On March 27, Sanford-Burnham’s chief business officer, Dr. Paul Laikind, appeared on BioCentury This Week, along with venture capitalist Brian Atwood, to examine how a major downturn in research and development spending is affecting drug development. Specifically, they discussed how pharmaceutical companies and venture capitalists are investing less in early stage development, potentially starving the pipeline for new drugs. Dr. Laikind noted that Sanford-Burnham is working to help fill this research gap:
“We are doing cutting-edge science, that’s always what we’ve been focused on,” said Dr. Laikind. “What we’ve done in the last five to ten years has invested significantly in the translational part of the equation. Not to become a pharmaceutical company…but to be able to push it [the science] further down the pipeline so that we can do collaborations…work with venture capitalists and work with big pharma to take projects farther forward.”
Watch R & D Goes Flatline: Part II to learn more about this burgeoning crisis and potential solutions.
Stem cells of many varieties hold a lot of promise for regenerative medicine. Their ability to continually self-replicate (produce more stem cells) and differentiate (specialize) into any number of cell types make them an enticing replacement for diseased or damaged tissue or as delivery vehicles for therapeutic molecules.The problem is that we still don’t know enough about many of the existing stem cell types to predict exactly how they will behave when transplanted into a patient. Each of the different types of stem cells has its unique repertoire of behaviors and its own benefits and drawbacks. In an editorial appearing online March 25 in the journal Experimental Neurology, Dr. Evan Y. Snyder hammers home the possible dangers of one very popular and oft-used type of stem cell. He highlights a paper appearing in the same issue of that journal, in which researchers from the Aristotle University of Thessaloniki in Greece and the Medical University of Vienna show that brain tumors develop when a mouse model of multiple sclerosis (MS) is transplanted with mesenchymal stem cells (MSCs) derived from bone marrow.
Dr. Kristiina Vuori, Sanford-Burnham’s president and director of our NCI-designated Cancer Center, was recently elected to the Board of Directors of the American Association for Cancer Research (AACR), the world’s oldest and largest professional organization focused on advancing cancer research. AACR promotes all aspects of cancer research, including basic, translational and clinical research into the origin, prevention, diagnosis and treatment of cancer. Founded in 1907, the organization has more than 27,000 members in 80 countries, and accelerates progress toward cancer prevention and treatment through research, education, communication and collaboration.
“This is a time of exciting progress in cancer research and the opportunity to translate that progress to patient benefit,” says Dr. Vuori. “ I am honored to have been elected to the AACR Board and excited for the opportunity to work with the AACR and the whole cancer community to further build on this extraordinary momentum.”
Whether online or in print, a scientific paper typically winds up sandwiched between two equally important – but completely unrelated – articles. But a scientific journal called Acta Crystallographica Section F recently did something completely different. They ran an issue entirely devoted to research from a single group – the Joint Center for Structural Genomics (JCSG), one of the NIH’s Protein Structure Initiative centers. JCSG is led by Dr. Ian Wilson at The Scripps Research Institute, with Dr. John Wooley at UC San Diego and Sanford-Burnham’s Dr. Adam Godzik leading the bioinformatics and data management part of the project.It’s unusual for a journal to dedicate an entire issue (35 papers total) to one research group, but that’s not the only thing that made this unique.
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.
The neural crest is a versatile population of stem cells found in a developing embryo. In humans, neural crest arises during the third to fourth weeks of pregnancy, and then the cells specialize into a diverse set of cells, including certain types of nerves, skin, bone and muscle. Scientists have long appreciated this crucial event in development – when it goes wrong, a number of skeletal and nervous system disorders can result. But they haven’t really been able to study it properly in the laboratory. That’s because of the transient nature of the neural crest – it typically only exists for about two weeks in humans (with few exceptions). After that, the cells have migrated away and differentiated into other tissue types. Dr. Alexey Terskikh (along with Dr. Marianne Bronner-Fraser at the California Institute of Technology, Sanford-Burnham’s Dr. Evan Y. Snyder, postdoctoral researchers Dr. Carol Curchoe and Dr. Jochen Maurer and others) recently discovered a way to overcome this problem. In a study published recently in the journal PLoS ONE, they developed a new protocol for generating early migratory neural crest cells from human stem cells.
“This new system allows us to dissect what happens during human development – something that is not accessible in any other way,” says Dr. Terskikh, associate professor in Sanford-Burnham’s Development and Aging Program.
Cells come and go throughout our lifetime. Some live a long time (like brain cells), while others constantly grow, divide and die. Cell death is a process that must be carefully managed – too many cells dying in the brain leads to neurodegenerative diseases like Alzheimer’s, while not enough cell death allows tumors to form. But not all cell death is the same. Apoptosis, often called “programmed cell death”, is neat and clean – seppuku-style cell suicide. Necrosis, on the other hand, is the messy, unplanned version of cell death – the kind that might cause pain and swelling.
Apoptosis begins by activating enzymes known as caspases, setting the cell on the path towards death – a good thing if they are cancer cells or cells infected with a virus. One caspase, known as caspase-8, is a double agent of apoptosis – depending on the conditions, it can promote either cell death or cell survival. What makes caspases-8 choose a side? A new study led by Dr. Douglas Green at St. Jude Children’s Research Hospital and Sanford-Burnham’s Dr. Guy Salvesen points the finger at a protein called FLIPL. Their study was published online March 2 in the journal Nature.
“We’ve known for some time that caspase-8 can play this dual role, but we didn’t know the molecular basis for the opposing functions. Knowing the mechanism may allow us to design therapies to defeat a cancer cell’s quest for immortality,” says Dr. Salvesen, director of the Apoptosis and Cell Death Research Program and dean of the Graduate School of Biomedical Sciences at Sanford-Burnham.
One of the problems with nanoparticles is that, well, they’re just so small, making them difficult to study. Researchers may have solved that problem by building an instrument that can detect nanoparticles as small as tens of nanometers (billionths of a meter). The research team was led by Dr. Andrew Cleland, professor of physics at the University of California, Santa Barbara, and included Sanford-Burnham’s Dr. Erkki Ruoslahti. The study was published on March 7 in the journal Nature Nanotechnology.
On April 21, Sanford-Burnham will partner with the HeadNorth Foundation for the third time to present Bring It!, a game show-style event that challenges teams to compete in a wide range of challenges. This year’s theme, “Rock on for Stem Cell Research” promises a full evening of networking and fun for a great cause, held at the Del Mar Fairgrounds Activity Center. HeadNorth is a San Diego-based nonprofit dedicated to providing help and hope for spinal cord injury survivors. It was founded in 2006 by Eric Northbrook after a motorcycle accident severed his spinal cord.
Stem cells have the unique ability to self-renew (make more stem cells) and differentiate (specialize into a number of different cell types). There are three main types of stem cells already on the scene: embryonic stem cells, adult stem cells and induced pluripotent stem (iPS) cells. iPS cells are engineered by reprogramming fully differentiated adult cells, often skin cells, back to a primitive state. Like their embryonic cousins, iPS cells can form all cell types. Researchers are currently working to harness the flexibility of stem cells to replace damaged tissue and treat conditions like diabetes and heart disease.
The iPS cell approach to regenerative medicine is tantalizing because these cells could be derived from a patient’s own cells and are therefore less likely to face immune rejection. In the past few weeks, however, a slew of papers have indicated that the therapeutic potential of iPS cells might be limited by reprogramming errors and genomic instability. Given these problems, researchers from Sanford-Burnham, Chung-Ang University in Korea, University of British Columbia, Harvard Medical School and elsewhere wondered if there might be a better way to regenerate lost tissue to treat conditions like heart disease and stroke. Writing March 4 in the Proceedings of the National Academy of Sciences, they outline a method to obtain a new kind of stem cell they call induced conditional self-renewing progenitor (ICSP) cells.
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?
In the process known as meiosis, a single cell divides into two cells. But instead of receiving two copies of each chromosome (that’s mitosis), each daughter cell receives only one copy, giving it half the number of chromosomes found in a normal adult cell. Those cells go on to become sperm or eggs – which together might produce an offspring that inherits half its chromosomes from each parent. Even though they aren’t needed until sexual maturity, females begin meiosis to make eggs in utero, while males don’t begin meiosis and sperm-making until after birth. The reason for this gender discrepancy? Nobody really knows.
“I’m a developmental biologist, not a reproductive expert,” says Dr. Gregg Duester, professor in Sanford-Burnham’s Development and Aging Program, “but it seems to me that by better understanding meiosis and sperm and egg production, we might better understand infertility – a problem that is estimated to affect about nine percent of couples.”
In 2006, an Australian group published a landmark paper in the journal Science, in which they identified an enzyme that is found in developing testes, but not ovaries. Without this enzyme, called Cyp26b1, mice prematurely initiate meiosis in the testes. Based on these results, the group concluded that Cyp26b1 must be what determines the timing of meiosis in females vs. males. They also went on to claim that it must be because Cyp26b1 degrades retinoic acid, a derivative of vitamin A. In the five years since, something like 25 papers have built on this paradigm – retinoic acid in the ovaries triggers meiosis, while Cyp26b1 in the testes keeps retinoic acid at bay and prevents meiosis from occurring at that time.
Just one problem – the paradigm is wrong.
Have you or a family member donated bone marrow or received a transplant? We’d love to hear what this type of research means to you. Please drop us a line in the comments below.
When patients receive a bone marrow transplant, they are getting a new population of hematopoietic stem cells. Fresh stem cells are needed when a patient is low on red blood cells, as in anemia, or white blood cells, which can be caused by cancer or even cancer treatments such as irradiation or chemotherapy. The problem is that a bone marrow transplant might not succeed because the transplanted stem cells don’t live long enough or because they proliferate too well, leading to leukemia.
To help determine how long a bone marrow (stem cell) graft will last, researchers have developed a mathematical model that predicts how long a stem cell will live and tested those predictions in a mouse model. The study, led by Dr. Christa Muller-Sieburg, was published online February 28 in the journal Proceedings of the National Academy of Sciences.
“It has long been assumed that stem cells are immortal – they continue to self-renew, thus generating more stem cells that collectively can outlast an individual’s life,” says Dr. Muller-Sieburg, professor in Sanford-Burnham’s Stem Cells and Regenerative Biology Program. “But now we have found that each stem cell is pre-programmed to self-renew only for a set amount of time that, in mice, ranges from a few months to several years. So we created a computer program that predicts that lifespan.”