Meet the 2009 Early Career Scientists.

Peter W. ReddienPeter W. Reddien
Whitehead Institute for Biomedical Research/Massachusetts Institute of Technology

Credit: ©2009 Kelly Lorenz/Whitehead Institute

Planarians are a kind of flatworm capable of regenerating almost any part of their body—from head to tail—and doing it quickly. A planarian that loses its head can regrow a new one in a week, and an entire flatworm can regenerate itself from a fragment that is only 1/300th the size of the original. Peter Reddien, of the Whitehead Institute for Biomedical Research at the Massachusetts Institute of Technology, wants to know what is in the planarian's tool kit that explains its remarkable regenerative feats. With a full arsenal of modern methods, including RNAi screening and genomic bioinformatics, Reddien's work is remaking the freshwater planarian, Schmidtea mediterranea, into a state-of-the-art model organism—one that, like the fruit fly or the mouse, will prove important for understanding fundamental aspects of biology. Reddien has analyzed 1,065 planarian genes so far and found similar human genes for well more than half of those required for normal regeneration. He is particularly interested in genes that kick regeneration into action and genes that control “regenerative polarity,” that is, genes that prompt an organism to grow one head or one tail instead of a second of either.

Aviv RegevAviv Regev
Massachusetts Institute of Technology

Credit: ©2009 Maria Nemchuk

While still a graduate student in Israel, Aviv Regev established and directed a bioinformatics team at Quark Biotech, a functional genomics company. Regev, who is now in the Department of Biology at the Massachusetts Institute of Technology and at the Broad Institute of MIT and Harvard, is combining computational and experimental approaches to investigate how complex gene regulation networks rewire themselves in response to genetic and environmental changes. Her studies in yeast will address how these remarkably flexible networks transform over different timescales—from rapid adaptations in response to changing nutrient availability to evolutionary changes in metabolism that have occurred over 300 million years. Her interest in evolutionary changes extends to gene regulation in human cancer cells and the physiological relationship between the malaria parasite and its human host. She has already identified new stages in the life cycle of the malaria parasite in its human host—insights that may lead to novel antimalarial drugs.

Christopher M. SassettiChristopher M. Sassetti
University of Massachusetts Medical School

Credit: ©2009 Robert Carlin

When tuberculosis bacteria enter a host, they hide inside immune cells in the lung and often cause no symptoms. This latent state of infection can persist for years before disease emerges, but until recently, no one knew how the bacteria acquired the nutrients to keep themselves alive inside immune cells. Christopher Sassetti, a microbiologist at the University of Massachusetts Medical School, solved that mystery when he invented a method to zero in on the genes that are essential for the survival of tuberculosis bacteria. The technique helped Sassetti identify a cluster of proteins used by the bacteria to feed itself by siphoning cholesterol from its host organism. Sassetti now wants to find out whether the pathogen or the host truly controls latency. Since latent bacteria are largely resistant to antibiotics, understanding how to coax them into an active state could lead to more effective treatments.

Kristin ScottKristin Scott
University of California, Berkeley

Credit: ©2009 Paul Fetters

Kristin Scott's father, a philosophy professor, sparked her early interest in learning about how the brain perceives the world, a mystery she now explores in her lab at the University of California, Berkeley. By mapping the neural circuits used by fruit flies to perceive taste, she uses the fly's relatively simple neural circuitry to reveal how animals with more complex nervous systems recognize and respond to cues in their environment. In 2004, Scott and her colleagues identified sensory neurons for different tastes and behaviors. She is using those cells as starting points to understand how the brain distinguishes different tastes and how perceptions of taste can be modified by experience.

Reuben J. ShawReuben J. Shaw
Salk Institute for Biological Studies

Credit: ©2009 Salk Institute for Biological Studies

People with type 2 diabetes have an elevated risk of cancer and Reuben Shaw, at the Salk Institute for Biological Studies, thinks he knows why. He's found a key hunger circuit inside cells that links the two conditions. This circuit tells cells to slow down and stop dividing when food—glucose—is scarce. High levels of glucose, such as those associated with diabetes, throw that circuit out of whack. This appears to trigger the malfunction of key genes in a signaling pathway that suppresses cancer. Shaw plans mouse studies to further explore this critical connection and tease out the precise role of each component of the signaling pathway. He'll also test whether drugs that treat diabetes might also help prevent cancer.

Anita SilAnita Sil
University of California, San Francisco

Credit: ©2009 Susan Merrell

Although upwards of 10 million people in the United States may be infected by Histoplasma—a sometimes harmless fungus, but one that can also cause vision loss and lung disease—few researchers study it. Anita Sil knew that basing her research program on that organism, which must be sequestered in biocontainment facilities, would be challenging. But she has already made the pathogen much more amenable to study in the lab. A scientist at the University of California, San Francisco, Sil has rapidly expanded the understanding of Histoplasma, leading the effort to sequence its genome and identifying key genes that trigger its conversion to harmful yeast in the human body. Over the next few years, she aims to learn exactly how Histoplasma infects and multiplies inside macrophages, the scouts of the immune system. Her work could lead to better treatments for serious human diseases caused by an underappreciated pathogen.

Maria SpiesMaria Spies
University of Illinois at Urbana-Champaign

Credit: ©2009 L. Brian Stauffer

Maria Spies gets right down to the single-molecule level to find out what happens when DNA helicases—molecular motors that drive DNA repair mechanisms—find problem locations in the genome where their activity is needed. Her most gripping single-molecule story so far involves the bacterial helicase that runs on a sort of DNA drag strip, a long stretch of nucleic acids into which Spies inserts recombination “hot spots.” Using lasers and fluorescent markers, Spies recorded the enzyme barreling down the DNA track, pausing at a recombination hot spot, and then changing speeds. Studies carried out by Spies's lab at the University of Illinois at Urbana-Champaign hint at how the numerous human versions of these enzymes work. The research is promising because helicases are thought to be involved in breast and ovarian cancer, premature aging, stunted growth, and ultra-sensitivity to sunlight.

Brent R. StockwellBrent R. Stockwell
Columbia University

Credit: ©2009 Eileen Barroso

Columbia University chemical biologist Brent Stockwell has invented several drug discovery technologies. As a graduate student, he founded a company, CombinatoRx, that develops combinations of FDA-approved drugs to fight disease. Today, he uses small molecules to reveal vulnerabilities in tumor cells, to stop the damage caused by protein misfolding in neurodegenerative disorders, and to illuminate basic mechanisms of cell death. To identify drug candidates that kill cells in a genetically selective manner, Stockwell uses cells engineered with a cancer-causing mutation and identical cells lacking the mutation. Both cell lines are treated with chemicals to find selectively lethal drug candidates. One such compound, dubbed erastin, selectively kills tumor cells with the cancer-promoting gene Ras and is being developed for clinical testing.

Hui SunHui Sun
University of California, Los Angeles

Credit: ©2009 Hui Sun

When Hui Sun set up his lab at the University of California, Los Angeles, he set his sights on a problem that had puzzled scientists for more than 30 years: How does vitamin A, a molecule essential for the eye, brain, immune system, reproductive systems, and developing embryo, get efficiently transported to highly specific tissue destinations by its carrier protein? His lab overcame numerous obstacles to discover the elusive molecular machinery that performs both the guiding and unloading functions. Using new techniques developed during this arduous process, he aims to reach some “high-hanging fruits” in biology—medically important signaling receptors that have not yet been identified by existing techniques. These receptors are ideal therapeutic targets for treating several major human diseases that are still largely incurable.

Toshiyasu TaniguchiToshiyasu Taniguchi
Fred Hutchinson Cancer Research Center

Credit: ©2009 Dean Forbes

As a physician in Tokyo, Toshiyasu Taniguchi treated many lymphoma patients with DNA-damaging chemotherapy, only to watch the drugs lose their power as the tumors developed resistance. He became a scientist to find ways to save more patients. Now at the Fred Hutchinson Cancer Research Center, Taniguchi is studying the role of DNA repair in promoting drug resistance in cancer cells. He identified a repair pathway that is often inactivated in patients with breast and ovarian cancers, as well as the childhood predisposition to cancer known as Fanconi anemia. Reactivation of the pathway, he discovered, can help tumors become resistant to chemotherapy drugs. Taniguchi intends to dig deeper into this mechanism of drug resistance and use the information he uncovers to develop drugs that will resensitize tumors to cancer therapies.

Joseph W. ThorntonJoseph W. Thornton
University of Oregon

Credit: ©2009 Paul Fetters

University of Oregon researcher Joseph Thornton has resurrected proteins more than 400 million years old to understand how today's hormones and their receptors evolved. He uses advanced biochemical and computational techniques to identify the genetic mutations by which ancient hormone receptor proteins took on modern-day functions. Thornton has also used x-ray crystallography to determine the atomic architecture of primordial receptors, revealing how their structures changed as they evolved the ability to bind new hormones. Thornton's interest in hormones blossomed during his 10 years as an environmental activist with Greenpeace, time he spent educating the public about the dangers of endocrine-disrupting chemicals—pollutants and substances in everyday products that interfere with the body's hormones. In discovering how hormones and their receptors evolved, Thornton has revealed why the molecules that drive our endocrine system are built as they are, and he has provided new ways of understanding how variation in their sequences and structures affects their functions.

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Jim Keeley 301-215-8858