Cory Dobson, Author at Sanford Burnham Prebys - Page 7 of 41

Author: Cory Dobson

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How a breast cancer advocate shapes research at Sanford Burnham Prebys

AuthorMiles Martin
Date

October 28, 2021

Karen McDonald and Svasti Haricharan talking in the lab

An end goal of all biomedical research is improving outcomes for patients living with illness, but far too often, patient’s voices are not heard in the process. Advocacy programs, such as those offered by the Susan G. Komen Breast Cancer Foundation, help give individuals battling illness a voice in the lab. They also provide critical insights for the researchers doing the science.

To learn more about the role of patient advocates in cancer research, we spoke with Svasti Haricharan, PhD, an assistant professor at Sanford Burnham Prebys, and Karen McDonald, a patient advocate working with Haricharan’s team. Karen, a retired computer applications professor, has been working with Svasti’s group since 2020 and has battled three forms of cancer in her life, including her current fight with metastatic breast cancer, which began in 2020.

Today, she is helping in the broader fight against cancer by bringing her unique perspective to the lab, both as a retired scholar and as a woman living with cancer.

What do patient advocates bring to the lab and why are they so important?

Karen: I was a neurology technician many years ago, so I have some science background, but I’m not an expert in the type of science that Svasti and her team do. I look at things from a patient’s point of view – not as a scientist or a doctor. I ask questions most patients would ask—but not necessarily questions scientists think about.

One of the things I’ve learned is that I need to have research presentations ahead of time—before a lab meeting—so I can figure out the technical terms. Once I’ve done that, I can bring a real-life perspective to the research—because the scientists aren’t treating patients. Svasti and her team thankfully welcome my input.

Svasti: I agree completely. Having an advocate really helps me and everybody else on the team see things in a completely different way. I think the experience also helps humanize scientists, because it’s easy, especially in biomedical research, to become so focused on the next paper or the next grant that we forget we came into research not to publish papers, but to do amazing science and help people. And having Karen’s perspective does influence what we do.

For example, there was a project on nutraceutical research, or using food as medicine, which a lot of funders don’t want to support because some people think it’s just made up. I was ready to give up on the project because it wasn’t getting support, but Karen brought up the point that patients would love to see this transitioned into the clinic because it’s less toxic with fewer side effects. I went to the top at Sanford Burnham Prebys and actually got funding to develop a drug to mimic the nutraceutical’s effects. I’m not sure this would have happened without Karen’s input—and now we are hopeful for the results.

How far have we come toward giving patients their due voice, and what are some hurdles we need to overcome?

Karen: As times have changed, physicians have stopped being thought of as gods and have started to be more human. They make mistakes. And women in particular have become more active in their healthcare because we were ignored for so long. When women started to speak up, doctors started to listen. I think is why patient advocacy started with breast cancer. Women are communicators and take an integral role in their family’s healthcare. But we still have a long way to go in terms of giving advocates’ voices full consideration.

Svasti: Karen brings up a great point here that women are more used to having to fight to have their voices heard, and that’s why breast cancer helped start the patient advocacy movement through organizations like Susan Komen. It’s beginning to spread beyond breast cancer as more funding agencies are including advocates as grant reviewers, because these are the people who are going to benefit directly from the research. 

I think one thing that’s still a problem is not taking an advocate’s input seriously enough. I often see grant applications where the advocate says that a project is very significant, but other reviewers find some nitpicky aspect of the research strategy they don’t like, and the grant doesn’t get funded. There must be a better way for patient advocates’ voices to be included, as opposed to just having them on a review panel to check a box.  

What’s something you’d want to tell people who may not know much about cancer research or patient advocacy? 

Karen: People need to take it upon themselves to learn more about how research is done. There is such a big divide between scientists and patients, and that’s part of why patients go unheard. Even when you ask your physician about the latest research, they don’t always know.

It’s great that we have the internet now to help. I have a friend with lymphoma and that’s what we spend our time doing – researching the latest science, because we want to make sure we’re in charge of driving our own bus, not letting others have full control.

We need an environment of open-mindedness and willingness to learn. And that goes for physicians as well. We need bridges to connect cancer researchers with the oncologists who are actually going to implement their work and help humanity. 

Svasti: That’s such an important idea because just like patient advocates, working with clinicians is sometimes a check box for researchers as well. It’s essential that we have meaningful collaborations—between science and medicine—that can advance research breakthroughs and improve patient outcomes. 

I once spoke at a conference that had both patient advocates and researchers, and an advocate came up to me after my talk and asked, “Well what are you doing about this? If your research is real and important, why aren’t you bringing this to clinicians to get this into a clinic to help me?” That really blew my mind, because even though my role is to study cancer in the lab, she was right. Just like we need patient advocates in the lab, scientists need to advocate for research that will help patients the most. 

Saying Goodbye to Dawn Dunsmore: A reflection from Josh Baxt

Dawn Dunsmore standing against a green foliage backgroundIn September 2021, we lost Dawn Dunsmore to breast cancer, a disease she fought for a decade. Dawn was one of Sanford Burnham Prebys’ many committed administrators, most recently in Carl Ware’s lab, before stepping down to pursue treatment. She was a mom, an adventurer, an animal lover, a stubborn fighter and a friend to many, myself included.

Dawn had the bad luck of developing triple-negative breast cancer—one of the deadliest—and  the good luck of being surrounded by people who loved her. She had been working for Carl for about two years when she told him about the lump in her chest. She was quickly diagnosed and treated, but the tumor soon returned.

“Dawn was approaching the end very quickly,” says Bobbie Larraga, Community Relations Manager and one of Dawn’s closest friends. “She was having seizures and difficulty breathing, and we were starting to make end-of-life plans.”

In the background, Carl, a world-renowned immunologist, helped Dawn get into a Moores Cancer Center clinical trial for an immunotherapy (PD-1 inhibitor) that takes the brakes off T cells, allowing them to attack tumors. PD-1 inhibitors work for about a third of patients and, fortunately, Dawn was one of them.

“It’s even crazier because breast cancer is not one that typically responds well to checkpoint inhibitors,” says Carl, who directs the Infectious and Inflammatory Disease Center at Sanford Burnham Prebys. “She was lucky to have that response.”

When they work, immunotherapies are like a little miracle, and Dawn did not take that lightly. She’d been given a reprieve and had things to do.

“She was just crazy for travel,” says Bobbie. “She went with her daughter to Spain. Italy, Indonesia, India, Central America. She went skydiving and was able to really check off things on her bucket list.”

But the cancer never quite went away. There were more treatments and surgeries and at 51, she finally ran out of options. Even in September, when the hospital would not release her, she was planning a trip to Yosemite.

Thinking Forward

There are so many stories. Bobbie shared how Dawn interviewed her when she first applied at Sanford Burnham Prebys (then the Burnham Institute); how they had an instant connection. Carl described the incredible work they accomplished, and how her support helped him keep it together when his wife was dying of Alzheimer’s. 

I don’t usually insert myself into the articles I write – it’s just not appropriate – but Carl asked if I would, and that got me thinking. I joined Sanford Burnham Prebys in 2008, and the first piece I wrote here was a news release for the faculty member Dawn was working for. I was pretty green and Dawn helped me through, the first time of many. She was a generous soul.

Dawn was one of our own and it hurts that she’s gone. Like many at our Institute, she worked long hours to shepherd papers and grants through and helped manage the labs where she worked. She didn’t complain, even when she had the right.

Her experience underscores Sanford Burnham Prebys’ important work. Immunotherapies were first tested in academic labs, much like ours. It also brings home that the statistics we read so often, five-year survival rates or whatever, are representations of real people. The long hours, the stress of so many deadlines, the weekends in the lab, there’s a reason for those. And it’s a good one.

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This enzyme is one of the hardest working proteins in the body

AuthorMiles Martin
Date

October 21, 2021

Rendering of a red-orange protein molecule on a black background

Researchers from Sanford Burnham Prebys have shown that a protein they identified plays a major role in the breakdown of hyaluronic acid, a compound found in the scaffolding between our cells. The findings, published recently in the Journal of Biological Chemistry, could have implications for epilepsy, cancer and other human diseases associated with hyaluronic acid and similar compounds.

They also shed light on one of the most active biochemical processes in the body. 

“Our body turns over hyaluronic acid at an extremely rapid rate, far faster than the other compounds surrounding our cells,” says senior author Yu Yamaguchi, MD, PhD, a professor in the Human Genetics Program at Sanford Burnham Prebys.

Hyaluronic acid, a common ingredient in cosmetic anti-aging products, is a one of several large sugar molecules known as glycosaminoglycans (GAGs). These are found naturally in the extracellular matrix, the complex network of organic compounds surrounding our cells that gives structure to our tissues. In addition to its structural role, the extracellular matrix is involved in regulating the immune system and is critical in the early development of connective tissues like cartilage, bone and skin.

“The extracellular matrix is found in every organ and tissue of the body, and malfunctions in its biochemistry can trigger or contribute to a variety of diseases, some of which we don’t even know about yet,” says Yamaguchi. His team studies how GAGs affect childhood diseases including congenital deafness, epilepsy and multiple hereditary exostoses, a rare genetic disorder that causes debilitating cartilage growths on the skeleton.

Hyaluronic acid is also known to be correlated with several health conditions, depending on its concentration in certain tissues. Reduced levels of hyaluronic acid in the skin caused by aging contribute to loss of skin elasticity and reduced capacity to heal without scarring. Levels of hyaluronic acid in the blood dramatically increase in alcoholic liver disease, fatty liver and liver fibrosis. In addition, hyaluronic acid levels have been correlated with increased tumor growth in certain cancers.

“These compounds are literally everywhere in the body, and we continue to learn about how GAG’s influence disease, but there’s also a lot we still don’t know about how these molecules are processed,” says Yamaguchi, “Research like this is about understanding what’s happening at the molecular level so we can later translate that into treatments for disease.” 

For this study, the team focused on a protein called TMEM2, which they had previously found to break down hyaluronic acid by cutting the longer molecule into manageable pieces for other enzymes to process further. Using mice as a research model, they selectively shut off the gene that codes for TMEM2 and were able to successfully measure precisely how much the absence of TMEM2 affects the overall levels of hyaluronic acid.

The answer: a lot.

“We saw up to a 40-fold increase in the amount of hyaluronic acid in the study mice compared to our controls,” says Yamaguchi. “This tells us that TMEM2 is one of the key players in the process of degrading this compound, and its dysfunction may be a key player in driving human diseases.” 

The team further confirmed this role of the TMEM2 protein by using fluorescent compounds that detect hyaluronic acid to determine where the TMEM2 protein is most active. They found the most activity on the surface of cells lining blood vessels in the liver and lymph nodes, which are known to be the main sites of hyaluronic acid degradation. 

“These findings refine our understanding of this critical biochemical process and set us up to explore it further in the interest of developing treatments for human diseases,” says Yamaguchi. “Hyaluronic acid is so much a part of our tissues that there could be any number of diseases out there waiting to benefit from discoveries like these.”

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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.” 

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How microbes shape human health: an interview with Andrei Osterman

AuthorMiles Martin
Date

October 7, 2021

Sanford Burnham Prebys Professor Andrei Osterman, PhD

In his work on the human microbiome, Sanford Burnham Prebys professor Andrei Osterman, PhD, has shown how the organisms living within us can be leveraged to boost human health for a humanitarian cause – the plight of malnourished children. 

Describe your research aimed to improve the gut microbiome in malnourished children.
In infants, it’s been well-established that conditions of severe poverty and food insecurity cause a delayed development of gut microbes, and that this results in stunted growth, numerous syndromes, and even death. My team has been collaborating with researchers at Washington University in St. Louis to develop foods that are designed to enhance the microbiome, and we’ve found that these can actually work to correct some of these pathologies. 

One study involved introducing microbes from undernourished Bangladeshi children into the guts of mice. When these mice were then fed a typical Bangladeshi diet, they exhibited a weaker immune response to the oral cholera vaccine. More importantly, this poor response could be repaired by establishing a more normal gut microbiome in the mice and providing them supplements to boost these microbes’ propagation.

What else can we learn from this research that could be applied more broadly?
From a humanitarian perspective, the progress we’ve made is so valuable that there is no question we will continue the work. But studying the microbiome in infants, regardless of their food security, can also provide us with new insights into the importance of the microbiome in human health. 

In a more recent study with collaborators from University of California San Diego and University of Southern California, we found that adding corn syrup to infant formula can enhance the populations of beneficial microbes they might otherwise have gotten from breast milk. 

We hope this is the first of many studies we work on with this team, because the transition of infants from breast milk or formula to conventional foods is thought to be the most drastic example of how the microbiome changes with diet. Studying infants and their diets at this early point in life could help reveal fundamental truths that we’ll be able to translate to other syndromes related to the microbiome in children and adults worldwide, regardless of food security. 

And this isn’t just speculation. Another study with the team in St. Louis used the same methods as the malnutrition study to develop supplementary foods, called “fiber snacks,” to correct microbiome imbalances in people with obesity. One might think that obesity would be the total opposite of malnutrition, but the microbiome is a key player in both. 

More broadly, gut microbes are already the most well-studied part of the human microbiome, and the list of health associations with these microbes extend well beyond the digestive tract, even into the immune system, affecting the risk for diseases like cancer or diabetes. There’s also a growing body of evidence that suggests that gut microbes can have a direct effect on the brain. For example, the microbiome is being studied closely in connection to autism spectrum disorder, since many people on the spectrum experience concurrent gastrointestinal syndromes.

What would you say is important to know for people not familiar with the subject?
We need to acknowledge that our body and many of its problems have a huge microbiome component. The human body is a complex organism, and we are still learning how the microbiome influences and is influenced by different health conditions. The next step is to incorporate the role of the microbiome into the design of new diagnostics and therapeutics—because this undoubtedly influences their effectiveness. We can’t ignore this aspect of our biology, and the time is ripe to improve our understanding of it and leverage it to our advantage. Moving forward, this is going to help us solve so many problems—from issues we’ve already started looking at like obesity and malnutrition, all the way through to problems we aren’t even aware of yet. 

What are the next steps for you and your team?
What we’re really interested in now is exploring new genomic technologies that are starting to revolutionize the field. The latest development is something called MAG genomics, short for metagenomically assembled genomes. This involves looking at the big picture, sequencing DNA from the whole microbiome at once in a way that is much faster and of much better quality than we’ve ever been capable of before. It’s like the difference between watching a movie on a clunky pixelated monitor from the 80’s and seeing that same movie on an HD monitor. Methods like this are moving us into a new paradigm in biomedical research, one that may be more complex, but also one that has the potential to substantially improve health outcomes for people around the world.

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Early-career scientists showcase their work at the 20th Annual Trainee Research Symposium

AuthorMiles Martin
Date

October 5, 2021

People presenting scientific posters at an outdoor event with tents and trees in the background

The scientific leaders of tomorrow gathered to showcase their work at the 20th Annual Trainee Research Symposium on September 23rd. The talented group of presenters included postdoctoral researchers, graduate students, and staff scientists from labs across Sanford Burnham Prebys. 

After introductory remarks by Sanford Burnham Prebys Student Network co-chairs Stephen Sakuma and Marie Berenguer, PhD, as well as president Kristiina Vuori, MD, PhD, the young scientists gave 20-minute podium presentations about their research, which were judged by a panel of Sanford Burnham Prebys faculty and staff. Speakers included:

•    Nirmalya Dasgupta, PhD (Postdoctoral Fellow, Adams lab)
•    Ceda Stamenkovic (Graduate Student, Sacco Lab)
•    Cynthia Lebeaupin, PhD (Postdoctoral Associate, Kaufman lab)
•    James Kezos, PhD (Postdoctoral Fellow, Ocorr Lab)
•    Zhijie Xia, PhD (Postdoctoral Fellow, Freeze lab)
•    Valeria Guglielmi, PhD (Postdoctoral Associate, D’Angelo lab)
•    Victoria Recouvreux, PhD (Staff Scientist, Commisso lab)
•    Jonatan Matalonga Borrel, PhD (Postdoctoral Associate, Dong lab)
•    Chiara Nicoletti, PhD (Postdoctoral Associate, Puri lab)

Cynthia Lebeaupin, PhD and Valeria Guglielmi, PhD were respectively awarded first and second place by the judges for their presentations, for which they’ll each receive a cash prize to go towards career development activities. Lebeaupin’s research focuses on the progression of fatty liver disease to liver cancer, and Guglielmi studies the role of nuclear pores the development of bone marrow cells. 

After the first two sessions of presentations, the keynote speech for the Symposium was given by Katherine Thompson-Peer, PhD, an assistant professor of developmental & cell biology at the University of California at Irvine.

Following the last podium presentation was a poster session where 30 early-career scientists were given the chance to present their work. A panel of judges selected the top three posters—presented by Shaun Lim from the Kumsta and Hansen labs, Aleksandr Arzamasov from the Osterman lab, and Michaela Lynott from the Colas lab—and they will also receive a cash prize. The day was capped off with closing remarks from Sanford Burnham Prebys CEO C. Randal Mills, Ph.D.

Congratulations to all the participants in this year’s Symposium, and a special thank you to the staff at the Office of Education, Training, & International Services (OETIS) for organizing the event. 
 

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Meet computational biologist Mallika Iyer

AuthorMonica May
Date

January 14, 2021

Mallika Iyer in front of computer with green protein

Iyer is studying how proteins “dance,” which could lead to better drugs and a deeper understanding of human health 

DNA is often the star of the show when we talk about the body, but proteins are the true front-line workers. Formed by DNA’s instructions, proteins begin as strings of chemical compounds and later fold into a 3D shape that dictates their job in the body. If scientists can solve a protein’s shape—a feat that often takes years or decades—they may be able to create better drugs or better understand disease.  

Biologist Mallika Iyer, a graduate student in the Godzik lab at Sanford Burnham Prebys, is harnessing the power of computers to unlock insights into protein structure and movement. We caught up with Iyer as she prepares to take the virtual stage at DASL (the Diversity and Science Lecture Series at UC San Diego) to learn more about her greatest hopes for her research and what makes her tick.
 

Did you always know you wanted to be a scientist?
I’ve known I wanted to be a scientist ever since I learned about the digestive system as a kid. I was fascinated by how the human body works—it’s the most well-thought-out machine ever. 

I didn’t, however, imagine myself being a computational scientist until much later. When I was in college, I realized that traditional lab work wasn’t for me. I began learning some basic coding after I graduated and was hooked. That transitioned into computational biology/bioinformatics.

What do you study, and what is your greatest hope for your research?
I study protein structure and flexibility. Proteins are often depicted as having a single structure, but they are actually very flexible and transition between many different conformations as a part of their function—sort of like a well-choreographed dance.

My greatest hope for my research, or this field in general, is that we will someday be able to predict the types of movements a protein undergoes during the course of its function, or “job.” Last year, the field saw a huge advancement in the prediction of protein structure (read more in The New York Times). But “structure” is only half the story. Being able to predict all the different conformations and movements would be incredibly useful for medicine—and very cool!

What do you wish people knew about science?
That being wrong is a huge part of science. Scientists are supposed to understand and explain how the world works. But that is something that involves a lot of trial and error! Being wrong is, in fact, the way we advance our knowledge.
 

A woman in workout clothes kneeling in front of a rock climbing wall​
Prior to the pandemic, Mallika’s happy place was
the climbing gym. “It’s a great way to exercise
both your body and mind, and I have found the
climbing community to be really friendly and
accepting,” she says.

When you aren’t working, where can you be found? Where is your happy place?
Prior to the pandemic, my happy place was actually the climbing gym. I was introduced to indoor rock climbing about two years ago, and I instantly fell in love it with. It’s a great way to exercise both your body and mind, and I have found the climbing community to be really friendly and accepting. What makes my gym even better is that it also has extra space to just hang out, work, read a book, and so on. So, I used to go there a lot!
 

What is the best career advice you have ever received? 
Use every opportunity you can to present your work and network with people. I try to present at as many conferences and symposia as I can, and simultaneously use that as a way to meet and network with others in the field. I’ve found that this allows me to practice answering questions about my work, which in turn enables me to think more critically about it. And it can also lead to new opportunities that further my research and career.

What do you wish people knew about Sanford Burnham Prebys?
That it has a graduate program! I think our program is really unique. Its small size means that each student gets a lot of attention, and we have an Office of Education, Training and International Services (OETIS) that really offers us a lot of great resources to help us shape our careers.
 

Learn more about the Institute’s Graduate School of Biomedical Sciences.

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On the path to personalized breast cancer treatments

AuthorMonica May
Date

October 24, 2019

Fleet Cancer series-breast cancer

Ruth Claire Black wasn’t entirely surprised when she was diagnosed with breast cancer six and a half years ago. Her mother had died at age 52 of breast cancer, only two years after she was first diagnosed, Black explained at our recent Fleet Science Center event. New treatments have allowed Black’s story to differ from her mother’s—but as breast cancer experts from Sanford Burnham Prebys and UC San Diego Health explained, there is still a long way to go. 

“There is a great misconception that breast cancer is extremely easy to treat and is always cured. But the truth is that one in three women with early-stage breast cancer will relapse and eventually die from the disease,” said speaker Rebecca Shatsky, MD, a breast cancer oncologist at UC San Diego Health. “We are learning there aren’t one or two kinds of breast cancer—there are up to 30 different subtypes. To cure breast cancer, we need to look at treatments through a personalized lens.” 

Breast cancer is the second most common cancer in American women. One in eight women will be diagnosed with breast cancer in her lifetime, and more than 40,000 women die each year from the cancer. Targeted treatments—such as those that block the HER2 receptor—and hormone-based therapies have extended survival. However, 30% of people with estrogen-positive breast cancer, the most common form, eventually stop responding to standard-of-care treatments, for reasons that are largely unknown.

Speaker Svasti Haricharan, PhD, assistant professor at Sanford Burnham Prebys, is working to change these realities. Her work centers on a breast cancer subtype caused by defects in DNA repair machinery—a genomic “spell check” that normally corrects DNA copy errors during cell division. Nearly 20% of people who do not respond to breast cancer treatment have mutations in this machinery. Working with Shatsky, Haricharan’s team identifies breast cancer samples that have DNA damage repair defects. Then she tests these samples against thousands of FDA-approved treatments—with the goal of finding an effective treatment. 

For people like Black, these advances can’t come soon enough. 

“We have so much information about breast cancer. We have great diagnostics. Because of these tests, I know I’m a carrier of the BRCA2 mutation. I also know that it’s only a matter of time until my cancer returns,” said Black, who is a member of Sanford Burnham Prebys’ Community Advisory Board. “But doctors don’t know what to do with all of this information. That’s why I’m so supportive of the work taking place at Sanford Burnham Prebys. They are taking this information and doing something with it.” 

This event was the third of our five-part “Cornering Cancer” series. Register today to join us for discussions on pancreatic cancer in November and pediatric brain cancer in December. 
 

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Scientists discover new survival strategy for oxygen-starved pancreatic cancer cells

AuthorMonica May
Date

October 23, 2019

Cancer tumor

Oxygen is essential to life. When fast-growing tumor cells run out of oxygen, they quickly sprout new blood vessels to keep growing, a process called angiogenesis. 

By blocking pancreatic cancer’s oxygen-sensing machinery—the same field of research studied by the winners of the 2019 Nobel Prize in Medicine—Sanford Burnham Prebys scientists have uncovered a new way that tumors turn on angiogenesis in an animal model. The discovery, published in Cancer Research, could lead to a treatment that is given with an anti-angiogenetic medicine, thereby overcoming drug resistance. 

“Treatment resistance is a major challenge for cancer treatments that block blood vessel growth,” says Garth Powis, D.Phil., professor and director of Sanford Burnham Prebys’ National Cancer Institute (NCI)-designated Cancer Center and senior author of the study. “Our research identifies a new way angiogenesis is activated, opening new opportunities to find medicines that might make existing cancer treatments more effective.” 

Many cancer treatments work by blocking angiogenesis, which rarely occurs in healthy tissues. However, these medicines eventually stop working, and the cancer returns, sometimes in as little as two months. Scientists have been researching why this treatment resistance occurs so it can be stopped.

In this study, the scientists focused on pancreatic cancer, which is notoriously desperate for oxygen and also difficult to treat. Fewer than 10% of people diagnosed with pancreatic cancer are alive five years later. 

To see how a pancreatic tumor responds to a disruption in its oxygen supply, the Sanford Burnham Prebys researchers used a mouse model to block an oxygen-sensing protein called HIF1A—which should cripple the tumor’s growth. Instead of dying, however, after about a month the cells multiplied—indicating they had developed a new way to obtain oxygen. 

Further work revealed that the cancer cells were clear and swollen with the nutrient glycogen (a characteristic also seen in some ovarian and kidney cancers). In response to the excess glycogen, special immune system cells were summoned to the tumor, resulting in blood vessel formation and tumor survival. Each of these responses represents a new way scientists could stop pancreatic tumors from evolving resistance to treatment.

“Our team’s next step is to test tumor samples from people with pancreatic cancer to confirm this escape mechanism occurs in a clinical setting,” says Powis. “One day, perhaps we can create a second medicine that keeps anti-angiogenic drugs working and helps more people survive pancreatic cancer.”    

Research reported in this press release was supported by the U.S. National Institutes of Health (NIH) (5F31CA203286, CA216424 and P30CA030199). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. The study’s DOI is 10.1158/0008-5472.CAN-18-2994. 
 

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Sanford Burnham Prebys welcomes U.S. Congressman Mike Levin

AuthorMonica May
Date

October 22, 2019

Congressman Mike Levin visits SBP

On October 1, 2019, U.S. Representative Mike Levin (D-CA) toured Sanford Burnham Prebys and met with several faculty members to learn more about the innovative biomedical research taking place in his backyard. Levin represents California’s 49th Congressional District, which includes North County San Diego, South Orange County and neighbors our La Jolla campus. 

The visit kicked off with a visit to a lab working to find medicines for a heart arrhythmia condition called atrial fibrillation (AFib), a disorder that hits home for Levin: His grandmother struggled with the disease. Levin peered into a microscope to view beating heart cells and learned how a team of experts from Sanford Burnham Prebys and Scripps Clinic are working to develop personalized treatments for the condition, which affects nearly six million Americans (meet the A-team.)

“Sanford Burnham Prebys is a great example of the vibrant biomedical research taking place in San Diego that has the potential to improve the quality of life for families across the country,” says Levin. “Seeing the Institute’s critical research up close and hearing firsthand how National Institutes of Health (NIH) funding has accelerated medical discovery only strengthens my commitment to supporting biomedical science. Following my visit to Sanford Burnham Prebys, I was proud to introduce legislation that would invest $10 billion in the NIH to support biomedical research, and I will continue to fight for this much-needed funding.”

Following the lab tour, Levin met with faculty members who—thanks to federally funded research—are working to find treatments for Alzheimer’s disease and addiction, and study the aging process to address age-related diseases such as cancer. The visit wrapped up in the lab of Hudson Freeze, PhD, the director of our Human Genetics Program, who studies a rare childhood disease called congenital disorders of glycosylation, or CDG. 

“Americans today are living longer and healthier lives because of federally funded medical research,” says Chris Larson, PhD, the adjunct associate professor of Development, Aging and Regeneration at the Institute who arranged the visit. “We are grateful that Mike took the time to sit down with us to learn about our NIH-funded work and how he can help support us on our mission to find cures for human disease.”

Editor’s note: Shortly after his visit Levin introduced legislation that calls for a $10 billion investment in biomedical research. 

Institute News

Sanford Burnham Prebys scientist joins historic effort to help children with rare disease

AuthorMonica May
Date

October 3, 2019

Hudson Freeze, PhD

Hudson Freeze, PhD, professor of Human Genetics at Sanford Burnham Prebys, has joined a historic effort that establishes—for the first time—a nationwide network of 10 regional academic centers, Sanford Burnham Prebys researchers and patient advocacy groups to address decades of unresolved questions surrounding congenital disorders of glycosylation, or CDG, a rare disease that affects children. The consortium is funded by a $5 million, five-year grant from the National Institutes of Health (NIH). 

“We are extremely pleased that the NIH is investing in an initiative that will improve the lives of people affected by CDG,” says Freeze, who leads efforts to develop and validate disease biomarkers that will aid in diagnoses, and measuring treatment benefits during clinical trials. “Although globally the number of people living with CDG is relatively small, the impact on the lives of these individuals and their families can be profound. We look forward to working with the patients, families, physicians, scientists and other stakeholders focused on this important study.”

CDG is caused by genetic mutations that disrupt how the body’s sugar chains attach to proteins. First described in the 1990s, today scientists have discovered more than 140 types of mutations that lead to CDG. Symptoms are wide-ranging, but can include developmental delays, movement problems and impaired organ function. Some children may benefit from a sugar-based therapy; however, developing treatments for those who need alternative treatment options has been hindered by a lack of natural history data—tracking the course of the condition over time—comprehensive patient registry, and reliable methods to establish the CDG type.

Working together, the consortium will overcome these hurdles by: 

  • Defining the natural history of CDG through a patient study, validating patient-reported outcomes and sharing CDG knowledge 
  • Developing and validating new biochemical diagnostic techniques and therapeutic biomarkers to use in clinical trials 
  • Evaluating whether dietary treatments restore glycosylation to improve clinical symptoms and quality of life

Freeze will lead the efforts to develop and validate biomarkers for CDG, working alongside the Children’s Hospital of Philadelphia and the Mayo Clinic. The principal investigator of the CDG Consortium Project is Eva Morava, MD, PhD, professor of Medical Genetics at the Mayo Clinic. The patient advocacy groups involved are CDG CARE and NGLY1.org. 

Sanford Burnham Prebys and CDG Care will host the 2020 Rare Disease Day Symposium and CDG Family Conference from February 28 to March 1 in San Diego, which welcomes researchers, clinicians, children with CDG and their families, and additional CDG community members. Register to attend.