in synchrony in a petri dish. Conklin explained that scientists now have the skills and technology to generate human stem cell models of cardiomyopathy (heart disease) and many other diseases in a dish.

Conklin went on to highlight four main ways that stem cells are contributing to human therapy. First is using stem cells to model diseases whose causes are still largely unknown (like with Parkinson’s disease). Second, genome editing of stem cells is a new technology that has the potential to offer cures to patients with genetic disorders like sickle cell anemia. Third, stem cells are known to secrete healing factors, and transplanting them into humans could be beneficial. Lastly, stem cells can be engineered to attack cancer cells and overcome cancer’s normal way of evading the immune system.

Before introducing the other panelists, Conklin made the final point that stem cell models are powerful because scientists can use them to screen and develop new drugs for diseases that have no treatments or cures. His lab is already working on identifying new drugs for heart disease using human induced pluripotent stem cells derived from patients with cardiomyopathy.

Scientists and Patient Advocates Speak Out

Malin Parmar, Lund University

Malin Parmar, Lund University

The first scientist to speak was Malin Parmar, a Professor at Lund University. She discussed the history of stem cell development for clinical trials in Parkinson’s disease (PD). Her team is launching the first in-human trial for Parkinson’s using cells derived from human pluripotent stem cells in 2016. After Parmar’s talk, John Lipp, a PD patient advocate. He explained that while he might look normal standing in front of the crowd, his PD symptoms vary wildly throughout the day and make it hard for him to live a normal life. He believes in the work that scientists like Parmar are doing and confidently said, “In my lifetime, we will find a stem cell cure for Parkinson’s disease.”

Adrienne Shapiro, Patient Advocate

Adrienne Shapiro, Patient Advocate

The next scientist to speak was UCLA Professor Donald Kohn. He discussed his lab’s latest efforts to develop stem cell treatments for different blood disorder diseases. His team is using gene therapy to modify blood stem cells in bone marrow to treat and cure babies with SCID, also known as “bubble-boy disease”. Kohn also mentioned their work in sickle cell disease (SCD) and in chronic granulomatous disease, both of which are now in CIRM-funded clinical trials. He was followed by Adrienne Shapiro, a patient advocate and mother of a child with SCD. Adrienne gave a passionate and moving speech about her family history of SCD and her battle to help find a cure for her daughter. She said “nobody plans to be a patient advocate. It is a calling born of necessity and pain. I just wanted my daughter to outlive me.”

Henry Klassen (UC Irvine)

Henry Klassen, UC Irvine

Henry Klassen, a professor at UC Irvine, next spoke about blinding eye diseases, specifically retinitis pigmentosa (RP). This disease damages the photo receptors in the back of the eye and eventually causes blindness. There is no cure for RP, but Klassen and his team are testing the safety of transplanting human retinal progenitor cells in to the eyes of RP patients in a CIRM-funded Phase 1/2 clinical trial.

Kristen MacDonald, RP patient

Kristen MacDonald, RP patient

RP patient, Kristen MacDonald, was the trial’s first patient to be treated. She bravely spoke about her experience with losing her vision. She didn’t realize she was going blind until she had a series of accidents that left her with two broken arms. She had to reinvent herself both physically and emotionally, but now has hope that she might see again after participating in this clinical trial. She said that after the transplant she can now finally see light in her bad eye and her hope is that in her lifetime she can say, “One day, people used to go blind.”

Lastly, Catriona Jamieson, a professor and Alpha Stem Cell Clinic director at UCSD, discussed how she is trying to develop new treatments for blood cancers by eradicating cancer stem cells. Her team is conducting a Phase 1 CIRM-funded clinical trial that’s testing the safety of an antibody drug called Cirmtuzumab in patients with chronic lymphocytic leukemia (CLL).

Scientists and Patients need to work together

Don Kohn, Catriona Jamieson, Malin Parmar

Don Kohn, Catriona Jamieson, Malin Parmar

At the end of the night, the scientists and patient advocates took the stage to answer questions from the audience. A patient advocate in the audience asked, “How can we help scientists develop treatments for patients more quickly?”

The scientists responded that stem cell research needs more funding and that agencies like CIRM are making this possible. However, we need to keep the momentum going and to do that both the physicians, scientists and patient advocates need to work together to advocate for more support. The patient advocates in the panel couldn’t have agreed more and voiced their enthusiasm for working together with scientists and clinicians to make their hopes for cures a reality.

The CIRM public event was a huge success and brought in more than 150 people, many of whom stayed after the event to ask the panelists more questions. It was a great kick off for the ISSCR conference, which starts today. For coverage, you can follow the Stem Cellar Blog for updates on interesting stem cell stories that catch our eye.

CIRM Public Stem Cell Event

CIRM Public Stem Cell Event

Accelerating the drive for new stem cell treatments

Acceleration

Acceleration is defined as the “increase in the rate or speed of something.” For us that “something” is new stem cell treatments for patients with unmet medical needs. Today our governing Board just approved a $15 million partnership with Quintiles to help us achieve that acceleration.

Quintiles was awarded the funding to create a new Accelerating Center. The goal of the center is to give stem cell researchers the support they need to help make their clinical trials successful.

As our President and CEO Randy Mills said in a news release:

randy-at-podium1CIRM President Randy Mills addresses the CIRM Board

“Many scientists are brilliant researchers but have little experience or expertise in running a clinical trial; this Accelerating Center means they don’t have to develop those skills; we provide them for them. This partnership with Quintiles means that scientists don’t have to learn how to manage patient enrollment or how to create a data base to manage the results. Instead they are free to focus on what they do best, namely science.”

How does it work? Well, if a researcher has a promising therapy and approval from the US Food and Drug Administration (FDA) to start a clinical trial, the Accelerating Center helps them get that trial off the ground. It helps them find the patients they need, get those patients consented and ready for the trial, and then helps manage the trial and the data from the trial.

The devil is in the details

Managing those details can be a key factor in determining whether a clinical trial is going to be successful. Last year, a study in the New England Journal of Medicine listed the main reasons why clinical trials fail.

Among the reasons are:

  • Poor study design: Selecting the wrong patients, the wrong dosing and the wrong endpoint, as well as bad data and bad site management cause severe problems.
  • Poor management: A project manager who does not have enough experience in costing and conducting clinical trials will lead to weak planning, with no clear and real timelines, and to ultimate failure.

We hope our partnership with Quintiles in this Accelerating Center will help researchers avoid those and the other pitfalls. As the world’s largest provider of biopharmaceutical development and commercial outsourcing services, Quintiles has a lot of experience and expertise in this area. On its Twitter page it’s slogan is “Better, smarter, faster trials” so I think we made a smart choice.

When Randy Mills first pitched this idea to the Board, he said that he is a great believer in “not asking fish to learn how to fly, they should just do what they do best”.

The Accelerating Center means scientists can do what they do best, and we hope that leads to what patients need most; treatments and cures.


Related Links:

Free public event will detail the many ways stem cells are used in clinical trials today

The hundreds of active stem cell clinical trials being run in the US, and indeed around the world, provide ample evidence that our favorite cells are truly multi-talented. There are so many different ways researchers are using them to develop therapies we would be hard-pressed to name them all. However, most fall into five general categories that will be discussed at a free public symposium CIRM is co-hosting in conjunction with the International Society for Stem Cell Research during its annual meeting in San Francisco.

Moscone at dusk

San Francisco’s Moscone Center is close to BART and Muni public transit

The free public event will run from 6:00 to 7:30 on Tuesday evening June 21 at the Moscone West convention center, room 2009, on the corner of Howard and Fourth streets in San Francisco. After a brief overview, four researchers will describe active clinical trials and how stem cells provide hope for therapies in different diseases.  The last half hour will be open for general questions from the audience.

All the details are at a special page on EventBright where you can register to attend. The evening will start with Bruce Conklin of the Gladstone Institutes providing an overview of the many ways to use stem cells, including his own work using them to create laboratory models of heart disease. Then:

  • Malin Parmar of Sweden’s Lund University will discuss a Parkinson’s disease trial where stem cells are used to replace vital brain cells destroyed by the disease;
  • Donald Kohn of the University of California, Los Angeles, will provide details of two trials that combine stem cells and gene therapy, one for sickle cell anemia and one for severe combined immune deficiency, also called Bubble Baby disease;
  • Henry Klassen of University of California, Irvine, will talk about using progenitor stem cells to deliver factors that can protect the photoreceptors in the eyes of patients who have a blinding condition;
  • Catriona Jamieson of the University of California, San Diego will describe the bad boy of the stem cell world, the cancer stem cell, and clinical trials she is conducting to attack those cells.

While some of the hundreds of current stem cell clinical trials will not produce the desired impact on their target diseases, they will all make strides toward learning how to optimize the great potential of stem cell therapies.

Right now CIRM is funding 16 different clinical trials in diseases as varied as HIV/AIDS and type 1 diabetes. Over the next 5 years we hope to add another 50 clinical trials to that list. The field of regenerative medicine is advancing. This event is a chance for you to understand the progress, and the challenges, that we face in bringing potentially life-changing, even life-saving therapies to the people who need it the most, the patients.