Raising awareness about mental health

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World Mental Health Day is observed on 10 October every year. It’s a time to try and raise awareness about mental health issues and the impact they have not just on the individual but their family, their community and all of us. The theme for World Mental Health Day 2021 is ‘mental health in an unequal world.’

Dr. Le Ondra Clark Harvey: Photo courtesy CCCBHA

To highlight the issues raised on World Mental Health Day we talked to one of CIRM’s newest Board member, Dr. Le Ondra Clark Harvey. She’s a psychologist and the CEO of the California Council of Community Behavioral Health Agencies (CCCBHA) a statewide advocacy organization representing mental health and substance use disorder non-profit agencies that collectively serve over 750 thousand Californians annually.

What made you want to be on the CIRM Board?

I was recommended to apply for the CIRM Board by a member of CCCBHA, the organization I am privileged to lead and serve. I saw the position as an opportunity to shed light on cognitive disorders that many do not readily think of when they think about stem cell research. The appointment also has personal meaning to me as I have a grandfather who is a cancer survivor and  who has an Alzheimer’s diagnosis.  Breast cancer has also affected women in my family, including myself, and I know that the research that CIRM funds can assist with finding a cure and providing accessible treatment options for all Californians. 

A lot of people might not think that stem cells would have a role in addressing mental health issues, what role do you think they can play?

You are correct, most people do not immediately think of stem cell therapies as a remedy to brain health disorders. However, there are many cognitive disorders and symptoms that can be mitigated, and hopefully someday ameliorated, as a result of stem cell therapies. For example, autism and other developmental disabilities, dementia, Alzheimer’s, Tourette’s and tardive dyskinesia.  

What are the biggest challenges we face in addressing mental health issues in this country?

Stigma remains a significant barrier that impacts the ability to provide – particularly among racially and ethnically diverse communities. In my own practice, I’ve seen how stigma can prevent individuals from entering into care even when access issues have been mitigated. Public awareness campaigns, and culturally specific advocacy efforts and practices must be integrated into treatment models in order to provide individuals with the specific care they need. 

Do you think that the widespread media attention paid to Naomi Osaka and Simone Biles has helped raise awareness about mental health and perhaps also reduced some of the stigma surrounding it?

Yes, I do. Also, the pandemic has opened many individuals eyes, and engendered a sense of empathy, about the prevalence and impact that isolation and loneliness can have on a person. 

Heads or tails? Stem cells help guide the decision

Two cell embryo

There are many unknown elements for what triggers the cells in an embryo to start dividing and multiplying and becoming every single cell in the body. Now researchers at the Gladstone Institutes in San Francisco have uncovered one of those elements, how embryos determine which cells become the head and which the tail.

In this CIRM-funded study the Gladstone team, led by Dr. Todd McDevitt, discovered almost by chance how the cells align in a heads-to-tail arrangement.

Todd McDevitt

They had created an organoid made from brain cells when they noticed that some of the cells were beginning to gather in an elongated fashion, in the same way that spinal cords do in a developing fetus.

In a news article, Nick Elder, a graduate student at Gladstone and the co-author of the study, published in the journal Development, says this was not what they had anticipated would happen: “Organoids don’t typically have head-tail directionality, and we didn’t originally set out to create an elongating organoid, so the fact that we saw this at all was very surprising.”

Further study enabled the team to identify which molecules were involved in signaling specific genes to switch on and off. These were similar to the process previously identified in developing mouse embryos.

“This is such a critical point in the early development of any organism, so having a new model to observe it and study it in the lab is very exciting,” says McDevitt.

This is not just of academic interest either, it could have real world implications in helping understand what causes miscarriages or birth defects.

“We can use this organoid to get at unresolved human developmental questions in a way that doesn’t involve human embryos,” says Dr. Ashley Libby, another member of the team. “For instance, you could add chemicals or toxins that a pregnant woman might be exposed to, and see how they affect the development of the spinal cord.”

CIRM Builds Out World Class Team With 5 New hires

Kevin Marks, CIRM’s new General Counsel. Photo courtesy Modern-Counsel.com

Following the passage of Proposition 14 CIRM has hired five new employees to help increase the team’s ability to respond to new challenges and responsibilities.

Prop 14, which was approved by voters in November 2020, gives CIRM $5.5 billion in new funding. Those funds mean CIRM can once again fund research from Discovery, through Translational and Clinical, as well as create new education and training programs. Prop 14 also adds new areas of focus for the Stem Cell Agency including creating an Accessibility and Affordability Working Group, expanding the Alpha Stem Cell Clinic network and creating new Centers of Excellence in underserved parts of California. To meet those new responsibilities the Agency has hired a highly talented group of individuals. Those include:

Kevin Marks is CIRM’s new General Counsel. Kevin studied Russian at college and originally wanted to be a diplomat, but when that didn’t work out he turned to the law. He became a highly accomplished, skilled advisor with global and domestic expertise and a history of delivering innovative legal and business results. He has served as Vice President and Head of Legal and Compliance at Roche Molecular Solutions, VP and General Counsel at Roche Molecular Diagnostics and VP and General Counsel at Roche Palo Alto, LLC.

“We are so delighted to have Kevin Marks join CIRM as a member of our executive Leadership Team,” says Maria T. Millan, MD, CIRM’s President and CEO. “He brings unique qualifications and critical skills during the formative phase and launch of our new strategic plan for California’s $5.5B investment in stem cell, genomics and regenerative medicine research and therapy development. As general counsel, he will oversee the legal department, human resources, grants management and operations at the Agency. Kevin has an established track record with global and domestic expertise and a history of delivering innovative legal and business solutions.”

“He is revered by his colleagues as an exceptional leader in his profession and in the community. Kevin is known for developing people as well as programs, and for promoting racial, ethnic and gender diversity.”

“I am incredibly honored to be joining CIRM at this stage of its journey,” says Marks. “I see the opportunity to contribute to positive patient outcomes–especially those patients with unmet medical needs–by working towards accelerating stem cell research in California as a member of the CIRM team as rewarding and perfectly aligned with my professional and personal goals.”

Pouneh Simpson as Director of Finance. Pouneh comes to CIRM from the Governor’s Office of Emergency Services in California, where she served as the Recovery Financial Administration Chief. At OES she worked with local, state, and federal government stakeholders on disaster recovery planning, exercises, and grant administration, specifically, overseeing the grant processing of all disaster recovery activity.

Prior to that Pouneh worked as the Chief Financial Officer of the Veterans Homes, where she managed finances at eight Veterans Homes with over 2,800 positions and $365 million in General Fund support. She also led the writing of legislation, regulations, policies and procedures for Cal Vet, overhauling the business and financial portions of eight Veterans Homes.

Mitra Hooshmand, PhD. as Senior Science Officer for Special Projects and Initiatives. Mitra joins CIRM after more than five years of leadership experience at Americans for Cures, a stem cell advocacy group. During this time, she mobilized hundreds of stakeholders, from scientists to national and local patient advocacy organizations, to generate support for CIRM’s mission.

Mitra has a PhD. in Anatomy and Biology from the University of California at Irvine. She also worked as a Project Scientist at the Sue and Bill Gross Stem Cell Research Center at UC Irvine, where she conducted and published academic and industry-partnered research in studies investigating the therapeutic benefit of human neural stem cell transplantation in preclinical models of spinal cord injury and aging.

Vanessa Singh, as Human Resources Manager. Vanessa has 15 years of experience working for the state of California, working at the Departments of General Services, Insurance and Human Services. In those roles she gained experience in performing, processing, developing, implementing, and advising on many personnel aspects such as compensation, benefits, classifying positions, recruitment and hiring, salary structure (exempt and civil service), organization structure, and retirement.

When COVID struck Vanessa stepped up to help. She worked as a Case Investigator for San Bernardino Local Health Jurisdiction, Department of Public Health, doing contact tracing. She talked to people diagnosed with coronavirus and collected information on people they may have had close contact with who may have been exposed to the virus.

Claudette Mandac as Project Manager Review. Claudette has more than seven years’ experience with UCSF’s Human Research Protection Program. In that role she prepared protocols for scientific, regulatory and ethical review, pre-screening submissions to ensure they were complete and consistent, and then routing them to the appropriate reviewers for administrative, expedited or Committee review. She also managed an Institutional Review Board Committee, preparing and distributing protocols for review by designated scientific and nonscientific reviewers, coordinating meetings, recruiting and training members, and maintaining records of conflicts of interest. At UCSF she annually helped process up to 3,000 IRB modifications, continuing reviews, and post-approval safety reports for domestic and international socio-behavioral or biomedical research.

Claudette has two degrees from U.C. Berkeley; one in Arts and History and another in Science, Conservation and Resource Studies.

A word from our Chair, several in fact

In 2005, the New Oxford American Dictionary named “podcast” its word of the year. At the time a podcast was something many had heard of but not that many actually tuned in to. My how times have changed. Now there are some two million podcasts to chose from, at least according to the New York Times, and who am I to question them.

Yesterday, in the same New York Times, TV writer Margaret Lyons, wrote about how the pandemic helped turn her from TV to podcasts: “Much in the way I grew to prefer an old-fashioned phone call to a video chat, podcasts, not television, became my go-to medium in quarantine. With their shorter lead times and intimate production values, they felt more immediate and more relevant than ever before.”

I mention this because an old colleague of ours at CIRM, Neil Littman, has just launched his own podcast and the first guest on it was Jonathan Thomas, Chair of the CIRM Board. Their conversation ranged from CIRM’s past to the future of the regenerative field as a whole, with a few interesting diversions along the way. It’s fun listening. And as Margaret Lyons said it might be more immediate and more relevant than ever before.

Cures, clinical trials and unmet medical needs

When you have a great story to tell there’s no shame in repeating it as often as you can. After all, not everyone gets to hear first time around. Or second or third time. So that’s why we wanted to give you another opportunity to tune into some of the great presentations and discussions at our recent CIRM Alpha Stem Cell Clinic Network Symposium.

It was a day of fascinating science, heart-warming, and heart-breaking, stories. A day to celebrate the progress being made and to discuss the challenges that still lie ahead.

There is a wide selection of topics from “Driving Towards a Cure” – which looks at some pioneering work being done in research targeting type 1 diabetes and HIV/AIDS – to Cancer Clinical Trials, that looks at therapies for multiple myeloma, brain cancer and leukemia.

The COVID-19 pandemic also proved the background for two detailed discussions on our funding for projects targeting the coronavirus, and for how the lessons learned from the pandemic can help us be more responsive to the needs of underserved communities.

Here’s the agenda for the day and with each topic there’s a link to the video of the presentation and conversation.

Thursday October 8, 2020

View Recording: CIRM Fellows Trainees

9:00am Welcome Mehrdad Abedi, MD, UC Davis Health, ASCC Program Director  

Catriona Jamieson, MD,  View Recording: ASCC Network Value Proposition

9:10am Session I:  Cures for Rare Diseases Innovation in Action 

Moderator: Mark Walters, MD, UCSF, ASCC Program Director 

Don Kohn, MD, UCLA – View Recording: Severe combined immunodeficiency (SCID) 

Mark Walters, MD, UCSF, ASCC Program Director – View Recording: Thalassemia 

Pawash Priyank, View Recording: Patient Experience – SCID

Olivia and Stacy Stahl, View Recording: Patient Experience – Thalassemia

10 minute panel discussion/Q&A 

BREAK

9:55am Session II: Addressing Unmet Medical Needs: Driving Towards a Cure 

Moderator: John Zaia, MD, City of Hope, ASCC Program Direction 

Mehrdad Abedi, MD, UC Davis Health, ASCC Program Director – View Recording: HIV

Manasi Jaiman, MD, MPH, ViaCyte, Vice President, Clinical Development – View Recording: Diabetes

Jeff Taylor, Patient Experience – HIV

10 minute panel discussion/Q&A 

BREAK

10:40am Session III: Cancer Clinical Trials: Networking for Impact 

Moderator: Catriona Jamieson, MD, UC San Diego, ASCC Program Director 

Daniela Bota, MD, PhD, UC Irvine, ASCC Program Director – View Recording:  Glioblastoma 

Michael Choi, MD, UC San Diego – View Recording: Cirmtuzimab

Matthew Spear, MD, Poseida Therapeutics, Chief Medical Officer – View Recording: Multiple Myeloma  

John Lapham, Patient Experience –  View Recording: Chronic lymphocytic leukemia (CLL) 

10 minute panel discussion/Q&A 

BREAK

11:30am Session IV: Responding to COVID-19 and Engaging Communities

Two live “roundtable conversation” sessions, 1 hour each.

Roundtable 1: Moderator Maria Millan, MD, CIRM 

CIRM’s / ASCC Network’s response to COVID-19 Convalescent Plasma, Cell Therapy and Novel Vaccine Approaches

Panelists

Michael Matthay, MD, UC San Francisco: ARDS Program

Rachael Callcut, MD, MSPH, FACS, UC Davis: ARDS Program 

John Zaia, MD, City of Hope: Convalescent Plasma Program 

Daniela Bota, MD, PhD, UC Irvine: Natural Killer Cells as a Treatment Strategy 

Key questions for panelists: 

  • Describe your trial or clinical program?
  • What steps did you take to provide access to disproportionately impacted communities?
  • How is it part of the overall scientific response to COVID-19? 
  • How has the ASCC Network infrastructure accelerated this response? 

Brief Break

Roundtable 2: Moderator Ysabel Duron, The Latino Cancer Institute and Latinas Contra Cancer

View Recording: Roundtable 2

Community Engagement and Lessons Learned from the COVID Programs.  

Panelists

Marsha Treadwell, PhD, UC San Francisco: Community Engagement  

Sheila Young, MD, Charles R. Drew University of Medicine and Science: Convalescent Plasma Program in the community

David Lo, MD, PhD,  UC Riverside: Bringing a public health perspective to clinical interventions

Key questions for panelists: 

  • What were important lessons learned from the COVID programs? 
  • How can CIRM and the ASCC Network achieve equipoise among communities and engender trust in clinical research? 
  • How can CIRM and the ASCC Network address structural barriers (e.g. job constrains, geographic access) that limit opportunities to participate in clinical trials?

Partners in health

From left to right: Heather Dahlenburg, Jan Nolta, Jeannine Logan White, Sheng Yang
From left to right: Heather Dahlenburg, staff research associate; Jan Nolta, director of the Stem Cell Program; Jeannine Logan White, advanced cell therapy project manager; Sheng Yang, graduate student, Bridges Program, Humboldt State University, October 18, 2019. (AJ Cheline/UC Davis)

At CIRM we are modest enough to know that we can’t do everything by ourselves. To succeed we need partners. And in UC Davis we have a terrific partner. The work they do in advancing stem cell research is exciting and really promising. But it’s not just the science that makes them so special. It’s also their compassion and commitment to caring for patients.

What follows is an excerpt from an article by Lisa Howard on the work they do at UC Davis. When you read it you’ll see why we are honored to be a part of this research.

Gene therapy research at UC Davis

UC Davis’ commitment to stem cell and gene therapy research dates back more than a decade.

In 2010, with major support from the California Institute for Regenerative Medicine (CIRM), UC Davis launched the UC Davis Institute for Regenerative Cures, which includes research facilities as well as a Good Manufacturing Practice (GMP) facility.

In 2016, led by Fred Meyers, a professor in the School of Medicine, UC Davis launched the Center for Precision Medicine and Data Sciences, bringing together innovations such as genomics and biomedical data sciences to create individualized treatments for patients.

Last year, the university launched the Gene Therapy Center, part of the IMPACT Center program.

Led by Jan Nolta, a professor of cell biology and human anatomy and the director of the UC Davis Institute for Regenerative Cures, the new center leverages UC Davis’ network of expert researchers, facilities and equipment to establish a center of excellence aimed at developing lifelong cures for diseases.

Nolta began her career at the University of Southern California working with Donald B. Kohn on a cure for bubble baby disease, a condition in which babies are born without an immune system. The blood stem cell gene therapy has cured more than 50 babies to date.

Work at the UC Davis Gene Therapy Center targets disorders that potentially can be treated through gene replacement, editing or augmentation.

“The sectors that make up the core of our center stretch out across campus,” said Nolta. “We work with the MIND Institute a lot. We work with the bioengineering and genetics departments, and with the Cancer Center and the Center for Precision Medicine and Data Sciences.”

A recent UC Davis stem cell study shows a potential breakthrough for healing diabetic foot ulcers with a bioengineered scaffold made up of human mesenchymal stem cells (MSCs). Another recent study revealed that blocking an enzyme linked with inflammation enables stem cells to repair damaged heart tissue. A cell gene therapy study demonstrated restored enzyme activity in Tay-Sachs disease affected cells in humanized mouse models.

Several cell and gene therapies have progressed to the point that ongoing clinical trials are being conducted at UC Davis for diseases, including sickle-cell anemia, retinopathy, muscle injury, dysphasia, advanced cancer, and Duchenne muscular dystrophy, among others.

“Some promising and exciting research right now at the Gene Therapy Center comes from work with hematopoietic stem cells and with viral vector delivery,” said Nolta.

Hematopoietic stem cells give rise to other blood cells. A multi-institutional Phase I clinical trial using hematopoietic stem cells to treat HIV-lymphoma patients is currently underway at UC Davis.

.Joseph Anderson

Joseph Anderson

“We are genetically engineering a patient’s own blood stem cells with genes that block HIV infection,” said Joseph Anderson, an associate professor in the UC Davis Department of Internal Medicine. The clinical trial is a collaboration with Mehrdad Abedi, the lead principal investigator.

“When the patients receive the modified stem cells, any new immune system cell, like T-cell or macrophage, that is derived from one of these stem cells, will contain the HIV-resistant genes and block further infection,” said Anderson.

He explained that an added benefit with the unique therapy is that it contains an additional gene that “tags” the stem cells. “We are able to purify the HIV-resistant cells prior to transplantation, thus enriching for a more protective cell population.

Kyle David Fink

Kyle David Fink

Kyle David Fink, an assistant professor of neurology at UC Davis, is affiliated with the Stem Cell Program and Institute for Regenerative Cures. His lab is focused on leveraging institutional expertise to bring curative therapies to rare, genetically linked neurological disorders.

“We are developing novel therapeutics targeted to the underlying genetic condition for diseases such as CDKL5 deficiency disorder, Angelman, Jordan and Rett syndromes, and Juvenile Huntington’s disease,” said Fink.

The lab is developing therapies to target the underlying genetic condition using DNA-binding domains to modify gene expression in therapeutically relevant ways. They are also creating novel delivery platforms to allow these therapeutics to reach their intended target: the brain.

“The hope is that these highly innovative methods will speed up the progress of bringing therapies to these rare neurodegenerative disease communities,” said Fink.Jasmine Carter, a graduate research assistant at the UC Davis Stem Cell Program.

Jasmine Carter, a graduate research assistant at the UC Davis Stem Cell Program, October 18, 2019. (AJ Cheline/UC Davis)

Developing potential lifetime cures

Among Nolta’s concerns is how expensive gene therapy treatments can be.

“Some of the therapies cost half a million dollars and that’s simply not available to everyone. If you are someone with no insurance or someone on Medicare, which reimburses about 65 percent, it’s harder for you to get these life-saving therapies,” said Nolta.

To help address that for cancer patients at UC Davis, Nolta has set up a team known as the “CAR T Team.”

Chimeric antigen receptor (CAR) T-cell therapy is a type of immunotherapy in which a patient’s own immune cells are reprogrammed to attack a specific protein found in cancer cells.

“We can develop our own homegrown CAR T-cells,” said Nolta. “We can use our own good manufacturing facility to genetically engineer treatments specifically for our UC Davis patients.”

Although safely developing stem cell treatments can be painfully slow for patients and their families hoping for cures, Nolta sees progress every day. She envisions a time when gene therapy treatments are no longer considered experimental and doctors will simply be able to prescribe them to their patients.

“And the beauty of the therapy is that it can work for the lifetime of a patient,” said Nolta.

Creating an on-off switch to test stem cell therapy for Parkinson’s Disease

Sometimes you read about a new study where the researchers did something that just leaves you gob smacked. That’s how I felt when I read a study in the journal Cell Stem Cell about a possible new approach to helping people with Parkinson’s Disease (PD).

More on the gob smacking later. But first the reason for the study.

We know that one of the causes of Parkinson’s disease is the death of dopamine-producing neurons, brain cells that help plan and control body movement. Over the years, researchers have tried different ways to try and replace those cells but getting the cells where they need to be and getting them to integrate into the brain has proved challenging.

A team at the University of Wisconsin-Madison think they may have found a way to fix that. In an article in Drug Target Review  lead researcher Dr. Su-Chun Zhang, explained their approach:

“Our brain is wired in such an accurate way by very specialized nerve cells in particular locations so we can engage in all our complex behaviors. This all depends on circuits that are wired by specific cell types. Neurological injuries usually affect specific brain regions or specific cell types, disrupting circuits. In order to treat those diseases, we have to restore these circuits.”

The researchers took human embryonic stem cells and transformed them into dopamine-producing neurons, then they transplanted those cells into mice specially bred to display PD symptoms. After several months the team were able to show that not only had the mice improved motor skills but that the transplanted neurons were able to connect to the motor-control regions of the brain and also establish connections with regulatory regions of the brain, which prevented over stimulation. In other words, the transplanted cells looked and behaved the way they would in a healthy human brain.

Now here comes the gob smack part. The team wanted to make sure the cells they transplanted were the reason for the improved motor control in the mice. So, they had inserted a genetic on-and-off switch into the stem cells. By using specially designed drugs the researchers were able to switch the cells on or off.

When the cells were switched off the mice’s motor improvements stopped. When they were switched back on, they were restored.

Brilliant right! Well, I thought it was.

Next step is to test this approach in larger animals and, if all continues to look promising, to move into human clinical trials.

CIRM is already funding one clinical trial in Parkinson’s disease. You can read about it here.

Exploring tough questions, looking for answers

COVID-19 and social and racial injustice are two of the biggest challenges facing the US right now. This Thursday, October 8th, we are holding a conversation that explores finding answers to both.

The CIRM Alpha Stem Cell Clinic Network Symposium is going to feature presentations about advances in stem cell and regenerative research, highlighting treatments that are already in the clinic and being offered to patients.

But we’re also going to dive a little deeper into the work we support, and use it to discuss two of the most pressing issues of the day.

One of the topics being featured is research into COVID-19. To date CIRM has funded 17 different projects, including three clinical trials. We’ll talk about how these are trying to find ways to help people infected with the virus, seeing if stem cells can help restore function to organs and tissues damaged by the virus, and if we can use stem cells to help develop safe and effective vaccines.

Immediately after that we are going to use COVID-19 as a way of exploring how the people most at risk of being infected and suffering serious consequences, are also the ones most likely to be left out of the research and have most trouble accessing treatments and vaccines.

Study after study highlights how racial and ethnic minorities are underrepresented in clinical trials and disproportionately affected by debilitating diseases. We have a responsibility to change that, to ensure that the underserved are given the same opportunity to take part in clinical trials as other communities.

How do we do that, how do we change a system that has resisted change for so long, how do we overcome the mistrust that has built up in underserved communities following decades of abuse? We’ll be talking about with experts who are on the front lines of this movement.

It promises to be a lively meeting. We’d love to see you there. It’s virtual – of course – it’s open to everyone, and it’s free.

Here’s where you can register and find out more about the Symposium

It’s all about the patients

Ronnie, born with a fatal immune disorder now leading a normal life thanks to a CIRM-funded stem cell/gene therapy: Photo courtesy of his mum Upasana

Whenever you are designing something new you always have to keep in mind who the end user is. You can make something that works perfectly fine for you, but if it doesn’t work for the end user, the people who are going to work with it day in and day out, you have been wasting your time. And their time too.

At CIRM our end users are the patients. Everything we do is about them. Starting with our mission statement: to accelerate stem cell treatments to patients with unmet medical needs. Everything we do, every decision we make, has to keep the needs of the patient in mind.

So, when we were planning our recent 2020 Grantee Meeting (with our great friends and co-hosts UC Irvine and UC San Diego) one of the things we wanted to make sure didn’t get lost in the mix was the face and the voice of the patients. Often big conferences like this are heavy on science with presentations from some of the leading researchers in the field. And we obviously wanted to make sure we had that element at the Grantee meeting. But we also wanted to make sure that the patient experience was front and center.

And we did just that. But more on that in a minute. First, let’s talk about why the voice of the patient is important.

Some years ago, Dr. David Higgins, a CIRM Board member and patient advocate for Parkinson’s Disease (PD), said that when researchers are talking about finding treatments for PD they often focus on the dyskinesia, the trembling and shaking and muscle problems. However, he said if you actually asked people with PD you’d find they were more concerned with other aspects of the disease, the insomnia, anxiety and depression among other things. The key is you have to ask.

Frances Saldana, a patient advocate for research into Huntington’s disease

So, we asked some of our patient advocates if they would be willing to be part of the Grantee Meeting. All of them, without hesitation, said yes. They included Frances Saldana, a mother who lost three of her children to Huntington’s disease; Kristin MacDonald, who lost her sight to a rare disorder but regained some vision thanks to a stem cell therapy and is hoping the same therapy will help restore some more; Pawash Priyank, whose son Ronnie was born with a fatal immune disorder but who, thanks to a stem cell/gene therapy treatment, is now healthy and leading a normal life.

Because of the pandemic everything was virtual, but it was no less compelling for that. We interviewed each of the patients or patient advocates beforehand and those videos kicked off each session. Hearing, and seeing, the patients and patient advocates tell their stories set the scene for what followed. It meant that the research the scientists talked about took on added significance. We now had faces and names to highlight the importance of the work the scientists were doing. We had human stories. And that gave a sense of urgency to the work the researchers were doing.

But that wasn’t all. After all the video presentations each session ended with a “live” panel discussion. And again, the patients and patient advocates were a key part of that. Because when scientists talk about taking their work into a clinical trial they need to know if the way they are setting up the trial is going to work for the patients they’re hoping to recruit. You can have the best scientists, the most promising therapy, but if you don’t design a clinical trial in a way that makes it easy for patients to be part of it you won’t be able to recruit or retain the people you need to test the therapy.

Patient voices count. Patient stories count.

But more than anything, hearing and seeing the people we are trying to help reminds us why we do this work. It’s so easy to get caught up in the day to day business of our jobs, struggling to get an experiment to work, racing to get a grant application in before the deadline. Sometimes we get so caught up in the minutiae of work we lose sight of why we are doing it. Or who we are doing it for.

At CIRM we have a saying; come to work every day as if lives depend on you, because lives depend on you. Listening to the voices of patients, seeing their faces, hearing their stories, reminds us not to waste a moment. Because lives depend on all of us.

Here’s one of the interviews that was featured at the event. I do apologize in advance for the interviewer, he’s rubbish at his job.

Scientists develop faster, smarter way to classify tumors using single-cell technology

Dr. Stephen Lin, CIRM Senior Science Officer

By Dr. Stephen Lin

Single-cell.  It is the new buzzword in biology.  Single-cell biology refers to the in-depth characterization of individual cells in an organ or similar microenvironment.  Every organ, like the brain or heart, is composed of thousands to millions of cells.  Single-cell biology breaks those organs down into their individual cell components to study the diversity within those cells.  For example, the heart is composed of cardiomyocytes, but within that bulk population of cardiomyocytes there are specialized cardiomyocytes for the different chambers of the heart and others that control beating, plus others not even known yet.  Single-cell studies characterize cell-to-cell variability in the body down to this level of detail to gain knowledge of tissues in a way that was not possible before.   

The majority of single-cell studies are based on next generation sequencing technologies of genetic material such as DNA or RNA.  The cost of sequencing each base of DNA or RNA has dropped precipitously since the first human genome was published in 2000, often compared to the trend seen with Moore’s Law in computing.  As a result it is now possible to sequence every gene that is expressed in an individual cell, called the transcriptome, for thousands and thousands of cells.   

The explosion of data coming from these technologies requires new approaches to study and analyze the information.  The scale of the genetic sequences that can be generated is so big that it is often not possible anymore for scientists to interpret the data manually as had been traditionally done.  To apply this exciting field to stem cell research and therapies, CIRM funded the Genomics Initiative which created the Centers of Excellence in Stem Cell Genomics (CESCG).  The goal of the CESCG is to create novel genomic information and create new bioinformatics tools (i.e. computer software) specifically for stem cell research, some of which was highlighted in past blogs.  Some of the earliest single-cell gene expression atlases of the human body were created under the CESCG. 

The latest study from CESCG investigators creates both new information and new tools for single-cell genomics.  In work funded by the Genomics Initiative, Stephen Quake and colleagues at Stanford University and the Chan-Zuckerberg Biohub studied tumor formation using single-cell approaches.  Drawing from one of the earliest published single-cell studies, the team had surveyed human brain transcriptome diversity that included samples from the brain cancer, glioblastoma. 

Recognizing that the data coming from these studies would eventually become too large and numerous to classify all of the cell types by hand, they created a new bioinformatics tool called Northstar to apply artificial intelligence to automatically classify cell types generated by single-cell studies.  The cell classifications generated by Northstar were similar to the original classifications created manually several years ago including the identification of specific cancerous cells. 

Some of the features that make Northstar a powerful bioinformatics tool for these studies are that the software is scalable for large numbers of cells, it performs the computations to classify cells very fast, and it requires relatively low computer processing power to go through literally millions of data points. 

The scalability of the tool was demonstrated on the Tabula Muris data collection, a single-cell compendium of 20 mouse organs with over 200,000 cells of data.  Finally, Northstar was used to classify the tumors from new single-cell data generated by the CESCG via samples of 11 patient pancreatic cancer patients obtained from Stanford Hospital.  Northstar correctly found the origins of cancerous cells from the specific diagnoses of pancreatic cancer that the patients had, for example cancerous cells in the endocrine cell lineage from a patient diagnosed with neuroendocrine pancreas cancer.  Furthermore, Northstar identified previously unknown origins of cancerous cell clusters from other patients with pancreatic cancer.  These new computational tools demonstrate how big data from genomic studies can become important contributors to personalized medicine.

The full study was published in Nature.