Top Stories - Drug Discovery

New TRI Facility in Downtown Orlando
Translational Research...

Florida Hospital and Sanford-Burnham announce the opening of the Florida Hospital –...

In Sanford-Burnham’s Conrad Prebys Center for Chemical Genomics, scientists use robots like this one to search hundreds of thousands of chemical compounds for the few that might become tomorrow’s new medicines.
Collaborating with Pfizer to...

Sanford-Burnham is the latest research organization to partner with Pfizer, Inc. as part of...

Scientists in Sanford-Burnham's Conrad Prebys Center for Chemical Genomics use robotic arms like this one to search for compounds that alter cellular behavior—precursors to new medicines.
Searching for new cancer...

Yesterday, we introduced a study in which scientists in Sanford-Burnham’s NCI-Designated Cancer...

"Disease in a dish" has great potential to accelerate drug discovery.
What is “Disease in a...

Frequently asked questions about “Disease in a Dish”, a cutting-edge, stem cell-based strategy...

Breathing new life into old medicines

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Discovering and developing new treatments for disease is a challenging, time-consuming, and expensive endeavor. For every drug that eventually makes it to the pharmacy, hundreds of compounds fail to deliver results and millions of dollars are spent without a direct return on investment. However, in these economically challenging times, existing drugs and compounds—whether in development, already on the market, or even ones that have failed clinical trials due to lack of efficacy—are being re-examined by pharmaceutical companies and research institutions. The goal of this approach—called drug repurposing— is to find potential new uses for these drugs.

Florida Department of Health and Sanford-Burnham to kick off collaborative research program

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Last week was a great one for medical researchers across the state of Florida. The state legislature and governor approved funding for the Collaborative Research Grant program between the Florida Department of Health and Sanford-Burnham Medical Research Institute. Starting in July, the program will provide scientists at universities and non-profit institutes throughout Florida with access to Sanford-Burnham scientists and our state-of-the-art technologies for drug discovery. This includes access to the Institute’s Conrad Prebys Center for Chemical Genomics.

Together with the Florida Department of Health, Sanford-Burnham will develop a competitive grant program, based on peer-review that will provide funds for collaborative projects between Florida-based research scientists and Sanford-Burnham’s fully operational, state-of-the-art drug discovery technology center based at Lake Nona.

Drug discovery case study: high-throughput screening of TNAP

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Editor’s note: this is the second in a series of posts highlighting drug screening studies in our Conrad Prebys Center for Chemical Genomics. Read the first post here.

Calcification of the medial layer of arteries is increasingly recognized as an important clinical problem. Medial vascular calcification (MVC) is the major cause of morbidity and mortality in generalized arterial calcification of infancy (GACI), and contributes to cardiovascular deterioration in Kawasaki disease (KD), chronic kidney disease (CKD), as well as in diabetes, obesity, and aging. MVC is thought to result from decreased circulating levels of the mineralization inhibitor, inorganic pyrophosphate (PPi).

Researchers at Sanford-Burnham have revealed that the development of MVC in mouse and rat models is accompanied by up-regulation of tissue-nonspecific alkaline phosphatase (TNAP), an enzyme whose primary function is to hydrolyze PPi, and thus, crucial in determining where mineralization occurs. Preliminary data have proven that upregulation of TNAP is sufficient to cause MVC and Sanford-Burnham scientists have developed potent drug-like inhibitors of TNAP.

Drug discovery case study: invadopodia and cancer metastasis

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Editor’s note: this is the first in a series of posts highlighting drug screening studies in our Conrad Prebys Center for Chemical Genomics. Read the second post here.

To metastasize, some types of cancer cells rely on invadopodia, cellular membrane projections that help them “walk” away from the primary tumor. To determine how cells control invadopodia formation, scientists at Sanford-Burnham took advantage of the technology and expertise of the Institute’s Conrad Prebys Center for Chemical Genomics to screen a collection of pharmacologically active compounds to identify those that either promote or inhibit the process.

The study identified several compounds that block invadopodia and found that many of the compounds targeted Cdks, a family of enzymes that were not previously associated with invadopodia. One of these enzymes, Cdk5, is required for the formation and function of invadopodia and for cellular invasion.

Presidential advisor John P. Holdren visits Sanford-Burnham at Lake Nona

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We’re always thrilled to have public officials visit our facilities in California and Florida, but last Friday was an especially exciting day for scientists and staff at Sanford-Burnham’s Lake Nona campus in Orlando, Fla. Dr. John P. Holdren, advisor to President Barack Obama, toured Orlando’s Medical City and spent time at the Sanford-Burnham site to learn about the promising research that is being conducted in our Diabetes and Obesity Research Center.

Dr. Holdren is assistant to President Obama for science and technology, director of the White House Office of Science and Technology Policy (OSTP), and co-chair of the President’s Council of Advisors on Science and Technology (PCAST). Congress established the OSTP in 1976 to advise the President and others within the Executive Office of the President on the effects of science and technology on domestic and international affairs. The OSTP also makes recommendations on the annual NIH budget.

A “twisted” grand opening ceremony

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“My goal is to cure diabetes,” Steven Smith, M.D., scientific director of the Florida Hospital – Sanford-Burnham Translational Research Institute for Metabolism and Diabetes (TRI), said boldly at the opening ceremony of the TRI’s new state-of-the-art facility in downtown Orlando on March 27. “We believe that personalized medicine is our best shot at discovering cures for our most serious health problems like diabetes.”

The ceremony’s highlight was the unveiling of a spectacular nine-foot double-helix DNA structure that will be placed at the main entrance of the building, symbolizing the fundamental research being conducted at the TRI, as well as the synergies and collaborations the TRI represents. Selected board members and presenters each added one illuminated “bar,” representing a nucleotide, to the double helix.

“This is one of those rare times when the reality far exceeds the dream,” said John Reed, M.D., Ph.D., CEO of Sanford-Burnham. “The TRI is a wonderful opportunity for our organization, which will bring more and more to life our slogan From Research, the Power to Cure. We’re very excited about this opportunity to take our relationship with Florida Hospital to the next level.”

Translational Research Institute establishes new research paradigm for metabolic diseases

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Florida Hospital and Sanford-Burnham today celebrate the opening of the Florida Hospital – Sanford-Burnham Translational Research Institute for Metabolism and Diabetes’ (TRI) new state-of-the-art facility in downtown Orlando, Fla., dedicated to the advancement of a new paradigm of personalized approaches to researching and treating diabetes and obesity.

“We are witnessing the rise of personalized medicine, most notably in cancer. Our goal at the TRI is to accelerate the advancement of personalized medicine in diabetes and obesity,” said Steven Smith, M.D., Sanford-Burnham professor and scientific director of the TRI.  “We are working to rapidly expand knowledge of complex genetic and molecular causes of diabetes and obesity so that we can better define disease subpopulations. By working independently and in partnership with industry, we hope to develop therapies and treatment approaches tailored to those subpopulations. Our ultimate goal is that our discoveries will someday lead to cures for certain patients.”

Obesity research advances to clinical testing

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Discoveries made in the laboratories of Sanford-Burnham will, for the first time, advance to the clinical research stage involving human studies at the Florida Hospital – Sanford-Burnham Translational Research Institute for Metabolism and Diabetes (TRI). The research will focus on orexin, an appetite-inducing hormone produced in the brain, which appears to resolve obesity without requiring a reduction in food consumption or elevation in physical activity. This research exemplifies the translational research focus at Sanford-Burnham and the TRI – advancing science from laboratory bench to patient bedside. The studies will provide insight into individual responses and contribute to the development of personalized therapies for treating metabolic diseases – a focus area for both the TRI and Sanford-Burnham.

Appetite-suppressing drugs have traditionally been the basis of weight-loss treatments since obesity is thought to be caused by excessive energy intake and low physical activity. However, appetite suppressants can produce unacceptable side effects and, after the treatment ends, patients usually the weight they lost. Recent data indicate that orexin leads to weight loss by releasing excess energy as heat instead of storing it.

Why the economy depends on federal funding for medical research

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When Sanford-Burnham CEO John Reed, M.D., Ph.D. traveled to Washington, D.C., in early February, he attended a variety of Capitol Hill briefings to discuss the importance of National Institutes of Health (NIH) funding for medical research. He pointed out that NIH grants account for approximately 80 percent of all funding for non-profit medical research institutions in the United States, such as Sanford-Burnham.

NIH grants contribute to the ultimate goal of developing new treatments for diseases and improving the quality of life for millions of Americans and people worldwide. The research supported by these grants also generates U.S. patents that fuel the biotechnology industry and creates thousands of jobs across the nation. NIH funding supports the training of our biomedical research workforce and strengthens the foundation of a 21st century knowledge-based economy.

Talking research in Washington, D.C.

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On February 2, Sanford-Burnham CEO Dr. John Reed traveled to Washington D.C., where he described at several Capitol Hill briefings how important NIH funding is to the life sciences sector and, in turn, to America’s economy. He and Scott Salka, CEO of CendR Inc., a biotech start-up that spun out of Sanford-Burnham in 2010, participated as part of CONNECT’s “Innovation 101” series of Capitol Hill Briefings on life sciences research.

CONNECT, a regional program that catalyzes the creation of innovative technology and life sciences products and companies in San Diego County, described the significance of this undertaking by saying, “As life science research institutions increase their focus on commercialization of discoveries and develop strategies to help start-up companies succeed, it is imperative that Congress and the Obama administration understand how federal research funding results in successful discoveries, start-ups, and job creation.”

Cancer drug discovery leaders come together at Sanford-Burnham

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Where do new medicines come from? The first step in the drug discovery process often involves screening small molecules (chemicals) to determine their potential to produce innovative biological research tools. Sanford-Burnham’s Conrad Prebys Center for Chemical Genomics uses robotic technology to sift through chemical compounds by the millions to find the few that could potentially be developed into new medicines

Taking stock: obesity research progress with Takeda

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Scientists from the Diabetes and Obesity Research Center and their colleagues from Florida Hospital recently returned from Japan, where they reviewed the progress that has been made at the mid-point of a research partnership with Takeda Pharmaceutical. The two-year collaboration focuses on the discovery and evaluation of new therapeutic approaches to obesity. In Japan, Sanford-Burnham scientists reported benchmark data that sets the stage for a key element in future drug development—the testing of obesity drug candidates.

“The data generated thus far lays the groundwork for analysis of how individuals respond differently to disease,” said Steven R. Smith, M.D., director of the Florida Hospital – Sanford-Burnham Translational Research Institute for Metabolism and Diabetes (TRI), where the clinical studies are being performed with volunteers. “This partnership with Takeda, TRI, and Sanford-Burnham establishes a model to accelerate the development of safe and effective therapies.”

What would Nature do?

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We all want to find the next miracle drug—especially the one that will cure an ailing loved one. But it can take researchers a long time—decades, sometimes—to discover and develop new medicines. Not only do scientists and doctors hope to create a therapy that works well, but it can’t cause too many side-effects. And even then, after all that time and effort to move the therapy from the lab bench to the patient’s bedside, the drug might stop working after a few months if the patient develops resistance to it.

How can we overcome this final hurdle?

Metabolomics fuels cancer drug discovery

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Genomics is a global look at all the DNA or genes in a cell or organism and proteomics refers to all the proteins. But these don’t necessarily tell the whole story about what’s going on inside a cell at a given moment. Metabolomics adds another layer of complexity, describing all the chemical reactions a cell uses to process nutrients and produce both energy and the chemical building blocks required for maintenance and growth.

Since cellular metabolism relies on an intricate and finely-tuned network of interconnected pathways involving many proteins and enzymes, it follows that many human diseases, including cancer, can throw metabolism off, changing the relative abundance of different metabolites (the chemicals involved in metabolism). Thus, the ability to detect and quantify such metabolic changes would make a very useful tool for evaluating the status of a disease and judging the effectiveness of a therapy.

Collaborating with Pfizer to speed drug discovery

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Sanford-Burnham is the latest research organization to partner with Pfizer, Inc. as part of Pfizer’s commitment to transforming research and development through a focus on translational medicine. The Centers for Therapeutic Innovation (CTI) is a research unit at Pfizer dedicated to open innovation through establishing global partnerships with academic research institutions to bridge the gap between discovery science and clinical applications.

“Pfizer is truly excited to work in this new partnership with leading experts from Sanford-Burnham Medical Research Institute to understand more about the mechanisms that drive diseases with high unmet medical need,” said Dr. Anthony Coyle, vice president and head of Pfizer’s Global Centers for Therapeutic Innovation.