children's health Archives - Sanford Burnham Prebys

Tag: children’s health

Institute News

Gut microbiome repair in children with severe acute malnutrition

AuthorScott LaFee
Date

October 2, 2024

child being spoon fed with family in background

Child malnutrition remains an alarming and appalling scourge.

In 2022, according to the World Health Organization, 148 million children in the world under 5 years were too short for their age (stunting) and another 45 million were too thin for their height (wasting) due to inadequate diet and nutrition.

Researchers around the world, including Andrei L. Osterman, PhD, professor in the Immunity and Pathogenesis Program at Sanford Burnham Prebys, have been investigating potential remedies, in particular some of the consequences of malnutrition, such as disturbed metabolism and immune/gut function.

In a new paper published October 2, 2024 in Science Translational Medicine, the multi-institutional team (including Osterman and colleagues at SBP) describe an interventional diet that essentially repairs the gut microbiome in children with moderate to severe acute malnutrition.

They conducted a three-month randomized controlled trial of a specialized food supplement in 12- to 18-month-old Bangladeshi children living in rural and urban slums with moderate acute malnutrition who had already been treated in hospital for severe acute malnutrition. The supplement, called microbiota-directed complementary food or MDCF-2, contains chickpea flour, peanut flour, soy flour, green banana, sugar, soybean oil and a vitamin-mineral premix, a formulation designed to promote the growth of therapeutic gut bacteria and improve the overall health and balance of the gut microbiome.

They found that MDCF-2 improved weight-for-age better than the traditional ready-to-use supplementary food (RUSF) used by relief agencies and others, which is composed of more traditional ingredients like rice, lentil, sugar, soybean oil and skimmed milk powder mixed with vitamins and minerals.

When excluding children unable to continue study participation due to severe flooding during the trial, the study authors also reported improvement of stunting at a faster rate. They tied these improvements in children’s health to Prevotella copri–associated metabolic changes.

P. copri (recently renamed as Segatella copri) is a bacterium found abundantly in the human gastrointestinal microbiome. Past studies have reported both positive and negative associations with health and disease. In the former, for example, healthy bacterial colonization of the gut has been positively correlated with conditions like inflammation, insulin resistance and diarrhea. It appears to be a major player in regulating dietary metabolism.

The bacterium is more common in non-Westernized populations consuming a diet rich in plants—the bacterium’s source of nutrients. In Western populations, it is associated with consumption of fruits and vegetables.

Genomic reconstruction of the metabolic potential of P. copri strains positively associated with infants’ health improvement confirmed their unique ability to utilize a large repertoire of plant-derived polysaccharides comprising MDCF-2 diet.

“This study can be viewed as a test of the generalizability of the efficacy and mechanism of action of MDCF-2 in acutely malnourished children,” said Osterman. “The main findings include the demonstration of significantly higher efficacy of MDCF-2 vs RUSF with respect to the improvement of (weight) growth.

“The success of the treatment was also manifest by beneficial changes in microbiome composition and by global changes of a range of serum protein biomarkers associated with healthy development.”

The findings, he said, also provide proof-of-concept that improving gut microbial health can be achieved using therapeutic nutrition and offers further guidance on how best to use microbiota-directed complementary foods.

Institute News

Coding clinic

AuthorGreg Calhoun
Date

August 6, 2024

Programming in a Petri Dish - AI series graphic

Rapidly evolving computational tools may unlock vast archives of untapped clinical information—and help solve complex challenges confronting healthcare providers

The wealth of data stored in electronic medical records has long been considered a veritable treasure trove for scientists able to properly plumb its depths.  

Emerging computational techniques and data management technologies are making this more possible, while also addressing complicated clinical research challenges, such as optimizing the design of clinical trials and quickly matching eligible patients most likely to benefit.  

Scientists are also using new methods to find meaning in previously published studies and creating even larger, more accessible datasets.  

“While we are deep in the hype cycle of artificial intelligence [AI] right now, the more important topic is data,” says Sanju Sinha, PhD, an assistant professor in the Cancer Molecular Therapeutics Program at Sanford Burnham Prebys. “Integrating data together in a clear, structured format and making it accessible to everyone is crucial to new discoveries in basic and clinical biomedical research.” 

Sinha is referring to resources such as the  St. Jude-Washington University Pediatric Cancer Genome Project, which makes available to scientists whole genome sequencing data from cancerous and normal cells for more than 800 patients.

Medulloblastoma tumor cells with hundreds of circular DNA pieces

The Chavez lab uses fluorescent markers to observe circular extra-chromosomal DNA elements floating in cancer cells. Research has shown that these fragments of DNA are abundant in solid pediatric tumors and associated with poor clinical outcomes. Image courtesy of Lukas Chavez.

The Children’s Brain Tumor Network is another important repository for researchers studying pediatric brain cancer, such as Lukas Chavez, PhD, an assistant professor in the Cancer Genome and Epigenetics Program at Sanford Burnham Prebys. 

“We have analyzed thousands of whole genome sequencing datasets that we were able to access in these invaluable collections and have identified all kinds of structural rearrangements and mutations,” says Chavez. “Our focus is on a very specific type of structural rearrangement called circular extra-chromosomal DNA elements.” 

Circular extra-chromosomal DNA elements (ecDNA) are pieces of DNA that have broken off normal chromosomes and then been stitched together by DNA repair mechanisms. This phenomenon leads to circular DNA elements floating around in a cancer cell.  

Sanju Sinha, PhD

Sanju Sinha, PhD, is an assistant professor in the Cancer Molecular
Therapeutics Program at  Sanford Burnham Prebys.

“We have shown that they are much more abundant in solid pediatric tumors than we previously thought,” adds Chavez. “And we have also shown that they are associated with very poor outcomes.” 

To help translate this discovery for clinicians and their patients, Chavez is testing the use of deep learning AI algorithms to identify tumors with ecDNA by analyzing the biopsy slides that are routinely created by pathologists to diagnose brain cancer. 

“We have already done the genomic analysis, and we are now turning our attention to the histopathological images to see how much of the genomic information can be predicted from these images,” says Chavez. “Our hope is that we can identify tumors that have ecDNA by evaluating the images without having to go through the genomic sequencing process.”  

Currently, this approach serves only as a clinical biomarker of a challenging prognosis, but Chavez believes it can also be a diagnostic tool—and a game changer for patients.  

“I’m optimistic that in the future we will have drugs that target these DNA circles and improve the therapeutic outcome of patients,” says Chavez.  

“Once medicine catches up, we need to be able to find the patients and match them to the right medicine,” says Chavez. “We’re not there yet, but that’s the goal.” 

Chavez is also advancing his work as scientific director of the Pediatric Neuro-Oncology Molecular Tumor Board at Rady Children’s Hospital in San Diego.  

“Recently, it has been shown that new sequencing technologies coupled with machine learning tools make it possible to compress the time it takes to sequence and classify types of tumors from days or weeks to about 70 minutes,” says Chavez. “This is quick enough to take that technology into the operating room and use a surgical biopsy to classify a tumor.  

“Then we could get feedback to the surgeon in real time so that more or less tissue can be removed depending on if it is a high- or low-grade tumor—and this could dramatically affect patient outcomes.  

“When I talk to neurosurgeons, they are always in a pickle between trying to be aggressive to reduce recurrence risk or being conservative to preserve as much cognitive function and memory as possible for these patients.  

“If the surgeon knows during surgery that it’s a tumor type that’s resistant to treatment versus one that responds very favorably to chemotherapy, radiation or other therapies, that will help in determining how to strike that surgical balance.” 

Lukas Chavez, PhD

Lukas Chavez, PhD, is an assistant professor in the Cancer Genome and Epigenetics Program at Sanford Burnham Prebys.

Artist’s rendering X-shaped chromosomes floating in a cell

Artist’s rendering of X-shaped chromosomes floating in a cell alongside circular extra-chromosomal DNA elements.

Rady Children’s Hospital has also contributed to the future of genomic and computational medicine through BeginNGS, a pilot project to complement traditional newborn health screening with genomic sequencing that screens for approximately 400 genetic conditions. 

“The idea is that if there is a newborn baby with a rare disease, their family often faces a very long odyssey before ever reaching a diagnosis,” says Chavez. “By sequencing newborns, this program has generated success stories, such as identifying genetic variants that have allowed the placement of a child on a specific diet to treat a metabolic disorder, and a child to receive a gene therapy to restore a functional immune system.”

Programming in a Petri Dish, an 8-part series

How artificial intelligence, machine learning and emerging computational technologies are changing biomedical research and the future of health care

  • Part 1 – Using machines to personalize patient care. Artificial intelligence and other computational techniques are aiding scientists and physicians in their quest to prescribe or create treatments for individuals rather than populations.
  • Part 2 – Objective omics. Although the hypothesis is a core concept in science, unbiased omics methods may reduce attachments to incorrect hypotheses that can reduce impartiality and slow progress.
  • Part 3 – Coding clinic. Rapidly evolving computational tools may unlock vast archives of untapped clinical information—and help solve complex challenges confronting health care providers.
  • Part 4 – Scripting their own futures. At Sanford Burnham Prebys Graduate School of Biomedical Sciences, students embrace computational methods to enhance their research careers.
  • Part 5 – Dodging AI and computational biology dangers. Sanford Burnham Prebys scientists say that understanding the potential pitfalls of using AI and other computational tools to guide biomedical research helps maximize benefits while minimizing concerns.
  • Part 6 – Mapping the human body to better treat disease. Scientists synthesize supersized sets of biological and clinical data to make discoveries and find promising treatments.
  • Part 7 – Simulating science or science fiction? By harnessing artificial intelligence and modern computing, scientists are simulating more complex biological, clinical and public health phenomena to accelerate discovery.
  • Part 8 – Acceleration by automation. Increases in the scale and pace of research and drug discovery are being made possible by robotic automation of time-consuming tasks that must be repeated with exhaustive exactness.
Institute News

Sharing science and stories at Rare Disease Day Symposium

AuthorGreg Calhoun
Date

March 7, 2024

Rare Disease Day 2024 group photo

The Sanford Burnham Prebys Rare Disease Day Symposium brought patients, families, physicians, scientists, industry experts and advocates together with a focus on congenital disorders of glycosylation.

Sanford Burnham Prebys, in partnership with CDG CARE and the Sanford Children’s Health Research Center, hosted a Rare Disease Day Symposium in San Diego from March 1-3, 2024. The goal of the event was to share the latest scientific developments from researchers studying congenital disorders of glycosylation (CDG), and to foster new perspectives, ideas and collaborations to accelerate the creation and implementation of better therapies and treatment plans for those living with CDG.

CDG is an umbrella term for more than 190 disorders caused by mutations that impair glycosylation; the complex process by which cells build long sugar chains that attach to proteins called glycoproteins. CDG affects fewer than 2,000 children worldwide. When glycosylation is impaired, the sugar molecules on many of the body’s proteins are absent or incomplete, leading to serious, often fatal, malfunctions in various organ systems throughout the body.

Since 2010, Hudson Freeze, PhD, the William W. Ruch Distinguished Endowed Chair, professor and director of the Human Genetics Program, and director of the Sanford Children’s Health Research Center at Sanford Burnham Prebys, has organized an annual Rare Disease Symposium, where scientists, doctors and families gather from around the world to discuss the latest research and meet other families coping with rare diseases.

“At Sanford Burnham Prebys, we’re committed to rare disease research,” says David Brenner, MD, president, CEO and Donald Bren Chief Executive Chair at Sanford Burnham Prebys, during his welcoming remarks. “We believe we can make a unique contribution to society with this work, and in so doing make the world a better place.”

Rare Disease Day Welcome speakers, Malin Burnham, Hudson Freeze, David Brenner

Brenner noted that Rare Research Day marked a time for academic medical centers across the US to celebrate the synergy between patients, families, physicians and scientists that is needed to advance research on all rare diseases, including CDG.

This was reflected throughout the symposium’s schedule and in the tenor of individual presentations. Patients and families were invited to give talks throughout the weekend to discuss the perspective of living with CDG or caring for a family member with CDG. The physicians and scientists who spoke consistently credited the patients and families for all they do to help raise funds and participate in research, including clinical trials that can add more appointments to already challenging calendars and routines.

The family reception on Friday, March 1, concluded the first day of the symposium with a more informal opportunity for patients, families, doctors and researchers to connect and socialize.

“This is the largest meeting we’ve ever had,” notes Freeze. “This gathering is an important part of nurturing the CDG research ecosystem by bringing experts together while also knitting us closer together with the people who really matter – the families.”

The symposium’s many sessions over three days included:

  • Friday, March 1
    • Scientific meeting
      • Introduction and welcome from Sanford Burnham Prebys president and CEO, David Brenner; Malin Burnham and Debra Turner, philanthropists and honorary trustees; and Congressional Representative Scott Peters from California’s 52nd Congressional District
      • Discussion of perspectives, challenges and triumphs led by parents, patients and advocates
      • Sessions on new therapies in development, the potential use of biotin as a treatment for many CDG patients, neurological disease, and gene therapy approaches, among others 
    • Poster session
    • Family reception
  • Saturday, March 2
    • Scientific meeting
      • Keynote address on “Accelerating Treatment and Cures for Rare Diseases” from Joni Rutter, PhD, director of the National Center for Advancing Translational Sciences in the National Institutes of Health
      • Additional conversation about the experiences of parents and advocates
      • Sessions on clinical trial updates; especially strong were drug repurposing efforts leading to new and unexpected potential treatments
    • Doctor-is-in-session
      • Brought together medical researchers, clinicians, advocates, patients and their families for an afternoon of hands-on collaboration in small groups
      • Prior “Doctor-is-in-session” events have led to profound experiences and unlikely partnerships
    • Evening reception
  • Sunday, March 3
    • CDG CARE Scientific and Family Conference
      • CDG clinical care and management sessions included neurophysiology and epilepsy, growth charts and hormonal abnormalities, puberty and bone health
      • CDG research sessions included genetics 101, CDG updates, organoids as disease models and clinical trials as a partnership between physicians and patients, among others
      • CDG resource exchange sessions included educational planning and advocacy, speech and technology, therapy interventions, special needs planning and behavioral health and family planning
Institute News

Sanford Burnham Prebys research plays a key role in developing microbiome-directed complementary food to help save malnourished children

AuthorScott LaFee
Date

January 4, 2024

A Bangladeshi mother and child in the Nutritional Rehabilitation Unit of the International Centre for Diarrhoeal Disease Research Hospital in Dhaka.

Among the consequences of childhood malnutrition is the underdevelopment of their gut microbiomes, critical to human health, from innate immunity to appetite and energy metabolism.

Although malnourished children gain some weight and grow better when fed a nutrient-rich diet, they do not catch up to their well-fed counterparts—and their gut microbiomes do not recover.

In a 2021 clinical trial, researchers at Washington University School of Medicine showed how a newly designed therapeutic food—a unique mix of peanuts, bananas and other foods dubbed microbiome-directed complementary food, or MDCF—more effectively nourished healthy gut microbial communities than standard dietary supplements.

Now, with bioinformatics support from Andrei L. Osterman, PhD, professor in the Immunity and Pathogenesis and Cancer Metabolism and Microenvironment programs at Sanford Burnham Prebys  and his colleagues Dmitry Rodionov, PhD, and Alex Arzamasov, the multi-institutional scientific team has published new research that identifies and describes the bioactive elements of microbiome-directed food.

“These are naturally occurring carbohydrate structures that could, in theory, be recovered in large quantities from the by-product streams of food manufacturing and be used to produce prebiotics,” said senior study author Jeffrey I. Gordon, MD, the Dr. Robert J. Glaser Distinguished University Professor at Washington University.

“We also have identified the microbes that process these food components, and in theory, there is potential for the organisms themselves to be part of a therapeutic intervention in children completely lacking these beneficial gut microbes.”

Osterman’s lab contributed bioinformatics analyses of 1,000 new metagenomically assembled genomes, or MAGs, representing the gut microbiomes of healthy Bangladeshi infants. The analyses included genome-based inference of the presence or absence in these MAGs of functional metabolic pathways for 106 major nutrients and intermediary metabolites.

“These predictions enabled the assessment of the microbiome-wide representation or enrichment of dietary carbohydrate utilization capabilities across numerous biospecimens from a randomized, controlled trial of MDCF in Bangladeshi children with moderate acute malnutrition,” said Osterman.

“The analyses helped elucidate glycan components of MDCF metabolized by bacterial taxa that are positively associated with healthy weight growth. The knowledge will help guide the therapeutic use of current MDCF and enable development of new formulations.”

Childhood undernutrition is a global scourge. In 2020, an estimated 149 million children under the age of 5 had stunted growth (low height for age), and 45 million exhibited stunting (low weight for height). More than 30 million children worldwide have moderate, acute malnutrition.

Undernutrition and its consequences are the leading causes of disease and death for children in this age range. An estimated 3 million children die each year due to poor nutrition and hunger.

Institute News

Hudson Freeze joins experts to discuss testing to help CAD-affected children

AuthorSusan Gammon
Date

November 10, 2023

Hudson Freeze, PhD at his desk in his office

Hudson Freeze joined an international panel of genetics experts on CAD deficiency: Beyond the genetics—a podcast offered by the Journal of Inherited Metabolic Disease.

The researchers shared how clinical and functional genomics tests can accelerate the diagnosis of CAD-deficient patients and enable their timely treatment with uridine, a nutritional supplement that has dramatically improved the lives of other children with the condition.

“The effect of uridine for some children with CAD deficiency is nothing short of amazing. These kids go from bedridden to interacting with people and moving around,” says Freeze, PhD, director of the Human Genetics Program at Sanford Burnham Prebys. 

CAD deficiency is a congenital disorder of glycosylation (CDG), an umbrella term for more than 170 disorders caused by mutations that impair glycosylation; the complex process by which cells build long sugar chains that attach to proteins called glycoproteins.

These tests allow us to identify CAD genetic variants, and to help affected children get the best treatment possible,” adds Freeze.
 

Institute News

Where science meets patients: Sanford Children’s Research Center hosts inaugural symposium

AuthorMiles Martin
Date

May 10, 2023

Sanford Children’s Research Center symposium group photo

The event celebrated 16 years of progress at the Center and connected scientists with the people most impacted by their work.

The Sanford Children’s Health Research Center at Sanford Burnham Prebys recently hosted its first-ever Children’s Health Research Symposium, which brought scientists and families together to learn about the latest research tackling childhood diseases.

“We’re all here because we want to improve the health of children,” said President and CEO David A. Brenner, MD, during his opening comments. “But this event also shows the amazing amount of collaboration and collegiality across San Diego, because we have all types of people together from different backgrounds who want to develop therapies and cures for children affected by disease.”

The Sanford Children’s Health Research Center was established in 2008 with the help of a generous gift from Institute namesake T. Denny Sanford. Since then, the Center has been a world leader in children’s health research.

“T. Denny Sanford made an investment in children’s health 15 years ago, and I think that investment has paid off pretty well so far,” said Center director Hudson Freeze, PhD, in his introduction to the first scientific session. Freeze is among the world’s leading experts on congenital disorders of glycosylation (CDG), a rare group of genetic disorders that can cause serious, sometimes fatal, malfunctions of different organs and systems in the body.

“We’ve published over 600 scientific papers, and about half of those are translational studies, which means they’re helping turn scientific discoveries into real treatments for patients,” adds Freeze.

Professor Hudson Freeze with the Omler family

Professor Hudson Freeze with the Omler family

The day included presentations from researchers at Sanford Burnham Prebys, as well as from other research organizations studying childhood diseases. However, the highlight of the event was the afternoon reception, in which scientists had the opportunity to mingle and share a meal with families affected by rare childhood diseases.

Professor José Luis Millán (center) with the Fischer family (left) and the Britt family (right)

Professor José Luis Millán (center) with the Fischer family (left) and the Britt family (right)

Each researcher briefly introduced the family affected by the illness the scientist studies. This list included many longtime friends of the Institute, such as Damian Omler, who lives with a rare form of CDG; and Morgan Fischer, who was born with soft bone disease. Today, thanks to the help of a drug developed based on the research of Institute professor José Luis Millán, PhD, Morgan is a thriving teenager. This drug is also helping other children living with soft bone disease, including 10-year-old Aubrey Britt, who was in attendance with her family as well.

“Something so important that we keep as a tradition for scientific events at our Institute is to involve families that have been touched by the work of our faculty,” said Freeze. “They’re why we’re all here.”

The full list of talks included: 

Sanford Children’s Health Research Center

  • José Luis Millán, PhD “Developing therapeutics for soft bones and ectopic calcification disorders”
  • Duc Dong, PhD “From hope for few to drug for many—why rare is precious”
  • Evan Snyder, MD PhD “A clinical trial using human neural stem cells for neuroprotection in perinatal asphyxia, a major cause of cerebral palsy in kids”
  • Anne Bang, PhD “Drug screens of human-induced pluripotent stem cell (hiPSC) derived neuronal networks on multi-electrode arrays”
  • Pamela Itkin-Ansari, PhD “Proinsulin misfolding in diabetes”
  • Yu Yamaguchi, MD PhD “Multiple hereditary exostoses—from genetics to potential drug targets”
  • Hudson Freeze, PhD “Fucose therapy: Revising bedrock biochemistry”

Sanford Health

  • David Pearce, PhD “From rare diseases to type-1 diabetes: Research that impacts children at Sanford Health”

Frontiers in Congenital Disorders of Glycosylation Consortium

  • Eva Morava, MD, PhD “Clinical trials in Glyco-land”
  • Ethan Perlstein, PhD “Precision drug repurposing: Patient avatar to pioneer study to Phase 3 trial”

UC San Diego

  • Lars Bode, PhD “Human milk-based therapeutics and diagnostics to protect preterm babies from necrotizing enterocolitis”
  • Stephanie Cherqui, PhD “Hematopoietic stem cell gene therapy for cystinosis: Mechanism of action and clinical trial update”
Institute News

Is cloud computing a game changer in cancer research? Three big questions for Lukas Chavez

AuthorMiles Martin
Date

February 22, 2023

Lukas Chavez, PhD

As an assistant professor at Sanford Burnham Prebys and director of the Neuro-Oncology Molecular Tumor Board at Rady Children’s Hospital, Lukas Chavez, PhD, leverages modern technology for precision diagnostics and for uncovering new treatment options for the most aggressive childhood brain cancers.

We spoke to Chavez about his work and asked him how modern technology—particularly cloud computing—is shifting the approach to cancer research.

How are you using new technologies to advance your research?

New technologies are helping us generate a huge amount of data as well as many new types of data. All this new information at our disposal has created a pressing need for tools to make sense of it and maximize their benefits. That’s where computational biology and bioinformatics come into play. The childhood brain cancers I work on are very rare, which has historically made it difficult to study large numbers of cases and identify patterns.

Now, data for thousands of cases can be stored in the cloud. By creating data analysis tools, we can reveal insights that we would never have seen otherwise. For example, we’ve developed tools that can use patient data in the cloud to categorize brain cancers into subtypes we’ve never identified before, and we’re learning that there are many more types of brain tumors than we’ve previously understood. We’re basically transforming the classic histo-pathological approach that people have studied for decades by looking at tumor tissues under the microscope and turning that into data science.

How is cloud computing improving cancer research in general?

Assembling big datasets delays everything, so I believe the main idea of cloud computing is really to store data in the cloud, then bring the computational tools to the data, not the other way around.

My team did one study where we assembled publicly available data, and basically downloaded everything locally. The data assembly process alone took at least two to three years because of all the data access agreements and legal offices that were involved.

And that is the burden that cloud computing infrastructures remove. All of this personalized cancer data can be centrally stored in the cloud, which makes it available to more researchers while keeping it secure to protect patient privacy. Researchers can get access without downloading the data, so they are not responsible for data protection anymore. It’s both faster and more secure to just bring your tools to the data.

Are there any risks we need to be aware of?

Like any new technology, we need to be clear about how we use it. The technology is another tool in the toolbox of patient care. It will never entirely replace physicians and researchers, but it can complement and assist them.

Also, because we use costly and sophisticated tools that are being built and trained on very specific patient groups, we need to be careful that these tools are not only helping wealthier segments of society. Ideally, these tools will be expanded worldwide to help everybody affected by cancer.

Institute News

How community collaboration shapes leukemia research at Sanford Burnham Prebys

AuthorMiles Martin
Date

October 4, 2022

Rena Johnson, Ani Deshpande, PhD, and Todd Johnson holding a large cardboard check for $25,000 from the Luke Tatsu Johnson Foundation

Since 2020, Todd and Rena Johnson, co-founders of the Luke Tatsu Johnson Foundation (LTJF), have helped fund the research of Associate Professor Ani Deshpande, PhD

But it all started with their son Luke. He had a very rare subtype of acute myeloid leukemia, one of the most difficult-to-treat cancers, and, sadly, he passed away from the disease in 2016. This inspired the Johnsons to become involved with fundraising and advocacy for cancer research.

“Our foundation started with a fundraising golf tournament to honor Luke, and that was about taking something so horrific and so horrible and finding a way to turn it into something positive,” says Rena. “If you can take that tragedy and put a positive spin on it, then everything around Luke and his name and his memory becomes positive.”

How “the stars and planets aligned” to bring the Johnsons to the Institute

In a remarkable coincidence, the Johnsons discovered on their first visit to the Institute that Deshpande’s research focuses on AF10 fusion AML, an extremely rare subtype of the disease that accounts for about 5 percent of cases. It’s also the subtype of AML that Luke had.

“It was a goosebumps-raising moment,” says Todd. “Once we visited Ani and saw his lab, we realized there was a lot more in common with our story and his research than we had realized before.”

“The stars and planets aligned and brought us to Ani,” adds Rena. 

Luke Tatsu Johnson

Luke Tatsu Johnson

As well as helping fund Deshpande’s research through LTJF and their partnership with the Rally! Foundation, the Johnsons are also on the Community Advisory Board (CAB) for the Institute’s Cancer Center, which advocates for cancer research by engaging the community. 

“The CAB does such a wonderful job of connecting the community with the scientists, and we’re so excited to be involved in that,” says Todd. “That’s fundamentally what we do as a foundation—we support the folks doing this work so that children and families down the road can have a different outcome from Luke’s.”
 

AML research “needs more support and needs more funding”

The Johnsons’ support helped the AML research team discover a new potential treatment for AML, which is currently in preclinical studies, after which they hope it will advance to clinical trials. The research team maintains that it would have been impossible to secure the NIH grants necessary to do these studies without the jump start given by the LTJF and the Rally! Foundation.

“We couldn’t do what we do without the Johnsons’ support,” says Deshpande. “We are so grateful to have them in our corner, and we’re confident that our work will help improve outcomes for kids like Luke down the line.”

Despite this progress, more research into AML and other leukemias is still needed. Leukemia is the most common cancer in children and teens. About 4,000 children are diagnosed with leukemia each year, and AML accounts for about a third of these cases.
 

Studying AML from all angles

To tackle this pressing problem, the Institute has established an AML disease team composed of researchers across labs and clinician partners. The team’s research falls into several large categories, including studying the genetics of AML, studying how the disease works in animal models and working to develop drugs that can target specific mutations associated with the disease, which are numerous. 

“AML has many different subtypes, so it’s been difficult for researchers to make major advances to treat all cases of AML,” says Deshpande, who co-leads the AML team with Professor Peter D. Adams, PhD “Most patients with AML are given the same treatments that have been used since the ’70s, which is why we want to look at AML from as many angles as possible.”

In addition to being difficult to treat, it is also challenging to get funding for AML research, particularly for the rarer subtypes. This makes the support of foundations such as LTJF even more vital to researchers like Deshpande. 

“This is exactly why AML research needs more support and needs more funding, because this is a much more difficult disease than other forms of leukemia,” says Todd. “Many patients don’t have positive outcomes, and the only way to turn that pendulum is to intensify our efforts and increase the amount of research being done.”

Institute News

Heating up cold brain tumors: An emerging approach to medulloblastoma

AuthorMiles Martin
Date

July 6, 2022

Cancer cells

Immunotherapy has revolutionized cancer treatment, but it doesn’t work on many childhood brain tumors. Researchers from Sanford Burnham Prebys are working to change that.

Brain tumors account for about a quarter of all cancer cases in children. Medulloblastoma, a particularly aggressive form of childhood brain cancer, often develops resistance to radiation and chemotherapy. Researchers from Sanford Burnham Prebys are working to solve this problem by harnessing the power of the immune system.

They describe the potential of this approach in their recently published paper in Genes & Development. 

“The brain’s location makes it very difficult to target medulloblastoma tumors with current therapies,” says first author Tanja Eisemann, PhD, a postdoctoral associate in the lab of Robert Wechsler-Reya, PhD “They’re also immunologically cold, which means they’re good at evading the immune system.” 

The researchers hypothesize that it may be possible to enhance the body’s immune response to medulloblastoma and help the body’s immune cells enter the brain, making treatment with immunotherapy possible.

“Immunotherapy has so much potential as a  cancer treatment, but its scope is limited right now,” says Eisemann. “We want to bring the benefits of this therapy to medulloblastoma patients and their families.”

Eisemann has been studying this approach in mice, and although the research is still at an early stage, she and her colleagues are highly optimistic about its potential.

“The brain has long been considered immune privileged, hidden from immune-system surveillance and immune responses. But we’re starting to see that this isn’t the case,” says Eisemann. “This is a rapidly evolving field, and I’m excited to be working in a lab on the forefront of that research.”

Institute News

Rare Disease Day gathers scientists, doctors and families

AuthorMiles Martin
Date

March 3, 2022

Large group of people gathered in front of marina at Sunset

The 2022 Rare Disease Day Symposium took place last weekend at the Dana On Mission Bay Resort in San Diego. The event, sponsored by Sanford Burnham Prebys and CDG CARE, brought together researchers, clinicians and families from around the world to discuss new medical breakthroughs and meet other families living with rare diseases.

The 2022 Rare Disease Day Symposium took place last weekend at the Dana On Mission Bay Resort in San Diego. The event, sponsored by Sanford Burnham Prebys and CDG CARE, brought together researchers, clinicians and families from around the world to discuss new medical breakthroughs and meet other families living with rare diseases.

Rare Disease Day is celebrated on the last day of February to raise awareness for rare diseases, defined by the United States government as those that affect fewer than 20,000 people. Although there are more than 7,000 individual types of rare diseases that affect more than 30 million people in the United States, this year’s conference gathered more than 200 people focused on CDG, an extremely rare group of genetic disorders that affect children. 

CDG, which stands for congenital disorders of glycosylation, occurs when sugar molecules on many of our proteins are absent or incomplete. CDG causes serious, often fatal, malfunctions in various organ systems throughout the body.

“This is a chance for the global CDG community to come together, support one another and continue to try to find treatments,” says Hudson Freeze, PhD, director of the Human Genetics Program at Sanford Burnham Prebys. “It’s always my favorite weekend of the year, and I’m thrilled that we’re able to do it again safely.” Freeze’s primary research focus is CDG, and he has personally worked with more than 300 patients. 

Exchanging knowledge
The three-day symposium opened Friday morning with introductory comments from three important figures and philanthropists in Sanford Burnham Prebys’ history: T. Denny Sanford, Malin Burnham and Debra Turner. Congressman Scott Peterson also spoke on the importance of funding medical discoveries. 

“Our job is to make a positive difference. We do that best when we all work together,” said Sanford in his video introduction. “Congratulations on all your work. You make me very proud.”

This year, 19 scientists and clinicians in total spoke on the latest research in modeling, treating and understanding CDG. The full program of presentations can be found here.

Connecting families
Although Rare Disease Day is an important opportunity to share the latest scientific research, one of the highlights of the event doesn’t involve science at all. To provide space for families to take a break from the presentations and socialize, staff and volunteers transformed the Bayside Conference Room of the Dana resort into a child care and respite area packed full of toys and games.

In addition to giving families space to play, Rare Disease Day hosted several group activities for families, including a magic show on Saturday and a surprise visit on Sunday morning from Disney’s Anna and Olaf.

​Longtime friend of the institute Damian Omler, a thirteen-year-old who is the only person living with his rare genetic mutation, had a great time dancing along to “Let it Go” and playing catch with his father, Donnie.

And while the joy in the respite conference room was palpable, there was something else, less tangible, in the air as well: hope.

“Meetings like this bring us hope and help us raise awareness for CDG,” says Donnie. “That gives us a sense of purpose each and every time we attend the conference. And we won’t stop, even 20 years from now.” 

Omler family

Damian Omler and his family, parents Donnie and Gracie and brother DJ, had a great time at Rare Disease Day the year (image credit: CDG CARE)