Sanford-Burnham Science Blog
Sanford-Burnham researchers identified 190 genes crucial to the function of TLR7 and TLR9, cellular...
HIV is a virus that weakens the immune system, leading to Acquired Immune Deficiency Syndrome...
Dr. Lutz Tautz and colleagues show how the breakup of two proteins interferes with the immune system...
Dr. Carl Ware has joined Sanford-Burnham’s faculty as director of the Infectious and...
Quebec (Photo by Martin St-Amant, Wikimedia Commons)
Calling all cytokine scientists…
What: 14th International Tumor Necrosis Factor Conference
When: July 7-10, 2013
Where: Loews Le Concorde, Quebec City, Canada
Who: Hosted by the International Cytokine Society; attended by more than 300 academic and biopharma industry scientists from around the world
Registration: Visit www.tnf2013.com
Drug-like chemical compound LTV-1 (foreground) blocks the action of mutant LYP protein in human immune cells, providing a potential new therapeutic for autoimmune diseases.
Originally published March 18, 2012
Autoimmune diseases, such as Type I diabetes and rheumatoid arthritis, are caused by an immune system gone haywire, where the body’s defense system assaults and destroys healthy tissues. A mutant form of a protein called LYP has been implicated in multiple autoimmune diseases, but the precise molecular pathway involved has been unknown. Now, in a paper published March 18 in Nature Chemical Biology, Sanford-Burnham researchers show how the errant form of LYP can disrupt the immune system. In doing so, they also found a potential new therapy for autoimmune diseases—a chemical compound that appears to inhibit this mutant protein.
Dr. Bruce Beutler (right) and his host, Dr. Carl Ware, director of Sanford-Burnham's Infectious and Inflammatory Disease Center
Bruce Beutler, M.D., professor and director of the Center for the Genetics of Host Defense at UT Southwestern, shared the 2011 Nobel Prize in Physiology or Medicine for his studies of the innate immune system. Working with mice, he discovered toll-like receptors, cellular sensors that recognize bacteria and activate inflammation. Dr. Beutler visited Sanford-Burnham’s La Jolla campus earlier this week to meet with colleagues and deliver a special lecture. He also serves on our Scientific Advisory Board.
While he was here, we sat down with Dr. Beutler and asked him about what inspired him to become a scientist, what he’s most proud of, where the field is headed, and how his life has changed since winning a Nobel.
Watch the video below to see what he said:
Drug-like chemical compound LTV-1 (foreground) blocks the action of mutant LYP protein in human immune cells, providing a potential new therapeutic for autoimmune diseases.
Autoimmune diseases, such as Type I diabetes and rheumatoid arthritis, are caused by an immune system gone haywire, where the body’s defense system assaults and destroys healthy tissues. A mutant form of a protein called LYP has been implicated in multiple autoimmune diseases, but the precise molecular pathway involved has been unknown. Now, in a paper published March 18 in Nature Chemical Biology, Sanford-Burnham researchers show how the errant form of LYP can disrupt the immune system. In doing so, they also found a potential new therapy for autoimmune diseases—a chemical compound that appears to inhibit this mutant protein.
Sumit Chanda, Ph.D.
In a healthy immune system, invading pathogens trigger a cascade of alerts and responses to fight off the infection. Sensors called toll-like receptors, or TLRs, act as one of the first lines of defense. Two of these sensors, known as TLR7 and TLR9, specifically recognize and respond to microbial RNA and DNA, respectively. But what determines how these TLRs get where they need to be and sound the alarm for pathogen infection? To answer this question, a team led by Sanford-Burnham’s Sumit Chanda, Ph.D. and colleagues used a technique known as RNA interference (RNAi) to silence each gene in the human genome one by one. In doing so, they were able to determine which genes are crucial for TLR7 and TLR9 functions and which are dispensable. In their study, published March 14 in Cell Host & Microbe, the team identified 190 proteins that contribute to our ability to detect and respond to microbial infection. These findings could help scientists develop new strategies to manipulate immune responses for treatment of autoimmune disorders and microbial infections.
Dr. Robert Rickert
Lymphoma is a cancer of the immune system. White blood cells divide again and again, spreading abnormally throughout the body. Lymphomas can arise from two types of white blood cells, T cells or B cells, which divide uncontrollably when the molecular mechanisms that keep them in check go awry. A new study led by Dr. Robert Rickert, professor and director of Sanford-Burnham’s Inflammatory Diseases Program, explores the roles of two enzymes, called SHIP and PTEN, in B cell growth and proliferation.
“PTEN usually gets all the attention,” Dr. Rickert explained. “But here we show for the first time that SHIP is also a major tumor suppressor in B cells.”
The results, published this week in The Journal of Experimental Medicine, show that SHIP and PTEN act cooperatively to suppress B cell lymphoma. This new information could impact several anti-lymphoma therapies currently in development.
A paper published online this week in the Proceedings of the National Academy of Sciences (PNAS) highlights a collaboration between two Sanford-Burnham scientists, one an immunologist in the Infectious and Inflammatory Disease Center and the other a cell communication expert in the Cancer Center.
Dr. Robert Rickert studies B cells, a type of white blood cell in the immune system that produces antibodies to neutralize foreign particles. Because they move around the body, immune cells are oddities compared to other types of cells.
“Other scientists worry about a process called anoikis, in which wandering cells are programmed to self-destruct,” Dr. Rickert explains. “In contrast, only some populations of B cells stay put, like those found in the marginal zone of the spleen.”
So it caught his attention one day when he heard his colleague Dr. Elena Pasquale talk about her work on integrins, a family of proteins located on the surface of many cell types. Integrins carry signals back and forth between the inside and outside of cells, allowing cells to adhere to their surroundings or other cells. Dr. Rickert knew that integrin signaling is required for B cells to remain in a particular region of the spleen, known as the marginal zone, but not why.
Scanning electron micrograph of HIV-1 budding (in green) from cultured lymphocyte. (Image courtesy of CDC)
HIV is a virus that weakens the immune system, leading to Acquired Immune Deficiency Syndrome (AIDS). Unfortunately, many people living with HIV and AIDS must also contend with weakened minds. Despite recent successes suppressing the infection, roughly half of all AIDS patients experience HIV-associated neurological disorders, or HAND, which range from mild cognitive impairment and memory loss to stroke or dementia. But to stop HAND, we have to know what causes it. According to surprising new research led by Dr. Marcus Kaul, assistant professor in Sanford-Burnham’s Infectious and Inflammatory Disease Center, it’s not necessarily the virus itself that damages neurons. It’s our own immune cells.
Dr. Carl Ware has joined Sanford-Burnham’s faculty as director of the Infectious and Inflammatory Disease Center (IIDC). Although this is the first time Dr. Ware has been employed at Sanford-Burnham, his roots with the Institute go back to 1996. That’s when he, Dr. John Reed, Dr. Guy Salvesen, and others began a collaborative project to study apoptosis and cell death. That same year, Dr. Ware joined the La Jolla Institute for Allergy and Immunology, where he led the Division of Molecular Immunology. Over the years, he has maintained strong ties with Sanford-Burnham.Dr. Ware’s research focuses on the fundamental pathways that control cytokines, a family of proteins involved in immune signaling. One group of cytokines, called tumor necrosis factors or TNF, are part of an intricate communication network between immune system cells.
“They’re complicated circuits,” says Dr. Ware. “There are more than two dozen proteins in this family and an equal number of receptors. The pathways involve hundreds of proteins. In infectious disease, these pathways are amplified in a very dramatic fashion. In autoimmune disease the pathways escape regulatory control entirely. Something just goes haywire. However, with any circuit, theoretically, you can rewire around it.”
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.”
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.
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.
We’re oversimplifying a little, but our genetic code works like this: DNA codes for messenger RNA (mRNA); mRNA takes that coded message out of the nucleus; tiny machines called ribosomes read the message in the mRNA and produce proteins; proteins do most of the work in the cell. However, there is another player in this pathway that has only come to light relatively recently—microRNAs(miRNAs).
