As the United States pauses to observe the 10th anniversary of the September 11th terrorist attacks, we reflect on the research advances that contribute to new counterterrorism measures—understanding anthrax, for example—and the health of our soldiers in Iraq and Afghanistan, including under-studied conditions such as traumatic brain injury (TBI) and post-traumatic stress disorder (PTSD). Here are a few examples, and these only cover discoveries made at Sanford-Burnham since September 11, 2001. Can you think of more? Please share your thoughts in the comments below.
Crystal Structure of Anthrax Lethal Factor complexed with a small molecule inhibitor
Dr. Fred Levine, director of the Sanford Children's Health Research Center
The Kenneth Rainin Foundation announced that Sanford-Burnham’s Dr. Fred Levine and Dr. Hudson Freeze will receive a 2011 Innovator Award for Inflammatory Bowel Disease (IBD) Research. The team will receive a $100,000, one-year grant for their idea to develop new IBD treatments by targeting a protein called HNF-4a.
HNF-4a is a nuclear receptor, meaning that it directly binds DNA and turns genes on or off in response to outside signals. HNF4a is found throughout the intestine, where it helps maintain structural integrity of the intestinal lining. Previous studies suggest that HNF4a might play a role in IBD. In a mouse model of IBD, lack of HNF4a increased disease severity. HNF4a levels are also low in intestinal biopsy samples from IBD patients. Given this information, it makes sense that enhancing HNF4a function might have the opposite effect, diminishing the disease. However, there hasn’t been a practical way to do that—until now.
Gianna Dragatto, a young patient with a rare disease called Congenital Disorders of Glycosylation (CDG), hopes to see you at Sanford-Burnham's 3rd Annual Rare Disease Symposium on February 24, 2012.
Dr. Eric Green, keynote speaker (photo by Maggie Bartlett)
What: 3rd Annual Sanford-Burnham Rare Disease Symposium
Where: Sanford-Burnham Medical Research Institute, La Jolla, Calif.
When: February 24, 2012
Keynote speaker: Dr. Eric Green, director of the National Human Genome Research Institute (NHGRI) at the NIH
Sanford-Burnham’s successful series of Rare Disease symposia is based on the concept that treatment of rare diseases requires participation and exchange among all stakeholders—scientists, physicians, affected patients and their families, support groups, granting agencies, industry, and philanthropists.
This year’s event, organized by Dr. Hudson Freeze, will focus on Glycosylation-Based Disorders: Discovery, Patients, and Progress Toward Treatments.
Save the date now. Program and registration information will be available soon. In the meantime, video and media coverage of last year’s event are available here.
In the movie Extraordinary Measures, Harrison Ford plays a glycobiologist.
If brides and grooms can have destination weddings, then scientists should be able to have destination research conferences. These types of conferences are increasingly popular as opportunities for scientists to experience fun locales while also interacting and exchanging ideas with a relatively intimate group of expert colleagues. The Gordon Research Conferences have been trendsetters with this format since the 1930s, sponsoring scientific meetings on a variety of topics at sites within the U.S. Starting in 1990, Gordon Conferences have been held in more exotic foreign locations, including Italy, Switzerland, Japan, England, Hong Kong… and even Texas.
Earlier this summer, Dr. Hudson Freeze, program director in Sanford-Burnham’s Sanford Children’s Health Research Center, chaired the Gordon Conference on Glycobiology in Lucca, Italy. 170 glycobiologists from around the world gathered to hear about exciting new developments in the science of carbohydrates (sugar molecules) and the complex molecules like proteins and lipids whose properties are influenced by incorporation of carbohydrates. Once a rather understudied area of biology, glycobiology has been transformed by the realization that carbohydrates mediate many of the key molecular interactions that govern cellular function. Meeting topics included the effects of sugar modifications during development, the role of carbohydrates in normal adult physiology and the involvement of carbohydrates in tissue engineering and repair, including their importance in stem cell biology.
Japanese fire belly newt (Cynops pyrrhogaster)
For nearly 250 years, generations of scientists believed that the older an animal gets, the less able it is to regenerate and replace damaged or diseased tissue. (Even Charles Darwin weighed in.) Everyone assumed that, as animals age, cellular resources become exhausted, DNA repair mechanisms break down, healing takes longer and tumors develop. As of today, however, that’s no longer the doctrine. It still might be harder and harder for humans to repair wounds and heal as we age, but it turns out that the humble newt is another story.
When injured, newts can regenerate limbs, tails or eyes right back to factory standards. Humans can only do that at the very tip of the finger and only under very limited circumstances. And according to a new study published today in the journal Nature Communications, old newts can do it just as well as young newts. The study focused on the newt’s optical lens, which can be removed entirely and, after the incision heals, completely regenerate in a single day. The study’s lead author, Dr. Goro Eguchi, began breeding newts and collecting lenses 16 years ago. Throughout the years since, lenses were removed 18 times from the same animals. By the time of the last tissue collection, they were at least 30 years old (very old, for a newt).
This video of three year-old Corinna is remarkable because it would seem so unremarkable if you didn’t know Corinna’s story—she looks just like any other kid. I had the pleasure of meeting this very special attendee at Sanford-Burnham’s 2nd Annual Rare Disease Day Symposium last February. Corinna was born with hypophosphatasia (HPP), a rare inherited disease that affects bone development, leaving her fragile and unable to walk. Lauren, Corinna’s mother, had brought her along to the symposium and was excited to meet the scientists studying HPP and hear about the latest research.
The family traveled from Philadelphia to be there that day – no small task, considering Corinna’s special needs and lack of mobility. I first talked to Lauren on the phone, helping her with directions from her hotel to the Sanford-Burnham campus. Then I waited for them outside and helped her get the stroller out of the taxi. I set it up while Lauren got Corinna out of the car. Corinna was blond, adorable, friendly—and just about the same size as my own daughter. My heart went out to them. I know how trying it can be to travel with a toddler, even under the best of circumstances.
Sanford-Burnham scientists are leading several exciting symposia over the next few months. Please follow the links below for more event and registration information.
2011 Signaling, Metabolism and Hypoxia Symposium
Chaired by Dr. Ze’ev Ronai
May 6, 2011, 2:00 – 5:30 p.m. (PDT)
Sanford-Burnham Medical Research Institute
10901 North Torrey Pines Road
La Jolla, California
2011 Glycobiology Gordon Research Conference
Chaired by Dr. Hudson Freeze
May 8 – 13, 2011
Il Ciocco Hotel
Lucca (Barga), Italy
Sanford-Burnham’s 33rd Annual Symposium: Structural Systems Biology
Chaired by members of the Bioinformatics and Systems Biology Program
Drs. Adam Godzik, Dorit Hanein, Andrei Osterman, Niels Volkmann
June 7, 2011, 9:00 a.m. – 5:15 p.m. (PDT)
Hilton La Jolla Torrey Pines
La Jolla, California
Cardiomyocyte Regeneration and Protection
Chaired by Dr. Mark Mercola
Sponsored by Abcam
June 20 – 21, 2011
Hilton La Jolla Torrey Pines
La Jolla, California
2011 Molecular Therapeutics of Cancer Research Conference
Chaired by Dr. Sara Courtneidge
Sponsored by the Cancer Molecular Therapeutics Research Association
July 10 – 14, 2011
Asilomar Conference Center
Pacific Grove, California
Seventh General Meeting of the International Proteolysis Society
Chaired by Dr. Guy Salvesen and Dr. Matthew Bogyo
October 16 – 20, 2011
Hilton San Diego Resort and Spa
San Diego, California
Left: electron microscopy view of actin. Right: Dr. Dorit Hanein's 3-D view.
Life is complicated. Even one tiny cell has a lot going on at any given time, even when things are running smoothly. Normal cellular functions and their emergency responses (like to injury or infection) are mostly carried out by proteins. Proteins tell other proteins what to do by carrying signals, tagging one another with chemical groups, chewing up other proteins or helping assemble new ones, and so on. They also help orchestrate which genes are turned on or off and when.
The cell itself is constantly sensing and reacting to constant environmental fluctuations, as are the individual proteins and other molecules. So how do you connect these two things?
“You can see a cell by eye, using a standard microscope. But you can’t see individual molecules that way,” explains Sanford-Burnham’s Dr. Dorit Hanein. “A cell is on the micrometer scale (one-thousandth of a millimeter), while an individual molecule is on the nanometer scale (one-millionth of a millimeter). That’s like the difference between walking the 500 miles from here [San Diego] to San Francisco, versus walking from here to the moon.”
What Dr. Hanein and other scientists need are techniques that allow them to look not just at the moon, but at the earth, the moon and everything in between.
A video by high school student Daniel Osterman, son of Sanford-Burnham investigator Dr. Andrei Osterman, takes a quick look at the basic biomedical research being conducted at the Institute. In particular, the piece focuses on Dr. Hudson Freeze’s research. Dr. Freeze recently organized Sanford-Burnham’s 2nd Annual Rare Disease Symposium, and studies a group of rare conditions called Congenital Disorders of Glycosolation (CDG), in which sugars fail to attach properly to proteins.
Kate Fischer with daughter Morgan, who is being treated for HPP.
There was a moment at our recent Rare Disease Symposium when Dr. Michael Whyte, a pediatrician from Shriner’s Hospitals in St. Louis, presented video of a patient who is participating in a clinical trial. The patient, Amy, suffers from hypophosphatasia (HPP), a genetic bone disease similar to rickets. The trial is for an enzyme replacement therapy developed collaboratively by Dr. Whyte, Dr. José Luis Millán and Enobia Pharma to treat HPP. Before treatment, Amy’s bones were so soft she had to be flown to the trial in an insulated box. She was weeks away from dying. In the video, she runs, jumps and kicks a ball. Hard not to be moved.
Enobia’s HPP drug is in Phase II clinical trials and looks quite promising. However, rare diseases present a difficult problem. While relatively few people suffer from any single rare disease, there are thousands of these conditions. Large pharmaceutical and biotech companies have a difficult time addressing them because they have not figured out how to make back their investments. But the issues go even deeper. How do you conduct a robust clinical trial on a new treatment when only a handful of people need to be treated? And how do you balance the regulatory environment to ensure that new, safe treatments can reach patients? In fact, how do you even diagnose a rare disease when so few physicians have any experience with it?
You might have thought Conrad Prebys had been given 50 yard-line seats to the Super Bowl—that’s how thrilled he was to visit Sanford-Burnham. Two years ago, Prebys made a $10 million gift to support chemical genomics at the Institute. He stopped by on February 10 to learn how the research at the Conrad Prebys Center for Chemical Genomics is progressing and to tour one of our labs.
First the tour. Dr. Hudson Freeze studies congenital disorders of glycosolation (CDG), a family of rare diseases in which defective enzymes fail to add necessary sugar chains to proteins, creating multiple medical issues. CDG is fatal in 20 percent of affected children. While visiting the Freeze lab, Prebys met several researchers and spoke via Skype with a CDG patient, a young woman in the Netherlands who has spent a significant portion of her life in hospitals. Researchers in the Freeze lab are looking for creative ways to fix the enzyme deficiencies that cause these conditions.
On February 25, 2011, Sanford-Burnham will hold its Second Annual Rare Disease Symposium at the Institute’s La Jolla, California campus. Chaired by Drs. Hudson Freeze and Yu Yamaguchi and sponsored by Enobia Pharma, the symposium will feature researchers and patient advocates from around the world. The symposium coincides with national Rare Disease Day on February 28.
In the U.S., diseases are classified as “rare” when they affect fewer than 200,000 people. But since there are around 7,000 such disorders, a total of 30 million Americans are affected. Because of the rarity of these diseases, patients and their families often struggle to find information, and many have started advocacy groups to raise awareness and reach out to other families who need help. These families can be a great help to researchers, having gained personal Ph.D.s in the intricacies of an uncommon disease. Several of these parent advocates will attend the event.
Margaret Mortimore has been a physical therapist for 26 years, many of those spent working with children. Each child she helps holds a special place in her heart, but John Taylor Williams IV, lovingly known as Rocket, made a particularly strong impression.
Rocket suffered from a congenital disorder of glycosylation (CDG), which impaired his muscle development and motor skills. “CDG affects nearly all of the body’s functions,” says Dr. Hudson Freeze, a pioneer in CDG research. “It prevents cells from attaching sugars to proteins, a biochemical process that has serious consequences when it does not function properly.”
When Margaret was asked to provide physical therapy for Rocket, she almost refused because her caseload was too large. She did agree to provide a consultation. “As soon as I walked in the door, I knew there was no way I wasn’t going to treat this little guy,” she says.
Sanford-Burnham researchers don’t often get the opportunity to meet patients who benefit from their research. But last month, a four-and-a-half year old girl named Alma came to La Jolla to visit Dr. Hudson Freeze’s laboratory. Alma and her family live in Iran, but were in the United States for six months while she received treatments at the Mayo Clinic. Alma has an inherited genetic disorder that causes her to suffer from developmental problems and a severe skin ailment. For most of her life, the cause of Alma’s health issues was unknown. But that has now changed, thanks to a new study led by Dr. Joseph Gleeson at the University of California, San Diego (UCSD). In the study, which appeared July 15 in the journal Cell, Dr. Gleeson, Dr. Freeze and their colleagues helped identify the gene mutation responsible for Alma’s condition. In doing so, they also uncovered a new inherited disease that will be classified within a family of similar conditions known as Congenital Disorders of Glycosylation (CDG).