FOCUS ON ALZHEIMER’S DISEASE

Despite years of research, Alzheimer’s continues to be a tremendously debilitating disease, both at the individual and societal level. Now, innovative research which could significantly shed light and give greater understanding of neurodegenerative diseases like Alzheimer’s is occurring within the NIH Common Fund High Risk High Reward (HRHR) research program. Within each of the four different programs in the HRHR portfolio, investigators are using novel approaches to tackle Alzheimer’s disease and other neurodegenerative disorders. For example, Dr. Howard Weiner, a Transformative Research Award recipient, is pursuing the intriguing hypothesis that the brain’s innate immune system may have a major role in aging and the development of Alzheimer’s disease. Another Transformative Research Award recipient, Dr. Nina Papvasiliou, has proposed to approach vaccine design in a completely new manner: her lab will create a novel vaccine using the “coat” of the human blood parasite (African trypanosome) to elicit a strong immune response which could be used in the development of therapeutic vaccines toward Alzheimer's disease. Dr. Timothy Lu, a New Innovator Award recipient, is using synthetic biology and nanotechnology to understand and treat the mechanisms underlying amyloid-associated diseases like Alzheimer’s. Dr. Saul Villeda, a recent awardee of the NIH Director’s Early Independence Award is using novel methods to determine how factors in the aging brain may modulate the brain’s capacity to create new neurons and how this may lead to onset of neurodegenerative diseases such as Alzheimer’s disease. As a final example, Dr. Lorna Role, a Pioneer Award recipient, is using mouse models to better understand cholinergic signaling which are important in mental decline in neurodegenerative disorders. These and other investigators in the HRHR program, by using unconventional approaches, may provide the breakthroughs needed to understand and treat Alzheimer’s disease. Below are examples of this innovative research with hyperlinks to abstracts.

Dr. Lorna Role, Dr. Nina Papavasilio, Dr. Saul Villeda

HRHR NEURODEGENRATIVE AND ALZHEIMER’S RELATED RESEARCH

The NIH Director’s New Innovator Awards

The NIH Director’s Pioneer Awards

The NIH Director’s Early Independence Award

The NIH Director’s Transformative Research Awards

Three NIH Director’s New Innovator Awardees selected for the 2012 Presidential Early Career Award in Science and Engineering (PECASE)

Three NIH Director’s New Innovator Awardees from 2011 have been selected this year for the highly prestigious PECASE Award. The Presidential Award is the highest honor bestowed by the United States government on scientists and engineers beginning their independent research careers. In addition to possessing extraordinary research potential, awardees also have a record of significant community service. The three New Innovator Awardees who have been selected for this year’s PECASE Award are Erez Lieberman-Aiden, Ph.D. (Harvard University), Steven T. Kosak, Ph.D. (Northwestern University) and Emanuel Maverakis, M.D, (University of California Davis). The NIH Director’s New Innovator initiative is a component of the NIH Common Fund and seeks to support exceptionally innovative early career stage investigators as they pursue bold, risky research ideas that have the potential to have an unusually broad impact on the biomedical/behavioral sciences.

Erez Liberman-Aiden, Ph.D.

Dr. Erez Lieberman-Aiden, a fellow at Harvard University, has been selected for the 2012 PECASE award by the White House Office of Science and Technology Policy. Dr. Lieberman-Aiden’s research accomplishments and fundamental contributions in a remarkably diverse variety of disciplines, including molecular biology, polymer physics, historical linguistics, wearable computing and mathematics, have set him apart from his peers. Through support from the NIH Director’s New Innovator Award, Dr. Lieberman-Aiden is developing tools to understand how genomes, RNAs, and proteins are organized in cells, which should enable deep new insights into the control of cellular function. Notable among Dr. Lieberman-Aiden’s many community service activities is the “Bears without Borders” charity, which he co-founded.

Steven T. Kosak, Ph.D.

Dr. Steven T. Kosak, an assistant professor in Cell and Molecular Biology at Northwestern University, has been selected for the 2012 PECASE award by the White House Office of Science and Technology Policy. The selection was based in part for his NIH Director’s New Innovator Award research proposal, which outlines an effort to bridge the relationship between form and function in the human nucleus. Dr. Kosak’s research regarding the dynamic architecture of the human genome will provide fundamental insight into essential cellular processes such as differentiation and cell cycle control and may also present new avenues for diagnosing and treating diseases that arise when these processes go awry. Dr. Kosak is also distinguished by his community service activities, including his Peace Corps service.

Emanuel Maverakis, MD

Dr. Emanuel Maverakis, MD, an Assistant Professor in the Division of Dermatology at the UC Davis Health System, was selected as an awardee for the 2012 PECASE award by the White House Office of Science and Technology Policy. Dr. Maverakis’s creativity has lead to conceptual leaps in the field of immunotherapy. Through support from the NIH Director’s New Innovator Award, Dr. Maverakis studies the immune cells isolated from patients with scleroderma and attempts to identify new therapeutic targets for medications. The underlying mechanisms he discovers may be applied to understanding and treating not only scleroderma, but perhaps many other important autoimmune diseases such as Crohn’s Disease, Celiac Disease, and diabetes mellitus type 1. Dr. Maverakis has engaged in many different community service activities, including helping disadvantaged youth.

NIH Press Release
White House Press Release

Three HRHR Awardees Elected Into the National Academy of Sciences

The National Academy of Sciences elected 84 new members and 21 foreign associates from 15 countries in recognition of their distinguished and continuing achievements in original research. Among the new members elected in 2012, three were NIH Common Fund High Risk -High Reward program awardees. Dr. Karl Deisseroth and Dr. Joseph M. DeSimone are recipients of the NIH Director's Pioneer Award. The NIH Director's Pioneer Award seeks to support individual scientists of exceptional creativity who propose pioneering -and possibly transforming approaches- to major challenges in biomedical and behavioral research. Dr. Xiawei Zhuang is a recipient of the NIH Director's Transformative Research Award. The NIH Director's Transformative Research Award is intended to provide support for inherently risky research projects that have the potential to create or overturn fundamental paradigms.

Karl Deisseroth, M.D., Ph.D.

Karl Deisseroth, M.D., Ph.D. Dr. Deisseroth is an Associate Professor in the Department of Bioengineering and the Department of Psychiatry and Behavioral Sciences at Stanford University in Stanford, CA and a Howard Hughes Medical Institute Early Career Scientist. He received a Ph.D. in neuroscience in 1998 and an M.D. in 2000, both from Stanford. Deisseroth combines bioengineering and psychiatry in studying intact neural circuits in the mammalian brain. Deisseroth was a Pioneer Awardee from 2005 to 2009. He used his Pioneer Award to launch a large-scale, systematic effort to map key neural circuit dynamics on the millisecond timescale. As part of this effort, he led the development of a new technique, termed “optogenetics,” which has revolutionized the neurosciences by enabling the optical control of specific neurons. Deisseroth's other honors include the Coulter Foundation Early Career Translational Research Award in Biomedical Engineering, the McKnight Foundation Technological Innovations in Neuroscience Award, the American Psychiatric Institute for Research and Education Young Faculty Award, and elected membership to the Institute of Medicine.

Joseph M. DeSimone, Ph.D.

Joseph M. DeSimone, Ph.D. Dr. DeSimone is the Chancellor's Eminent Professor of Chemistry at the University of North Carolina at Chapel Hill and the William R. Kenan, Jr. Distinguished Professor of Chemical Engineering at North Carolina State University. He received a Ph.D. in polymer chemistry from Virginia Tech in 1990. DeSimone's research in polymer science has covered a broad range of fields, including green manufacturing, medical devices, and nanomedicine. He is using the Pioneer Award to develop new approaches for delivering promising biological therapeutics to specific sites in the body via inhalation and minimally invasive ionotophoretic devices, which use local electrical currents to move drugs into tissues. Underlying his approach is a novel technology for making specifically shaped biological particles based on processes adapted from the semiconductor industry. DeSimone’s other honors include the 2010 AAAS Mentor Award, the 2008 Lemelson-MIT prize, and elected memberships to the National Academy of Engineering and the American Academy of Arts and Sciences.

Xiawei Zhuang, Ph.D.

Xiawei Zhuang, Ph.D. Dr. Zhuang is a Howard Hughes Medical Institute Investigator, Professor of Chemistry and Chemical Biology and a Professor of Physics at Harvard University. She received her Ph.D. in Physics from the University of California, Berkley in 1996. Dr. Zhuang combines single-molecule biology and bioimaging to develop and apply advanced optical imaging techniques to study the behavior of individual biological molecules and complexes in vitro and in live cells. Zhuang, along with co-Principal Investigator Dr. Xiaoliang (Sunney) Xie, is using the NIH Director's Transformative Award to develop a quantitative, high-resolution map of cellular architecture of E. coli with single-molecule sensitivity, nanometer-scale spatial resolution and molecular specificity of each individual gene and to profile changes of this architecture in response to environmental conditions with a set of bioimaging and systems biology tools. This research advances fundamental microbiology and cell biology, but may also suggest new therapeutic targets for bacteria-based infectious diseases. Zhuang’s other honors include the 2011 Sackler International Prize in Biophysics, the 2010 Max Delbruck Prize in Biological Physics, the 2008 Coblentz Awards, and a MacArthur Fellowship.

Understanding Obesity

'Eat less, move more.' You've probably heard this mantra for weight loss success repeated many times. Yet despite our best intentions to trim calories and walk around the block, obesity has reached epidemic proportions in the United States.

Obesity has more than doubled among U.S. children ages 2 through 5 during the past 30 years, and has more than tripled among tweens and teens. More than one-third of adults in the United States are obese. The consequences of this epidemic are far-reaching. Tens of millions of Americans face an increased risk of type 2 diabetes, heart disease, high blood pressure, certain cancers, osteoarthritis, and other serious health problems associated with excess body fat. In addition to the burden of obesity on the healthcare system, there is the burden of discrimination and stigma at the personal level. As anyone who has cursed their bathroom scale can tell you, obesity seems to be a complex disorder that defies the conventional wisdom regarding calories in and calories out.

Common Fund Obesity Research

Several researchers supported by the NIH Common Fund are striving to better understand the causes of obesity. These exceptional individuals, who are funded through the High Risk-High Reward program, are being encouraged to pursue innovative approaches and to follow them in expected or unexpected directions. By bringing their unique perspectives and abilities to bear on this important health challenge, these visionary scientists may transform how we prevent and treat obesity and obesity-related conditions in the future.

Julie Parsonnet, M.D., Stanford University

Dr. Parsonnet is examining the link between the increasing rate of childhood obesity and decreasing rate of childhood infections. While these trends may be coincidental, she postulates there is a cause and effect relationship.

Over the last 40 years there has been a multifold increase in obesity in American children. During this time, childhood infections have been declining due to changes in family size, improvements in hygiene, the addition of new vaccines, and other preventive health measures. Dr. Parsonnet hypothesizes that frequent, chronic and/or severe prenatal and childhood infections prevent weight gain, overweight and obesity in children. She additionally hypothesizes that early acquisition of specific chronic infections, such as herpes viruses and Helicobacter pylori infection, protect against obesity.

Infections influence a number of critical factors that affect weight gain, including energy expenditure, appetite, and fat cell growth and metabolism. Dr. Parsonnet and her team are monitoring children from conception through at least five years of age, and ultimately through adolescence and adulthood, to determine how infectious diseases influence body weight. Infection in the children is being measured by the monitoring and reporting of daily symptoms and signs by parents, and by following the development of detectable antibodies against a number of microbes. The mechanisms by which infection might alter weight gain are being explored by measuring resting energy expenditure and levels of cell signaling proteins that are released by fat cells and other cell types. Dr. Parsonnet's goal is to determine whether a significant proportion of the increase in weight in U.S. children over the last 40 years is related to children leading healthy, uninfected lives.

Learn more about Dr. Parsonnet's research:

Kevin Niswender, M.D., Ph.D. and Aurelio Galli, Ph.D., Vanderbilt University School of Medicine

Dr. Niswender, a specialist in metabolism and diabetes, and Dr. Galli, a biophysicist who studies drug addiction, have teamed up to explore the potential molecular link between how the body processes sugars and mental illness. These researchers aim to transform the approach to studying obesity by analyzing parallel changes in insulin and dopamine signaling.

Drs. Niswender and Galli hypothesize that consumption of high-fat, high-sugar foods leads to disruptions in how insulin works in our brains. This disruption could lead to impaired dopamine signaling, which in turn might causing over-consumption of foods by altering the brain's 'reward' circuitry.

Utilizing a rodent model of diet-induced obesity, they are measuring insulin action and dopamine signaling in the brain. Armed with an array of cutting-edge tools, they seek to define the specific regions of the brain that are involved in the pathology of obesity, as well as the molecular mechanisms involved in changes in these regions. Subsequently, they hope to correct the pathological alterations. By understanding how changes in insulin and dopamine signaling cause changes in feeding behavior, their findings could lead to the development of new therapeutic interventions to treat obesity and associated diseases.

Learn more about the research of Dr. Niswender and Dr. Galli:

Martin J. Blaser, M.D., New York University School of Medicine

Trillions of microorganisms, including bacteria such as Helicobacter pylori, have resided in the guts of humans for tens of thousands of years. Dr. Blaser speculates that over time there have been changes in the composition of these microbes due to modernization, and that these changes may be playing a role in the increasing incidence of obesity.

Dr. Blaser hypothesizes that common antibiotic treatments may be unintentionally causing changes in the composition of the bacterial populations that normally live in our stomach and intestines, and that these changes are then inherited by subsequent generations. He is examining the relationships among the presence of microbes in the digestive system of mothers and children; the physiology of gastric hormones, inflammation, and immunity; the hormonal and metabolic changes that occur as a result of changes in antibiotic treatment; and the incidence of childhood obesity. Dr. Blaser aims to better understand the importance of the microbes that live within us and how the presence or absence of these microorganisms may lead to conditions such as obesity.

Learn more about Dr. Blaser's research:

Learn More About NIH Obesity Research And Resources

NIH obesity research

Through its research mission, the NIH seeks to identify genetic, behavioral, and environmental causes of obesity; to understand how obesity leads to type 2 diabetes, cardiovascular disease, and other serious health problems; and to build on basic and clinical research findings to develop and study innovative prevention and treatment strategies.
Learn more at: http://obesityresearch.nih.gov/

National Collaborative on Childhood Obesity Research (NCCOR)

The NIH, the Centers for Disease Control and Prevention (CDC), and the Robert Wood Johnson Foundation together launched the NCCOR to address the problem of childhood obesity in America.
To learn more, please visit: www.nccor.org

NIH obesity research funding opportunities
Obesity-related research solicitations that are currently open for submission of applications for funding are listed at: http://obesityresearch.nih.gov/funding/funding.htm. Detailed information, including names of individuals to contact with questions, is provided through the links associated with each solicitation.

Clinical trials
ClinicalTrials.gov is a registry of federally and privately supported clinical trials conducted in the United States and around the world. ClinicalTrials.gov gives you information about a trial's purpose, who may participate, locations, and phone numbers for more details. This information should be used in conjunction with advice from health care professionals.
To find clinical trials, visit www.clinicaltrials.gov/ and search for terms such as "obesity" and "childhood obesity".

Learn more about obesity from MedlinePlus
Scan overviews, multimedia, references and more to learn about the latest research and news on topics related to obesity at http://www.nlm.nih.gov/medlineplus/obesity.aspx.

Training opportunities

Explore research and training opportunities on the NIH campus ranging from summer programs for high school students to employment for postdoctoral scientists (intramural), as well as learn about NIH-supported pre-doctoral and postdoctoral training opportunities at universities and other institutions across.
Learn more at http://www.nih.gov/Training.htm.

NIH Director’s New Innovator Erez Lieberman Aiden Named the 2011 Grand Prize Winner for the GE & Science Prize for Young Life Scientists

Erez Lieberman Aiden, one of the recipients of an NIH Director’s New Innovator Award, has been named the grand prize winner for the GE & Science Prize for Young Life Scientists. Lieberman Aiden was selected for this prestigious award based on a worldwide competition for young investigators. The selection was primarily based on 1,000 word essays describing the researcher’s dissertation studies. Lieberman Aiden’s essay, based on his doctoral studies at Harvard and MIT with Eric Lander and Martin Nowak, identified a novel method for determining the 3-D structure of nuclear DNA in human cells. His novel approach to studying the human genome led him and his colleagues to discover that active and inactive portions of the genome are separated within the nucleus. His doctoral studies have led to discoveries that now enable new areas for genome research for a number of disciplines in the life sciences. Furthermore, his finding that the genome folds into a dense, unknotted structure known as a fractal globule is a fundamental discovery in physics because theoretical physicists have hypothesized that the structure exists but now have the first tangible example for this type of polymer.

In addition to his studies on the human genome, Lieberman Aiden also recently developed a new, quantitative approach, together with Jean Baptiste Michel at Harvard University, for the analysis of culture using digitized books. His novel discoveries in several disciplines clearly illustrate his uniqueness and innovative research directions. He currently is fellow at the Harvard Society of Fellows and a visiting faculty member at Google.

Your Brain on Anesthesia

Have you ever had surgery or another medical procedure requiring general anesthesia? Did the practitioner tell you it would be as if you were sleeping? Well, Emery Brown, M.D., Ph.D., professor of anesthesiology at Harvard Medical School and professor of computational neuroscience at M.I.T., would prefer it be described differently. In a recent review article published in the New England Journal of Medicine, Brown and his colleagues examine the dissimilarities as well as the parallels between general anesthesia, sleep, and coma. Brown equates anesthesia not with being in a sleep state but being in a drug-induced coma. This research, supported in part by an NIH Director’s Pioneer Award, assembles information from clinical and neurophysiological research disciplines. Using data culled from monitoring clinical signs and electroencephalogram (EEG) patterns, the researchers assessed changes in brain activity through all stages of the procedure, from pre-induction, through initial administration and maintenance, to emergence and recovery. The analysis indicates that though it is common to describe general anesthesia as going to sleep, there are noteworthy differences, most markedly in how the anesthetic drugs alter the way the brain transmits information, that make it more like going into a coma. Brown’s research provides a foundation for further research on the human brain during states of sleep and coma that may lead to new approaches to general anesthesia.

Reference:
Robert S. Schwartz, Emery N. Brown, Ralph Lydic, Nicholas D. Schiff. General Anesthesia,Sleep, and Coma. New England Journal of Medicine, 2010; 363 (27): 2638.

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