Michael Jackson Archives - Sanford Burnham Prebys

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Institute News

Curebound awards two grants to Sanford Burnham Prebys scientists

AuthorGreg Calhoun
Date

February 12, 2025

split photo of Brooke Emerling and Michael Jackson
Brooke Emerling, PhD, is director of the Cancer Metabolism and Microenvironment Program. Michael Jackson, PhD, is senior vice president for Drug Discovery and Development in the Conrad Prebys Center for Chemical Genomics.

The San Diego-based philanthropic organization has awarded $43 million in cancer research to date

Curebound recently announced the awarding of 17 grants in December 2024 for a total of $8.25 million in funding to advance cancer research in 2024.

Two new grants will support cancer research conducted by scientists at Sanford Burnham Prebys. Since 2014, 32 Curebound grants have supported projects that included scientists at the institute.

A workaround for a tricky target

The TP53 gene contains the blueprint for constructing a protein called tumor protein p53. This protein is considered a tumor suppressor because it helps cells grow in a controlled manner.

When cell growth goes awry, however, the TP53 gene is a common culprit as the most frequently mutated gene in cancers. While this ubiquity has placed a bullseye on the mutated tumor protein p53 for aspiring drug developers, it has proven tricky to target directly.

Brooke Emerling, PhD, director of the Cancer Metabolism and Microenvironment Program, and her collaborators have shown that the growth of cancer cells with a mutated TP53 gene is dependent on lipid enzymes called phosphatidylinositol-5-phosphate 4-kinases (PI5P4K). Emerling and her collaborators have identified compounds that break down these enzymes.

The researchers have demonstrated the ability of these compounds to target and eliminate cancer cells with a mutated TP53 gene without harming normal cells. Curebound will support the team’s ongoing efforts to work around the difficult-to-target tumor protein p53 by instead targeting PI5P4K.

Next, the group plans to optimize the compounds that break down PI5P4K to develop cancer drugs that are strong candidates for future clinical trials.

Curebound collaborators: Patrick Kearney, PhD, director of Medicinal Chemistry in the Conrad Prebys Center for Chemical Genomics, and Eric Wang, PhD, assistant professor in the Cancer Molecular Therapeutics Program.

Boosting the immune system against lung cancer

The immune system is one of the main defenses of the human body to fend off harmful pathogens and invasive cells such as cancer. Among all white blood cells, a particular cell type, called a T cell, can directly kill cancer cells and therefore plays an essential role in building anti-tumor immune responses.

Immunotherapies that boost the anti-cancer capabilities of T cells have revolutionized the way we treat cancer, especially in blood cancers such as leukemia, lymphoma and myeloma. More recently, immunotherapies are rapidly advancing to become mainstream treatments for solid cancers as well.

Currently, however, less than a third of patients with lung cancer benefit from immunotherapies. Pandurangan Vijayanand, MD, PhD, the William K. Bowes Distinguished Professor at the La Jolla Institute for Immunology, discovered that certain T cells called cytotoxic T lymphocytes have molecular features associated with a robust immune response against lung cancer tumors. His work has identified new targets for lung cancer immunotherapy.

Curebound will support Vijayanand’s collaboration with Michael Jackson, PhD, senior vice president for Drug Discovery and Development in the Conrad Prebys Center for Chemical Genomics, to use this research to identify agents to boost tumor immune responses.

The research team’s work has the potential to identify a new class of immunotherapy drugs for patients with lung cancer.

Curebound collaborator: Changlu Liu, PhD, director of Receptor Pharmacology in the Conrad Prebys Center for Chemical Genomics.

Pandurangan Vijayanand

Pandurangan Vijayanand, MD, PhD, is the William K. Bowes Distinguished Professor at the La Jolla Institute for Immunology.

Institute News

How AI can make drug discovery faster, better and cheaper

AuthorMichael R. Jackson, PhD
Date

September 30, 2024

image derived from cryo-electron microscopy of SBI-4710, a small molecule inhibitor discovered at Sanford Burnham Prebys
An image derived from cryo-electron microscopy of SBI-4710, a small molecule inhibitor discovered at Sanford Burnham Prebys (in white) bound into the glutaryl-CoA binding pocket of the GCDH protein, a cancer drug target. Residing in a nearby pocket is flavin adenine dinucleotide (orange), a co-factor. The image was generated by a team of researchers, including Merve Demir, PhD; Jianhua Zhao, PhD; Eduard Sergienko, PhD; Steve Olson, PhD and Ze’ev Ronai, PhD, who are collaborating to develop a first-in-class drug to inhibit this enzyme as a therapeutic for the treatment of melanoma. Generating a detailed structural understanding of how an inhibitor binds to a target enables an AI-driven process of compound optimization, greatly accelerating the drug development process.

In an essay, Michael R. Jackson, PhD, senior vice president for drug discovery and development at Sanford Burnham Prebys, explains.

Apart from the occasional moment of serendipity, the development of first-in-class drugs has always been more grind than grand, requiring as much as a decade and hundreds of millions of dollars to bring a new medicine to market. Most drug discovery efforts never reach that goal.

The more we learn about the molecular details of life — the previously unseen and unknown biology of different molecules and how they interact in health and disease — the more complex we realize it is, leaving much uncertainty as to what to target with a drug and how best to achieve desired results.

Indeed, the overall success rate of discovering new drugs, especially small molecules, has not dramatically improved over the past 20 years. While incremental advances have occurred, considerable risk and uncertainty remains in every step of the process.

Artificial intelligence (AI) and related advances are poised to change this reality, and rapidly. They are reshaping almost every stage of the drug discovery process, from identifying drug targets and simulating molecular interactions to designing drugs de novo (entirely from scratch) and accurately predicting which are most likely succeed before actual testing or clinical trials.

AI promises transformational progress in discovering drug. We can work faster, cheaper and more efficiently.

Perhaps the most impactful step to be improved is the selection of which molecule (typically a protein) to target with a drug. In a marriage of medical informatics and bioinformatics, data scientists are using AI to merge huge multi-omic datasets to reveal the mechanisms of disease, and which targets should be drugged. Downstream of this critical decision are three stages of drug development all of which seem destined to be revamped by AI:

First, for small molecule drugs we need to find a chemical that interacts with the selected drug target in a way that prevents, inhibits or erases a disease or its symptoms. Traditionally, this might entail screening 500,000 or more random chemicals in the hope that a few will bind (so called hits) that can be further developed into a drug.

Technologies like cryo-electron microscopy now allow us to visualize the three-dimensional structure of biomolecules alone or in complexes. We can see at the molecular level precisely how a chemical, found in a screen, fits into a protein target, not unlike a key into a lock or a jigsaw piece into a puzzle.

Exactly how a chemical binds informs on whether it inhibits, promotes or alters the function of the drug target. It can help medicinal chemists optimize the fit of the bound chemical.

With that information, emerging artificial intelligence tools can tap into and help make sense of vast, ever-growing databases, then suggest the most promising chemicals, which are similar to screening hits but can be calculated to fit the pocket better.

And in a huge step, AI- driven processes can be deployed to identify completely new binding chemicals that are chemically different from screening hits. This is achieved by a process called “in silico docking,” in which the fit of billions of different chemicals is calculated. A massively parallel computational effort is required to accomplish this scale of activity. It was not achievable until the advent of AI chips.

This is research driven by calculated hypothesis, not educated guesswork, and it happens in silico, meaning through computer modeling and simulation. It’s all virtual, compressing years of work into months, weeks or days. AI and machine learning processes have put this stage of the drug discovery process on steroids.

Second, drugs need to have other properties beyond simply binding to their target so that they can be taken as once-a-day pills, safe as well as efficacious. Recent advances in deep learning techniques allow the drug like properties of a chemical to be more accurately predicted by a computer. As this can be done very rapidly and before a chemical is made, it allows a medicinal chemist to focus on making only those compounds that have properties suitable to be a drug. While predicting drug properties is not new, AI has greatly enhanced predictive power, impacting the pace and success rates.

Third, human testing can be much more precise. Designed drugs can be refined to meet extremely specific medical needs. You have data to show which drug candidates are most likely to be effective for different types of patients and diseases and in combination with other drugs. As a result, clinical trials can be more focused, shorter and less costly. Remedies can get to patients who need them faster.

All of this happens universally. Most data is shared. Used effectively, AI informs everybody’s work, though human ingenuity and innovation remain critical. Scientists still need to interpret the data and make ensure that hypotheses are rigorously tested.

The future of drug discovery and development is simply bigger and better with AI. Researchers aren’t limited to what they’ve discovered or learned alone or in their labs. They now have tools to explore and exploit boundless troves of data and knowledge generated by the entire scientific enterprise.

Progress and achievement won’t come without bumps and glitches, of course. There are fundamental issues to address, such as access to the enormous computing powers and resources necessary to effectively use AI, new imaging technologies and other tools. Researchers, labs and institutions unable or unwilling to embrace these technologies may be left behind.

Going all in on AI isn’t just the smart choice. It’s the only choice.

Programming in a Petri Dish, an 8-part series

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

Institute News

Acceleration by automation

AuthorGreg Calhoun
Date

September 5, 2024

Programming in a Petri Dish - AI series graphic

Increases in the scale and pace of research and drug discovery are being made possible by robotic automation of time-consuming tasks that must be repeated with exhaustive exactness.

Humans have long been fascinated by automata, objects that can or appear to move and act of their own volition. From the golems of Jewish folklore to Pinocchio and Frankenstein’s Creature—among the subjects of many other tales—storytellers have long explored the potential consequences of creating beings that range from obedient robots to sentient saboteurs.

While the power of our imagination preceded the available technology for such feats of automation, many scientists and engineers throughout history succeeded in creating automata that were as amusing as they were examples of technical mastery. Three doll automata made by inventor Pierre Jaquet-Droz traveled around the world to delight kings and emperors by writing, drawing and playing music, and they now fascinate visitors to the Musée d’Art et d’Histoire of Neuchâtel, Switzerland.

While these more whimsical machinations can be found in collections from the House on the Rock in Spring Green, Wis., to the Hermitage Museum in Saint Petersburg, Russia, applications in certain forms of labor have made it so more modern automation is located in factories and workshops. There is no comparing the level of automation at research institutions to that of many manufacturing facilities more than 110 years since the introduction of the assembly line, nor should there be given the differing aims. However, the mechanization of certain tasks in the scientific process has been critical to increasing the accessibility of the latest biomedical research techniques and making current drug discovery methods possible.

researcher at work in Prebys Center

As a premier drug discovery center, the Conrad Prebys Center for Chemical Genomics team is well-versed in using automation to enable the testing of hundreds of thousands of chemicals to find new potential medicines.

“Genomic sequencing has become a very important procedure for experiments in many labs,” says Ian Pass, PhD, director of High-Throughput Screening at the Conrad Prebys Center for Chemical Genomics (Prebys Center) at Sanford Burnham Prebys. “Looking back just 20-30 years, the first sequenced human genome required the building of a robust international infrastructure and more than 12 years of active research. Now, with how we’ve refined and automated the process, I could probably have my genome sampled and sequenced in an afternoon.”

While many tasks in academic research labs require hands-on manipulation of pipettes, petri dishes, chemical reagents and other tools of the trade, automation has been a major factor enabling omics and other methods that process and sequence hundreds or thousands of samples to capture incredible amounts of information in a single experiment. Many of these sophisticated experiments would be simply too labor-intensive and expensive to conduct by hand.

Where some of the automation of yore would play a tune, enact a puppet show or tell a vague fortune upon inserting a coin, scientists now prepare samples for instruments equipped with advanced robotics, precise fluid handling technologies, cameras and integrated data analysis capabilities. Automation in liquid handling has enabled one of the biggest steps forward as it allows tests to be miniaturized. This not only results in major cost savings, but also it allows experiments to have many replicas, generating very high-quality, reliable data. These characteristics in data are a critical underpinning for ensuring the integrity of the scientific community’s findings and maintaining the public’s trust.

Ian Pass headshot

Ian Pass, PhD, is the director of High-Throughput Screening at the Conrad Prebys Center for Chemical Genomics.

“At their simplest, many robotic platforms amount to one or more arms that have a grip that can be programmed to move objects around,” explains Pass. “If a task needs to be repeated just a few times, then it probably isn’t worth the effort to deploy a robot. But, once that step needs to be repeated thousands of times at precise intervals, and handled the exact same way each time, then miniaturization and automation are the answers.”

As a premier drug discovery center, the Prebys Center team is well-versed in using automation to enable the testing of hundreds of thousands of chemicals to find new potential medicines. The center installed its first robotics platform, affectionately called “big yellow,” in the late 2000s to enable what is known as ultra-high-throughput screening (uHTS). Between 2009 and 2014, this robot was the workhorse for completing over 100 uHTS of a large chemical library. It generated tens of millions of data points as part of an initiative funded by the National Institutes of Health (NIH) called the Molecular Libraries Program that involved more than 50 research institutions across the US. The output of the program was the identification of hundreds of chemical probes that have been used to accelerate drug discovery and launch the field of chemical biology.

“Without automation, we simply couldn’t have done this,” says Pass. “If we were doing it manually, one experiment at a time, we’d still be on the first screen.”

Over the past 10 years the Center has shifted focus from discovering chemical probes to discovering drugs. Fortunately, much of the process is the same, but the scale of the experiments is even bigger, with screens of over 750,000 chemicals. To screen such large libraries, highly miniaturized arrays are used in which 1536 tests are conducted in parallel. Experiments are miniaturized to such an extent that hand pipetting is not possible and acoustic dispensing (i.e. sound waves) are used to precisely move the tiny amounts of liquid in a touchless, tipless automated process. In this way, more than 250,000 tests can be accomplished in a single day, allowing chemicals that bind to the drug target to be efficiently identified. Once the Prebys Center team identifies compounds that bind, these prototype drugs are then improved by the medicinal chemistry team, ultimately generating drugs with properties suitable for advancing to phase I clinical trials in humans.

Within the last year, the Prebys Center has retired “big yellow” and replaced it with three acoustic dispensing enabled uHTS robotic systems using 1536 well high-density arrays that can run fully independently.

“We used to use big yellow for just uHTP library screening, but now, with the new line up of robots, we use them for everything in the lab we can,” notes Pass. “It has really changed how we use automation to support and accelerate our science. Having multiple systems allows us to run simultaneous experiments and avoid scheduling conflicts. It also allows us to stay operational if one of the systems requires maintenance.”

One of the many drug discovery projects at the Prebys Center focuses on the national epidemic of opioid addiction. In 2021, fentanyl and other synthetic opioids accounted for nearly 71,000 of 107,000 fatal drug overdoses in the U.S. By comparison, in 1999 drug-involved overdose deaths totaled less than 20,000 among all ages and genders.

Like other addictive substances, opioids are intimately related to the brain’s dopamine-based reward system. Dopamine is a neurotransmitter that serves critical roles in memory, movement, mood and attention. Michael Jackson, PhD, senior vice president of Drug Discovery and Development at the Prebys Center and co-principal investigator Lawrence Barak, MD, PhD, at Duke University, have been developing a completely new class of drugs that works by targeting a receptor on neurons called neurotensin 1 receptor or NTSR1, that regulates dopamine release.

The researchers received a $6.3 million award from NIH and the National Institute on Drug Abuse (NIDA) in 2023 to advance their addiction drug candidate, called SBI-810, to the clinic. SBI-810 is an improved version of SBI-533, which previously had been shown to modulate NTSR1 signaling and demonstrated robust efficacy in mouse models of addiction without adverse side effects.

Michael Jackson profile photo

Michael Jackson, PhD, is the senior vice president of Drug Discovery and Development at the Conrad Prebys Center for Chemical Genomics.

Prebys Center researchers at work

The funding from the NIH and NIDA will be used to complete preclinical studies and initiate a Phase 1 clinical trial to evaluate safety in humans.

“The novel mechanism of action and broad efficacy of SBI-810 in preclinical models hold the promise of a truly new, first-in-class treatment for patients affected by addictive behaviors,” says Jackson.

Programming in a Petri Dish, an 8-part series

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

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

Sanford Burnham Prebys event explores the science behind addiction

AuthorGreg Calhoun
Date

August 2, 2024

Nicholas Cosford, PhD, co-director of the Cancer Molecular Therapeutics Program, presents an overview of the many links between addiction and cancer.

Scientists and clinicians from three local research institutions converged July 31 to discuss new ways to treat multiple addictions at Sanford Burnham Prebys open house

The  NCI-designated Cancer Center at Sanford Burnham Prebys welcomed San Diego community members to the institute’s campus on July 31, 2024 for an open house focused on addiction research.  The Cancer Center team developed the event in partnership with scientists from Scripps Research and the University of California San Diego School of Medicine.

Ze’ev Ronai, PhD, director of the Sanford Burnham Prebys Cancer Center, formally opened the event and welcomed attendees before introducing David A. Brenner, MD, president and CEO of Sanford Burnham Prebys.

William Gerhart, chair of the Sanford Burnham Prebys board of trustees

William Gerhart, chair of the Sanford Burnham Prebys board of trustees, delivered welcoming remarks focused on the potential benefits to families of improving the treatment and prevention of addiction and addiction-associated cancers.

“As I have learned more about the research being presented here, I am impressed by just how much of a powerhouse we have on this mesa regarding both cancer and addiction science,” said Brenner.

William Gerhart, chair of the Sanford Burnham Prebys board of trustees; Nicholas Cosford, PhD, co-director of the Cancer Molecular Therapeutics Program; and Michael Jackson, PhD, senior vice president of Drug Discovery and Development at the Conrad Prebys Center for Chemical Genomics (Prebys Center), also provided opening remarks emphasizing the collaborative nature of the featured research as well as the potential benefits to families of improving the treatment and prevention of addiction and addiction-associated cancers.

Attendees had the opportunity to learn from and interact with the following scientists at stations featuring posters describing research underway at all three represented institutions:

In addition to his welcoming comments, Cosford also presented an overview of the many links between addiction and cancer.

  • Douglas Sheffler, PhD, is an associate professor in the Center for Therapeutics Discovery at Sanford Burnham Prebys. Sheffler discussed a drug discovery effort focused on treating nicotine addiction.
  • Benjamin Mckenna, PhD, is an assistant clinical professor of psychiatry at UC San Diego School of Medicine and staff psychologist at Veterans Affairs San Diego Healthcare System. Mckenna presented on the same drug as Sheffler with an update on phase I clinical trial results regarding safety, optimal dosage and efficacy.
  • Steven Olson, PhD, executive director of Medicinal Chemistry at the Prebys Center, presented on work being conducted at the center in collaboration with Jackson. Olson described a drug being studied as an alternative to opioids that has shown promising benefits for reducing pain and addiction-related behavior.
  • Kokila Shankar, PhD, is a postdoctoral associate at Sanford Burnham Prebys working in the Cosford lab. Shankar detailed efforts to find new drugs to treat alcohol use disorder, which is estimated to cause approximately one of every 25 cancer diagnoses.
  • Bryan Cruz, PhD, is a postdoctoral fellow at Scripps Research working in the lab of Marisa Roberto, PhD, vice chair and Paul and Cleo Schimmel Endowed Chair in the Department of Molecular Medicine. Cruz discussed his research to uncover new ways of treating alcohol use disorder rooted in posttraumatic stress disorder, and thereby reduce cancer cases associated with excessive alcohol consumption.
  • Valentina Vozella, PhD, is a postdoctoral researcher in the Department of Molecular Medicine at Scripps Research. She also is a member of the Roberto lab. Vozella presented on studies regarding the effect of social isolation on the development of alcohol use disorder during adolescence, as well as on potential methods of treatment and prevention.

Participants were able to tour the Prebys Center, which is the institute’s comprehensive center for drug discovery and chemical biology. Visitors were able to see how the center’s researchers can quickly test the potential effectiveness of hundreds of thousands of compounds to find new prospective treatments. Many scientists at Sanford Burnham Prebys partner with the Prebys Center to conduct drug discovery searches based on new research findings, including several of the event’s poster presenters.

The open house featured a reception with remarks from Robert Anthenelli, MD, a professor in the Department of Psychiatry at UC San Diego School of Medicine. Anthenelli’s research focuses on developing new or improved treatments for cancer-causing tobacco and alcohol use disorders. He shared insights he has gained as a physician-scientist working in this area over the past 30 years.

The reception also included concluding remarks from Helen Eckmann, EdD, an NCI-designated Cancer Center Community Advisory Board member. The board hosts the center’s open house events. Its members strive to bridge the gap between biomedical science and the people who need it most: patients and the families and friends who love and support them.

Institute News

The Science Behind Addiction

AuthorGreg Calhoun
Date

July 25, 2024

Science Behind Addiction graphic

Scientists and clinicians from three local research institutions converge July 31 to discuss new ways to treat multiple addictions at Sanford Burnham Prebys Open House

The NCI-designated Cancer Center at Sanford Burnham Prebys welcomes San Diego community members to the institute’s campus for an open house focused on addiction research.  The Cancer Center team developed the event in partnership with scientists from Scripps Research and the University of California San Diego School of Medicine.

The event will take place Wednesday, July 31, 2024, at 3:30 pm at 10901 N. Torrey Pines Road in La Jolla. More information and the online registration form are located on the institute’s website.

Attendees will meet scientists working to better understand the science behind addiction. Here’s a sneak peek of presenters and topics:

  • Douglas Sheffler, PhD, is an associate professor in the Center for Therapeutics Discovery at Sanford Burnham Prebys. Sheffler will discuss a drug discovery effort focused on treating nicotine addiction.
  • Benjamin Mckenna, PhD, is an assistant clinical professor of psychiatry at UC San Diego School of Medicine and staff psychologist at Veterans Affairs San Diego Healthcare System. Mckenna will present on the same drug as Sheffler with an update on phase I clinical trial results regarding safety, optimal dosage and efficacy.
  • Michael Jackson, PhD, is senior vice president of Drug Discovery and Development at the Sanford Burnham Prebys Conrad Prebys Center for Chemical Genomics and co-director of the Cancer Molecular Therapeutics Program in the institute’s NCI-Designated Cancer Center. Jackson will talk about a drug being studied as an alternative to opioids that has shown promising benefits for reducing pain and addiction-related behavior.
  • Kokila Shankar, PhD, is a postdoctoral associate at Sanford Burnham Prebys working in the lab of Nicholas Cosford, PhD, co-director of the NCI-Designated Cancer Center’s Cancer Molecular Therapeutics Program. Shankar will detail efforts to find new drugs to treat alcohol use disorder, which is estimated to cause approximately one of every 25 cancer diagnoses.
  • Bryan Cruz, PhD, is a postdoctoral fellow at Scripps Research working in the lab of Marisa Roberto, PhD, vice chair and Paul and Cleo Schimmel Endowed Chair in the Department of Molecular Medicine. Cruz will discuss his research to uncover new ways of treating alcohol use disorder rooted in posttraumatic stress disorder, and thereby reduce cancer cases associated with excessive alcohol consumption.
  • Valentina Vozella, PhD, is a postdoctoral researcher in the Department of Molecular Medicine at Scripps Research. She also is a member of the Roberto lab. Vozella will present on studies regarding the effect of social isolation on the development of alcohol use disorder during adolescence, as well as on potential methods of treatment and prevention.
  • Robert Anthenelli, MD, is a professor in the Department of Psychiatry at UC San Diego School of Medicine. Anthenelli’s research focuses on developing new or improved treatments for cancer-causing tobacco and alcohol use disorders. He will share some of his insights as a physician-scientist working in this area over the past 30 years.

In addition to poster presentations from speakers, guests will have the opportunity to talk with  scientists, clinicians and research advocates during an informal evening reception.

The NCI-designated Cancer Center open house events are hosted by the center’s Community Advisory Board. Its members strive to bridge the gap between biomedical science and the people who need it most: patients and the families and friends who love and support them.

Institute News

Opinion: Including researchers of diverse backgrounds makes science more accurate and applicable

AuthorAlessandra Sacco, Michael Jackson and Svasti Haricharan
Date

June 14, 2023

Photo of a pipette and test tubes

America has always been an experiment, an ongoing enterprise to determine how and how well people of different races, cultures and experiences might govern and live together. It’s an experiment that extends to every aspect of our lives. We celebrate our diversity and inclusivity through the food we eat, the languages we speak and the stories we tell.

Unfortunately, universities and other research institutions in the United States often do not have stories to tell about diversity and inclusion. People of color and women who aspire to careers in academic research are frequently discouraged early on from entering the grueling pipeline (which may extend more than a decade) by the lack of opportunities, access and accommodation.

It is no accident that non-White and female scientists are significantly and consistently underrepresented in the ranks of U.S. academic faculty: approximately 30 percent are female, just 6 percent are Black or Hispanic. Despite recent social awareness and movements toward change, the composition of tenure-track or tenured underrepresented faculty of color in the U.S. increased by only 1 percentage point (11 percent to 12 percent) between 2013 and 2019.

There are fundamental reasons why well-intentioned platitudes and policies regarding science and education don’t reflect reality. Neil A. Lewis Jr., a communications professor at Cornell University, wrote in a 2022 essay in Nature Human Behavior that “What counts as ‘good science’ tends to be research approaches that prioritize the experiences of dominant groups, and not approaches developed to prioritize people placed on the margins of society.”

He added, “The topics that count are ones that fit with the ‘master narratives’ in the field, and not the ‘counter narratives’ that sometimes emerge from marginalized groups.”

Many studies have demonstrated that the more diverse a research team is, the more likely its findings are to move fields forward and create new technologies and inventions. Simultaneously, research conducted by scientists who do not belong to dominant groups is more likely to be ignored by the larger research community, resulting in the so-called “diversity-innovation paradox” that slows scientific progress.

Historically, scientific and clinical studies have addressed research and health questions primarily through the prism of White males, overlooking or ignoring potential — or even likely differences — that might be found in women or people of color. As late as 1977, for example, the Food and Drug Administration recommended excluding women of childbearing potential from phase 1 and early phase 2 drug trials.

This is changing. It’s now well-documented that males and females differ in their response to drug treatment. Likewise, among different ethnicities. Inclusion is now law, and new research points to improved representation among communities of color in most clinical trials.

The embrace of science, technology, engineering and mathematics, or STEM, in public education has become a fundamental force for long-term good. The more children of every size, shape and color who are exposed to these disciplines, the more diverse and energized future generations of scientists, engineers and health professionals will be.

However, we are still in the first steps toward making this journey more accessible to marginalized groups. There is no mainstream movement yet in this direction. The ability to break into the upper echelons of academia continues to be constrained not only by race and ethnicity, but by privilege, with first-generation students facing many more barriers than those with at least one parent with a higher education degree. Scientists who are from the LGBTQ community also face significant challenges to finding acceptance for their research and their identity in academia.

A new educational program at Sanford Burnham Prebys, an independent biomedical research institute in La Jolla, attempts to remedy this singular reality. Funded by a grant from The Conrad Prebys Foundation, the institute has welcomed a group of 13 graduate students and postdoctoral fellows from diverse backgrounds and identities, all of whom will be working in labs, gaining hands-on experience in drug discovery and translational medicine from industry-trained researchers.

They come from near and far, having previously studied at places like San Diego State University, University of San Diego, University of Barcelona and Hong Kong University of Science and Technology. Their research interests are diverse: new treatments for breast and pancreatic cancers, how DNA repairs itself, regenerating heart muscle and how the brain protects itself from Alzheimer’s disease.

The goal is to provide these young scientists with advanced research training that will better position them to not just have successful, productive careers, but also become role models and leaders in biomedical research.

The Prebys Foundation fellows, as they are called, represent a small step in the right direction. Similar efforts are needed elsewhere, everywhere, at small and large institutions, laboratories and places where the work of science gets done.

As a nation, we must be committed to planting the seeds of new generations of scientists through programs like STEM. And when they begin to mature, we must provide the water and nutrients to ensure our young scientists bear fruit for a very long time.

Alessandra Sacco, PhD, is vice dean and associate dean of student affairs in the Graduate School of Biomedical Sciences at Sanford Burnham Prebys, and co-director of the fellowship program. Michael Jackson, PhD, is senior vice president for drug discovery and development and co-director in the Conrad Prebys Center for Chemical Genomics, and co-director of the fellowship program. Svasti Haricharan, PhD, is associate director for training and education in the NCI-Designated Cancer Center at Sanford Burnham Prebys. All live in San Diego.

This story originally appeared in San Diego Union-Tribune.

Institute News

Sanford Burnham Prebys researchers awarded Curebound grants

AuthorMiles Martin
Date

March 20, 2023

Aninyda Bagchi, PhD, Linda Bradley, Lukas Chavez, PhD, Nicholas Cosford, PhD, and Michael Jackson, PhD

Each year, Sanford Burnham Prebys joins Padres Pedal the Cause, an annual fundraising event that raises money for Curebound which awards collaborative cancer grants in the San Diego area.

These grants include Discovery Grants, which provide seed funds for high-risk/high-reward research in the earliest phases, and Targeted Grants, which are larger awards ($500K) that help translate promising discoveries into treatments for the clinic.

In the 2022-2023 Curebound Research portfolio, five researchers from Sanford Burnham Prebys were awarded grants: Associate Professor Anindya Bagchi, PhD, Professor Linda Bradley, PhD, Assistant Professor Lukas Chavez, PhD, Professor Nicholas Cosford, PhD, and Professor Michael Jackson, PhD

2022 Discovery Grant: Treating incurable pediatric brain tumors 
Bagchi and Chavez will collaborate to advance a new therapeutic approach for medulloblastoma, the most common childhood brain tumor. They will be focusing on a gene called MYC, found only in the deadliest forms of medulloblastoma. This form of brain cancer is currently untreatable, but Bagchi and Chavez recently discovered a molecule that can help control the activity of the MYC gene and potentially inhibit the growth of medulloblastoma tumors. The researcher holds promise to reveal a new treatment approach for this incurable cancer. 

The grant is titled “Decoding the Role of the Long Non-Coding RNA PVT1 in Medulloblastoma.”

2023 Targeted Grant: Discovering a new immunotherapy drug for melanoma
Bradley will be working with Soo Jin Park, MD, from UC San Diego Health to advance a new immunotherapy approach for malignant melanoma. Despite recent advances, this type of skin cancer still causes thousands of deaths in the U.S. each year. The goal of their project is to develop a new drug for melanoma that can reactivate the tumor-killing properties of the patient’s own immune system. This therapeutic approach has the potential to destroy tumors that are resistant to existing therapies, which could help save lives.

The grant is titled, “Advancing Immune Checkpoint Inhibition of PSGL-1 for Treatment of Malignant Melanoma.
 

2022 Discovery Grant: Developing drugs for bone-metastatic prostate cancer
Cosford will work with Christina Jamieson, PhD, from the University of California, San Diego, to advance a new treatment approach for prostate cancer that has spread to the bones. Bone is the most common place for prostate cancer to metastasize, and this form of cancer is currently incurable. The researchers will look for drugs that can kill tumor cells by inhibiting autophagy, a process that promotes tumor progression. The results of the study could identify a new drug ready for clinical trials.

The grant is titled “Pre-Clinical Development of New Autophagy Targeting Drugs for Bone Metastatic Prostate Cancer.”

2022 Discovery Grant: Repurposing drugs for deadly childhood brain cancer
Jackson and Chavez will collaborate to identify new treatment options for ependymoma, an aggressive pediatric brain tumor and leading cause of death among childhood cancer patients. The researchers will screen patient tumor cells against drugs already approved by the FDA for other conditions, looking for drugs that could be repurposed to fight these tumors. Because FDA-approved drugs are known to be safe for humans, this may prove to be the quickest way to help patients currently living with this cancer. 

The grant is titled “High Throughput-Screen for Inhibitors of Pediatric Ependymoma.”

Institute News

Conrad Prebys Foundation provides $3 million for pediatric brain cancer research

AuthorSusan Gammon
Date

April 7, 2021

Conrad Prebys Foundation Award

Conrad Prebys was an extraordinary man and a passionate philanthropist. Today, his generosity extends beyond his life through the Conrad Prebys Foundation.

This year, the Foundation provided $3 million to Robert Wechsler-Reya, PhD, and his team of researchers to advance a potential drug to treat medulloblastoma—the most common malignant brain tumor in children.

Children with medulloblastoma often receive aggressive treatment (surgery, radiation and chemotherapy), but many still die of their disease, and survivors suffer long-term effects from therapy. Safer and more effective therapies are desperately needed.

Wechsler-Reya recently combined forces with Michael Jackson, PhD, senior vice president of Drug Discovery and Development, to find a drug(s) that would inhibit the growth of Group 3 medulloblastoma, the most aggressive form of the disease. Using high-throughput screening technology, they identified a compound that reduces levels of a protein called MYC, which is found at exceptionally high levels in Group 3 medulloblastoma, as well as in cancers of the blood, breast, lung and prostate.

“An effective MYC inhibitor could have a major impact on the survival and quality of life of patients with medulloblastoma,” says Wechsler-Reya. “We identified a compound that reduces levels of MYC in medulloblastoma cells, but now we need to learn how it works to optimize it as an anti-cancer drug and advance studies toward the clinic.

“Historically, pharmaceutical companies and funding agencies have under-invested in childhood cancers, and the majority of drugs currently used to treat these cancers were originally developed for adult cancer,” adds Wechsler-Reya. “We believe that effective drugs for pediatric brain tumors must be developed—and this award from the Foundation will help us achieve this goal.”

“We are profoundly grateful to Conrad for his generosity over the years,” says President Kristiina Vuori, MD, PhD “He has a special legacy at our Institute, which was renamed Sanford Burnham Prebys in 2015 to honor him. We are now thankful to his Foundation for including us in their inaugural grant cycle, and for supporting the critical work we do to benefit children and others suffering from cancer.”

The Conrad Prebys Foundation allocated $78 million in its inaugural grant cycle to fund 121 projects. The awards reflect areas of personal interest to Conrad Prebys—including visual and performing arts, higher education, health care, youth development and animal conservation.

Sanford Burnham Prebys joins a long list of recipients, which included other prominent San Diego institutions such as Rady Children’s Hospital, KPBS, San Diego State University, Scripps Research, Museum of Contemporary Art San Diego and the La Jolla Music Society.

Institute News

Sanford Burnham Prebys awarded Padres Pedal the Cause grants to advance cancer research

AuthorMonica May
Date

September 13, 2019

Sanford Burnham Prebys - Padres Pedal the Cause; team riders at SBP

Sanford Burnham Prebys scientists have been awarded two collaborative grants with Rady Children’s Hospital and UC San Diego Health from Padres Pedal the Cause (PPTC), an annual fundraiser that aims to accelerate cancer cures. The projects unite the complementary strengths of clinicians and scientists with the hope of uncovering new treatments for colorectal, lung, breast and prostate cancers. 

The grants stem from the record-breaking $2.94 million raised by thousands of participants in the November 2018 event. Launched in 2013, all of the proceeds raised by PPTC stay in San Diego to fund collaborative research that brings us closer to a world without cancer. Past PPTC grants have supported our Institute’s research into cancers of the breast, skin, brain, colon, pancreas and more.

The funded projects are described below:

  • Protecting the gut and halting colon cancer growth (Svasti Haricharan, PhD, and Scott Peterson, PhD, of Sanford Burnham Prebys; Soumita Das, PhD, and Pradipta Ghosh, MD, of UC San Diego Health; Debashis Sahoo, PhD, of UC San Diego Health and Rady Children’s Hospital; and Sherry C. Huang, MD, of Rady Children’s Hospital)

This project will discover and characterize a pathway in the gut that normally protects the gut barrier from microbes—and is lost during the initiation of colon cancers. The researchers aim to uncover a therapeutic target that protects the gut from cancer-causing microbes and halts the formation and progression of colon polyps. The team will also validate biomarkers for detecting polyps in the colon at high risk for progressing to colon cancer.

  • A new pathway to fractioning cancer (Michael Jackson, PhD, of Sanford Burnham Prebys; and Seth Field, MD, PhD, of UC San Diego Health)

To effectively combat cancer, therapies directed at new targets must be developed. A protein called GOLPH3 has been shown to drive the growth of several cancers, including lung, breast, prostate and colorectal cancers. This project aims to find a compound that blocks GOLPH3, which would add a unique approach to the arsenal of cancer treatments.

The seventh annual Padres Pedal the Cause event takes place on November 16, 2019. Participants will cycle, run, walk, spin or volunteer in support of a world without cancer. Join our team or volunteer at our aid station in Mountain Hawk Park in Chula Vista.

Institute News

Cancer Center Open House Showcases SBP Scientists

AuthorHelen Hwang
Date

November 14, 2017

Cancer Center Open House November 2017

SBP’s Cancer Center Open House on November 9, 2017 enlightened visitors from the community on the topic of “The Science Behind Personalized Cancer Medicine,” as four diverse scientific labs showcased posters and demonstrated how we are  translating biomedical research into innovative treatments for patients. 

Garth Powis, D.Phl.., head of the National Cancer Institute-designated Cancer Center at SBP, said the Open House “provides a service to those who have been touched by cancer in some way. By sharing our latest research, we want to be able to show that there is hope, that we are making advances, and at this Open House in particular, share how new technologies are changing the way we conduct our research, and eventually bring our discoveries to cancer patients.” 

One of the labs featured was SBP President, Kristiina Vuori, Ph.D., a respected scientist with wide-ranging research that includes brain cancer and acute myeloid leukemia (AML). Ben Finlay, PhD, emphasized how important “collaboration was at SBP” and explained how researchers work closely with Scripps Blood and Marrow Transplant Program to collect patient tumor samples to find a cure for AML. 

Robert Wechsler-Reya, PhD, who discussed personalized cancer care for children with brain tumors. As a world-renowned expert on medulloblastoma, Dr. Wechsler-Reya also works closely with doctors at Rady Children’s Hospital to discuss individual pediatric tumor cases, in addition to his role as SBP researcher.  

Michael Jackson, PhD, senior vice president, led the tour of the Prebys Center for Drug Discovery where he demonstrated the high-speed drug screening robot arm in action, showing how state-of-the-art technology is a vital tool in testing new drugs to find cancer cures. 

“Decoding tumor response at the single-cell level” was the topic featured in the laboratory of Peter Adams, Ph.D. Simply put, if you treat a tumor and kill 99 percent of the cancer cells, but 1 cell left contains a mutation that can cause the tumor to grow again, the cancer treatment isn’t effective for the patient. By better understanding each cell, science can translate into robust treatments.   

The public event, which attracted more than 140 people, included a wide array of visitors from a busload of high school biology students from Monte Vista High School to Board Trustees. For some people, it was the first time they visited our Institute to learn about our pioneering research while others took the opportunity to revisit old friends and a scientific organization they support with great passion. 

Your support is so important to continuing our research. Click to donate now.

Check out the Facebook album of the Cancer Center Open House.  

The next Cancer Center Open Houses will be held on Thursday, June 14, 2018 and Thursday, November 8, 2018. Please check back for more details and registrations.