Nine Stanford faculty receive NIH funding for innovative research
Outside-of-the-box thinking from nine Stanford University researchers has earned them funding from the National Institutes of Health from a program designed to encourage high-risk, high-reward approaches to science.
The nine Stanford researchers are among 81 recipients of the 2012 NIH Director's Pioneer Awards, New Innovator Awards and Transformative Research Awards. This year's total funding, from the NIH Common Fund and multiple NIH institutes and centers, is approximately $155 million.
NIH director Francis Collins, MD, PhD, noted that the funding "provides opportunities for innovative investigators in any area of health research to take risks when the potential impact in biomedical and behavioral science is high."
Stanford has two of the 10 recipients of this year's NIH Director's Pioneer Awards. Each award carries a five-year, $2.5 million grant to be used in highly innovative approaches that have the potential to affect a broad area of biomedical or behavioral research.
Christina Smolke, PhD, associate professor of bioengineering, will use her Pioneer Award funding to explore the use of synthetic biology platforms and biosynthesis strategies — the use of microbes to produce complex chemicals — to dramatically advance natural-product drugs. Natural products and compounds inspired by them make up the bulk of successful drugs, but challenges to their discovery, synthesis and manufacture limit the number of candidates that can be seriously explored and tested as drugs.
Smolke's approaches could transform the manufacturing scale and efficiency of these microbial systems and make possible the synthesis of an important class of molecules exhibiting diverse pharmacological activities.
"We're working on the tools that will lead to new capabilities for probing natural biosynthetic pathways and shed light on nature's biosynthesis processes. Ultimately, this will lead us to the discovery and scalable synthesis of new and desperately-needed therapeutic molecules," said Smolke.
Anne Brunet, PhD, associate professor of genetics, will use her funding to study how longevity can be inherited across generations.
"It is very clear that our life span is influenced by our genes and our environment; for example, our diet, or if we are exposed to toxins," said Brunet. "We are excited to understand whether longevity can also be influenced by a third component: the environment to which our parents or grandparents were exposed."
Brunet will explore data from her lab suggesting that changes to chromatin — which helps package the DNA in the nucleus — could influence not only the life span of an individual organism, but also that of its descendants.
"We feel this research has potential to revolutionize our understanding of complex diseases, in particular age-dependent disorders such as cardiovascular diseases, type-2 diabetes, cancer and Alzheimer's disease," said Brunet, who is also a member of the Stanford Cancer Institute.
New Innovator Awards
Three Stanford faculty members will receive New Innovator Awards, designed to fund innovative research by investigators who are within 10 years of completing their education or clinical residency, but who have not yet received an R01 grant, which is the most common mode of NIH funding, or another equivalent type of NIH support. Each award provides $1.5 million over five years.
Alexander Urban, PhD, assistant professor of psychiatry and behavioral sciences, will use his funding to study the effects of large copy number variants, or CNVs, on neuropsychiatric disease. CNVs arise when stretches of DNA sequence are either deleted or duplicated in an individual's genome. Most CNVs range from a few hundred to several tens of thousands of base pairs — chemical units of DNA — in length. Certain large CNVs (up to a few million base pairs long) can strongly predispose people to neuropsychiatric diseases such as schizophrenia and autism.
Urban will focus on the molecular mechanisms through which such large CNVs exert their debilitating effects, using various next-generation sequencing approaches to study both genetic and epigenetic phenomena that may be interacting with these large CNVs. This type of exploration is often hampered by lack of access to relevant human tissues (most notably the brain) that carry a given disease-associated CNV. He will surmount this barrier by using lines of induced pluripotent stem cells from patients with neuropsychiatric-disease-associated CNVs.
Rajat Rohatgi, MD, PhD, assistant professor of oncology, will use his New Innovator funding to continue his studies of an antennae-like cellular protrusion called the primary cilium that detects and processes optical, chemical and mechanical signals in a cell's environment.
"Primary cilia are sophisticated machines used by most cells for communication with other cells and the environment," said Rohatgi. "They play particularly important roles in the development of many of our organs, and damaged cilia can lead to birth defects affecting the brain, heart and skeleton."
Rohatgi, who is also a member of the Stanford Cancer Institute, will investigate how this ciliary machine is built from its component parts, how it functions to process signals and how it malfunctions in human disease.
Bianxiao Cui, PhD, assistant professor of chemistry, will use her award to study the role defective neurons play in the progress of neurodegenerative diseases. Her work focuses on the neuron's axon, the thin — but in some instances, very long — arm that extends from the neuron. Packages of proteins and other materials are transported along axons, and defects to this process can cause a "traffic jam"; scientists suspect that this accumulation of molecules could contribute to various neurodegenerative diseases, such as Alzheimer's.
Cui's group is proposing a daring approach that uses physical force to regulate package transport in live cells. In particular, they plan to engineer optical and magnetic forces that can stall cargoes to create traffic jams in axons. She hopes that this new approach will allow her to investigate whether blocking axonal transport is sufficient to induce neuronal degeneration, and also how neurons respond to axonal traffic blockage.
Jan Carette, PhD, assistant professor of microbiology and immunology, will use his award funding to study the genetic underpinnings of dengue virus infection, with the goal of gaining fundamental insights into the life cycle of this rapidly emerging virus.
Dengue virus, transmitted via mosquito bites, causes about 250,000 cases of severely debilitating hemorrhagic fever annually in at least 100 tropical and subtropical countries. There is no approved vaccine or antiviral treatment available for what has become a global-health scourge. Carette's lab will use novel genetic approaches to discover human genes critical for virus infection. (Recent work by Carette and his associates has thrown light on how another virus, Ebola, gains entry into human cells.) If his team can identify critical host factors that dengue virus uses to establish a successful infection, the findings could lead to the development of viable new antiviral therapies.
Transformative Research Awards
These awards, open to both individuals and teams of investigators, were created to support research projects that have the potential to create or overturn fundamental paradigms. The amount of these five-year awards varies.
Karl Deisseroth, MD, PhD, professor of bioengineering and of psychiatry and behavioral sciences, studies the brain as a complex biological system, exploring the extreme challenges of gathering high-resolution local information in specific parts of the brain, while maintaining a global perspective across the entire brain system.
The $22.48 million award he received will allow his interdisciplinary team to continue working on an approach, known as CLARITY, that may someday elucidate brain circuitry abnormalities involved in complex psychiatric diseases such as depression, PTSD, drug abuse, autism and schizophrenia.
"Specifically, we've united the tools of chemical engineering, molecular genetics and optics to gather detailed and specific information from within an intact brain," said Deisseroth, "However, these tools are not limited to the brain alone. They can be applied to study any intact biological system."
Research on CLARITY was launched through Stanford's CNC Program, an interdisciplinary effort that includes key investigators Liqun Luo, Krishna Shenoy, Marc Levoy and Philippe Mourrain.
Helen Blau, PhD, the Donald E. and Delia B. Baxter Professor and a member of Stanford's Institute for Stem Cell Biology and Regenerative Medicine, will use her $4.3 million award to explore whether it is possible to transiently induce the lengthening of telomeres, which are DNA caps that protect the ends of chromosomes. Abnormal telomere shortening has been implicated in many human diseases.
"We are really excited about this approach because it could aid in maintaining stem cells in a proliferative, non-senescent state for longer periods, enhancing their utility as disease models and for drug screening," said Blau. "In addition, the technology could prove useful in treating diseases characterized by prematurely shortened telomeres, like Duchenne muscular dystrophy. The most exciting aspect is that the potential applications are so broad; the impact on regenerative medicine could be immense."
Ben Barres, MD, PhD, chair and professor of neurobiology, will use his $2 million award to test the idea that humans' superior cognitive ability arises because human astrocytes have evolved to have better synapse-controlling abilities than those of other animals.
Astrocytes outnumber neurons 5-to-1 in the human brain. Barres' lab has previously shown that chemical signals secreted by these cells are critical in the formation and function of synapses, the electrochemical contact junctions via which individual neurons communicate with one another.
His team will purify mouse and human astrocytes to a high degree and compare their ability to induce synapse formation and activity. If human astrocytes are more effective in forming synapses, they will then identify the relevant secreted chemical signal, bioengineer mice whose astrocytes can produce and secrete it, and see whether these mice have improved cognitive abilities.
Writers Krista Conger, Bruce Goldman, Andrew Myers and Bjorn Carey contributed to this report.
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