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| | Iannis Aifantis
New York University Medical Center
Credit: ©2009 Thomas Semkow
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| Iannis Aifantis, a cancer biologist at the NYU Langone Medical Center, has made major strides toward understanding and developing new treatments for T-cell acute lymphocytic leukemia, a common form of leukemia in children. He recently discovered a molecular door by which T cells, the soldiers of the immune system, slip into spinal fluid and the brain after they become malignant. Blocking this process could save thousands of lives each year. Aifantis is now testing hundreds of potential drugs that might slam that door shut and prevent malignant T cells from reaching the nervous system. At the same time, he is learning what goes awry in blood stem cells that transform into leukemic T cells. Such insights may provide even more ways to combat deadly blood cancers. |
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| | Luís A. Amaral
Northwestern University
Credit: ©2009 Andrew Campbell
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| Northwestern University's Luís Amaral wants to build the Google Maps of cellular organization. Although the available data about cellular components—tens of thousands of genes, tens of thousands of proteins, and the countless interactions between them—are staggering, Amaral says navigating that cellular information should really be no more complex than getting around the United States. What's missing is the cellular equivalent of the electronic and paper maps that make it easy to choose the best route from among hundreds of thousands of air, train, and bus routes, and millions of miles of roadway linking the roughly 20,000 U.S. communities. Amaral is using computational methods to create an equivalent cartographic approach for molecular biology. He hopes that such interactive maps will speed development of smarter therapies for a range of diseases. |
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| | Peter Baumann
Stowers Institute for Medical Research
Credit: ©2009 Don Ipock
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| Weekends often find Peter Baumann working with a colony of lizards that reside in sand-filled pens, in a reptile facility managed by his wife, Diana. He wants to understand how these lizards thrive and reproduce in the absence of males, a phenomenon found in a few dozen vertebrate species. It's a side project for Baumann, whose week-day research at the Stowers Institute focuses on learning how chromosome ends are protected from being mistaken as DNA breaks. The telomere, a repeating chain of DNA sequence found at each chromosome end, plays a critical role in that protection. However, telomeres get smaller each time a cell divides, a process that may act as a biological clock by signaling the cell to stop dividing after a certain point. Baumann is expanding his research to investigate how the enzyme that builds telomeres, telomerase, is created and controlled. His research could help identify compounds that limit the life span of tumor cells. |
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| | James E. Bear
University of North Carolina at Chapel Hill
Credit: ©2009 Paul Fetters
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| Whenever a cell needs to move, the network of tiny filaments that forms its structure and provides stability is constantly being broken down and remade. The remodeling of the cell's cytoskeleton must happen in a matter of seconds to enable organisms to grow or wounds to heal. Biologist James Bear, at the University of North Carolina at Chapel Hill, studies how proteins called coronins alter the remodeling of the normally rigid and highly ordered cytoskeleton so that a more flexible framework can take its place. The transition to the more motile form can be problematic—flexibility is what enables cancer cells to metastasize—and Bear is intrigued by the fact that the protein coronin 1C is found at very high levels in melanoma, a deadly form of skin cancer. He is now investigating whether the protein could serve as a marker for predicting which tumors might spread. |
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| | Bradley E. Bernstein
Massachusetts General Hospital
Credit: ©2009 Maria Nemchuk
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| Many scientists suspect changes in the regulatory scaffolding surrounding the genome may be as important as changes in the genome itself in causing diseases such as cancer. Bradley Bernstein of Massachusetts General Hospital believes it is critical to analyze this DNA-protein packaging, called chromatin, on a genome-wide scale to understand its full impact. So he developed new research tools to do just that. In a large-scale study of the proteins that package DNA, Bernstein and his colleagues mapped a family of switches that keep certain genes off until the right time in an organism's development. He now plans to investigate how chromatin helps stem cells decide when to commit to developing into a particular cell type. |
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| | Daniel I. Bolnick
University of Texas at Austin
Credit: ©2009 Sasha Haagensen
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| Daniel Bolnick's deep fascination with how species evolve has led him to study threespine stickleback fish on Vancouver Island, British Columbia. He and other scientists are the beneficiaries of the thousands of lakes and streams that were created when the giant glaciers melted at the end of the last Ice Age. These waters were colonized by the stickleback's marine ancestors, which were remarkably successful in adapting to various niches in their new habitats. Today, the environmental variations among the lakes make them the perfect setting for Bolnick to explore how the fish coevolve with other organisms. Bolnick, who is based at the University of Texas at Austin, wants to determine why each lake harbors a distinctive community of parasites. He will then measure how sticklebacks' immune systems have evolved to fight off the parasites found in any given lake. Sorting out these responses may improve understanding of chronic parasite-borne diseases that affect humans. |
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| | Sean F. Brady
The Rockefeller University
Credit: ©2009 Zach Veilleux
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| Sean Brady went to college thinking he wanted to study plants. He ended up digging in the dirt, sifting through the genes of the microbes that live there for pharmaceutical gold. Each spoonful of soil teems with thousands of bacteria, but because most of these grow poorly in lab dishes, scientists have just begun to catalog their genetic diversity. Brady, who is at Rockefeller University, circumvents this problem by constructing large libraries of raw bacterial DNA pulled from the dirt. He uses the cloned genetic material to discover and biosynthesize small molecules that might be useful medicinally. Starting with soil collected from around the world, he has already hit on a number of new antibiotics, and he hopes to discover many more potential new drugs. |
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| | Martin D. Burke
University of Illinois at Urbana-Champaign
Credit: ©2009 L. Brian Stauffer
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| Martin Burke, a chemical biologist at the University of Illinois at Urbana-Champaign, excels at creating new ways to generate diverse chemical compounds. Now he is on the hunt for small molecules that can imitate proteins that malfunction in diseases, such as cystic fibrosis. Burke calls his targets “molecular prosthetics,” because he hopes they may be able to help a person compensate for missing or dysfunctional proteins, much like a prosthetic hand can substitute for a hand lost to injury or disease. His sights are set specifically on developing a molecular prosthesis for a protein called cystic fibrosis transmembrane conductance regulator (CFTR). The protein transports chloride ions across the cell membrane, and scientists made the connection between cystic fibrosis and CFTR mutations 20 years ago—yet neither gene therapy nor other CFTR delivery systems have resulted in a successful treatment. By installing functional modules that carry out the work of CFTR along a molecular backbone, Burke wants to build a synthetic replacement for CFTR. He believes such a prosthesis could be the prototype for treating a raft of diseases caused by protein deficiencies. |
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| | Howard Y. Chang
Stanford University School of Medicine
Credit: ©2009 Mark Yamaguma
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| Every skin cell is not the same, and dermatologist Howard Chang wants to know why. For example, how is it that skin on the scalp generates long hairs, but skin on the bottom of the foot doesn't? Chang, who is at Stanford University School of Medicine, is focusing on how noncoding RNAs influence these developmental decisions. As their name implies, these molecules don't serve as templates for protein production. Instead, noncoding RNAs help cells identify their position in the body and activate the appropriate genes—so skin cells on the head can behave differently than those on the feet. The human genome holds the instructions for producing as many noncoding RNAs as proteins, but scientists lack the tools to decipher their function based on the DNA sequences that encode them. Chang wants to define the rules that determine noncoding RNAs' structure and activities, so that scientists can find them and predict how they behave inside cells. |
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| | Martin J. Cohn
University of Florida, Gainesville
Credit: ©2009 Sarah Kiewel
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| University of Florida scientist Martin Cohn has followed his own path from anthropology to developmental biology to understand the evolution of limbs. Along the way, he has studied jawless fish, legless snakes, five-limbed chickens, and, most recently, the relationship between limb and genital development in rodents. Yet Cohn's research has a human focus. In the last 30 years, genitourinary malformations have doubled and now affect 1 in every 250 live births in the United States. But researchers' basic scientific knowledge of how genitalia develop has lagged. Turning to embryonic mice for a mammalian model, Cohn is uncovering a surprisingly ancient gene network in the developing genital tubercle, an embryonic structure that gives rise to male and female genitalia. By bridging developmental genetics, evolution, and ecotoxicology, he hopes that understanding how these genes regulate development in different vertebrates will illuminate the origins of these disorders. |
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| | Jeremy S. Dasen
New York University Medical Center
Credit: ©2009 Thomas Semkow
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| Jeremy Dasen is deciphering the molecular code that helps developing motor neurons in the spinal cord connect with the muscles they control. Understanding this code, which relies on a large family of genes that produce proteins called Hox factors, may help scientists restore motor neuron function in people whose spinal cords have been damaged by trauma or disease. Dasen, who is at the New York University School of Medicine, has found that Hox proteins are not just present in motor neurons; they are pervasive throughout the nervous system. He plans to explore whether Hox proteins in interneurons and sensory neurons, which control motor neuron firing patterns and transmit feedback about muscle action, help assemble the complete circuits that control walking and running. |
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| | Russell A. DeBose-Boyd
University of Texas Southwestern Medical Center at Dallas
Credit: ©2009 Paul Fetters
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| Twenty million Americans take drugs called statins every day to lower their levels of low-density lipoprotein, or LDL, cholesterol. In some people, statins are highly effective, cutting LDL cholesterol levels by 50 percent. But statins have a paradoxical effect because the body's built-in feedback systems respond to plummeting cholesterol levels by telling cells to rev up cholesterol synthesis. Russell DeBose-Boyd, a biochemist at the University of Texas Southwestern Medical Center at Dallas, thinks this important class of drugs can be improved by understanding the regulation of an enzyme called HMG-CoA reductase, which spurs cholesterol synthesis. Statins block this enzyme, but also inhibit its degradation. As the enzyme accumulates, more statins are needed—thus limiting the drugs' effectiveness. By unwinding the complicated molecular pathways that control the degradation of HMG-CoA reductase, DeBose-Boyd hopes to make statins work better—or find alternative cholesterol-lowering therapies. |
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| | Karl Deisseroth
Stanford University
Credit: ©2009 L.A. Cicero/Stanford News Service
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| A practicing psychiatrist, Karl Deisseroth wants to understand how changes in brain circuitry lead to depression, Parkinson's disease, and other brain disorders. Dissatisfied with the research tools available for examining neural circuits in a functioning brain, he began making his own. In the process, he and his team created a new field of research called “optogenetics.” Deisseroth has reengineered neurons in living mice so those cells carry light-sensitive proteins harvested from microbes. Now researchers can precisely trigger those neurons with light—a flash of blue light switches the brain cells on, and a pulse of yellow light turns them off. It promises to provide deep insights into how brains work—and what goes wrong with specific neural circuits during illness. Already, Deisseroth's light show has offered clues to the sleeping disorder narcolepsy—and many more flashes of insight will surely follow. |
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| | Xinzhong Dong
The Johns Hopkins University School of Medicine
Credit: ©2009 Paul Fetters
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| Pain, itch, and gentle touch. Johns Hopkins University School of Medicine neuroscientist Xinzhong Dong is uncovering the molecular and cellular basis of all three, with an eye toward better treatments for chronic pain and itch. As a postdoctoral fellow, Dong discovered a family of 50 receptor proteins that mediate these sensations in mice. Now, he is combining genetic and behavioral studies in mice with electrophysiology, biochemistry, and molecular biology to reveal how the signals triggered by these receptors are processed as they travel from the skin to the spinal cord. Using the mice as a model, he wants to understand how neurons generate the type of itch that does not respond to antihistamine medications, such as the profound itching some people experience when they take the malaria medication chloroquine. |
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| | Michael A. Dyer
St. Jude Children's Research Hospital
Credit: ©2009 St. Jude Biomedical Communications
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| St. Jude Children's Research Hospital neurobiologist Michael Dyer has made significant and innovative contributions to the fields of developmental neurobiology, cell cycle regulation, stem cell biology, developmental therapeutics, and cancer genetics. Dyer studies the mechanisms that determine how neurons grow and differentiate. As part of a project involving genes for the eye cancer retinoblastoma, Dyer disproved a 100-year-old principle in science. He discovered that mature neurons can divide. Dyer's work may one day lead to regenerative therapies that do not require stem or progenitor cells. His research may also contribute to our understanding of cancer by determining what makes some cells more likely to become cancerous. |
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Jim Keeley
