Immunology Archives - Sanford Burnham Prebys
Institute News

Perkins Fellow Trains Immune System Against Melanoma

AuthorGreg Calhoun
Date

May 15, 2024

Sanford Burnham Prebys scientist works on new methods to boost the body’s natural defenses against melanoma and other cancers

When she was growing up in India, Sreeja Roy, PhD, looked up to her father as he applied his scientific knowledge to care for the patients in his medical practice.

“He was my inspiration,” says Roy. “I found that I was particularly good at biology, and I liked learning about the mechanisms of how things work. Along the way, I realized I didn’t want to be a medical doctor and began focusing on biomedical research—and I fell in love with it.”

After earning her undergraduate degree in biotechnology from The Australian National University in Canberra, Roy obtained a master’s degree in infection biology from the Universität zu Lübeck in Germany. She returned to The Australian National University for her doctoral degree in immunology with an emphasis on viral vector-based vaccine immunology. After completing graduate school, Roy worked as a postdoctoral researcher at Albany Medical Center in New York before joining Sanford Burnham Prebys in September 2021 as a postdoctoral associate in the Immunity and Pathogenesis Program.

“I had been working on basic science in Albany,” notes Roy. “I really wanted to do translational research so I could work on things that would benefit people much sooner. That is why I chose to move to Sanford Burnham Prebys and focus on cancer immunotherapy.”

Roy’s background in immunology prepared her to enter the emerging field of cancer immunotherapy. This discipline involves developing treatments that enhance the human body’s innate immune response to better locate and dispose of cancer cells. She learned about an opportunity to support her interest in translational immunotherapy through the Jean Perkins Foundation Fellowship.

Roy received one of two prestigious fellowships designed to support postdoctoral researchers in the lab of Carl Ware, PhD, director of the Infectious and Inflammatory Diseases Center and professor in the Immunity and Pathogenesis Program.

“The Jean Perkins Foundation Fellowship has been fantastic,” says Roy. “I can work without the pressure of writing an academic grant, which allows me to focus on the science and be more productive.”

Roy’s project at the Ware lab involves making immunotherapies more effective in treating melanoma, the deadliest form of skin cancer.

“Unfortunately, some tumors never respond to immunotherapy treatments,” explains Roy. “Also, tumors can initially begin to shrink before becoming resistant to a treatment.”

Under Ware’s direction, Roy is testing ways to enhance existing immunotherapies through the lymphotoxin-β receptor, which is found on some types of immune cells.

“When the immune system encounters a foreign substance that may cause an infection, a sample of the invader can be shuttled to the lymph nodes as a way of learning about the threat and generating a better immune response,” explains Roy. “Depending on which tissues are being infected, the lymph nodes cannot always be involved, so an active lymphotoxin-β receptor is able to approximate their effect by organizing immune cells in something akin to training centers so that a better attack can be launched.”

Roy and the Ware lab are developing ways to take advantage of the lymphotoxin-β receptor’s ability to recruit and train immune cells as an approach to making immunotherapies more effective.

“If I can target the lymphotoxin-β receptor signaling against tumors, does that enhance the anti-tumor immunity?” asks Roy. “Do the tumors become more responsive to the treatments now? That is what we’re trying to find out.”

With the help of the Jean Perkins Foundation Fellowship, Roy is determined to continue developing her translational science expertise and find ways to improve the effectiveness of immunotherapies for melanoma and other cancers.

“We’ve made quite a bit of progress,” says Roy. “I look forward to sharing our results and seeing how this project advances from the bench to the bedside.”

Institute News

A strange research ecosystem: Discussing Lyme disease with Victoria Blaho

AuthorMiles Martin
Date

December 22, 2021

As an infectious disease immunologist studying Lyme disease, Victoria Blaho is one of a rare breed.

Sanford Burnham Prebys assistant professor Victoria Blaho, PhD, investigates the biochemical signals of the immune system and how they impact our bodies’ abilities to fight pathogenic infections, a branch of immunology that has become much less popular since the advent of antibiotics in the early 20th century.

Blaho’s disease of choice is Lyme disease, an unusual tick-borne bacterial infection that affects some 476,000 people in America each year, a number that is on the rise.

We caught up with Blaho to talk about why Lyme disease research is important, the progress being made and the work that remains in studying this strange and burdensome disease.

Why is Lyme disease research important?
Blaho: Lyme research is a very small field for a disease that is becoming bigger and bigger every year. Case counts are increasing for Lyme disease all over the world, and people get very sick from it. Some people are infected, take antibiotics and that’s the end of it. But others have chronic symptoms like arthritis or carditis that can last for years and become completely debilitating.

What makes Lyme difficult to study?
Blaho: One reason is that Lyme is an unusual infection from a microbiological standpoint. In the early days of Lyme research, there were studies showing that the bacteria that caused the disease, Borrelia burgdorferi, could change its physical form from a corkscrew shape to dormant blobs—and the blobs could be causing extended disease. This is a problem because scientists haven’t agreed on the true cause of chronic Lyme disease.

To make matters worse, a lot of the medical field still believes Lyme is easily curable with antibiotics, and if people are still having problems, then it’s psychosomatic. This makes it harder to get support for research into the longer-term inflammatory effects of Lyme. These politics make Lyme disease research a strange ecosystem of patients, physicians, researchers and funding agencies, and this is a barrier to learning more about the disease and helping people find relief.

How does your work enter the picture?
Blaho: I’ve been working on Lyme disease for over 15 years, since I was PhD student. It started because Celebrex was hugely popular at the time to treat arthritis, but nobody had ever studied it in the arthritis that emerges in Lyme disease. Celebrex inhibits an enzyme of the immune system that triggers inflammation, so we figured that Celebrex might work just as well in Lyme arthritis as in other types. But research on mice didn’t bear this out.
Inflammation doesn’t just peter out when an infections clears. The immune system has to clean up the mess. We discovered in mice that Celebrex inhibits the resolution of inflammation after Lyme disease has resolved, so the arthritis never went away.

Since then, my career has focused on exploring the signaling molecules that regulate inflammation and its resolution. These molecules affect all parts of the immune system and provide us with a whole host of different potential therapeutic targets for inflammatory diseases like chronic Lyme.

What are the next steps for your Lyme research and for the field at large? 
Blaho: My own immediate next step is to take the work I’ve been doing here at Sanford Burnham Prebys and connect it directly back to my original work with Lyme. My team here is currently working on a signaling molecule called S1P, and while we haven’t studied it in Lyme yet, we think there are connections between it and the immune mediators we first found through those Lyme studies.

Our next steps are to look for the protein that carries S1P in mice with Lyme disease. This protein is associated with disease susceptibility in other inflammatory illnesses like diabetes and cardiovascular disease, and we think it has a role to play in Lyme as well. We’re also planning to partner with the Bay Area Lyme Foundation to see if we can find changes in this protein in their collection of human samples.

More broadly, I think this field is hungry for innovation because there have been a small number of scientists focusing on it. If older ideas about Lyme being simple to treat were the complete picture, we’d already be able to better diagnose and treat patients. But we’re just not there yet.

Lyme may be a lot cleverer than we originally thought, but if we’re able to embrace new technologies and ideas and continue to push forward with new work, we’ll be able to find innovative approaches to fight Lyme and, ultimately, to help people suffering from this horrible disease.

Institute News

An evening with autoimmune disorder experts

AuthorMonica May
Date

June 26, 2019

On June 20, 2019, nearly 100 community members, including many people living with autoimmune disorders and their loved ones, joined us at our latest SBP Insights event. The discussion featured unique perspective from three experts—a scientist, a doctor and a patient—on a single topic: autoimmune disorders. 

More than 50 million Americans have an autoimmune disorder, such as Crohn’s disease, psoriasis or rheumatoid arthritis. These conditions are often painful, chronic and debilitating. For unknown reasons, more than 80 percent of these patients are women. 

Scientists know these disorders occur when the immune system mistakenly attacks healthy tissue. But researchers still don’t understand why immunosuppressive treatments don’t work for everyone or know the initial trigger that causes the immune system to misfire. Answers to these fundamental questions could unlock insights that lead to new, effective medicines. 

“Before I was diagnosed, I thought doctors had it all sorted out. Now I know there is so much they don’t know,” says 17-year-old Madison Koslowski, who was diagnosed last year with juvenile idiopathic arthritis. She uses a wheelchair and cane for mobility while she works with her doctor to find a treatment that relieves her intense joint pain. “Right now, my friends are planning their future and figuring out where they will go to college. But for me, there are so many unknowns. I don’t know if I’m going to respond to the next medicine we try or if I will be really sick. I feel like my life is on pause. I have no idea when it will start again.”

Madison traveled from Los Angeles with her mother and a friend to hear race-car driver Angela Durazo speak about her journey with rheumatoid arthritis and learn what’s on the horizon for autoimmune treatments (read Angela’s story).

Following Angela’s presentation, Carl Ware, PhD, professor and director of the Infectious and Inflammatory Diseases Center at Sanford Burnham Prebys, took the stage and provided an overview of the science behind autoimmune disease. Ware also described his ongoing research collaboration with Eli Lilly, which recently led to a new Phase 1 clinical trial for autoimmune disorders. 

Hal Hoffman, MD, chief, division of allergy, immunology and rheumatology at UCSD and Rady Children’s Hospital, wrapped up the discussion with an overview of how he and his team are turning to rare immune disorders to understand the conditions as a whole. A Q&A followed the brief presentations. 

17-year-old Madison Koslowski (right), who was diagnosed last year with juvenile idiopathic arthritis, poses with race-car driver Angela.

17-year-old Madison Koslowski (right), who was diagnosed last year with juvenile idiopathic arthritis, poses with race-car driver Angela.

The discussion was moderated by Zaher Nahle, PhD, CEO of the Arthritis National Research Foundation.

Join us at our next SBP Insights discussion, which focuses on pancreatic cancer and takes place on November 21, 2019. Event details.

Institute News

SBP surfers rule!

Authorsbraun
Date

August 21, 2015

Did you know that SBP has a surfing team?  Not only do we have a team, but we have a winning team!  Last weekend, Carl Ware, full-time immunologist and part-time surfer, led the SBP team to victory in the Luau and Legends of Surfing Invitational, a contest held in San Diego that raises funds for the UC San Diego Moores Cancer Center.

Surf contest 4

For the past 22 years the Luau has attracted some of the most respected men and women in surfing history, along with business leaders, scientists, local politicians and national celebrities, all surfing for a cure. The event has raised more than $7 million for cancer research, improved public awareness of the need for better therapies, and always creates unlimited fun for participants and spectators.

“The Luau and Legends Invitational hits both of my passions, science and surfing.  I’ve been surfing in the event for about 10 years,” said Ware. “Raising money for cancer research is great, but I especially treasure surfing with my son and teammates.”

Surf contest 3

Each competitive team consists of four members and a surf legend. This year the SBP team included Carl Ware, his son Austin, Jeff Timpson, Loni Christiansen, and surf legend Tom Ortner. Austin lives in Australia and is a sports psychologist and surf coach.  Jeff, who does a remarkable head stand on his board, and Loni, who surfs a stylish switch foot, are local sufers that frequent Swami’s break.  Ortner is a living legend from La Jolla who surfed professionally in the 1970’s.

The SBP team raised an impressive $15,000 for the Cancer Center.

SBPSurfTeam2015JeffDevine

Other notable surf stars that participated in the event were Robert August and Mike Hynson. Stars of the classic surf film Endless Summer, Pat O’Connell, Robert “Wingnut” Weaver, and Rob Machado and many others.

“We won for cancer research, and now we are planning a world tour to help defeat cancer,” added Ware.

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Carl Ware, PhD, is the director of SBP’s Infectious and Inflammatory Disease Center.