grants Archives - Sanford Burnham Prebys
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Kelly Kersten awarded Melanoma Research Alliance grant to support research on melanoma immunotherapy

AuthorGreg Calhoun
Date

May 2, 2025

The newly created Paul Walks – MRA Young Investigator Award in Memory of Chad Johnson is part of the alliance’s $9.3 million commitment to melanoma research funding in 2025.

Kelly Kersten, PhD, an assistant professor in the Cancer Metabolism and Microenvironment Program at Sanford Burnham Prebys, was awarded a new type of grant from the Melanoma Research Alliance (MRA). The funding will support Kersten’s research on reactivating “exhausted” immune cells within melanoma tumors to restore their cancer-fighting ability and improve the effectiveness of melanoma immunotherapy.

“Inside tumors, immune cells often lose their strength to attack cancer,” said Kersten. “Our work is focused on understanding and reversing this exhaustion to make therapies more effective for more people.”

The MRA is the world’s leading nonprofit funder of melanoma research. The organization created the Paul Walks – MRA Young Investigator Award in Memory of Chad Johnson to providesupport for the next generation of scientists driving innovation against melanoma.

“Our Young Investigator Awards fuel the creativity and drive of early-career scientists whose work can redefine the future of melanoma research.” said Joan Levy, PhD, MRA Chief Science Officer.

The new grant pays tribute to Chad Johnson, a beloved friend and surfer who died from his melanoma diagnosis at age 55. Funding for the award was made possible through “Paul Walks,” a community fundraiser organized by Chad’s lifelong friend, Paul Giobbi.

The Paul Walks – MRA Young Investigator Award in Memory of Chad Johnson is part of MRA’s $9.3 million commitment to fund melanoma research in 2025, supporting more than 30 researchers across the U.S., Europe and Australia. Melanoma remains the deadliest form of skin cancer, with more than 100,000 people expected to be diagnosed this year and one death every hour in the U.S. alone.

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Curebound awards two grants to Sanford Burnham Prebys scientists

AuthorGreg Calhoun
Date

February 12, 2025

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.

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Guglielmi awarded grant to further investigate genetic condition that results in soft, deformed bones and lost teeth

AuthorScott LaFee
Date

January 9, 2025

Hypophosphatasia (HPP) is a rare genetic disorder in which bones and teeth fail to take up sufficient calcium and phosphorus needed to achieve proper hardness and strength. Defective mineralization results in bones that are soft and prone to fracture and deformity, and the loss of teeth. Occasionally, HPP can cause death due to complications.

Prevalence varies by severity and age of onset. It is rarest but most severe at birth (1 in 100,000 live births), with lower prevalence and milder forms in later years. The condition can manifest at any age.

The cause of HPP is a mutation in an enzyme called tissue-nonspecific alkaline phosphatase (TNAP), which plays a critical role in skeletal and dental mineralization. In 2015, an enzyme replacement therapy developed by José Luis Millán, PhD, a professor in the Human Genetics Program at Sanford Burnham Prebys, was approved to treat pediatric onset HPP, dramatically improving patients’ lifespan and quality of life.

But the effects of TNAP deficiency appears to extend beyond faulty mineralization. HPP patients also experience altered immune responses, suggesting TNAP might have a role in immune cells.

Recently, Soft Bones, an advocacy group for HPP patients, awarded Valeria Guglielmi, PhD, a postdoctoral associate in Maximiliano D’Angelo’s lab, with a one-year, $25,000 seed grant to further investigate the involvement of TNAP in inflammatory responses and immune cell functions.

“This study is in line with my broad interest  for immune cells and their contribution to tissue homeostasis and diseases,” said Guglielmi. “I am excited to explore an entirely new area of investigation on HPP.

“Indeed, very little is known about the role of TNAP in the immune system and only a few studies have provided evidence of TNAP involvement in immune cell function. By uncovering how TNAP deficiency affects inflammatory responses, our research represents the first step toward designing interventions to improve immune system dysfunctions in HPP patients.”

Read Soft Bones’ full news release on the award to Guglielmi on Facebook and Instagram.

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How a protein component of nuclear pore complexes regulates development of blood cells and may contribute to myeloid disorders

AuthorCommunications
Date

June 5, 2024

Nuclear pore complexes (NPCs) are channels composed of multiple proteins that ferry molecules in and out of the nucleus, regulating many critical cellular functions, such as gene expression, chromatin organization and RNA processes that influence cell survival, proliferation, and differentiation.

In recent years, new studies, including work by Maximiliano D’Angelo, PhD, associate professor in the Cancer Metabolism and Microenvironment Program at Sanford Burnham Prebys, have noted that NPCs in cancer cells are different, but how these alterations contribute to malignancy and tumor development—or even how NPCs function in normal cells—is poorly understood.

In a new paper, published June 5, 2024 in Science Advances, D’Angelo with first author Valeria Guglielmi, PhD, and co-author Davina Lam, uncover Nup358, one of roughly 30 proteins that form the NPCs, as an early player in the development of myeloid cells, blood cells that if not formed or working properly leads to myeloid disorders such as leukemias.

The researchers found that when they eliminated Nup358 in a mouse model, the animals experienced a severe loss of mature myeloid cells, a group of critical immune cells responsible for fighting pathogens that are also responsible for several human diseases including cancer. Notably, Nup358 deficient mice showed an abnormal accumulation of early progenitors of myeloid cells referred as myeloid-primed multipotent progenitors (MPPs).

“MPPs are one of the earliest precursors of blood cells,” said D’Angelo. “They are produced in the bone marrow from hematopoietic stem cells, and they differentiate to generate the different types of blood cells.

Maximiliano D’Angelo and Valeria Guglielmi

“There are different populations of MPPs that are responsible for producing specific blood cells and we found that in the absence of Nup358, the MPPs that generate myeloid cells, which include red blood cells and key components of the immune system, get stuck in the differentiation process.”

Fundamentally, said Gugliemi, Nup358 has a critical function in the early stages of myelopoiesis (the production of myeloid cells). “This is a very important finding because it provides insights into how blood cells develop, and can help to establish how alterations in Nup358 contribute to blood malignancies.”

The findings fit into D’Angelo’s ongoing research to elucidate the critical responsibilities of NPCs in healthy cells and how alterations to them contribute to immune dysfunction and the development and progression of cancer.

“Our long-term goal is to develop novel therapies targeting transport machinery like NPCs,” said D’Angelo, who recently received a two-year, $300,000 Discovery Grant from the American Cancer Society to advance his work.


This research was supported in part by a Research Scholar Grant from the American Cancer Society (RSG-17-148-01), the Department of Defense (grant W81XWH-20-1-0212) and the National Institutes of Health (AI148668).

The study’s DOI is 10.1126/sciadv.adn8963.

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New roles for autophagy genes in cellular waste management and aging

AuthorCommunications
Date

January 3, 2024

Autophagy genes help extrude protein aggregates from neurons in the nematode C. elegans.

Autophagy, which declines with age, may hold more mysteries than researchers previously suspected. In the January 4 issue of Nature Aging, it was noted that scientists from the Buck Institute, Sanford Burnham Prebys and Rutgers University have uncovered possible novel functions for various autophagy genes, which may control different forms of disposal including misfolded proteins—and ultimately affect aging.

“While this is very basic research, this work is a reminder that it is critical for us to understand whether we have the whole story about the different genes that have been related to aging or age-related diseases,” said Professor Malene Hansen, PhD, Buck’s chief scientific officer, who is also the study’s co-senior author. “If the mechanism we found is conserved in other organisms, we speculate that it may play a broader role in aging than has been previously appreciated and may provide a method to improve life span.”

These new observations provide another perspective to what was traditionally thought to be occurring during autophagy.

Autophagy is a cellular “housekeeping” process that promotes health by recycling or disposing of damaged DNA and RNA and other cellular components in a multi-step degradative process. It has been shown to be a key player in preventing aging and diseases of aging, including cancer, cardiovascular disease, diabetes and neurodegeneration. Notably, research has shown that autophagy genes are responsible for prolonged life span in a variety of long-lived organisms.

The classical explanation of how autophagy works is that the cellular “garbage” to be dealt with is sequestered in a membrane-surrounded vesicle, and ultimately delivered to lysosomes for degradation. However, Hansen, who has studied the role of autophagy in aging for most of her career, was intrigued by an accumulation of evidence that indicated that this was not the only process in which autophagy genes can function.

“There had been this growing notion over the last few years that genes in the early steps of autophagy were ‘moonlighting’ in processes outside of this classical lysosomal degradation,” she said. “Additionally, while it is known that multiple autophagy genes are required for increased life span, the tissue-specific roles of specific autophagy genes are not well defined.”

To comprehensively investigate the role that autophagy genes play in neurons—a key cell type for neurodegenerative diseases—the team analyzed Caenorhabditis elegans, a tiny worm that is frequently used to model the genetics of aging and which has a very well-studied nervous system. The researchers specifically inhibited autophagy genes functioning at each step of the process in the neurons of the animals, and found that neuronal inhibition of early-acting, but not late-acting, autophagy genes, extended life span.

An unexpected aspect was that this life span extension was accompanied by a reduction in aggregated protein in the neurons (an increase is associated with Huntington’s disease, for example), and an increase in the formation of so-called exophers. These giant vesicles extruded from neurons were identified in 2017 by Monica Driscoll, PhD, a collaborator and professor at Rutgers University.

“Exophers are thought to be essentially another cellular garbage disposal method, a mega-bag of trash,” said Caroline Kumsta, PhD, co-senior author and assistant professor at Sanford Burnham Prebys “When there is either too much trash accumulating in neurons, or when the normal ‘in-house’ garbage disposal system is broken, the cellular waste is then being thrown out in these exophers.

“Interestingly, worms that formed exophers had reduced protein aggregation and lived significantly longer. This finding suggests a link between this process of this massive disposal event to overall health,” said Kumsta. The team found that this process was dependent on a protein called ATG-16.2.

The study identified several new functions for the autophagy protein ATG-16.2, including in exopher formation and life span determination, which led the team to speculate that this protein plays a nontraditional and unexpected role in the aging process. If this same mechanism is operating in other organisms, it may provide a method of manipulating autophagy genes to improve neuronal health and increase life span.

“But first we have to learn more—especially how ATG-16.2 is regulated and whether it is relevant in a broader sense, in other tissues and other species,” Hansen said. The Hansen and Kumsta teams are planning on following up with a number of longevity models, including nematodes, mammalian cell cultures, human blood and mice.

“Learning if there are multiple functions around autophagy genes like ATG-16.2 is going to be super important in developing potential therapies,” Kumsta said. “It is currently very basic biology, but that is where we are in terms of knowing what those genes do.”

The traditional explanation that aging and autophagy are linked because of lysosomal degradation may need to expand to include additional pathways, which would have to be targeted differently to address the diseases and the problems that are associated with that. “It will be important to know either way,” Hansen said. “The implications of such additional functions may hold a potential paradigm shift.” 
 
DOI: 10.1038/s43587-023-00548-1

Institute News

Presenting The Conrad Prebys Foundation fellows

AuthorMiles Martin
Date

May 15, 2023

Thanks to a generous grant from The Conrad Prebys Foundation, a diverse group of early-career researchers will gain hands-on experience in drug discovery and translational medicine.

A new educational program at Sanford Burnham Prebys has welcomed a diverse group of early-career scientists to learn how to transform research discoveries into treatments for human diseases. The program was made possible by a generous grant from The Conrad Prebys Foundation as part of its mission to increase the diversity of San Diego’s biomedical workforce.

“Our mission at The Conrad Prebys Foundation is to create an inclusive, equitable and dynamic future for all San Diegans,” says Grant Oliphant, CEO at The Conrad Prebys Foundation. “San Diego is one of the top areas in the country for biomedical research, and we’re pleased to partner with Sanford Burnham Prebys to help strengthen the pipeline of diverse talent in life sciences research.”

Graduate students and postdoctoral fellows selected for the program will complete projects at the Institute’s Conrad Prebys Center for Chemical Genomics (Prebys Center), the nation’s leading nonprofit drug discovery center. The Prebys Center specializes in finding new medicines for diseases with a substantial unmet medical need in order to develop better therapies. 

“Thank you to The Conrad Prebys Foundation. I am beyond grateful for their support,” says predoctoral Prebys fellow Michael Alcaraz, who will complete his project on the links between aging and brain disease with Professor Peter D. Adams, PhD, and Steven Olson, PhD, executive director of Medicinal Chemistry at the Prebys Center. 

To help fulfill the Foundation’s mission, Sanford Burnham Prebys students and postdocs from historically underrepresented groups were encouraged to apply for the new program.

“Promoting diversity in the biomedical workforce is a founding principle of our educational program,” says Alessandra Sacco, PhD, vice dean and associate dean of Student Affairs in the Graduate School of Biomedical Sciences at Sanford Burnham Prebys. Sacco will oversee the new program alongside Dean Guy Salvesen, PhD, and Professor Michael Jackson, PhD

“Working actively to train people from all backgrounds gives opportunities to people who may not otherwise have had them—and it also improves the quality of the research itself,” she adds.

“Translational research is one of the biggest priorities in biomedicine right now because it’s how we turn discoveries into actual medicines,” says Sacco. “This program gives students and postdocs an opportunity to build the skills they need for translational research jobs in academia or industry.”

The fellowship will culminate in a final symposium next spring, where the fellows will present their research to their peers and to the wider community. 

“I’m looking forward to gaining more experience and making my contribution to the translational science at the Prebys Center,” says predoctoral Prebys fellow Merve Demir, who will complete a structural biochemistry project with Assistant Professor Jianhua Zhao, PhD, and Eduard Sergienko, PhD, director of Assay Development at the Prebys Center. 

The full list of fellows includes:
 

Postdoctoral Fellows

– Karina Barbosa Guerra [Deshpande Lab, Ed Sergienko co-mentor]
“SGF29 as a novel therapeutic target in AML”
 
– Merve Demir [Zhao Lab, Ed Sergienko co-mentor]
“Structural studies of MtCK and GCDH enzyme drug targets”
 
– Jerry Tyler DeWitt [Haricharan Lab, TC Chung co-mentor]
“Investigating the unique molecular landscape of ER+ breast cancer in black women” 
 
– Alicia Llorente Lope [Emerling Lab, Ian Pass co-mentor]
“Exploring PI5P4Kγ as a novel molecular vulnerability of therapy-resistant breast cancer” 
 
– Van Giau Vo [Huang Lab, TC Chung co-mentor]
“Identifying enhancers of SNX27 to promote neuroprotective pathways in Alzheimer’s disease and Down Syndrome”
 
– Xiuqing Wei [Puri Lab, Anne Bang co-mentor]
“Selective targeting of a pathogenetic IL6-STAT3 feedforward loop activated during denervation and cancer cachexia”

 

Predoctoral Fellows

– Michael Alexander Alcaraz [Adams Lab, Steven Olson co-mentor]
“Activating the NAMPT-NAD+ axis in senescence to target age-associated disease”
 
– Shea Grenier Davis [Commisso Lab, Steven Olson co-mentor]
“Examining PIKfyve as a potential therapeutic target in pancreatic cancer” 
 
– Patrick Hagan [Cosford Lab, Ian Pass co-mentor]
“Discovery and development of novel ATG13 degrading compounds that inhibit autophagy and treat non-small-cell lung cancer”
 
– Texia Loh [Wang Lab, Ed Sergienko co-mentor]
“Investigating the role of HELLS in mediating resistance to PARP Inhibition in small-cell lung cancer”
 
– Michaela Lynott [Colas Lab, TC Chung co-mentor]
“Identification of small molecules inhibiting ATF7IP-SETDB1 interacting complex to improve cardiac reprogramming efficiency”
 
– Tatiana Moreno [Kumsta Lab, Anne Bang co-mentor]
“Identifying TFEB/HLH-30 regulators to modulate autophagy in age-related diseases”
 
– Utkarsha Paithane [Bagchi Lab, TC Chung co-mentor]
“Identification of small-molecule enhancers of Honeybadger, a novel RAS/MAPK inhibitor” 
 

Institute News

Sanford Burnham Prebys researchers awarded Curebound grants

AuthorMiles Martin
Date

March 20, 2023

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.”

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Jerold Chun receives a very special Alzheimer’s grant

AuthorMiles Martin
Date

May 13, 2022

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

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

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

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

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

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

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

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

Institute News

Randal Kaufman included in $12 million initiative to improve hemophilia treatment

AuthorMiles Martin
Date

March 8, 2022

The new project will help researchers better understanding why current gene therapy treatments aren’t working.

A multi-institute research collaboration including Sanford Burnham Prebys has just received a $12 million grant from the National Heart, Lung, and Blood Institute to improve hemophilia therapy. The award will fund three projects that could lead to safer and potentially curative treatments for the disorder. One of these projects will be led by Randal J. Kaufman, PhD, who directs the Degenerative Diseases Program at Sanford Burnham Prebys.

How viruses could be help treat hemophilia
Hemophilia is an X-linked genetic condition that prevents the blood from clotting properly. It occurs in about one out of 5,000 male births. In patients with severe forms of the disease, internal or external bleeding can be life threatening. Standard treatments for severe hemophilia involve intravenously replacing the clotting proteins that patients are unable to produce adequately on their own. However, a gene therapy approach uses viruses as a delivery mechanism to provide the body with the information it needs to start making its own clotting factors.

“Several companies have taken this forward into clinical trials, and in some of these trials, the patients initially looked like they were cured,” says principal investigator Roland W. Herzog, PhD, the Riley Children’s Foundation Professor of Immunology at Indiana University School of Medicine. “But what they all have in common is that they need to deliver a lot of the virus in order to get the desired results, and over time, clotting factor levels started to decline. So it’s clear that we need to further study the biology of this phenomenon.”

How this grant will help improve the process
In hemophilia A, which accounts for about 80% of all cases, patients do not produce enough of a clotting protein called factor VIII (FVIII). To better understand the mechanisms that are mitigating the effects of current drug candidates, Herzog is teaming up with some of the nation’s leading experts. 

Their program will focus on three major projects in gene therapy for hemophilia A:

  • Project 1 will focus on cellular toxicity and stress that can be induced by FVIII protein production. This project is led by Kaufman. 
  • Project 2 will focus on molecular virology and the development of viral vectors used in gene therapy to deliver the FVIII-encoding gene.This project is led by Indiana University School of Medicine professor of pediatrics Weidong Xiao, PhD
  • Project 3 will examine the immune system and its role in the interference of FVIII production over time. It is jointly led by Herzog and Ype P. de Jong, MD, PhD, assistant professor of medicine at Cornell University. 

Together, they hope to provide new insight that can lead to lower levels of toxicity and improved longevity of FVIII production in patients who are treated with gene therapy for hemophilia.

“This is an incredibly significant and urgent medical question, and it requires the synergy of multiple groups with different expertise to come together and solve a problem that they wouldn’t be able to solve on their own,” says Herzog. “My hope is that our studies will help the field as a whole move toward curing hemophilia A.”

The grant is titled “Toward Safer Gene Therapy for Hemophilia A” (P01HL160472). This post was adapted from a press release published by Indiana University School of Medicine.

Institute News

New CIRM grant to fund research internships for underrepresented high school students

AuthorMiles Martin
Date

January 25, 2022

Thanks to a new grant awarded to Sanford Burnham Prebys by the California Institute for Regenerative Medicine (CIRM), 57 California high school students from underrepresented groups will have the chance to complete a paid internship at the Institute for the next five consecutive summers.

The $509,000 grant was awarded to Paula Checchi, PhD, Alessandra Sacco, PhD, and Evan Snyder, MD, PhD

The mission of CIRM is to accelerate stem cell research and provide treatment to patients with unmet medical needs. And although CIRM directly funds faculty, many of their initiatives also focus on training the next generation of stem cell researchers. Late last year, Sanford Burnham Prebys received $5 million from CIRM to fund new training programs aimed at PhD students and postdoctoral researchers.

“One of the benefits of a program like this is that we’ll be able to inspire students early to pursue biomedical research,” says Checchi, a principal investigators on the grant and longtime educator of high school and undergraduate students. “A lot of students might not even realize that pursuing a STEM degree is an option for them, and that’s something we want to change.” 

The new grant was awarded as part of CIRM’s SPARK Training Program, a diversity, equity and inclusion (DEI) initiative that targets high school students without access to summer research internship opportunities due to socioeconomic constraints. This grant is one of 11 awarded by CIRM to research institutions across California.

“At the high school level, a lot of research internships are unpaid, which can alienate a lot of students, especially if they’re also part of a group that isn’t represented well in scientific research to begin with,” says Checchi. “Programs like this help flip that script and will contribute to increased diversity in science over the long term.”

In addition to getting hands-on research experience, interns will also participate in community outreach, patient advocacy and other educational activities under the mentorship of experienced professors.

“The research element is obviously important, but programs like this also help students develop into confident, capable young scientists who are able to inspire those around them,” says Checchi. “We’re trying to plant the seed for these bright young minds to flourish.”