Big boost for HIV research

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A research team led by Dr. John Young, professor at the Salk Institute for Biological Studies, and Dr. Sumit Chanda, associate professor at Sanford-Burnham, was awarded a $21 million Program Project Grant from the National Institutes of Health (NIH). This funding will allow the team to analyze the innate immune response (the body’s earliest defenses) against HIV infection using a systems biology approach. This large-scale initiative aims to increase our understanding of all the body’s cellular and molecular factors that work together to respond to HIV-1 infection and how these factors influence a patient’s prognosis.

Salvatore Albani & the Zen of translational medicine

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Dr. Salvatore Albani is a champion of translational medicine – the philosophy that research findings shouldn’t be confined to the laboratory, but “translated” into new therapies that treat disease. With both a Ph.D. and M.D., Dr. Albani embodies the bridge between the laboratory and the hospital. As the new director of translational research in Sanford Burnham’s Infectious and Inflammatory Diseases Center, he plans on expanding this discipline at the Institute.

“I first fell in love with Sanford-Burnham because of the emphasis on translational medicine. I joined the faculty at a moment of dramatic transformation, in which immense intellectual resources have made the Institute a worldwide technology leader,” Dr. Albani said. “And these exciting new ideas can be brought to fruition. For the first time, I’m in a place that thinks like I do.”

Chemical Genomics and the Art of Discovery

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Inflammation – one of the body’s earliest responses to infection or injury – can help the healing process when it’s closely controlled by the immune system. Mismanaged inflammation, however, can contribute to a variety of disorders, such as autoimmune diseases or allergic reactions. The immune system maintains this careful balance in part through the activity of a protein known as NF-κB. When triggered by cellular damage, infectious bacteria or some other molecular signal, NF-κB binds to DNA and turns on genes that activate inflammation. Since NF-κB acts like a master inflammation regulator, it makes an attractive target for researchers hoping to manipulate the immune response in patients suffering from either too much or too little inflammation.

A bi-coastal Sanford-Burnham research team led by Dr. Greg Roth in Lake Nona, Orlando, Fla. and Dr. John Reed in La Jolla, Calif. recently used the robotic technology in the Conrad Prebys Center for Chemical Genomics (Prebys Center) to screen a collection of more than 100,000 chemical compounds to find that one needle-in-a-haystack (or handful of needles) capable of blocking NF-κB. In a pair of studies published in ACS Chemical Biology (March 19, 2010) and the Journal of Medicinal Chemistry (May 18, 2010), they discovered a chemical compound that selectively impairs NF-κB activity under certain conditions. By inhibiting NF-κB this way, the compound has the potential to dampen potentially harmful inflammation without shutting down the whole immune system.

Influenza and nanomachines

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Drs. Sumit Chanda and Erkki Ruoslahti have received write-ups at two very distinct sites. Dr. Chanda’s flu research, which was published in February in Nature, was recently highlighted by the National Institute of Allergy and Infectious Disease, one of the National Institutes of Health. The work, a collaboration with Mount Sinai , Salk and GNF, identified 295 human proteins and other molecules  that influenza A strains must harness to infect a cell.  As the article points out,  the flu virus contains only 11 proteinsand must rely on our own cellular machinery to keep going. In many ways, these host factors may be better targets for treatment.

Current flu drugs are aimed directly at the influenza virus. But the flu virus mutates readily and these frequent changes allow it to gain resistance to antiviral drugs. However, if a drug were to be targeted to factor in the human host instead of being aimed directly at the virus, the pathogen’s ability to escape through mutation would be thwarted.

Meanwhile, Dr. Ruoslahti, who cofounded the Sanford-Burnham, UC Santa Barbara Center for Nanomedicine, was quoted in an article about robots at CNBC. Dr. Ruoslahti has been working with engineers at UC Santa Barbara to create nanorobots to home in on diseased cells.

“At this point, we can increase the activity of any anticancer drug by three fold or better,” he says. “We get more drug to the tumor and that makes a huge difference. If you can increase its concentration, the side effects remain the same, but the effectiveness is higher.”

From Research, the Power to Cure

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Playing off Sanford-Burnham’s slogan, Dr. Tomas Mustelin, adjunct professor and head of Amgen’s Seattle site, gave a talk last week on an issue at the heart of the institute: translational medicine. As a former academic scientist and now a leader in one of the country’s top pharmaceutical companies, Dr. Mustelin gave the packed audience a fascinating overview of what it takes to translate basic research into a marketable drug and the role that scientists, society and government play in the process.

“We scientists are quite privileged to be trusted by society to conduct research and develop therapeutics for patients with diseases like cancer or rheumatoid arthritis,” Dr. Mustelin told the audience. “We all have relatives who have experienced a serious disease, so we know it’s a task not to be taken lightly.”

Translating science into treatments

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New medicines must travel a long road from original idea to FDA approval. For the past several years, the scientific community has had an ongoing discussion on how we can smooth that path, so that new treatments reach patients sooner.

Recently, Domenico Fasci and Philip McQuary, two Sanford-Burnham Ph.D. students, entered a week-long intensive training program at the Eureka Institute to earn certifications in translational medicine. The program seeks to help physicians, scientists and business professionals better understand the mechanisms that slow down new medicines and work together to develop innovative solutions.

Another look at pandemic flu

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The San Diego-Union Tribune has a nice article today about pandemic flu.  One flu over: Lessons of the H1N1 Pandemic provides some interesting overviews from a number of flu experts on what went right and wrong (and what could yet happen) in the fight against H1N1. Among the experts were Sanford-Burnham researchers Dr. Robert Liddington and Dr. Sumit Chanda, who have both done extensive research on flu.

“We dodged a bullet,” said Sumit Chanda.

Science as art

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This award-winning image, Osteoclasts – The key to proper bone health, was created by Melanie Hoefer, Ph.D., a postdoctoral scientist in the Robert Rickert laboratory.Two different cell types drive the bone remodeling process. Osteoblasts synthesize bone matrix while osteoclasts resorb mineralized bone. The balance of bone formation and bone degradation determines the overall health of the bone. Thus, a dysregulated activity of those two cell types can result in osteopetrosis, osteoporosis or osteolytic lesions, which are characteristically seen in diseases such as osteoarthritis, rheumatoid arthritis and bone-metastasizing cancers.

“The photograph depicts mouse osteoclasts, which can be generated in vitro by stimulating cells isolated from the bone marrow,” says Dr. Hoefer. “By studying osteoclasts in culture, we aim to increase our understanding of their activity and hope to learn more about how bone degradation is regulated.”

In 2009 Dr. Hoefer  received first place in the BioEASI (Bio-Education and Art for Science Innovation) Science As Art contest for her image.