Jerold Chun Archives - Sanford Burnham Prebys

Tag: Jerold Chun

Institute News

Jerold Chun receives a very special Alzheimer’s grant

AuthorMiles Martin
Date

May 13, 2022

Jerold Chun, MD, PhD

Jerold Chun, MD, PhD, has been awarded a new grant for $250,000 from the Coins for Alzheimer’s Research Trust (CART) Fund, an initiative by Rotary International to encourage exploratory and developmental Alzheimer’s research projects. Chun’s two-year project will explore how virus-like elements in our DNA could play a role in the development of Alzheimer’s disease.

“We are so grateful for the support of CART and the Rotarians,” says Chun. “They’ve shown over the years that small contributions to Alzheimer’s research can add up to make a huge impact.”

Ancient viruses in our genome
Chun’s project will explore how Alzheimer’s disease relates to endogenous genes in our genome that are very similar to parts of modern viruses. This is because they originated from viruses that infected our ancient ancestors. Over millions of years of evolution, these viruses became a normal part of our genomic makeup. 

Chun and other researchers suspect that these viral-like genes may be able to form virus-like particles that move through connections among our brain cells. They hypothesize that this process could promote neurodegenerative diseases like Alzheimer’s. “This new grant from CART will help us figure out how these genes and particles work, which is a first step toward thinking about how we might leverage it for treatments.”

Funding research with spare change
CART began in the mid-1990s with an ambitious idea: Could collecting the pocket change of Rotary International members accumulate enough to support Alzheimer’s disease?

The idea was launched in 1996 at Rotary Clubs in South Carolina; and at every meeting, members were asked to donate their loose change to a fund for Alzheimer’s research. The idea exploded from there. Over time, individual clubs started donating portions of their fundraising proceeds, and donations even began to come in from non-Rotary members as CART’s reputation grew.

The fund has awarded more than $10 million in grants to more than 40 institutions since its inception. This year, one of those grants was awarded to Chun to explore a new direction for Alzheimer’s research. This is the first CART grant to be awarded to a Sanford Burnham Prebys researcher.

“Grants like this are important because they give scientists the resources to pursue brand-new research areas,” says Chun. “Every major scientific discovery starts somewhere, and this type of support gives us that starting place, for which we’re really grateful.”

Institute News

How Sanford Burnham Prebys is helping map the brain

AuthorMiles Martin
Date

October 11, 2021

Computer rendering of blue-green neurons and yellow electrical signals

By joining forces with hundreds of researchers across the country, a team from the Chun Lab at Sanford Burnham Prebys are working to create a comprehensive map of the human brain, in the hopes of leveraging that knowledge to better treat brain disorders.

Researchers in the lab of Sanford Burnham Prebys professor Jerold Chun, MD, PhD, have helped the NIH create a cellular atlas of the motor cortex – the area of the brain responsible for movement. Their work, published recently in the journal Nature, is the flagship paper for the NIH’s BRAIN initiative, a massive multi-institution project to unravel the mysteries of the human brain.

“There are hundreds of billions of cells in the brain, and identifying and classifying all the different types of brain cells is just too big a job for any single lab,” says Chun, who is a coauthor on the study. “Similar to efforts in particle physics, hundreds of neuroscientists have now come together and it’s really exciting for us to be part of this major effort.”

The NIH Brain Research through Advancing Innovative Neurotechnologies® (BRAIN) Initiative aims to revolutionize our understanding of the human brain to more effectively diagnose, treat and prevent neurological diseases and disorders. Since its launch in 2013, the BRAIN Initiative has awarded more than 900 grants to research institutions across the country, totaling $1.8 billion. 

Chun is one of the principal investigators of the BRAIN Initiative Cell Census Network (BICCN), a subset of the Initiative that aims to develop a database of all the brain cell types in humans, mice, and non-human primates.

“While the project is about exploring the brain, what we’re really interested in over the long term is the clinical applications,” says study coauthor Carter Palmer. “Understanding the nuances of the brain and how the trillions of neural connections really work is going to lead us to new targets for therapies and diagnostics so we can help people heal.” Palmer is a graduate student in Chun’s lab, alongside fellow co-authors Christine Liu and William Romanow.

There are over 150 billion cells in the average human brain and well over a thousand different cell types, depending on how you characterize them. With such a vast landscape to track, many different types of data are needed to develop a comprehensive atlas of the brain.

For their part, the Chun Lab provided single-cell transcriptomes for human brain cells, focusing on the motor cortex. Single cell transcriptomes provide a measure of how hundreds to thousands of genes are expressed in individual cells and can provide hints as to what functions those cells are serving. This process also provides a molecular definition of cell types, making it easier for researchers to identify and classify them.

“Looking at how genes are expressed gives us a wealth of information on what cells are doing, how they develop and how they’re interacting with other cells,” says Palmer. “And when our data feed into the data from other teams, we start to get a much clearer picture of what’s happening in the brain than has ever been possible.” 

Their flagship Nature paper is one of seventeen in a special edition of the journal, chronicling recent advances by hundreds of BICCN researchers. The team also contributed to a second paper in the issue, which expands on the first by comparing the motor cortex cells of humans, mice, and marmosets. These publications speak not only to the expertise of Chun and his colleagues, but to the power of collaborative, interdisciplinary work to achieve previously unheard-of research goals.

“Fifty years ago, a project like this would have been impossible, because we just didn’t have the technology or even basic knowledge to collaborate on such a large scale,” says Chun. “Huge initiatives like BRAIN are an important part of the future of scientific research, and we’re thrilled we were able to contribute to this milestone in neuroscience.” 

Institute News

Marathon tradition continues for Sanford Burnham Prebys scientist despite pandemic

AuthorMonica May
Date

December 15, 2020

Jerold Chun running

Jerold Chun is one of only two people to run the Honolulu Marathon every year since 1973

When the Honolulu Marathon went virtual this year, Jerold Chun, MD, PhD, knew that skipping it wasn’t an option. He’s one of only two people who have run the race every year since 1973—the first year of the event—and this would be his 48th marathon to date.

“I ended up completing it on a Saturday morning on a treadmill,” says Chun. “I have to say that was quite a mind-numbing change from running in beautiful Honolulu! But this was the right thing to do to keep both marathoners and their many supporters safe.”

For Chun, who is a fifth-generation Hawaiian, running is more than just a way to stay in shape. The marathon is a tradition for his family, spearheaded by his father until his passing in 2002. Now the event also serves as a way to honor his father’s memory.

When he’s not training for the marathon, Chun can be found in his lab, where he’s working to understand the root cause of Alzheimer’s disease. His team recently discovered a new process in the brain that is linked to Alzheimer’s and might be stopped by existing HIV medicines—which have near-term treatment potential.


“In school we learned that all cells have the same DNA,” explains Chun. “However, our research showed that in the brains of patients, this wasn’t true because of DNA recombination. This process ‘mixed and matched’ a key Alzheimer’s gene into lots of new and different forms, many of which weren’t found in healthy people.”

Jerold Chun and his brothers, Daven and Hingson in 1973

Jerold Chun (middle) and his brothers, Daven (left) and Hingson (right), catch their breath at the 1973 marathon, the first year of the race. Daven is now an internal and sports medicine physician, and Hingson is a cardiologist, both living in Honolulu.

Watch Jerold Chun run his 45th Honolulu marathon.

To create these new gene variants, reverse transcriptase—an infamous HIV enzyme—was required. This suggests that existing HIV medications, which halt reverse transcriptase, might be useful for treating Alzheimer’s disease.

Chun often uses a run as a way to think through tough problems he encounters in his research. He also sees many parallels between marathon running and the discovery process.

“Most research is more like a marathon than a sprint,” says Chun. “Our recent Alzheimer’s discovery is a great example of that. We encountered many ups and downs and starts and stops over the decades. But in the long run, we may be on the heels of an effective Alzheimer’s treatment.”

Institute News

Top neuroscientists gather at Sanford Burnham Prebys’ annual symposium

AuthorMonica May
Date

November 18, 2019

Symposium organizers Jerold Chun (fourth from right), Randal Kaufman (second from left), Barbara Ranscht (third from right) and Huaxi Xu (far left), pose with the speakers

A mother who no longer remembers her son. A daughter who took doctor-prescribed pain medication and slipped into addiction. A father who has trouble grasping a pen and eventually becomes unable to walk. Neurological disorders are some of the most painful and complex conditions our society faces today. Yet much about the brain remains unknown, hindering our ability to help people with these disorders.

To help shed light on the brain’s mysteries, on November 1, 2019, more than 250 neuroscientists gathered at Sanford Burnham Prebys’ one-day symposium to share their latest discoveries. Organized by professors Jerold Chun, MD, PhD; Randal Kaufman, PhD; Barbara Ranscht, PhD; and Huaxi Xu, PhD, the event attracted scientists from around the world eager to learn more about biological clues that are leading to effective therapies. Read the full list of the invited speakers and their talks.

“Nearly every day we read about the toll neurological diseases such as Alzheimer’s, dementia, mental health disorders and more take on our society,” said Kristiina Vuori, MD, PhD, president of Sanford Burnham Prebys, in her introductory address. “Our symposium brings together scientists at the frontiers of brain research who share their latest discoveries to open new paths toward new and better treatments.”

More than 50 million Americans are affected by neurological disorders, including Alzheimer’s disease, dementia, addiction and more, according to the National Institute of Neurological Disorders and Stroke. Most of these conditions are not well addressed by current medicines.

At the symposium, world-renowned scientists from Stanford University, Mount Sinai, University of Vienna and other top-tier institutes gave talks describing their strategies to uncover the molecular basis of brain disorders and how these discoveries are advancing potential therapies. A national plan to address Alzheimer’s and other dementia types was described by Eliezer Masliah, MD, the National Institute of Aging’s director of the Division of Neuroscience.

“This was my first scientific conference, and it was perfect for learning about a wide range of cutting-edge brain research,” said attendee Jaclyn Beck, a PhD student at UC Irvine who studies the role of the brain’s immune cells, called microglia, in Alzheimer’s disease. “I have several pages of notes from the talks detailing findings I want to investigate and people I want to contact.”

For the past 40 years, our Institute has invited leading experts on one scientific topic to share their latest research at an annual symposium. By encouraging connection and collaboration, we hope to inspire insights that improve human health. The 41st annual symposium will take place in November 2020 and focus on the biology of organelles, specialized pouches within cells that carry out critical functions such as generating power and breaking down waste, and its role in health and disease.

Institute News

10 questions for Alzheimer’s expert Jerold Chun of Sanford Burnham Prebys

AuthorMonica May
Date

September 21, 2019

Jerold Chun, MD PhD

Alzheimer’s is one of the most frightening diseases of our time. Of the top 10 causes of death in the U.S., it is the only disease for which no effective or preventative treatment exists. Recent clinical trial failures have only deepened the pain of patients and their families.

To learn about the state of Alzheimer’s research in the wake of these setbacks—and whether there is hope on the horizon—we caught up with Alzheimer’s expert Jerold Chun, MD, PhD, professor and senior vice president of Neuroscience Drug Discovery at Sanford Burnham Prebys. Chun and his team recently published a Nature study that suggests a potential Alzheimer’s treatment may be closer than we think. 

  1. Why has Alzheimer’s disease become so prevalent? Are we better at diagnosing the disease?
    The number of people with Alzheimer’s disease is rising because of the aging Baby Boomers generation—which makes up more than 20% of the U.S. population. As a result, the number of those living with the condition is projected to more than double by 2050 to nearly 14 million people. This will place an incredible economic and social burden on our society—unless a treatment is found.
  2. Are there any treatments that work for Alzheimer’s disease?
    No disease-modifying therapies exist. The medicines a patient can receive today just treat symptoms. For example, cholinesterase inhibitors and N-methyl D-aspartate antagonists treat cognitive symptoms, such as memory loss, confusion and problems with thinking and reasoning—but they aren’t able to stop the disease. 
  3. Is it possible to prevent Alzheimer’s?
    Multiple studies from this year’s Alzheimer’s Association International Conference centered on this topic. Evidence suggests that adopting healthy lifestyle choices such as eating a healthy diet, not smoking, exercising regularly and stimulating the mind may decrease the risk of cognitive decline and dementia.

    It is encouraging to know that preventing Alzheimer’s may be partially within our control. However, it is undeniable that even individuals who live a healthy lifestyle will still develop Alzheimer’s. We need to remain laser focused on developing effective preventions and treatments.

  4. Do we know the cause of Alzheimer’s? What are the latest theories?
    In short, no. We know that clumps of amyloid-beta and tau proteins in the brain are linked to the disease. We also know that in rare cases genes are involved, because Alzheimer’s can run in families—but this accounts for less than 1% of cases. New research points to unique gene changes within the brain, called somatic gene recombination, as a new potential factor. Some data also implicate aspects of the immune system. It’s most likely that multiple factors lead to disease—and that an effective treatment will tackle Alzheimer’s from several angles.
  5. How would you describe the pipeline of Alzheimer’s treatments in development?
    The pipeline of Alzheimer’s treatments is in dire need of expansion. As of February 2019, only 132 drugs were under evaluation in clinical trials. Nearly half of these compounds target beta-amyloid. 

    For comparison, there are nearly 4,000 compounds under development for cancer—which affects almost three times as many Americans each year. We certainly need to continue to invest in cancer treatments—but clearly there is an urgent need to fill the Alzheimer’s pipeline, and an even greater need to find an approach that actually works.

  6. Tell us more about your research. What did you find? What are the next steps? 
    In school we learned that all cells have the same DNA. However, in our recent research we found that in the brains of patients, the DNA in the Alzheimer’s-linked APP gene can be “mixed and matched” into many different, new forms, some of which aren’t found in healthy individuals. To create these new gene variants, reverse transcriptase—best known as an enzyme infamously used by HIV—is required. This suggests that existing HIV medications—called reverse transcriptase inhibitors—which halt reverse transcriptase, might be useful as a near-term treatment for Alzheimer’s disease. A doctor can prescribe these medicines now as an “off-label” use for the treatment of Alzheimer’s disease. However, prospective clinical trials are needed to test the efficacy and side-effect profiles of these medicines in actual Alzheimer’s disease patients.
  7. Are humans the only species that get Alzheimer’s disease? 
    To our knowledge, yes. No other animal has the intellectual and cognitive capacity exhibited by humans. For this reason, scientists have developed animal models that exhibit symptoms and pathologies that approximate the disease. 
  8. How far away are we from an effective Alzheimer’s treatment? Years or decades? 
    What excites me about my team’s findings is that, if true, a partially effective treatment may be available now. Reverse transcriptase inhibitors are medicines currently used to treat HIV and hepatitis B, and have been safely used for 30 years with millions of patient-years of experience. New medicines based on this approach could lead to next-generation drugs with better efficacy and safety.

    Other agents in the Alzheimer’s pipeline currently in development are many years away from an effective treatment. And, it could take an additional 30 years for such agents to have the same level of proven safety as reverse transcriptase inhibitors. Nevertheless, new therapeutics must be pursued. Hopefully, our adult children will have great medical options in their future.

  9. What is the biggest hurdle to developing an Alzheimer’s treatment? 
    A major hurdle is securing funding for early, innovative research. The National Institutes of Health (NIH) is granting more funding than ever before to tackle this disease. However, many people aren’t aware that the NIH overwhelmingly finances projects that are scientifically conservative, which in the case of Alzheimer’s disease has failed to produce effective medicines. Funding that enables scientists to explore new, bold frontiers can be transformational in leading to important advances. This is an area where philanthropic donations can have a major impact—especially now, as the field strives to “think outside of the amyloid box” and explore new approaches.
  10.  Are you hopeful for the future? Why or why not?
    I am absolutely hopeful for the future. Advances in fundamental brain science will lead to new treatments for Alzheimer’s disease. Our work will hopefully be a start to a world where our children don’t have to live in fear of this disease.

About Jerold Chun 
Jerold Chun, MD, PhD, is a world-renowned neuroscientist who seeks to understand the brain and its diseases. His research has discovered genomic mosaicism and somatic gene recombination, surprising phenomena whereby cells in the brain actually have different genomic DNA sequences that can change with disease states. Chun’s research continues to shed light on Alzheimer’s disease, Parkinson’s disease, multiple sclerosis and other neurodegenerative diseases as well as neuropsychiatric disorders and substance abuse.