Improving Human Health Archives - Sanford Burnham Prebys

Category: Improving Human Health

Institute News

Cancer Moonshot satellite summit held at Sanford Burnham Prebys

AuthorJessica Moore
Date

July 7, 2016

Moonshoot attendees

Our institute was one of ten sites in the U.S. selected to co-host an official summit as part of the kick-off for Vice President Joe Biden’s Cancer Moonshot. This $1 billion initiative “aims to make more therapies available to more patients, while also improving our ability to prevent cancer and detect it at an early stage.” The funds support new cancer research programs within the NIH and the Departments of Defense and Veterans Affairs, as well as data sharing infrastructure and efforts by the FDA to expedite development of new cancer drugs and diagnostics.

The SBP event, held on the same day as the Vice President’s summit in Washington, DC, brought together oncologists, cancer researchers, cancer survivors and their families, developers of cancer therapeutics, and leaders of key institutions making an impact on cancer in southern California. This diverse participation provided opportunities to make connections, get inspired, and find potential collaborators.

The program included an explanation of how scientific leaders are shaping the initiative, a videocast of the vice president’s speech, and three panel discussions of hopes and concerns for the program. The inside take on the Moonshot’s development was given by María Elena Martínez, PhD, professor of Family Medicine and Public Health at the UC San Diego Moores Cancer Center, one of 30 experts on the Blue Ribbon Panel that is developing recommendations for action.

Several messages emerged from SBP’s summit, including:

  • Sustained research funding is required to ensure significant progress
  • Improving clinical trials (enhancing participation and streamlining approvals) is key to accelerate the pace of drug development
  • Data sharing systems must be built up to reap maximum benefits from cutting-edge methods of profiling tumors

The event was covered by multiple local news outlets, including KPBS and KUSI, and livestreamed through Facebook (video available here and here).

Garth Powis, D.Phil., director of the NCI-designated Cancer Center at SBP, was called to take part in the summit in Washington, DC.

“It was worthwhile to be there and see how the White House is interacting with the NCI,” Powis said. “Much of the focus was on big data. GSK is working with the Department of Energy to get the Veterans Administration organized and IBM is using their super computer ‘Watson’ to consolidate patient records.”

The Moonshot promises to accelerate cancer research in San Diego, given its position as a major hub for biomedical science, though no funds have yet been distributed.

 

Institute News

Cancer metabolism symposium highlights hot area in cancer research

AuthorJessica Moore
Date

June 27, 2016

Tak Maria Jorge

The third Cancer Metabolism Symposium held at Sanford Burnham Prebys Medical Discovery Institute (SBP) June 22-23, 2016, attracted a full house of attendees from across San Diego. Its success likely results from the impressive roster of speakers invited by organizers Jorge Moscat, PhD, professor and director of the Cancer Metabolism and Signaling Networks Program, and Maria Diaz-Meco, PhD, also a professor in that program. The presenters included numerous thought leaders in the field from such prestigious institutions as the Koch Institute for Integrative Cancer Research at MIT, the Dana Farber Cancer Institute at Harvard Medical School, and Memorial Sloan Kettering Cancer Center.

The aim of research on cancer metabolism is simple—to find ways to starve tumors of the fuels and building blocks they need to grow. This strategy is gaining attention (see this recent New York Times feature) because of the increasing evidence that cancer cells obtain and use nutrients differently than normal cells. Plus, there appear to be a few common ways in which cancer cells’ metabolism becomes deranged, making it a much simpler target than oncogenic mutations, which tumor cells accumulate almost exponentially.

Several new drugs that interfere with metabolism have shown promise in clinical trials for numerous types of cancer. Nonetheless, there’s still a lot to learn. Since tumor cells rely on the same metabolic pathways as normal cells, researchers must pinpoint cancer’s weaknesses—the enzymes and nutrients on which cancer cells rely far more than normal cells. Many of these differences were discussed at the symposium, opening doors for new ways to stop cancer.

Institute News

SBP scientists reflect on progress in diabetes research

AuthorDeborah Robison
Date

June 23, 2016

ADA

“The most significant advances in diabetes treatment, which were underscored at the ADA meeting, is the clinical evidence that two newer classes of anti-diabetic drugs significantly improve cardiovascular outcomes and overall mortality. These drug families are insulin secretion enhancers such as liraglutide (LEADER trial) and drugs that promote glucose elimination in the urine, such as canagliflozin and empagliflozin (EMPA-REG OUTCOME trial). This has major impact because reducing the risk of heart disease is always the end goal in treating diabetes—the association with heart disease is what makes type 2 diabetes so serious. These trials also present a remarkable opportunity for basic researchers—many of us, including several here in Lake Nona, study how drugs in these classes affect metabolism. The answers to those questions should lead to new drug targets that are even more specific and precision-oriented.”

Peter Crawford, MD, PhD
Associate Professor and Director
Cardiovascular Metabolism Program

“From the sessions that I saw, there was a significant emphasis on combination treatments—either combining two or more already approved drugs that have related functions or generating fusions of multiple protein drugs. An example of the former is the combination of basal insulin and glucagon-like peptide-1 receptor agonists to control fasting and post-meal glucose levels, respectively. With regards to fusion proteins, there were many posters and presentations highlighting efforts to generate dual and triple combinations that would lower glucose and aid weight loss. These approaches may reduce the need for patients to take multiple drugs and therefore improve efficacy and patient adherence.”

Julio Ayala, PhD
Associate Professor
Integrative Metabolism Program
ADA Thomas R. Lee Career Development Award Recipient ’14

“During the ADA meeting two symposia and numerous other presentations examined evidence implicating gut microbiota in the development of type 1 and type 2 diabetes. I am personally enthusiastic about the potential of novel therapeutic strategies that either prevent harmful changes in gut microbiota or even directly transplant “therapeutic” microbial species. Nevertheless, our current understanding of the potential mechanisms is very limited due to the complex factors affecting the microbiome such as the host’s genetics and the environment (diet, antibiotic use, history of infections etc.).”

George Kyriazis, PhD
Assistant Professor
Integrative Metabolism Program

“Of particular interest to me were the symposia on experimental strategies for understanding how the brain controls metabolism. Specifically, optogenetics and magnetogenetics are emerging as two powerful research tools for this purpose, and involve genetically modifying neurons to express either light- or magnetic field-sensitive proteins so that their activity can be controlled with fiber optic light or magnets, respectively. These sophisticated techniques will help investigators delineate which regions in the brain play a critical role in regulating blood glucose, which could lead to more effective therapies for diabetes and obesity.”

Melissa Burmeister, PhD
Staff Scientist
Dr. Julio Ayala Lab

 

Institute News

New drug combination may lead to treatment for childhood brain cancer

AuthorJessica Moore
Date

March 14, 2016

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Researchers at SBP have identified a new combination therapy for the most aggressive form of medulloblastoma, a fast growing type of pediatric brain cancer. The study, published  in Cancer Cell, is expected to lead to a clinical trial to confirm the benefits of the novel drug combination. Continue reading “New drug combination may lead to treatment for childhood brain cancer”

Institute News

Scientists identify promising new melanoma drug

Authorsgammon
Date

November 25, 2015

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A new drug discovered by scientists at Sanford Burnham Prebys Medical Discovery Institute (SBP) may show promise for treating skin cancers that are resistant or unresponsive to today’s leading therapies.

In the United States, 5 million people are treated annually for skin cancer, and 9,000 people die from the deadliest form—melanoma—according to the US Department of Health and Human Services.

The new compound, named SBI-756, targets a specific molecular machine known as the translation initiation complex. These structures are in every cell and play the critical role of translating mRNA into proteins. In cancer cells the complex is impaired, producing extra protein and providing a growth advantage to tumors. SBI-756 causes the translation complex to dissociate, and was shown to inhibit melanoma cell growth in the study, published today in Cancer Research.

“The unique target of SBI-756 makes it especially promising for use in combination therapy,” said Ze’ev Ronai, senior author and scientific director of SBP’s La Jolla campus. “A major issue limiting the effectiveness of current melanoma therapies is that tumors become resistant to treatment. Combining drugs that come at a melanoma from different angles may help overcome the problem of drug resistance.”

About 50% of melanomas are caused by mutations in a specific gene called BRAF. Patients with these tumors are commonly prescribed vemurafenib, a BRAF inhibitor that shrinks tumors. However, many patients experience a relapse within weeks, months, or even years because tumors evolve and become resistant to the drug. A similar phenomenon is seen in mice, where treatment of BRAF melanomas results in an initial response, but 3-4 weeks later the tumors return.

The team found that if SBI-756 is co-administered with vemurafenib, the tumors disappeared and most importantly, they did not reoccur. Even in mice with advanced/late stage BRAF driven cancer, the reappearance of . These data suggests that SBI-756 provides a significant advantage in overcoming tumor resistance.

“The ability of this compound to delay or eliminate the formation of resistant melanomas is very exciting,” said Ronai.

In other forms of melanoma, caused by mutations in the genes NRAS and NF1—which are known as unresponsive to BRAF drugs—administering SBI-756 alone significantly the scientists found. The team is now testing whether combining SBI-756 with existing drugs used for treating these types of melanomas can make the tumors disappear.

Drugs that target the translation initiation complex have been intensely pursued in the past few years, not just for melanoma, but for a wide array of cancers. SBI-756 is considered a first-in-class drug because it is the first successful attempt to target a specific part of the complex called eIF4G1.

In fact, SBI-756 is the culmination of seven years of work in Ronai’s group—testing and tweaking the drug’s features to help it bind to the target more readily and to make it easier to formulate. The resulting compound is a significant improvement over the initial version.

“It appears that the dose we need to administer is very low. Even in the experiments where the drug was administered to mice with tumors over a significant period of time, we have not found any toxicity,” Ronai said.

“The finding of SBI-756 is also exciting for the possible treatment of diseases other than cancer, such as neurodegenerative diseases, where the activity of the translation initiation complex is reported to be higher,” said professor Nahum Sonenberg of McGill University, a world renowned leader in the field of protein translation.

“We hope that we’re going to come up with the next generation of the compound that can go into clinical trials—first in melanoma but likely in other tumors,” Ronai said.

The study was performed in collaboration with the Conrad Prebys Center for Chemical Genomics at SBP, Lady Davis Institute for Medical Research, Sir Mortimer B. Davis-Jewish General Hospital, McGill University (Canada), the National Cancer Institute, MD Anderson Cancer Center, and Yale University.

Institute News

Get the flu shot before it’s hot

AuthorGuest Blogger
Date

November 17, 2015

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Flu season is arriving, and the U.S. Centers for Disease Control and Prevention is putting out a plea for everyone 6 months and older to get their flu shots—the sooner, the better.

You may have heard the news that last season’s vaccine was weak against one flu strain in particular: H3N2, which is the most deadly. To understand why, you’d have to know a bit about how vaccines work.

What is the flu vaccine, exactly?

The standard flu shot contains three inactivated flu viruses. The purpose of these inactivated viruses is to prompt your body to generate antibodies that will be ready to fight off the real flu.

Although some versions of the vaccine include a fourth virus, this season’s standard ‘trivalent’ shot contains:

  • An influenza A (H1N1)-like virus;
  • An influenza A (H3N2)-like virus; and
  • An influenza B virus.

Of these, the influenza A (H3N2) virus and the influenza B virus strains have changed from the 2014-2015 season.

How is the vaccine designed?

Although your age and health also play a role, the closer flu vaccine is to the circulating viruses, the better chance for protection. However, to get a close “match” is a bit of a guessing game because viruses evolve rapidly and sometimes unpredictably.

Adding to the challenge is that U.S. manufacturers need at least 6 months lead time to generate enough doses for a given season: about 171 to 179 million will be generated for 2015-16, for example. The standard vaccine is made in chicken eggs, which takes a while. But scientists are also pursuing faster methods: cell-based flu vaccines, which are already approved in Europe.

Based partly on surveillance data from more than 100 national influenza centers around the world, the World Health Organization issues its recommendations for flu strains in February of each year, to give enough time for private manufacturers to start producing doses (though some manufacturers, based on a best guess, start producing vaccines even earlier). The U.S. Food and Drug Administration makes the final decision about which strains the U.S. will include in its vaccines.

How do researchers measure success?

How well a vaccine does each season is informed by constant surveillance. Experts from the CDC take data from the U.S. Flu Vaccine Effectiveness Network, a collaboration between the CDC and five institutions across the United States. The sites are clinical settings, meant to represent the U.S. as a whole, where patients with flu-like symptoms are tested (using reverse transcription polymerase chain reaction) to confirm if they have the flu, and how genetically different it is from the vaccine strain.

Why did last year’s vaccine perform so poorly?

According to the CDC, last season’s vaccine was only about 19% effective at preventing flu (or, more precisely, a person’s chance of seeking medical treatment for flu). In contrast, in the past decade, the effectiveness rates have been more in the range of 60%, though the estimates are by no means precise.

A study published in the journal Cell this past summer shows that the main reason was ‘antigenic’ drift: the circulating H3N2 acquired mutations, one in particular that prevented a person’s antibodies from recognizing it.

Where can I learn more?

For all you ever wanted to know about flu, check out the CDC’s flu pages. For a weekly U.S. influenza surveillance report by the CDC — if you’re into charts and graphs, you’ll like this — check out FluView. (FluView is also available as a free app on iTunes.) Note that it’s not appropriate to compare rates across different regions or seasons because of differences in the number of specimens tested and different testing practices.

But if you get the flu

Although there are some drugs approved by the FDA to treat the flu, most have to be taken within 48 hours of onset to be effective.

At SBP, Dr. Jessica von Recum is working on a new approach for influenza therapy. She is using ex vivo human lung tissue to screen for novel antiviral compounds that target proteins in the host (that’s you) that the virus needs to complete its life cycle. Jessica is starting by blocking host cell proteins called proteases to stop viruses from replicating. This is just one approach—she plans to target other proteins as well.

To read more about Dr. von Recum’s research and the unique way that SBP is funding her research, click here.

This post was written by Kelly Chi, a freelance writer.

 

Institute News

SBP Collaborates with NIH’s Translational Science Center on pancreatic cancer

Authorsgammon
Date

October 13, 2015

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The National Center for Advancing Translational Sciences (NCATS) has initiated a novel collaborative study with Pamela Itkin-Ansari, PhD., to screen for drugs that reprogram pancreatic cancer cells back to a normal, non-threatening phenotype.

The collaboration is based on Itkin-Ansari’s research and development of a screening platform to find drugs that induce the overexpression of E47, a protein that binds to specific DNA sequences, causing cells to differentiate to acinar cells—cells with normal pancreatic cell traits and characteristics.

“I’m delighted to be working with NCATS on a project that may lead to better treatments for pancreatic cancer patients,” said Itkin-Ansari, adjunct professor in the Development, Aging, and Regeneration Program at SBP. “The Center will be screening novel compounds as well as approved drugs that can be repurposed, potentially accelerating the clinical development process due to their known safety profiles and characterized mechanisms.”

The outlook for patients with pancreatic cancer is very poor. Among people diagnosed with the disease, 80 percent are dead within the first year, and 90 percent the year after that. And pancreatic cancer is one of the few cancers for which survival has not improved substantially in 40 years.

One reason pancreatic cancer is so deadly is that there are no good detection tools to diagnose the disease in the early stages, so by the time most patients are diagnosed the cancer has spread to the liver or other areas of the body. Another reason is that there are really no good treatments—response to chemotherapy and radiation is poor.

NCATS was established by the National Institutes of Health (NIH) to transform the translational science process so that new therapies for disease can be delivered to patients faster. For drug discovery collaborations, the Center works with academic investigators that are biology and disease experts that have demonstrated a novel approach, a primary screening platform that they can adapt, and a follow-up critical path for the project.

Dr. Itkin-Ansari pointed out that technical guidance provided by the Conrad Prebys Center for Chemical Genomics at SBP was instrumental in validation of her screening platform. “Their experience in developing high throughput screening assays, such as the one that will be used in this collaboration, is unparalleled in the nonprofit research sector” said Itkin-Ansari.

“NCATS has a history of success in novel therapeutic approaches and I’m hopeful that our collaboration will result in identification of a proof-of-concept compound for advancing studies on reprogramming as an intervention for pancreatic cancer.”

The research will be funded by the Marian and Ralph Falk Medical Research Trust.

Institute News

Cancer metabolism 101

Authorsgammon
Date

April 21, 2015

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“Feed me!” Cancer is caused by the uncontrolled proliferation of cells. Their rapid growth comes with a voracious appetite to support their nutritional demands. To satisfy these demands, cancer cells rewire their metabolism. Increasingly, scientists are looking to exploit the metabolic differences between normal and cancer cells for the development of new anti-cancer therapies. Continue reading “Cancer metabolism 101”

Institute News

Sanford-Burnham researcher awarded American Federation for Aging Research award

Authorsgammon
Date

December 23, 2014

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Malene Hansen, PhD, associate professor in our Development, Aging, and Regeneration Program has been awarded the Julie Martin Mid-Career Award in Aging Research. The award includes a new grant to continue her research in the field of aging. Hansen is a three-time American Federation for Aging Research (AFAR) grant recipient. AFAR’s grants are given to scientists at institutions nationwide based on hard work, ingenuity, and leadership that advance cutting-edge research to help us live healthier, longer lives. Continue reading “Sanford-Burnham researcher awarded American Federation for Aging Research award”