Major league baseball star and his wife turn to IVF to conceive child free of Huntington’s Disease

Joe Smith, pitcher for the Houston Astros, and his wife, sports reporter Allie LaForce. Smith’s family carries the gene for Huntington’s Disease. Photo courtesy of Huntington’s Disease Society for America website.

For many couples, one of the most monumental moments in life is the decision made to conceive a child together and start a family. The usual questions that come to mind typically relate to simple matters such as potential baby names, diapers, clothes, pacifiers, cribs, blankets, and stuffed animals. New parents will also think about what customs, languages, and set of principles they want to pass along to their child. But what if there was something they didn’t want to pass along to their child? What if there was a 50/50 chance of unintentionally passing along a debilitating genetic condition? For Houston Astros pitcher Joe Smith and his wife, sports reporter Allie LaForce, this situation was a devastating reality.

Joe’s grandmother and mother were both diagnosed with Huntington’s Disease (HD), so he has seen first hand the debilitating effects of this condition. HD is a genetically inherited, neurological condition that causes the progressive breakdown of nerve cells in the brain and has no known cure. It gradually deteriorates a person’s mental and physical abilities, making it difficult to recall things, walk, or even speak. According to statistics from Huntington’s Disease Society for America (HDSA), every child of a parent with HD has a 50/50 chance of inheriting the disease. Furthermore, there are approximately 30,000 Americans living with HD and 200,000 at-risk of inheriting the condition. It is because of these high risks that Joe and Allie have decided to conceive a child with the aid of in-vitro fertilization (IVF).

Through IVF, an ovum and sperm are combined outside the body to create a fertilized egg. This egg can be implanted into a woman’s uterus, allowing it to grow and develop. However, there is additional technology known as preimplantation genetic diagnosis (PGD) that can be used alongside IVF. With PGD-IVF, the fertilized eggs can be genetically tested before implantation. In Joe and Allie’s instance, PGD-IVF can be used to screen for HD, ensuring that the fertilized egg does not carry the disease prior to implantation.

In an interview with Morgan Radford on The Today Show, Joe and Allie discuss in detail how HD has impacted their loved ones and their decision to use PGD-IVF. The interview is available here.

In the interview, Joe Smith is quoted as saying, “I’m just taking out a 50/50 chance…I just want that [HD] gone.”

The California Institute for Regenerative Medicine (CIRM) has recently approved a $6 million grant geared towards HD. This funding is for late stage testing needed to apply to the US Food and Drug Administration for permission to start a clinical trial in people. You can read more details about this award from a previous blog post here.

A new stem cell derived tool for studying brain diseases

Sergiu Pasca’s three-dimensional culture makes it possible to watch how three different brain-cell types – oligodendrocytes (green), neurons (magenta) and astrocytes (blue) – interact in a dish as they do in a developing human  brain.
Courtesy of the Pasca lab

Neurological diseases are among the most daunting diagnoses for a patient to receive, because they impact how the individual interacts with their surroundings. Central to our ability to provide better treatment options for these patients, is scientists’ capability to understand the biological factors that influence disease development and progression. Researchers at the Stanford University School of Medicine have made an important step in providing neuroscientists a better tool to understand the brain.

While animal models are excellent systems to study the intricacies of different diseases, the ability to translate any findings to humans is relatively limited. The next best option is to study human stem cell derived tissues in the laboratory. The problem with the currently available laboratory-derived systems for studying the brain, however, is the limited longevity and diversity of neuronal cell types. Dr. Sergiu Pasca’s team was able to overcome these hurdles, as detailed in their study, published in the journal Nature Neuroscience.

A new approach

Specifically, Dr. Pasca’s group developed a method to differentiate or transform skin derived human induced pluripotent stem cells (iPSCs – which are capable of becoming any cell type) into brain-like structures that mimic how oligodendrocytes mature during brain development. Oligodendrocytes are most well known for their role in myelinating neurons, in effect creating a protective sheath around the cell to protect its ability to communicate with other brain cells. Studying oligodendrocytes in culture systems is challenging because they arise later in brain development, and it is difficult to generate and maintain them with other cell types found in the brain.

These scientists circumvented this problem by using a unique combination of growth factors and nutrients to culture the oligodendrocytes, and found that they behaved very similarly to oligodendrocytes isolated from humans. Most excitingly, they observed that the stem cell-derived oligodendrocytes were able to myelinate other neurons in the culture system. Therefore they were both physically and functionally similar to human oligodendrocytes.

Importantly, the scientists were also able to generate astrocytes alongside the oligodendrocytes. Astrocytes perform many important functions such as providing essential nutrients and directing the electrical signals that help cells in the brain communicate with each other. In a press release, Dr. Pasca explains the importance of generating multiple cell types in this in vitro system:

“We now have multiple cell types interacting in one single culture. This permits us to look close-up at how the main cellular players in the human brain are talking to each other.”

This in vitro or laboratory-developed system has the potential to help scientists better understand oligodendrocytes in the context of diseases such as multiple sclerosis and cerebral palsy, both of which stem from improper myelination of brain nerve cells.

This work was partially supported by a CIRM grant.

Breakthrough for type 1 diabetes: scientist discovers how to grow insulin-producing cells

Matthias Hebrok, PhD, senior author of new study that transformed human stem cells into mature, insulin-producing cells. Photo courtesy of UCSF.

More often than not, people don’t really think about their blood sugar levels before sitting down to enjoy a delicious meal, partake in a tasty dessert, or go out for a bicycle ride. But for type 1 diabetes (T1D) patients, every minute and every action revolves around the readout from a glucose meter, a device used to measure blood sugar levels.

Normally, the pancreas contains beta cells that produce insulin in order to maintain blood sugar levels in the normal range. Unfortunately, those with T1D have an immune system that destroys their own beta cells, thereby decreasing or preventing the production of insulin and in turn the regulation of blood sugar levels. Chronic spikes in blood sugar levels can lead to blindness, nerve damage, kidney failure, heart disease, stroke, and even death.

Those with T1D manage their condition by injecting themselves with insulin anywhere from two to four times a day. A light workout, slight change in diet, or even an exciting event can have a serious impact that requires a glucose meter check and an insulin injection.

There are clinical trials involving transplants of pancreatic “islets”, clusters of cells containing healthy beta cells, but these rely on pancreases from deceased donors and taking immune suppressing drugs for life.

But what if there was a way to produce healthy beta cells in a lab without the need of a transplant?

Dr. Matthias Hebrok, director of the UCSF diabetes center, and Dr. Gopika Nair, postdoctoral fellow, have discovered how to transform human stem cells into healthy, insulin producing beta cells.

In a news release written by Dr. Nicholas Weiler of UCSF, Dr. Hebrok is quoted as saying “We can now generate insulin-producing cells that look and act a lot like the pancreatic beta cells you and I have in our bodies. This is a critical step towards our goal of creating cells that could be transplanted into patients with diabetes.”

For the longest time, scientists could only produce cells at an immature stage that were unable to respond to blood sugar levels and secrete insulin properly. Dr. Hebrok and Dr. Nair discovered that mimicking the “islet” formation of cells in the pancreas helped the cells mature. These cells were then transplanted into mice and found that they were fully functional, producing insulin and responding to changes blood sugar levels.

Dr. Hebrok’s team is already in collaboration with various colleagues to make these cells transplantable into patients.

Gopika Nair, PhD, postdoctoral fellow that led the study for transforming human stem cells into mature, insulin-producing cells. Photo courtesy of UCSF.

Dr. Nair in the article is also quoted as saying “Current therapeutics like insulin injections only treat the symptoms of the disease. Our work points to several exciting avenues to finally finding a cure.”

“We’re finally able to move forward on a number of different fronts that were previously closed to us,” Hebrok added. “The possibilities seem endless.” 

Dr. Hebrok, who is also a member of the CIRM funded UCSF Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, was senior author of the new study, which was published February 1, 2019 in Nature Cell Biology.

CIRM has funded three separate human clinical trials for T1D that total approximately $37.8 million in awards. Two of these trials are being conducted by ViaCyte, Inc. and the third trial is being conducted by Caladrius Biosciences.

Tips on how to be a great Patient Advocate from three of the best Advocates around

No one sets out to be a Patient Advocate. It’s something that you become because of something that happens to you. Usually it’s because you, or  a loved one or a friend, becomes ill and you want to help find a treatment. Whatever the reason, it is the start of a journey that often throws you into a world that you know nothing about: a world of research studies and scientific terminology, of talking to and trying to understand medical professionals, and of watching someone you love struggle.

It’s a tough, demanding, sometimes heart-breaking role. But it’s also one of the most important roles you can ever take on. Patient Advocates not only care for people afflicted with a particular disease or disorder, they help them navigate a new and scary world, they help raise money for research, and push researchers to work harder to find new treatments, maybe even cures. And they remind all of us that in the midst of pain and suffering the human touch, a simple kindness is the most important gift of all.

But what makes a great Patient Advocate, what skills do you need and how can you get them? At CIRM we are blessed to have some of the most amazing Patient Advocates you will ever meet. So we asked three of them to join us for a special Facebook Live “Ask the Stem Cell Team” event to share their knowledge, experience and expertise with you.

The Facebook Live will be finalized in the upcoming weeks and posted on our Facebook Page so stay tuned!

The three experts are:

Gigi McMillan

Gigi McMillan became a Patient Advocate when her 5-year-old son was diagnosed with a brain tumor. That has led her to helping develop support systems for families going through the same ordeal, to help researchers develop appropriate consent processes and to campaign for the rights of children and their families in research.

Adrienne Shapiro

Adrienne Shapiro comes from a family with a long history of Sickle Cell Disease (SCD) and has fought to help people with SCD have access to compassionate care. She is the co-founder of Axis Advocacy, an organization dedicated to raising awareness about SCD and support for those with it. In addition she is now on the FDA’s Patient Engagement Collaborative, a new group helping the FDA ensure the voice of the patient is heard at the highest levels.

David Higgins

David Higgins is a CIRM Board member and a Patient Advocate for Parkinson’s Disease. David has a family history of the disease and in 2011 was diagnosed with Parkinson’s. As a scientist and advocate he has championed research into the disease and strived to raise greater awareness about the needs of people with Parkinson’s.

Please join us for our Facebook Live event on Patient Advocates and feel free to share information about the event with anyone you think would be interested.

Rare Disease Gets Big Boost from California’s Stem Cell Agency

UC Irvine’s Dr. Leslie Thompson and patient advocate Frances Saldana after the CIRM Board vote to approve funding for Huntington’s disease

If you were looking for a poster child for an unmet medical need Huntington’s disease (HD) would be high on the list. It’s a devastating disease that attacks the brain, steadily destroying the ability to control body movement and speech. It impairs thinking and often leads to dementia. It’s always fatal and there are no treatments that can stop or reverse the course of the disease. Today the Board of the California Institute for Regenerative Medicine (CIRM) voted to support a project that shows promise in changing that.

The Board voted to approve $6 million to enable Dr. Leslie Thompson and her team at the University of California, Irvine to do the late stage testing needed to apply to the US Food and Drug Administration for permission to start a clinical trial in people. The therapy involves transplanting stem cells that have been turned into neural stem cells which secrete a molecule called brain-derived neurotrophic factor (BDNF), which has been shown to promote the growth and improve the function of brain cells. The goal is to slow down the progression of this debilitating disease.

“Huntington’s disease affects around 30,000 people in the US and children born to parents with HD have a 50/50 chance of getting the disease themselves,” says Dr. Maria T. Millan, the President and CEO of CIRM. “We have supported Dr. Thompson’s work for a number of years, reflecting our commitment to helping the best science advance, and are hopeful today’s vote will take it a crucial step closer to a clinical trial.”

Another project supported by CIRM at an earlier stage of research was also given funding for a clinical trial.

The Board approved almost $12 million to support a clinical trial to help people undergoing a kidney transplant. Right now, there are around 100,000 people in the US waiting to get a kidney transplant. Even those fortunate enough to get one face a lifetime on immunosuppressive drugs to stop the body rejecting the new organ, drugs that increase the risk for infection, heart disease and diabetes.  

Dr. Everett Meyer, and his team at Stanford University, will use a combination of healthy donor stem cells and the patient’s own regulatory T cells (Tregs), to train the patient’s immune system to accept the transplanted kidney and eliminate the need for immunosuppressive drugs.

The initial group targeted in this clinical trial are people with what are called HLA-mismatched kidneys. This is where the donor and recipient do not share the same human leukocyte antigens (HLAs), proteins located on the surface of immune cells and other cells in the body. Around 50 percent of patients with HLA-mismatched transplants experience rejection of the organ.

In his application Dr. Meyer said they have a simple goal: “The goal is “one kidney for life” off drugs with safety for all patients. The overall health status of patients off immunosuppressive drugs will improve due to reduction in side effects associated with these drugs, and due to reduced graft loss afforded by tolerance induction that will prevent chronic rejection.”

Gene therapy and blood stem cells cure sickle cell disease patients

Sickle-shaped blood cells. The cells become lodged in blood vessels, causing strokes or excruciating pain as blood stops flowing. Photo courtesy of Omikron/Science Source

Blood is the lifeline of the body. The continuous, unimpeded circulation of blood maintains oxygen flow throughout the body and enables us to carry out our everyday activities. Unfortunately, there are individuals whose own bodies are in a constant battle that prevents this from occurring seamlessly. They have something known as sickle cell disease (SCD), an inherited condition caused by a mutation in a single gene. Rather than producing normal, circular red blood cells, their bodies produce sickle shaped cells (hence the name) that can become lodged in blood vessels, preventing blood flow. The lack of blood flow can cause agonizing pain, known as crises, as well as strokes. Chronic crises can cause organ damage, which can eventually lead to organ failure. Additionally, since the misshapen cells don’t survive long in the body, people with SCD have a greater risk of being severely anemic and are more prone to infections. Monthly blood transfusions are often needed to help temporarily alleviate symptoms. Due to the debilitating nature of SCD, important aspects of everyday life such as employment and health insurance can be extremely challenging to find and maintain.

An estimated 100,000 people in the United States are living with SCD. Around the world, about 300,000 infants are born with the condition each year, a statistic that will increase to 400,000 by 2050 according to one study. Many people with SCD do not live past the age of 50. It is most prevalent in individuals with sub-Saharan African descent followed by people of Hispanic descent. Experts have stated that advances in treatment have been limited in part because SCD is concentrated in poorer minority communities.

Despite these grim statistics and prognosis, there is hope.

The New York Times and Boston Herald recently released featured articles that tell the personal stories of patients enrolled in a clinical trial conducted by bluebird bio. The trial uses gene therapy in combination with hematopoietic (blood) stem cells (HSCs) to give rise to normal red blood cells in SCD patients.

Here are the stories of these patients. To read the full New York Times article, click here. For the Boston Herald article, click here.

Brothers, Emmanuel “Manny” 21 and Aiden Johnson 7 at their home in Brockton, Massachusetts. Both brothers were born with sickle cell disease. Photo courtesy of Matt Stone for MediaNews Group/Boston Herald

Emmanuel “Manny” Johnson was the very first patient in the SCD trial. He was motivated to participate in the trial not just for himself but for his younger brother Aiden Johnson, who was also born with SCD. Manny has a tattoo with Aiden’s name written inside a red sickle cell awareness ribbon.

In the article Manny is quoted as saying “It’s not only that we share the same blood disease, it’s like I have to do better for him.”

Since receiving the treatment, Manny’s SCD symptoms have disappeared.

Brandon Williams received the stem cell gene therapy to replace sickle cells with healthy red blood cells. The tattoo on his right forearm is in honor of his sister, Britney, who died of sickle cell disease. Photo courtesy of Alyssa Schukar for The New York Times

For Brandon Williams of Chicago, the story of SCD is a very personal one. At just 21 years old, Brandon had suffered four strokes by the time he turned 18. His older sister, Britney Williams, died of sickle cell disease at the age of 22. Brandon was devastated and felt that his own life could end at any moment. He was then told about the SCD trial and decided to enroll. Following the treatment, his symptoms have vanished along with the pain and fear inflicted by the disease.

Carmen Duncan participated in the stem cell gene therapy trial and no longer has sickle-cell symptoms. She wants to join the military, something that wasn’t an option until now. Photo courtesy of Sean Rayford for The New York Times

The NY Times piece also profiles Carmen Duncan, a 20 year old from Charleston, South Carolina. She had her spleen removed when she was just two years old as a result of complications form SCD. Duncan spent a large portion of her childhood in hospitals, coping with the pain in her arms and legs from blocked blood vessels. She enrolled in the SCD trial as well and she no longer has any signs of SCD. Duncan had aspirations to join the military but was unable to because of her condition. Now that she is symptom free, she plans to enlist.

This SCD clinical trial has multiple trial sites across the US, one which is the UCSF Alpha Stem Cell Clinic , a CIRM funded clinic specializing in the delivery of stem cell clinical trials to patients. CIRM awarded a $7,999,999 grant to help establish this site.

Media shine a spotlight on dodgy stem cell clinics

A doctor collects fat from a patient’’s back as part of an experimental stem cell procedure in Beverly Hills, Calif. on Dec. 5, 2014. (Raquel Maria Dillon / Associated Press)

For several years now, we have been trying to raise awareness about the risks posed by clinics offering unproven or unapproved stem cell therapies. At times it felt as if we were yelling into the wind, that few people were listening. But that’s slowly changing. A growing number of TV stations and newspapers are picking up the message and warning their readers and viewers. It’s a warning that is getting national exposure.

Why are we concerned about these clinics? Well, they claim their therapies, which usually involve the patient’s own fat or blood cells, can cure everything from arthritis to Alzheimer’s. However, they offer no scientific proof, have no studies to back up their claims and charge patients thousands, sometimes tens of thousands of dollars.

In the LA Times, for example, reporter Usha Lee McFarling, wrote an article headline “California has gone crazy for sketchy stem cell treatments”. In it she writes about the claims made by these clinics and the dangers they pose:

“If it sounds too good to be true, it is. There is no good scientific evidence the pricey treatments work, and there is growing evidence that some are dangerous, causing blindness, tumors and paralysis. Medical associations, the federal government and even Consumer Reports have all issued stern warnings to patients about the clinics.”

In Denver, the ABC TV station recently did an in-depth interview with a local doctor who is trying to get Colorado state legislators to take legal action against stem cell clinics making these kinds of unsupported claims.

Chris Centeno of the Centeno-Schultz Clinic, who’s specialized in regenerative medicine and research for more than a decade, said too many people are simply being scammed.

“It’s really out of control,” he told the station.

ABC7 did a series of reports last year on the problem and that may be prompting this push for a law warning consumers about the dangers posed by these unregulated treatments which are advertised heavily online, on TV and in print.

In California there is already one law on the books attempting to warn consumers about these clinics. CIRM worked with State Senator Ed Hernandez to get that passed (you can read about that here) and we are continuing to support even stronger measures.

And the NBC TV station in San Diego recently reported on the rise of stem cell clinics around the US, a story that was picked up by the networks and run on the NBC Today Show.

One of the critical elements in helping raise awareness about the issue has been the work done by Paul Knoepfler and Leigh Turner in identifying how many of these clinics there are around the US. Their report, published in the journal Cell Stem Cell, was the first to show how big the problem is. It attracted national attention and triggered many of the reports that followed.

It is clear momentum is building and we hope to build on that even further. Obviously, the best solution would be to have the Food and Drug Administration (FDA) crack down on these clinics, and in some cases they have. But the FDA lacks the manpower to tackle all of them.

That’s where the role of the media is so important. By doing stories like these and raising awareness about the risks these clinics pose they can hopefully help many patients avoid treatments that will do little except make a dent in their pocket.

Targeted treatment for pediatric brain tumors shows promising results

Image of medulloblastoma

Imagine sitting in the doctor’s office and being told the heartbreaking news that your child has been diagnosed with a malignant brain tumor. As one might expect, the doctor states that the most effective treatment option is typically a combination of chemotherapy and radiation. However, the doctor reveals that there are additional risks to take into account that apply to children. Since children’s tiny bodies are still growing and developing, chemotherapy and radiation can cause long-term side effects such as intellectual disabilities. As a parent, it is painful enough to have to watch a child go through chemotherapy and radiation without adding permanent damage into the fold.

Sadly, this scenario is not unique. Medulloblastoma is the most prevalent form of a pediatric brain tumor with more than 350 children diagnosed with cancer each year. There are four distinct subtypes of medulloblastoma, with the deadliest being known as Group 3.

Researchers at Sanford Burnham Prebys Medical Discovery Institute (SBP) are trying to minimize the collateral damage by finding personalized treatments that reduce side effects while remaining effective. Scientists at SBP are working with an inhibitor known as LSD1 that specifically targets Group 3 medulloblastoma in a mouse model. The study, published in Nature Communications, showed that the drug dramatically decreased the size of tumors grown under the mouse’s skin by shrinking the cancer by more than 80 percent. This suggested that it could also be effective against patients’ tumors if it could be delivered to the brain. The LSD1 inhibitor has shown promise in clinical trials, where it has been tested for treating other types of cancer.

According to Robert Wechsler-Reya, Ph.D., senior author of the paper and director of the Tumor Initiation and Maintenance Program at SBP: “Our lab is working to understand the genetic pathways that drive medulloblastoma so we can find better ways to intervene and treat tumors. This study shows that a personalized treatment based upon a patient’s specific tumor type might be within our reach.”

Dr. Wechsler-Reya’s work on medulloblastoma was, in part, funded by the CIRM (LA1-01747) in the form of a Research Leadership Award for $5,226,049.

CIRM-supported Type I Diabetes treatment enters clinical trials in Europe

Viacyte images

ViaCyte’s President & CEO, Paul Laikind

ViaCyte, a company that CIRM has supported for many years, has announced international expansion of a clinical trial to test their therapeutic PEC-Direct product in patients with Type I Diabetes.

The first European patient in Brussels was implanted with the PEC-Direct product candidate that, in animal models, is able to form functional beta cells. Patients with Type I Diabetes are unable to control blood glucose levels because their immune system attacks insulin-producing beta cells, which are responsible for regulating blood sugar.

viacyte device

ViaCyte PEC-Direct product candidate

The hope is that PEC-Direct would eliminate the need for patients to take daily doses of insulin, the current treatment standard to prevent the side effects of high blood glucose levels, such as heart disease, kidney damage and nerve damage.

The PEC-Direct product is implanted under the skin. The progenitor cells inside it are designed to mature in to human pancreatic islet cells, including glucose-responsive insulin-secreting beta cells, following implant. These are the cells destroyed by Type 1 Diabetes

In this first phase of the clinical trial, patients are administered a subtherapeutic dose of the drug to ensure that that the implants are able to generate beta cells in the body. The next part of the trial will determine whether or not the formed beta cells are able to produce appropriate levels of insulin and modulate blood glucose levels. A sister trial is currently underway in North America as well. This work is a collaboration between ViaCyte and The Center for Beta Cell Therapy in Diabetes.

Separately, ViaCyte has also made important headway to make stem cells more effective in different types of diseases by programming them to evade the immune system. This progress has been cited by the Global Human Embryonic Stem Cells Market report as a key development in growing the overall global stem cell market.

CIRM is proud to be a supporter of companies such as ViaCyte that are conducting groundbreaking research to make stem cell therapy an effective and realistic treatment option for many different diseases.

 

 

A Bridge to the future for stem cell students

cirmbridges2016-2042_600px_0

Students present their research finding at the 2016 CIRM Bridges conference

One of the programs people here at CIRM love is our Bridges to Stem Cell Research Awards. These are given to undergraduate and master’s level college students, to train the next generation of stem cell scientists. How good a program is it? It’s terrific. You don’t have to take my word for it. Just read this piece by a great stem cell champion, Don Reed. Don is the author of two books about CIRM, Stem Cell Battles and California Cures! so he clearly knows what he’s talking about.

ADVENTURES ON “BRIDGES”: Humboldt State Stem Cell Research

By Don C. Reed

Imagine yourself as a California college student, hoping to become a stem cell researcher. Like almost all students you are in need of financial help, and so (let’s say) you asked your college counselor if there were any scholarships available.

To your delight, she said, well, there is this wonderful internship program called Bridges, funded by the California Institution for Regenerative Medicine (CIRM) which funds training in stem cell biology and regenerative medicine — and so, naturally, you applied…

If you were accepted, how might your life change?

https://www.cirm.ca.gov/our-funding/research-rfas/bridges

After doing some basic training at the college, you would receive a grant (roughly $40,000) for a one-year internship at a world-renowned stem cell research facility. What an incredible leap forward in your career, hands-on experience (essentially a first job, great “experience” for the resume) as well an expert education.

Where are the 14 California colleges participating in this program? Click below:

https://www.cirm.ca.gov/our-funding/funded-institutions

Let’s take a look at one of these college programs in action: find out what happened to a few of the students who received a Bridges award, crossing the gap between studying stem cell research and actually applying it.

HSU information is courtesy of Dr. Amy Sprowles, Associate Professor of Biological Sciences and Co-Director of the Bridges program at Humboldt State University (HSU), 279 miles north of San Francisco.

Dr. Amy Sprowles

“The HSU Bridges program”, says Dr. Sprowles, “was largely developed by four people: Rollin Richmond, then HSU President, who worked closely with Susan Baxter, Executive Director of the CSU Program for Education and Research in Biotechnology, to secure the CIRM Bridges initiative; HSU Professor of Biological Sciences Jacob Varkey, who pioneered HSU’s undergraduate biomedical education program”, and Sprowles herself, at the time a lecturer with a PhD in Biochemistry.

The program has two parts: a beginning course in stem cell research, and a twelve-month internship in a premiere stem cell research laboratory. For HSU, these are at Stanford University, UC Davis, UCSF, or the Scripps Research Institute.

Like all CIRM Bridges programs, the HSU stem cell program is individually designed to suit the needs of its community.

Each of the 15 CIRM Bridges Programs fund up to ten paid internships, but the curriculum and specific activities of each are designed by their campus directors. The HSU program prepares Bridges candidates by requiring participation in a semester-long lecture and stem cell biology laboratory course before selection for the program: a course designed and taught by Sprowles since its inception.

She states, “The HSU pre-internship course ensures our students are trained in fundamental scientific concepts, laboratory skills and professional behaviors before entering their host laboratory. We find this necessary since, unlike the other Bridges campuses, we are 300+ miles away from the internship sites and are unable to fully support this kind of training during the experience. It also provides additional insights about the work ethic and mentoring needs of the individuals we select that are helpful in placing and supporting our program participants”.

How is it working?

Ten years after it began, 76 HSU students have completed the CIRM Bridges program at HSU. Of those, the overwhelming majority (over 85%) are committed to careers in regenerative medicine: either working in the field already, or continuing their education toward that goal.

But what happened to their lives? Take a brief look at the ongoing careers of a “Magnificent Seven” HSU Bridges scientists:

CARSTEN CHARLESWORTH: “Spurred by the opportunity to complete a paid internship at a world class research institution in Stem Cell Biology, I applied to the Humboldt CIRM Bridges program, and was lucky enough to be accepted. With a keen interest in the developing field of genome editing and the recent advent of the CRISPR-Cas9 system I chose to intern in the lab of a pioneer in the genome editing field, Dr. Matthew Porteus at Stanford, who focuses in genome editing hematopoietic stem cells to treat diseases such as sickle cell disease. In August of 2018 I began a PhD in Stanford’s Stem Cell and Regenerative Medicine program, where I am currently a second-year graduate student in the lab of Dr. Hiro Nakauchi, working on the development of human organs in interspecies human animal chimeras. The success that I’ve had and my acceptance into Stanford’s world class PhD program are a direct result of the opportunity that the CIRM Bridges internship provided me and the excellent training and instruction that I received from the Humboldt State Biology Program.”

ELISEBETH TORRETTI: “While looking for opportunities at HSU, I stumbled upon the CIRM Bridges program. It was perfect- a paid internship at high profile labs where I could expand my research skills for an entire year… the best fit (was) Jeanne Loring’s Lab at the Scripps Research Institute in La Jolla, CA. Dr. Loring is one of the premiere stem cell researchers in the world… (The lab’s) main focus is to develop a cure for Parkinson’s disease. (They) take skin cells known as fibroblasts and revert them into stem cells. These cells, called induced pluripotent stem cells (iPSCs) can then be differentiated into dopaminergic neurons and transplanted into the patient…. My project focused on a different disease: adenylate-cyclase 5 (ADCY5) — related dyskinesia. During my time at Dr. Loring’s lab I learned incredibly valuable research skills. I am now working in a mid-sized biotch company focusing on cancer research. I don’t think that would be possible in a competitive area like San Diego without my experience gained through the CIRM Bridges program.”

BRENDAN KELLY: “After completing my CIRM internship in Dr. Marius Wernig’s lab (in Stanford), I began working at a startup company called I Peace. I helped launch this company with Dr. Koji Tanabe, whom I met while working in my host lab. I am now at Cardiff University in Wales working on my PhD. My research involves using patient iPSC derived neurons to model Huntington’s disease. All this derived from my opportunity to partake in the CIRM-Bridges program, which opened doors for me.”

SAMANTHA SHELTON: “CIRM Bridges provided invaluable hands-on training in cell culture and stem cell techniques that have shaped my future in science. My CIRM internship in John Rubenstein’s Lab of Neural Development taught me amazing laboratory techniques such as stem cell transplantation as well as what goes into creating a harmonious and productive laboratory environment. My internship projects led to my first co-first author publication.

After my Bridges internship, I joined the Graduate Program for Neuroscience at Boston University. My PhD work aims to discover types of stem cells in the brain and how the structure of the brain develops early in life. During this time, I have focused on changes in brain development after Zika virus infection to better understand how microcephaly (small skulls and brains, often a symptom of Zika-DR) is caused. There is no doubt that CIRM not only made me a more competitive candidate for a doctoral degree but also provided me with tools to progress towards my ultimate goal of understanding and treating neurological diseases with stem cell technologies.”

DU CHENG: “Both my academic and business tracks started in the CIRM-funded…fellowship (at Stanford) where I invented the technology (the LabCam Microscope adapter) that I formed my company on (iDU Optics LLC). The instructor of the class, Dr. Amy Sprowles, encouraged me to carry on the idea. Later, I was able to get in the MD-PhD program at Weill Cornell Medical College because of the invaluable research experiences CIRM’s research program provided me. CIRM initiated the momentum to get me where I am today. Looking back, the CIRM Bridges Program is an instrumental jump-starter on my early career… I would not remotely be where I am without it.…”

CODY KIME: “Securing a CIRM grant helped me to take a position in the Nobel Prize winning Shinya Yamanaka Lab at the Gladstone Institutes, one of the most competitive labs in the new field of cell reprogramming. I then explored my own reprogramming interests, moving to the Kyoto University of Medicine, Doctor of Medical Sciences Program in Japan, and building a reprogramming team in the Masayo Takahashi Lab at RIKEN. My studies explore inducing cells to their highest total potential using less intrusive means and hacking the cell program. My systems are designed to inform my hypotheses toward a true お好みの細胞 (okonomi no cybo) technology, meaning ‘cells as you wish’ in Japanese, that could rapidly change any cell into another desired cell type or tissue.”

Sara Mills

SARA MILLS: “The CIRM Bridges program was the key early influencer which aided in my hiring of my first industry position at ViaCyte, Inc. Also a strongly CIRM funded institution, I was ultimately responsible for the process development of the VC-01™ fill, finish processes and cGMP documentation development. Most recently, with over two years at the boutique consulting firm of Dark Horse Consulting, Inc., I have been focusing on aseptic and cGMP manufacturing process development, risk analysis, CMC and regulatory filings, facility design and project management to advise growing cell and gene therapy companies, worldwide.”

Like warriors fighting to save lives, these young scientists are engaged in an effort to study and defeat chronic disease. It is to be hoped the California stem cell program will have its funding renewed, so the “Bridges” program can continue.

For more information on the Bridges program, which might help a young scientist (perhaps yourself) cut and paste the following URL:

https://www.cirm.ca.gov/our-impact/internship-programs

One closing paragraph perhaps best sums up the Bridges experience:

“During my CIRM Bridges training in Stanford University, I was fortunate to work with Dr. Jill Helms, who so patiently mentored me on research design and execution. I ended up publishing 7 papers with her during the two-year CIRM internship and helped making significant progress of turning a Stem Cell factor into applicable therapeutic form, that is currently in preparation for clinical trial by a biotech company in Silicon Valley. I also learned from her how to write grants and publications, but more importantly, (to) never limit your potential by what you already know.” — Du Cheng