Cancer Center Archives - Page 4 of 11 - Sanford Burnham Prebys
Institute News

Seminar Series: extrachromosomal DNA and the metabolic circuits of cancer immune suppression

AuthorScott LaFee
Date

March 25, 2024

The ongoing Sanford Burnham Prebys seminar series will feature a pair of speakers on March 27, from noon to 1p.m., in the Fishman Auditorium. They will be presenting on two topics: extrachromosomal DNA and the tumor microenvironment.

First, Owen Chapman, PhD, a postdoctoral research scientist in the lab of Lukas Chavez, PhD, will discuss clinical and genomic features of circular extrachromosomal DNA (ecDNA) in medulloblastomas, a type of brain tumor.

EcDNA is DNA found off chromosomes, either inside or outside the nucleus of a cell. In a study published last year, Chavez (senior author), Chapman (first author) and colleagues reported that patients with medulloblastomas containing ecDNA are twice as likely to relapse after treatment and three times as likely to die within five years of diagnosis.

The second presentation will be by Kevin Tharp, PhD assistant professor in the Cancer Metabolism and Microenvironment Program. Tharp, who joined Sanford Burnham Prebys in December 2023, studies how tumors manipulate their mitochondria to improve survivability and how those cellular mechanics can be leveraged to create more effective therapies.

Institute News

Sanford Burnham Prebys Cancer Center seminar on March 25

AuthorGreg Calhoun
Date

March 25, 2024

The Sanford Burnham Prebys Cancer Center is hosting a special seminar on Monday, March 25, from noon to 1 p.m. at the Fishman Auditorium in Building 4 on the Sanford Burnham Prebys campus, 10901 North Torrey Pines Road, La Jolla, Calif., 92037.

The seminar’s featured speaker is Eric S. Fischer, PhD, professor of biological chemistry and molecular pharmacology at Harvard University. Fischer will discuss the topic, “Molecular Mechanisms of Ubiquitin Ligases– From Structure to Therapies.” More details on the seminar subject are available in the abstract below.

Abstract:  Small molecules that induce protein degradation through ligase-mediated ubiquitination have shown considerable promise as a new pharmacological modality. Thalidomide and related immunomodulatory drugs provided the clinical proof of concept while significant progress has recently been made towards chemically induced targeted protein degradation using heterobifunctional small molecule ligands. Fischer will present recent work to develop a better understanding of the molecular principles that govern neo-substrate recruitment and its application to the development of small molecule degraders.

For more information on the seminar, please contact Valerie Alanis at valanis@sbpdiscovery.org

Pizza and refreshments will be served.

Institute News

New genome mapping tool may uncover secrets for treating blood cancers

AuthorGreg Calhoun
Date

February 1, 2024

The outlook for patients with acute myeloid leukemia (AML), a deadly set of blood cancers that is difficult to treat, has remained dire for decades, especially among patients who are not eligible for bone marrow transplantation.

More than 30% of treated patients will never achieve complete remission using current chemotherapies and, even when chemotherapy treatments work, most patients relapse within five years without a transplant.

While prior research has begun to unravel the genetic underpinnings of the disease, more inquiry is needed to understand the genetic variation within the roughly 15 AML subtypes and how that variation might affect treatment strategies.

“In addition to the one to eight average genetic mutations in AML patients found in traditional sequencing studies, experiments employing high-resolution optical genomic mapping have found approximately 40 to 80 rare genomic structural variants per patient,” says Kristiina Vuori, MD, PhD, Pauline and Stanley Foster Distinguished Chair and professor in the Sanford Burnham Prebys Cancer Center’s Cancer Molecular Therapeutics Program. “We wanted to take these structural variant findings in AML to the next level by connecting them with patients’ sensitivity or resistance to current cancer treatments.”

Kristiina Vuori, MD, PhD

In a paper published January 18, 2024, in Cancers, a multidisciplinary team of biologists, bioinformaticians and clinicians from Sanford Burnham Prebys, Bionano Genomics Inc. and Scripps MD Anderson were the first to associate genomic structural variants (SVs) in AML patients with drug sensitivities.

“SVs are changes to the genome in which sections of 50 or more base pairs in a strand of DNA have been errantly deleted, duplicated, inverted or translocated,” explains Darren (Ben) Finlay, PhD, first author on the manuscript and research associate professor in the Sanford Burnham Prebys Cancer Center.

“Such changes amount to different combinations of DNA gains, losses or rearrangements. When cells use these altered instructions in the DNA to make proteins or carry out other functions, it is like a chef trying to cook with a recipe that is missing steps, has them in the wrong order or includes more or less of the key ingredients.”

Darren (Ben) Finally, PhD

Scientists have become more able to find SVs as next-generation genomic analysis technologies and techniques have improved. Research has shown that SVs contribute to the development and progression of cancer, including blood cancers. Of particular concern among SVs are DNA changes that join two otherwise distant genes. This event, called gene fusion, is known to drive certain pediatric and blood cancers.

Finlay, Vuori and colleagues analyzed SVs in samples from 23 AML patients and found their genomes featured 16-45 extremely rare SVs within genes but not seen in healthy volunteers’ samples. The scientists detailed the patients’ SVs using a technique called optical genome mapping. This tool tags DNA in specific locations to create recognizable sequences, unwinds and straightens the genomic DNA for linear scanning, and converts the imaged sequences into digital representations of DNA molecules. Because it directly images DNA rather than relying on algorithmic analyses, optical genome mapping is better than next-generation sequencing at finding SVs throughout the entire genome, especially large SVs, the researchers said.

To begin building the connection between SVs and drug sensitivity, the scientists tested samples from each patient with 120 FDA-approved drugs, and experimental treatments currently in phase III clinical trials. This allowed the researchers to map out how strongly each patient’s sample reacted with each drug.

Next, the investigators used statistical analysis to compare the SVs within the optical genome mapping results with the findings from the drug sensitivity tests. The team found 61 statistically significant interactions between SVs and existing cancer therapies. In one interaction, the group demonstrated that a commonly used AML drug, Idarubicin, and two similar compounds (Daunorubicin and Epirubicin) were more effective in leukemia samples with a specific insertion in a gene that carries the instructions for a signaling enzyme that helps nerves communicate with muscles. These and other examples lend support to the scientists’ hypothesis that optical genome mapping could be used to develop personalized treatment plans that account for patients’ SVs.

“In this pilot study, our hope was to identify structural variants that could be used as new biomarkers for current AML drugs as well as to identify other drugs that could be repurposed to treat leukemia patients,” says Finlay.

“Ensuring patients receive the most effective drugs on the market through personalized treatment and identifying new potential therapies for AML are critically important,” adds Vuori, senior author on the study. “Especially for patients who do not achieve remission with current standard chemotherapies or who are ineligible for bone marrow transplants or clinical trials.”
 

Cancers 2024, 16(2), 418; https://doi.org/10.3390/cancers16020418

Institute News

A year-end note from David Brenner

AuthorDavid Brenner
Date

December 19, 2023

This past year — my first full calendar year as president and CEO of Sanford Burnham Prebys — has been exciting and immensely rewarding. We’ve accomplished a lot and, more importantly, laid the groundwork for a wealth of future achievements.

It begins with having a plan. We are in the midst of a biomedical revolution, one in which the old ways of thinking about and doing science no longer address the complexities of modern research or the greater needs in public health.

Sanford Burnham Prebys is particularly positioned to adapt and lead in this new world by combining distinct and powerful resources with a unified mission driven by ambitious goals that emphasize disease-focused centers combined with enabling technology programs.

Of course, doing so requires a brilliant faculty, one that boasts exceptional skills and vision not just in this moment, but in the years to come. Our faculty know what to do. Our newest faculty promise to further propel and elevate. In less than a year, we have hired eight early-career scientists and physicians, an unprecedented number in such a short time.

They are among the best and brightest, coming from elite labs and institutions across the country: Shengie Feng, PhD (Howard Hughes Medical Institute and UCSF); Kelly Kersten, PhD (UCSF); Angela Liou, MD (Children’s Hospital of Philadelphia) Sanjeev Ranade, PhD (Gladstone Institutes); Sanju Sinha, PhD (National Cancer Institute); Xueqin Sherine Sun, PhD (Cold Spring Harbor Laboratory); Kevin Tharp, PhD (UCSF); and Xiao Tian, PhD (Harvard Medical School).

A couple have already started their next chapters of their careers at Sanford Burnham Prebys, including already landing new grants! Others begin in January or March. Please welcome them.

These eight scientists represent the first wave. There are more to come, the benefit of Denny Sanford’s landmark gift early in 2023.

It has been a robust year in science at Sanford Burnham Prebys, too.

The Cancer Center received a merit extension from the NCI related to its support grant, a rare recognition of ongoing excellence. The Prebys Center for Chemical Genomics continues to be the go-to place for drug discovery, highlighted by a trio of recent awards totaling almost $25 million to pursue novel leads and promising therapies to treat all manners of addiction.

Sanford Burnham Prebys researchers are pushing boundaries across disciplines, from DNA loops in pediatric brain tumors and a sugar with anti-cancer properties to a heart attack study that could change regenerative medicine and discovering that an incurable liver disease might just be curable.

We’ve also welcomed two new trustees: Michael R. Cunningham, PhD and Lori Moore.

It’s been a busy year. It’s been a good year.

With all of you, next year will be even better.

Institute News

From postdoc to PI, it’s a journey. Don’t forget to pack some support

AuthorSanju Sinha
Date

December 15, 2023

The journal Nature Cancer asked a dozen early-career investigators to share their thoughts and experiences about starting their own labs in 2023. Among them: Sanju Sinha, PhD, who joined Sanford Burnham Prebys in June. Below is his essay. You can read the rest here.

Don’t forget to pack support 

Against the backdrop of a world emerging from a pandemic, starting my laboratory in 2023 was a whirlwind of excitement and anxiety, against the backdrop of a world emerging from a pandemic.

The goal for my laboratory is to understand cancer initiation and use this knowledge to develop preventative therapies—a goal appreciated by many, yet understudied and underfunded. We are aiming to achieve this by developing computational techniques based on machine-learning and leveraging big data from various sources, such as healthy tissues, pre-cancerous lesions and tumors. This journey has taken several unexpected turns, with its fair share of delights and challenges.

One significant hurdle appeared early: hiring. I recall the advice I received: “Forget it, you can’t hire a postdoc as an early-stage laboratory.” This made me ponder—if I were to choose right now, would I pursue a postdoc? My immediate answer was no. It struck me then: the traditional postdoc route needed a revamp.

Determined to instigate change, I introduced a new role: computational biologist. This position, an alternative to a postdoc, was tailored for transitioning to industry and offered better pay. The response was staggering—more than 400 applications.

Now, I’m proud to lead a fantastic team of three computational biologists from whom I am continually learning. This experience taught me a valuable lesson: crafting roles that serve both the goals of the laboratory and the career aspirations of the applicants can make a world of difference. I urge new principal investigators to shatter norms and design roles that provide fair compensation and smooth industry transition—reflecting the reality of the current job market.

However, the path to establishing a new laboratory was not without setbacks. Rejection is common in this field. I have already experienced a grant rejection and, considering the average grant success rate, I am prepared for many more.

Amid these challenges, my support system proved to be my lifeline. I’m grateful to be part of Sanford Burnham Prebys, which has proved to be more than just a top biomedical research institution. It is a community that provides unparalleled support for early principal investigators through generous startup packages, administrative assistance, hiring and grant-writing guidance, and a network of compassionate peers and mentors.

Equally important is my personal support system—my family, partner and friends who remind me that there is life beyond science, helping me maintain my well-being. This balance, I have realized, is the most crucial tool for anyone on a similar journey—so do not forget to pack support for the ride.

Institute News

The “Eph” system may pave the way for novel cancer therapies

AuthorSusan Gammon
Date

November 27, 2023

Over the past three decades, researchers have been investigating an important cell communication system called the “Eph system,” and the evidence implicating the system in cancer is staggering.

The Eph system is comprised of multiple Eph receptors and their ligands—ephrins—and are involved in contact-dependent communication between cells. They play essential roles in regulating various cellular processes.

Modern studies have shed light on the Eph system’s role in tumor expansion, invasiveness, metastasis, cancer stem cell maintenance and therapy resistance.

This month, Elena Pasquale, PhD, published a review in Nature Reviews Cancer that summarizes the current state of research on the Eph system and its links to cancer progression and drug resistance.

“The Eph system has many critical functions during the development of tissues and organs, but it also has the capacity to either promote or suppress cancer progression and malignancy” says Pasquale. “In cancer, the activities of the Eph system can differ depending on the circumstances—for example, which Eph receptors and ligands are present in a tumor cell, the types of tumor cells in which they function, and the characteristics of these cells.”

“It’s this remarkable versatility that makes the Eph system a compelling but also challenging target for potential therapies,” says Pasquale.

“The aims of this review were to comprehensively survey the large body of data regarding various aspects related to Eph signaling in tumors and to highlight potential strategies for therapeutic targeting,” says Pasquale. “Overall, while significant progress has been made in deciphering the Eph system in cancer, there is much more to learn.

“Gaining a deeper understanding of how the Eph system functions in cancer is challenging but will be essential for the development of targeted therapies and personalized treatment approaches for patients.”

Institute News

A former Sanford Burnham Prebys postdoc writes about science and social responsibility

AuthorScott LaFee
Date

October 18, 2023

The laboratory, with its precise protocols and sterile tools, seems far removed from the often discordant chaos of U.S. society. But science does not happen in a socio-political vacuum, says  Eric Lau, PhD, a former student and postdoc at Sanford Burnham Prebys, and research institutions shouldn’t pretend otherwise.

Writing in Nature Reviews Cancer, Lau, now an Assistant Professor in the Department of Tumor Microenvironment & Metastasis at the Moffitt Cancer Center & Research Institute in Tampa, Fl., calls for scientific institutions to become proactive against discrimination and to speak out against oppression while prioritizing diversity, equity and inclusion.

In a deeply personal essay, Lau chronicles his personal struggles to overcome both xenophobia and the “delusional and detrimental model minority myth” of Asian-American kids, plus persistent homophobia and hate-mongering.

Science and the relationships formed with mentors, such as Kristiina Vuori, Wei Jiang, Robert Abraham, Gen-Sheng Feng and Ze’ev Ronai, as well as a handful of close colleagues at Sanford Burnham Prebys, were life- and career-affirming, he said, “but sadly all too rarely seen in the broader world.”

“Our nation claims to celebrate diversity and immigration….Yet racism and xenophobia are being amplified by governors who viciously traffic vulnerable migrants to other states and by Supreme Court justices who eviscerate affirmative action and approve anti-LGBT+ discrimination,” Lau writes.

“As much as most researchers might prefer to ‘just focus on the science,’ we cannot expect our teams to produce the best science if we turn a blind eye to those being discriminated or the discriminators.”

Willful ignorance and complacency are not options.

Eric Lau headshot in lab coat with old Sanford-Burnham logo

Lau says research institutions can and should take actions to mitigate the socio-political adversity that burdens their team members. Leadership cannot be performative—rather, it must be substantive, transparent and persistent. DEI programs must be built to produce intended results, with zero-tolerance for discrimination.

Lau concludes with a version of Martin Niemoller’s poem “First they came,” written in 1946 about the silence of German intellectuals and clergy (including Niemoller) during the rise of Nazism.
 

First they came for the socialists, and I did not speak out—
Because I was not a socialist.
Then they came for the trade unionists, and I did not speak out—
Because I was not a trade unionist.
Then they came for the Jews, and I did not speak out—
Because I was not a Jew.
Then they came for me—and there was no one left to speak for me.

 

Scientists, says Lau, must speak up and often.
For themselves.
For others.
For everyone.

Institute News

Svasti Haricharan joins the very first Stop & Talk podcast

AuthorSusan Gammon
Date

September 12, 2023

Svasti Haricharan, PhD, was the first guest on Stop & Talk—a new podcast offered by The Conrad Prebys Foundation. In the broadcast, Svasti shares how she came to be a research leader in therapy-resistant breast cancer and how race affects clinical outcomes.

Early in her career, Svasti would have to present her research over IPA beers in the UK. (She learned to love beer as she connected with her scientific community.) While completing her postdoctoral training in Texas, her boss asked her to help him write a grant application on cancer disparities and how race affects cancer outcomes. At the time, she had no idea that this was an issue because no one had ever brought it up in her 12 years of training. Since then, she’s taken a deep dive into who gets studied, why, and how to ensure that we help more people in the general population living with cancer.

Join Svasti and Grant Oliphant, the CEO of The Conrad Prebys Foundation, for this important conversation about diversity, science, changing the world, and what it means to be open to multiple viewpoints.

Institute News

Ronai discusses new AI-supported breast cancer findings on Arabic-language TV

AuthorScott LaFee
Date

August 7, 2023

This month, researchers in Sweden published a study in The Lancet Oncology that compared the efficacy of artificial intelligence-supported mammogram screening versus the standard double reading by radiologists.

The researchers found in their randomized trial that AI-supported mammography screenings are safe, almost halved radiologists’ workload, and detected cancers that reviewing doctors missed.

Not surprisingly, the findings garnered international news coverage. Breast cancer is a global health threat, with more than 2.3 million women worldwide diagnosed each year and nearly 700,000 deaths.

Ze’ev Ronai, PhD, director of the Cancer Center at Sanford Burnham Prebys, was among experts interviewed by global media to provide context to the Swedish findings. He was interviewed on Alhurra, a U.S. government-owned Arabic-language satellite TV news channel that broadcasts internationally outside of the U.S.

You can watch the interview here. It’s in Arabic, but essentially Ronai said:

“This randomized trial of over 80,000 women offers an important advance for early detection of breast cancer, based on AI support of radiologist workload. AI will assist but not replace the role of radiologists in these assessments, and thus, is expected to enable radiologists to attend to more difficult cases. Caution from detections of less harmful lesions (which was one of the outcomes in this study), requires more training and careful validation. Overall, this is an important and safe advance in our quest for early detection of cancer, in this case, breast cancer.”

Institute News

Preuss internship celebrates 15 years of inspiring young scientists

AuthorMiles Martin
Date

August 2, 2023

“I liked how hands-on everything was,” says Preuss intern Amayrani Calderon “The scientists would show us how to do the experiment but then let us do it ourselves. I’d never had that type of experience in a lab before.”

Each year, Sanford Burnham Prebys welcomes a cohort of high school interns from the Preuss School, whose students strive to be the first in their family to graduate from college. This year’s Preuss interns learned hands-on research skills from scientists at the Institute’s NCI-designated Cancer Center and about career possibilities in STEM beyond research.

“My favorite part of the program and about Sanford Burnham Prebys is all the diverse people I met,” says Alejandra Ruiz Ramirez, who is first-generation Mexican American. “I had mentally prepared myself not to see any scientists that look like me, or to potentially be stereotyped as a Mexican American woman, but that isn’t what happened at all. Everybody I met was very welcoming.”

The Preuss internship is an intensive three-week program designed to jumpstart the careers of the next generation of scientific researchers. This year, the first two weeks were spent learning state-of-the art research techniques, such as staining cells for immunohistochemistry and separating proteins with gel electrophoresis.

“Seeing a real lab was a lot different than what I expected,” says Preuss intern Mohamed Haghi-Mohamed. “At school we just do labs on our desks, but seeing the incubators and other machines really changed my perspective and on how science works in the real world.”

For the final week of the program, interns shadowed staff scientists working in various labs throughout the Cancer Center, where they saw the research process firsthand.

“Consuming a lot of media makes you see science as always exciting and fast-paced, but it’s a very different experience actually working in the lab day to day,” says Preuss intern Juan Lomas Hoeung. “Sometimes there’s a lot of downtime but other times things are hectic.

The Preuss internship program also included activities outside of the lab, including panel discussions with scientists, a tour of the Conrad Prebys Center for Chemical Genomics, and a workshop on diversity and equity and STEM. The interns also had lunch with Institute staff each day, where they had the chance to learn and ask questions about varied STEM careers such as research administration, science communication, and philanthropy.

“We wanted the students to see that there are varied paths to a career in STEM, and that these paths aren’t always linear,” says Victoria Carrillo, senior program administrator for the Cancer Center, who oversaw the Preuss internship along with faculty organizer Svasti Haricharan, PhD.

The program culminated in a celebratory luncheon with students, researchers and Institute staff, where the interns had the opportunity to share what they’ve learned from their experience at Sanford Burnham Prebys.

“This was the best environment to learn in because the people here are some of the most expressive and passionate people I’ve met when they’re in the lab talking about what they do,” says Hoeung. “Everybody was so enthusiastic.”