Renowned philanthropist and businessman T. Denny Sanford passed away July 18, 2026 in his hometown of Sioux Falls, South Dakota. He was 90 years old.
Renowned philanthropist and businessman T. Denny Sanford passed away July 18, 2026 in his hometown of Sioux Falls, South Dakota. He was 90 years old.
A self-made billionaire, Sanford had spent recent decades diligently spreading that wealth through philanthropy, primarily focusing on education, health services and biomedical research. His motto: “Aspire to inspire before you expire.”
“Denny was larger than life. He loved people, philanthropy, business and golf. He was my supporter and advisor, but more importantly, my confidant and friend. Denny was fascinated by science and education, especially in advancing ideas and efforts that would make lives better, both in terms of health and in well-being,” said David Brenner, CEO and president of Sanford Burnham Prebys Medical Discovery Institute.
“His generosity was manifest, from supporting research and treatment of rare children’s diseases to stem cells to recruiting new generations of bright, young scientists to carry on the work. He loved to hear about how his philanthropic investments have benefited young people.”
Sanford Burnham Prebys was a frequent beneficiary. In 2007, for example, Sanford gave the institute $20 million through Sanford Health, the largest rural health system in the U.S. and a longtime beneficiary of Sanford. The gift helped the then-called Burnham Institute to create the Sanford Children’s Health Research Center. A year later, Sanford donated $30 million to create the Sanford Consortium for Regenerative Medicine, with the Institute as a founding member.
Two years later, Sanford donated $50 million and The Burnham Institute became the Sanford-Burnham Medical Research Institute. In 2023, he gave $70 million to Sanford Burnham Prebys to launch an ambitious plan to recruit up to 20 new scientists.
Sanford has been an honorary trustee at Sanford Burnham Prebys since 2009.
“Long before Denny’s and my names became inextricably linked through the Sanford Burnham Prebys Medical Discovery Institute, we shared a common goal to make an impact in our communities and to serve others,” said Malin Burnham, who has served on its board of directors since 1982. “Denny embodied that purpose throughout his life, generously investing himself and his resources to benefit others, often with truly transformational results.”
“Denny’s commitment to health and medicine was extraordinarily broad and deep,” noted Donald Kearns, MD, chair of the Board of Directors at Sanford Burnham Prebys and president emeritus of Rady Children’s Hospital-San Diego. Indeed he partnered with and supported specialized pediatric care for local families through the hospital, Sanford Children’s Clinic in Oceanside and the Children’s Primary Care Medical Group.
Sanford fundamentally believed that basic research and the benefits derived were driven and sustained by the people who do it. That was most evident in his philanthropy supporting education and in supporting new generations of scientists, said Brenner.
“Denny was a visionary committed to making a better world. His $70 million gift to recruit new faculty—the young investigators who will be future leaders—was a transformational investment in the continued strength of biomedical research at Sanford Burnham Prebys and across the Torrey Pines Mesa.,” said Brenner.
Sanford was born in Saint Paul, Minn. in 1935 during the Great Depression. His mother died of breast cancer when he was four years old. “She had been in the hospital for about a year before she died, so I have no memory of her at all,” Sanford recalled, but her death would inspire significant, subsequent support of cancer research by her son.
His father passed when he was 20.
“We have a lot of heart disease in my family,” he told the Horatio Alger Association, which honored him in 2016. “My father had several heart attacks throughout my childhood. My older brother had a fatal heart attack at the age of 40. I also had a heart attack at the age of 44, but I have had good health since then. But the loss of my father when I was still so young was a major blow to me.
“He was the most caring person I ever met. He never graduated high school because he had to help support his family. He was very giving, and I think my ideas about philanthropy, which is such an important part of my life today, came from him.”
Sanford did graduate from high school—and the University of Minnesota in 1959. In the following years, Sanford would be a sales representative for industrial cork and building materials. He started a distribution company that he transformed into a manufacturing and research firm.
In 1986, he purchased a small bank in Sioux Falls, South Dakota with $80 million in assets, then created a credit card business: United National Corp., with its two subsidiaries, First Premier Bank and Premier Bankcard, soon had a $1 billion portfolio of credit card loans.
The scope of Sanford’s philanthropy is staggering.
He has donated more than $1 billion to Sanford Health, a system of 48 medical centers, 211 clinics and 160 senior living centers in the upper Midwest, California and Florida, including funding to establish the Edith Sanford Breast Center in honor of his mother.
In addition, Sanford has made multi-million dollar gifts to the Sanford Underground Research Facility, the Sioux Falls Development Foundation, the Sioux Falls Zoo and Aquarium and the Children’s Home Society of South Dakota.
A part-time resident of San Diego, Sanford has made similar and substantial gifts to a host of local institutions: UC San Diego, National University, the Salk Institute, San Diego Public Library and the Zoological Society of San Diego.
To date, it’s estimated Sanford’s total philanthropy is approximately $2 billion.
“We are on earth to provide for other people, not just ourselves and our families,” Sanford said before his induction into South Dakota’s Hall of Fame in 2007. “We all have the opportunity to work a little bit harder and help someone else, not just ourselves.”
Remembrances
“One of the greatest gifts of my 20-plus-year friendship with Denny was learning how deeply he cared about helping others. Whether we were talking about life, philanthropy or our Institute, he always brought the conversation back to making a difference. He believed that a truly meaningful life is measured by the impact you have on people’s lives. That philosophy has stayed with me ever since and continues to guide the mission and purpose of our biomedical research.”
Kristiina Vuori, MD, PhD
Professor
Cancer Genome and Epigenetics Program
Pauline and Stanley Foster Distinguished Chair
“I’ve always felt Denny was the older, wiser brother I never had. First time I saw his smile and those blue eyes with shirt to match, I knew I was in friendly territory. But friendly was quite an understatement. Right from the beginning, he wanted to know what we at the institute and me personally could do for kids. He was all about kids, especially those who didn’t get all the normal genes like the rest of us. Those blue eyes were quick to glow when meeting some of the kids we’ve worked with, and especially those few we’ve ‘saved.’ Those eyes teared up easily when he met the kids that neither of us could help. But their smiles would coax out a broad grin on that man’s kind and generous face.
“Whenever we had a big meeting inviting families, scientists and physicians, Denny was right there to welcome everyone and let them know how important they were to him. He showed it all the time. The kids and families wrote him thank you notes and, years later, he’d ask me about some of them.
“They asked about him too. Last year I went to a meeting in Sioux Falls and Denny said, ‘Let’s get together.’ I thought he meant a friendly drink. Not Denny. He’s the surprise man, asking me, “What do you need, pal?” I was caught totally off guard, speechless. He quickly added, ‘Not for you, for the kids.’
“He was generous, but you had to pull your own weight. We mostly got there. Just like 20 years before, being around my ‘big brother’ was all I needed. Of course, seeing that blue-eyed smile always charmed me. In May, he came to my birthday party, maybe he knew it would be our last time. I’ll miss those eyes, that man and his advice.”
Hudson Freeze, PhD
Director, Sanford Children’s Research Center
Professor
William W. Ruch Distinguished Endowed Chair
“Denny Sanford’s passing marks the loss of a truly extraordinary philanthropist whose vision, generosity and unwavering belief in the power of people to make a difference will be felt for generations.
“His support was instrumental in bringing Dr. David Brenner to Sanford Burnham Prebys, setting in motion the recruitment of world-class scientists whose discoveries continue to advance human health.
“Beyond our institute, Denny’s commitment to improving lives touched countless organizations and communities through his remarkable philanthropy. His legacy lives on not only in the buildings that bear his name, but in the scientific breakthroughs, healthier lives and brighter futures made possible by his generosity. As we honor his memory, we do so with deep gratitude and a renewed commitment to carry forward the vision he so passionately believed in.”
Lori Moore
Vice Chair, Sanford Burnham Prebys Board of Directors
“Over the fifteen years I have directed the Prebys Center for Chemical Genomics and the Center for Therapeutics Discovery, I have seen what it means for an institution to be shaped by Denny Sanford’s vision.
“Denny did not merely support biomedical research in the abstract: He embraced, and then championed, the harder and less certain part of our mission — the part that moves beyond understanding the molecular basis of disease into discovering first-in-class drugs for the diseases that have proven so stubbornly difficult to treat.
“That expansion of ambition was not the safe path. It was the visionary one, and it took someone who grasped the big picture: that transformational advances in healthcare for all begin with someone willing to fund the decades-long, uncertain crossing from biology to medicine.
“The pipeline of emerging therapeutics we are advancing today — for pain, for addiction, for cancer, for neurodegeneration — exists in large measure because Denny believed that ‘curing incurable diseases’ was a worthy investment, not a naive one. The tribute he would value most is not words, but the work itself — bringing these drugs to the patients who need them. That is the promise his generosity made possible, and the one we strive to keep.”
Michael Jackson, PhD
Senior Vice President, Drug Discovery and Development
Conrad Prebys Center for Chemical Genomics
Director, Center for Therapeutics Discovery
Associate Director, Translational Initiatives
“As a board member of Sanford Burnham Prebys, what I admired most about Denny was that his generosity didn’t just fund buildings or research. It gave big ideas the chance to become breakthroughs and helped transform our institute into a place capable of changing the future.
“As a San Diegan, I believe our fair city is healthier, stronger and more hopeful because he chose to invest here. His vision lives on in the discoveries we make, the patients we help and the lives we improve.
“As a person, Denny made me think bigger about what philanthropy can accomplish, and to believe that each of us can be a part of something greater than ourselves. His legacy will continue to inspire me—and many others—to do the very best we can, just as he did.”
Katherine Chapin
Sanford Burnham Prebys Board of Directors
“Like so many in our Sanford Burnham Prebys family, I am deeply saddened by the passing of Denny Sanford, who was a remarkable philanthropist, visionary and long-time friend. Denny’s unwavering belief in the power of scientific discovery shaped our institute and empowered our scientists to pursue breakthroughs that will bring hope to patients and families for generations to come.
“His legacy extends far beyond his extraordinary philanthropy. He inspired all of us to think bigger, dream bolder and recognize the power of philanthropy to accelerate medical discovery. As we mourn his passing, we also celebrate a life devoted to improving the human condition and making a lasting impact. There is no greater tribute we can offer than to carry his vision forward by cultivating a community of philanthropists who share his passion for discovery and are committed to ensuring that Sanford Burnham Prebys remains a place where bold science continues to change lives.”
Sandy Liarakos
Vice President, Philanthropy
Institute News
Sanford Burnham Prebys completes major renewable energy upgrades
Sanford Burnham Prebys recently completed a sweeping round of solar energy upgrades, including the installation of 1,690 solar panels, and 50 car charging stations, which are now available for employee use. These upgrades, which also include the implementation of new power storage infrastructure, are the latest in a series of major sustainability projects spearheaded by Sanford Burnham Prebys over the last two decades.
“Energy is one of the most important resources we have, and a critical part of supporting the Institute’s biomedical research is making sure our facilities can use and maintain that resource sustainably,” says John Reed, director of facilities at Sanford Burnham Prebys. “If we can benefit employees in the process by giving them access to electric car charging and saving them some gas money, that’s just a bonus.”
The upgrades will save a significant amount of energy for the Institute and could reduce yearly carbon emissions by as much as 696 metric tons. According to the EPA’s Greenhouse Gas Equivalencies Calculator, this is as much as the yearly emissions of 83 average homes.
“This is a major shift in the way our Institute consumes energy,” adds Reed.
The new solar panels cover the roofs of Building 5, 6, and 7, as well as the parking structure, known informally to employees as Building 8.
“It’s a bit of a joke that Building 8 is the least productive place on campus since it’s always just been a parking structure,” says Reed. “But with these upgrades, we won’t be able to say that anymore.”
This is not the first time Sanford Burnham Prebys has shown itself to be a leader in sustainability. In 2015, Sanford Burnham Prebys was recognized as a national trailblazer in water conservationafter a decade-long initiative to reduce waste by using recycled water for irrigation and cooling, as well as repurposing wastewater from water purification systems. The Institute also replaced its tropical plants with drought-resistant landscaping in 2007.
Employees interested in using the car charging ports for their electric vehicle will need to download the PowerFlex app on their mobile device, create an account with their institutional email address and provide some information about the vehicle. See powerflex.com for more information.
Institute News
New CIRM grant to fund research internships for underrepresented high school students
Thanks to a new grant awarded to Sanford Burnham Prebys by the California Institute for Regenerative Medicine (CIRM), 57 California high school students from underrepresented groups will have the chance to complete a paid internship at the Institute for the next five consecutive summers.
The mission of CIRM is to accelerate stem cell research and provide treatment to patients with unmet medical needs. And although CIRM directly funds faculty, many of their initiatives also focus on training the next generation of stem cell researchers. Late last year, Sanford Burnham Prebys received $5 million from CIRM to fund new training programs aimed at PhD students and postdoctoral researchers.
“One of the benefits of a program like this is that we’ll be able to inspire students early to pursue biomedical research,” says Checchi, a principal investigators on the grant and longtime educator of high school and undergraduate students. “A lot of students might not even realize that pursuing a STEM degree is an option for them, and that’s something we want to change.”
The new grant was awarded as part of CIRM’s SPARK Training Program, a diversity, equity and inclusion (DEI) initiative that targets high school students without access to summer research internship opportunities due to socioeconomic constraints. This grant is one of 11 awarded by CIRM to research institutions across California.
“At the high school level, a lot of research internships are unpaid, which can alienate a lot of students, especially if they’re also part of a group that isn’t represented well in scientific research to begin with,” says Checchi. “Programs like this help flip that script and will contribute to increased diversity in science over the long term.”
In addition to getting hands-on research experience, interns will also participate in community outreach, patient advocacy and other educational activities under the mentorship of experienced professors.
“The research element is obviously important, but programs like this also help students develop into confident, capable young scientists who are able to inspire those around them,” says Checchi. “We’re trying to plant the seed for these bright young minds to flourish.”
Institute News
Mark your calendars: Padres Pedal the Cause is back
Sanford Burnham Prebys is gearing up for next year’s Padres Pedal the Cause (PPTC), an annual fundraising race that invites participants to cycle, spin, run or walk to support cancer research in the San Diego area. The event, scheduled for April 9, 2022, at Petco Park, is currently planned to be held in person for the first time since the beginning of the pandemic.
Leveraging the power of San Diego PPTC was founded in 2013 by two-time lymphoma survivor Bill Koman and his wife, Amy. Thankful for the lifesaving care that Bill received, the Koman family was determined to pay it forward to ensure that others had the same outcome. With this goal in mind, the couple created PPTC, a cancer fundraising cycling challenge operating in partnership with the San Diego Padres.
Since the inaugural ride of PPTC, the organization has raised more than $15 million and funded 73 collaborative research projects in San Diego, including six clinical trials. They’ve also expanded and grown, merging with the Immunotherapy Foundation under a new name: Curebound.
Together, these two organizations share the belief that discovering a cure for cancer can be made possible by harnessing the unique power of San Diego—home to three nationally recognized National Institutes of Health cancer institutions and a renowned pediatric hospital. Last year, Curebound welcomed two new research partners: La Jolla Institute for Immunology and Scripps Research. They join Sanford Burnham Prebys, Moores Cancer Center at UC San Diego, the Salk Institute, and Rady Children’s Hospital in collaborating to accelerate cancer research into cures.
A pivotal year for Padres Pedal the Cause This is an important year for PPTC. After a record-breaking event in 2019—which had almost 3,000 participants and raised more than $3 million—COVID-19 presented challenges. The next PPTC event wasn’t held until spring 2021, moving to a virtual format due to the pandemic.
That event had 1,578 participants and raised $1.5 million. And while these numbers demonstrate the commitment of the Pedal the Cause community to continue their good work despite the pandemic, the amount is less than that received for the 2019 event, demonstrating the obstacles the community faced to raise those funds.
Now, PPTC is ready to ride at full speed for the first time in more than two years.
Join Team Sanford Burnham Prebys Padres Pedal the Cause ’22 will take place on April 9, 2022, at Petco Park, and registration is now open for the Sanford Burnham Prebys team. Whether you’re ready to ride, run, walk, spin, participate virtually or even just cheer from the sidelines, 100% of every dollar raised funds lifesaving cancer research.
Ride with Sanford Burnham Prebys this April, and help us create a world without cancer.
There are now two experimental vaccines for COVID-19 that are more than 90% effective—a remarkable development that has made the world collectively exhale. We caught up with our leading COVID-19 researchers to get their take on the update—including whether we are “out of the woods” and where they were when they heard the news.
Sumit Chanda, PhD, virologist I was at work, obsessively refreshing my browser to follow the election results when the first press release about the Pfizer vaccine popped up. When I heard 90% efficacy, I was super excited. I had sort of a sigh of relief. Then I read the fine print, and I started to have more guarded optimism. I’m not popping the champagne yet. But I’m putting it on ice.
The 90% measurement was taken starting only one week after the second booster shot. That’s not a lot of time, and with a pretty small number of people. What I am really looking for is how many people are protected two months and six months after the booster shot. That’s when I’m going to get really excited. We know that 90% is the ceiling, now we need to know where the floor is. Even if efficacy drops from 90 to 70%, that is still really great.
This is also why we will likely need multiple vaccines, and with different mechanisms of protection. This vaccine also has to be kept at -70 degrees Celsius, which presents a logistical challenge to say the least. Most doctor’s offices don’t have this type of specialized equipment, not to mention rural areas or less developed countries.
Today’s news that the Moderna vaccine is at least as effective as Pfizer’s is equally great news. However, we are still going to need antivirals. Between people who may not respond to these vaccines, can’t get the vaccines, or simply don’t want to take them, there is still going to be a lot of people who catch COVID-19. Luckily there are some antiviral options that are looking really good, including an antibody from Lilly that just got Emergency Use Authorization from the FDA.
With all this said, this is unequivocally good news. I am optimistic that we will have several vaccines that are usable in the next couple months. But for now, we need to mask up and keep social distancing.
Step inside Sumit Chanda’s lab where he and his colleagues are racing to find a potential treatment for COVID-19.
Carl Ware, PhD, immunologist and clinical trial participant
I first heard the news about the Pfizer vaccine on the radio when I was listening to KPBS’ surf report (Scott Bass is a poet). As an immunologist studying coronaviruses and a volunteer in the Moderna vaccine trial, I’m following all of the results closely. I immediately turned the volume up.
NBC San Diego spoke with Dr. Carl Ware about his experience participating in a clinical trial testing Moderna’s vaccine for COVID-19.
The news is very encouraging, and certainly shines a brighter light at the end of the proverbial tunnel. 90% effectiveness is very impressive. My excitement is mostly based upon earlier trial results showing that the vaccines are safe and effective in stimulating the immune system. However, those trials only involved several hundred people in comparison to the tens of thousands of volunteers in the latest results, so these developments are very encouraging. It gives us a much better understanding of how the vaccine may work in the general population.
However, questions will need to be answered about the efficacy in people over the age of 65 and other susceptible populations, the longevity of immunity, and long-term safety. Fortunately, these results will be scrutinized by scientists that are the best in the world. I have full confidence in their analysis.
The effort to make a vaccine so quickly is truly an outstanding accomplishment. It’s not a race to be first, but first to stop the virus. This war against an unseen enemy will require multiple strategies to truly end this pandemic. Right now I am keeping an eye out for data that shows the long-term protection of these vaccines, and looking forward to results from my colleague Sumit Chanda, who has been racing to find existing drugs that could treat people who do become sick with COVID-19.
I learned about the Pfizer-BioNTech vaccine news last Monday morning. I had just woken up and was enjoying a cup of coffee when I read the press release. Here, they reported the results to date of their vaccine clinical trial showing 90% protection from COVID-19 infection. I felt very happy and very hopeful. Being from Spain, one of the countries that has been most affected by COVID-19, and having all my family over there, I felt this was the news we all have been waiting for a long time.
While this 90% might not hold by the end of the trial as more cases are reported, it still brings a lot of hope. Especially since many vaccines currently under clinical trials, including Moderna’s, use a similar approach. So we have even more reasons to be optimistic.
Future challenges for these vaccines will be to determine if they can prevent transmission from asymptomatic people with COVID-19. As clinical trial participants were not tested for COVID-19 throughout the study, and only symptomatic cases were reported, the question remains as to whether vaccinated people can still transmit the disease.
We also still don’t know how long the protection elicited by the vaccine lasts, which will determine whether and how frequently we will need a vaccine boost. In addition, more data are needed to evaluate if these vaccines can protect against severe COVID-19 or whether different age groups or ethnicities are protected. Only time will tell.
Meet the scientists on the front lines with coronavirus, including Dr. Martin-Sancho.
Institute News
Stem cell Prop. 71 saved lives. It’s successor, Prop. 14, will save more—maybe yours.
Those who argue that Proposition 14—which will continue to fund stem cell research that foresightful Californians approved in 2004 via Proposition 71—is no longer necessary unfortunately have a narrow view of stem cell science.
All one needs to do is to think back to our world before California’s emergence as the “Mecca” for this science to realize how different—for the better —we are and can continue to be in this state.
These accomplishments extend beyond the numbers. Yes, CIRM has enabled more than 90 clinical trials involving more than 4,000 patients with more than 75 diseases; produced more than 800 patent applications; published more than 3,000 contributions to scientific knowledge in the form of peer-reviewed papers; and created numerous new jobs, companies and programs that drew tax-paying citizens to California from other states.
And yes, there have been actual cures. Bone marrow transplantation is a stem cell-based therapy that has the ability to cure conditions such as sickle cell anemia, “bubble baby” disease, certain cancers, metabolic diseases, even HIV. CAR T-cell therapy, one of the newest and most exciting cell-based treatments against a range of cancers, is a stem cell-based therapy. Novel drugs can now cure formerly incurable cancers because they attack cancer stem cells.
And indeed, there are now treatments on the horizon for devastating maladies. People living with spinal cord injury, brain conditions such as multiple sclerosis, Parkinson’s disease, and stroke; eye conditions such as macular degeneration; psychiatric disorders; diabetes; even COVID-19, can hope for a better future because of stem cells’ ability either to address the problem directly, or to make therapeutic “caregiver” molecules, or to better model the disease(s) to enable novel drug discovery.
However, stem cell biology’s most profound legacy is likely how it has changed society’s vision of itself. When it comes to our life, we have come to view ourselves not as rigid beings, but flexible, malleable creatures who accept no boundaries—because we know the repairing power of stem cells.
Alzheimer’s patients are no longer institutionalized but rather placed in enriched environments. Children with autism are given aggressive early intervention. Parkinson’s patients are taught ballroom dancing.
We are encouraged to exercise into old age and to take up challenging tasks to keep our brains sharp. All of these notions are stem cell biology’s contribution to our very nature and our perceptions of being human.
Indeed, passing Proposition 14 may have the greatest immediate and lasting impact on most Californians’ well-being than any other measure on the ballot. And our use of these life-saving strategies is once again being threatened in Washington D.C., just as it was in 2004. Please continue this life-saving research by voting Yes on Proposition 14.
Evan Snyder, MD, PhD, is professor and director of the Center for Stem Cells and Regeneration program at Sanford Burnham Prebys. He is regarded as one of the “fathers of the stem cell field” and was named a “stem cell revolutionary” by Forbes. Snyder was the first to isolate human neural stem cells, which will soon be tested as a treatment for premature newborns, and served two terms as Chairman of the FDA’s Cellular, Tissue, and Gene Therapy Advisory Committee. His lab explores the basic biology of stem cells and their therapeutic potential, particularly for brain disorders such as Parkinson’s disease and bipolar disorder.
Sanford Burnham Prebys scientist publishes two papers that bring us one step closer to understanding—and potentially treating—the devastating condition.
For millions of families and caregivers around the world, the need for an effective treatment for Alzheimer’s disease remains urgent despite the ongoing pandemic. Now, two studies from Timothy Huang, PhD, who was recently promoted to assistant professor in the Degenerative Diseases Program at Sanford Burnham Prebys, bring us one step closer to understanding the root cause of the disease.
Brain protein may help protect against Alzheimer’s disease
Previous research from Huang and his colleagues showed that a neuronal protein called SORLA helps reduce production of toxic amyloid beta protein that accumulates and leads to Alzheimer’s disease. Given this important role, Huang decided to dig deeper to understand SORLA’s “job” inside the brain.
In a paper featured on the cover of The Journal of Neuroscience, Huang and his team analyzed mice that produce high levels of SORLA and studied the effects of enhancing SORLA on the brain. This work showed that higher levels of SORLA resulted in elongated neurites, structures that extend from neurons, and improved the repair and regeneration of axons—the cable-like fibers that neurons use to communicate. These findings suggest that drugs that increase levels of SORLA might help protect the brain against Alzheimer’s disease and may even help people with a spinal cord injury.
Huang describes the findings as “the tip of the iceberg” and is eager to learn more about this important protein—with the ultimate goal of identifying potential targets for drugs that could slow the progression of Alzheimer’s disease.
A new model for studying Alzheimer’s disease
Many of the mutations associated with Alzheimer’s disease are found in a brain cell type called microglia. However, unlike other cells, mouse microglia are very different from human microglia. Because scientists primarily use mouse models to understand disease, this difference limits their ability to understand how microglial mutations lead to Alzheimer’s disease.
To overcome this hurdle, Huang and his team took on the formidable task of creating human stem cell lines that contain Alzheimer’s mutations found in human microglia. The scientists then tracked the downstream effects of these mutations in the cells, including epigenetic and gene expression changes, which revealed many new, previously unknown relationships between Alzheimer’s-associated genes. The findings were published in the Journal of Experimental Medicine.
More studies are needed to fully understand the how these interactions alter the course of Alzheimer’s disease—which can now be answered using this new model. Huang, who describes the work as “one of the most challenging and ambitious projects I’ve worked on so far” believes the cell line may also be used to help screen for potential Alzheimer’s disease drugs.
Meet Carl Ware, PhD, director of the Infectious and Inflammatory Disease Center at Sanford Burnham Prebys. After a career of studying how viruses wreak havoc on our health, he now becomes a “subject” in a COVID-19 clinical trial.
What inspired you to enroll in a COVID-19 clinical trial? I’m an immunologist working on coronaviruses. I understand the science of vaccines and the protection provided against infections. I also know how important clinical trials are to developing safe and effective vaccines. I trust the science, so I stepped up to volunteer for the vaccine trial. Who better than an immunologist to be part of this grand experiment?
Are you nervous? Excited is more accurate.
Do you know which vaccine you’re getting? Yes, the RNA-based vaccine by Moderna. It’s not a live virus! The vaccine uses a small part of the virus that allows the virus to attach to lung cells. To cause disease, a virus must replicate inside a cell. The infected cell dies, releasing large numbers of new viruses. The progeny virus infects more lung cells, producing more virus that reaches levels that are easily spread to other people. The vaccine stimulates the immune system to block the virus from entering and replicating in the lung cells, stopping the infection and spread to other persons.
How many people are in the trial? About 30,000 people will participate. The volunteers are placed into two groups receiving either the vaccine or a placebo. The study is “blinded,” so I don’t know which group I’m in, but I’m hoping it’s not the placebo group. The preliminary tests of this new vaccine indicate it is safe and stimulates the immune system. However, proof of safety and effectiveness requires a large number of volunteers. More volunteers are needed to complete the goal of 30,000.
How will you be evaluated during the trial? Following the first injection, I will report my symptoms every night for a week using a simple, very cool app on my cell phone. A month later, I will receive a booster and follow the same procedure with the phone app. I have two more visits to the site at six months and a year to determine if the vaccine stimulated long-lasting immunity.
How will it be determined if the vaccine works? All sorts of tests will be used to measure the response of my immune system. No worries, volunteers in the trial will not be infected with the virus!
The trial is open to anyone who wants to participate, especially those persons most vulnerable, with serious diseases; front-line and essential workers; those over 65, Black and Latinx persons, and people with other health risks. There are several test centers around the San Diego area. More information on volunteering is at eStudySite.
Institute News
Scientists “turn back time” on cancer using new stem cell reprogramming technique
Discovery opens new research avenues that may help catch cancer early and identify potential preventive treatments
Scientists at Sanford Burnham Prebys Medical Discovery Institute have reprogrammed cancer cells back into their pre-cancer identity—opening new doors for studying how cancer develops and how it might be prevented. The research, published in Stem Cell Reports, may lead to tests that identify cancer early on, when it can be more easily treated, and uncover preventive treatments that stop cancer before it starts.
“We believe we have been able to contribute to one of the major goals of modern cancer research: creating next-generation models for studying how cancer develops from its earliest state,” says Evan Snyder, MD PhD, professor and director of the Center for Stem Cells & Regenerative Medicine at Sanford Burnham Prebys and senior author of the study. “We essentially took an adult cancer that has accumulated many mutations and pushed it back to the earliest stages of development, allowing us to emulate a tumor’s premalignant state. Then we watched cancer emerge from normal cells before our eyes.”
Turning back the clock on cancer
In the study, the scientists set out to transform cells from anaplastic thyroid tumors—an aggressive, fast-growing cancer that is nearly always diagnosed at late stages—into induced pluripotent stem cells (iPSCs). These cells model the embryonic cells that are present at the earliest stages of human development and can become any cell in the body. While iPSCs are used today to create unlimited supplies of cells for research and therapeutic purposes—usually to correct abnormalities—the scientists recognized that tumor-derived iPSCs could be used to study the development of cancer.
However, this feat turned out to be easier said than done. The standard reprogramming method didn’t work, requiring the researchers to hunt for a different method that would induce the cancer cells to reset. Inhibiting a protein called RAS was the key ingredient that coaxed these thyroid cancer cells to become normal iPSC cells.
“We have named the pathway that is critical for making a cancer cell act as if it were a normal cell its ‘reprogram enablement factor,’” explains Snyder. “That factor will likely be different for every cancer and, in fact, may help in defining that cancer type.
“For this cancer type, which we examined in our study as a proof-of-concept, the reprogram enablement factor turned out to be blunting an overactive RAS pathway,” Snyder continues. “Our results suggest that losing control of RAS was the ‘big bang’ for this cancer—the very first event that leads to out-of-control cell growth and development of a tumor.”
The scientists next plan to reprogram additional cancers—including brain and lung cancer—into iPSCs to determine their “reprogram enablement factors.” If successful, they will next map the molecular changes that occur immediately before and after the tumors develop, which could reveal early signals of cancer and new preventive or early treatment measures.
“Unlike other cells, cancer cells are notoriously resistant to reprogramming,” says Snyder. “Our study is the first to successfully reprogram cancer cells into completely normal iPSCs, which opens new doors for cancer research.”
A team effort
The first author of the study is Yanjun Kong of Sanford Burnham Prebys and Shanghai Jiao Tong University. Yang Liu of Sanford Burnham Prebys is a co-corresponding author. Additional study authors include Ryan C. Gimple of UC San Diego; Rachael N. McVicar, Andrew P. Hodges and Jun Yin of Sanford Burnham Prebys; and Weiwei Zhan of Shanghai Jiao Tong University.
This study was funded by the Stem Cell Research Center & Core Facility at Sanford Burnham Prebys and by the China Scholarship Council (201606230202). The study’s DOI is 10.1016/j.stemcr.2020.07.016.
Institute News
Dinah Conyers Ruch: The power of investing in human health
Long-time supporter Dinah Conyers Ruch discusses the impact of giving to biomedical research—especially COVID-19 efforts—and the importance of investing in human health.
How were you introduced to Sanford Burnham Prebys? My grandson John, whom we called “Rocket,” was born with a rare disease known as CDG, or Congenital Disorders of Glycosylation. Our doctors were able to quickly diagnose this disease thanks to CDG expert Hudson Freeze at Sanford Burnham Prebys Medical Discovery Institute. Dr. Freeze works closely with the families of children impacted by rare diseases like CDG and has now become a lifelong friend. Though we weren’t able to save Rocket, we have kept his legacy alive by supporting Dr. Freeze through a fund that continues to study this disease and fight for a cure.
What about the Institute’s mission compels you to keep giving? Over ten years ago, our family’s experience with Rocket showed us the promise and power of science to understand and improve human health. Today, we continue to be inspired by the dedication and passion of the scientists who devote their careers to often neglected diseases like CDG, which impacts thousands of children worldwide. When I started to hear about COVID-19 earlier this year, another intractable disease, I initially felt powerless. Then I started to receive emails from the Institute about the efforts underway to study the virus, and I knew I wanted to do something immediately. Private philanthropy can be a powerful catalyst for change and progress especially when you have trusted partners like the scientists at Sanford Burnham Prebys.
What inspired you to give to Dr. Sumit Chanda’s research? Dr. Chanda’s efforts to understand and find treatments for COVID-19 are essential not just in the short-term but also well into the future. When I learned about the drug repositioning strategy, which involved screening more than 12,000 approved drugs, I understood that this research could save time, money and, most important of all, lives. Dr. Chanda shared his larger vision too, which includes expanded research capacity, multiple scientific leaders, and strategic partners from across the globe. This excited me. This is a vision that is responsive and forward-looking and it confirmed my interest in boosting the efforts through philanthropy.
Why should someone else give back to pandemic research? Put simply, the need couldn’t be greater. The pandemic has changed American life so quickly. The devastating effects of COVID-19 go beyond our health and include rampant unemployment, economic uncertainty and broken social safety nets. Investing in therapies now can improve not just our human health but also our societal outlook. Scientists at the Institute have long led the path from research to power a cure. I have seen it firsthand. And I am more confident than ever that the COVID-19 research today will lead to greater health tomorrow. I hope others will join me in supporting this important work.
Join Dinah
Join Dinah in supporting COVID-19 research at Sanford Burnham Prebys through our first-of-its-kind matching gift opportunity—which doubles all donations dollar-for-dollar up to $500,000. For more information contact Rachael McCabe at rmccabe@sbpdiscovery.org or make a gift online.
