Obama, Collins Laud $5B in NIH Stimulus Funds, Much for Genomics

The National Institutes of Health has awarded more than 12,000 grants totaling around $5 billion so far under the economic recovery and stimulus package, the White House said today.

President Barack Obama commuted to Bethesda this morning to announce the funding as a milestone, to unveil a $175 million grant for cancer genomics, and to tour the NIH campus.

In late-morning speeches before a crowd of NIH staff, President Obama, Health and Human Services Secretary Kathleen Sebelius, and NIH Director Francis Collins loosely outlined how the $5 billion in grants over two years — nearly half of NIH’s total $10 billion appropriation under the American Recovery and Reinvestment Act — will stimulate research and create jobs.

A number of genomics-focused programs will be funded under the stimulus package, including $175 million over two years for The Cancer Genome Atlas, a joint effort between the National Human Genome Research Institute and the National Cancer Institute, according to a fact sheet released today by the White House.

“This ambitious effort promises to open new windows into the biology of all cancers, transform approaches to cancer research, and raise the curtain on a more personalized era of cancer care,” Collins said in a statement, describing the TCGA funding as “an excellent example of how the Recovery Act is fueling discoveries that will fundamentally change the way we fight disease and improve our lives.

"We are about to see a quantum leap in our understanding of cancer," Collins said.

NCI and NHGRI will also each commit $50 million in non-Recovery Act funds to the Genome Atlas over this two-year period, according to NCI.

"We know that this kind of investment will also lead to new jobs: tens of thousands of jobs conducting research, manufacturing and supplying medical equipment, and building and modernizing laboratories and research facilities," Obama said in a statement.

At the event, Collins told the NIH assembly that the grants "will fund trailblazing research into treating and preventing our most scary diseases.

“Since arriving [at NIH] six weeks ago I’ve spent a lot of time reviewing some of these grants — I wanted to see what was there — and they propose some of the most innovative and creative directions for research that I have ever seen in 16 years at NIH,” the new NIH director told the crowd.

More than $1 billion of the grant funding is dedicated to using technologies developed through the NIH’s genomics programs, specifically through the Human Genome Project, the White House said.

For cancer, heart disease, and many other areas, researchers will use Recovery Act funding for genomics and genetics-based research approaches to pursue knowledge about these diseases.

According to the White House, over the two years of recovery funding NIH stimulus grants will support studies including:

• Seeking to use microRNAs to predict which patients have tumors that will spread throughout the body;

• Conducting genomic sequencing of individuals with autism and their parents in order to find causes for the disease in the genome and in the environment and to develop and test diagnostic screening tools;

• Cataloging genetic changes associated with oral cancer in order to identify and guide treatment of pre-malignant lesions;

• Sequencing the genomes of more than 10,000 individuals with known risk factors for heart disease in order to identify those risk genes;

• Comparing the genomes of individuals with high and low HDL cholesterol levels in order to accelerate development of drugs that reduce the risk of heart attack;

• Examining the genes of more than 7,000 heart failure patients to identify variants that will enable doctors to identify those at risk for heart failure;

• Identifying genetic markers for increased risk of hypertension, obesity, cardiac hypertrophy, and kidney failure in African Americans;

• Finding markers that circulate in the blood that may signal the onset of a plaque rupture or of thrombosis;

• Analyzing biomarker and genetic data from international atrial fibrillation patient pools in search of markers to identify patients that will benefit from statin therapy.

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Search Engines, Genomics, Medical Literature: Tag Clouds come to PubMed via LigerCat

“… LigerCat is a search tool for NCBI’s PubMed that uses tag clouds to provide an overview of important concepts and trends. LigerCat aggregates multiple articles in PubMed, summing their MeSH descriptors and presenting them in a cloud, weighted by frequency “.

LigerCat is an abbreviation for Literature and Genomics Resource Catalog, which is a free PubMed search tool developed in 2009 as part of the Biology of Aging project at the MBLWHOI Library at the Woods Hole Marine Biological Laboratory.

LigerCat is great news for geneticists or anyone involved in translational research, a fairly effortless means of data mining for dynamic links to a very complex literature.

LigerCat can be used to search in several ways: 1) to locate and select a list of individual journal titles indexed in PubMed, 2) search using terms from the National Library of Medicine’s Medical Subject Heading (MeSH) list, 3) search using keywords, 4) search on Genes found in the NCBI databases.

Do you want to know more?

for more reading:

• Do you hate Pubmed? Here is the solution!
• Getcloudlet Brings Tag Clouds Plus Better Search Terms On Google Search Engine
• GoPubMed – “Searching is now Sorted”

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NIH Grants $45M for Genome Science Centers

The National Institutes of Health has pledged $45 million in grants to establish two new genomics centers at the University of North Carolina at Chapel Hill and at the Medical College of Wisconsin (MCW), as well as to continue funding existing centers at Johns Hopkins University and at the University of Southern California.

The two new Centers of Excellence in Genomic Science at UNC and MCW will pursue genomics studies of mental health and gene regulation, respectively.

Under the new grants, MCW will receive around $8 million over three years and UNC will reap around $8.6 million over five years from the National Human Genome Research Institute and the National Institute of Mental Health.

Johns Hopkins' genomics center will receive around $16.8 million over five years to continue epigenetics of disease studies and USC will use around $12 million over the same period to conduct computational and informatics-based research of genetic variation and disease.

"Our aim is to foster the formation of innovative research teams that will develop genomic tools and technologies that help to advance human health," NHGRI's Acting Director, Alan Guttmacher said in a statement. "Each of these centers is in a position to tackle some of the most challenging questions facing biology today."

The grant to UNC will support the Center for Integrated Systems Genetics (CISGen), where scientists will seek to identify genetic and environmental factors that underlie and contribute to psychiatric disorders.

CISGen will use mouse models and computational biology to study genetic and environmental factors of such disorders, and it will develop new mouse strains specifically to study relevant behavioral traits. These models will serve as a resource of genomic studies screening for genetic variants that are linked to human psychiatric disorders.

"We can use the mouse to narrow the search space from billions of possibilities to only hundreds or even dozens," CISGen co-director and UNC Assistant Professor Fernando Pardo-Manuel de Villena said in a statement. "It's like the PowerBall when you know four or five of the six numbers for sure."

"We chose the hardest problems out there, the ones that have been most resistant to scientific inquiry in humans," explained Patrick Sullivan, CISGen's other co-director and a distinguished professor at the UNC School of Medicine. "We chose to study mouse versions of psychiatric traits potentially relevant to autism, depression and anxiety, and antipsychotic drug side effects and response to treatment."

In Wisconsin, the new center is a collaboration between the Medical College of Wisconsin, the University of Wisconsin, Madison, and Marquette University.

The team at MCW will focus on developing tools for analyzing the proteins that bind to particular DNA regions in an effort to understand the relationship between changes in protein-DNA interactions.

"What is needed, and what we will develop in this center, is technology that is able to identify all of the proteins that are interacting with the genome, even if we do not know in advance what their function may be," said the center's co-Director, Michael Oliver, a professor at MCW's Biotechnology and Bioengineering Center and the Human and Molecular Genetics Center.

Other NIH-funded Centers of Excellence in Genomic Science include centers at the California Institute of Technology, Harvard Medical School, Stanford University, Arizona State University, Yale University, and the Dana-Farber Cancer Institute.

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"Achilles' heel of a sizable share of melanomas" - Mutations That May Improve Skin Cancer Treatmen

Mutations in the protein tyrosine kinase gene ERBB4 contribute to — and may provide hints about treating — a subset of melanoma, according to a paper by researchers from the National Institutes of Health and Johns Hopkins University that appeared in the advanced, online edition of Nature Genetics this week.

The team sequenced protein tyrosine kinase or PTK genes in 29 individuals with melanoma. Their search uncovered dozens of somatic mutations affecting the kinase domain of 19 different PTK genes. When they looked at the same 19 genes in another 79 melanoma patients, the researchers found that almost a fifth of those tested harbored mutations in ERBB4.

And, they reported, knocking down the mutated form of ERBB4 or using a drug that targeted the gene slowed the growth of melanoma cell lines, suggesting it might be useful to evaluate ERBB4 status in melanoma patients.

Researchers at the NIH Intramural Sequencing Center sequenced all 86 PTK family genes in tumor samples from 29 individuals with melanoma, picking out somatic mutations by comparing the tumor with matched normal tissue.

Overall, the team detected 30 somatic mutations affecting 19 different PTK genes. When the team sequenced the coding regions of these 19 genes in another 79 melanoma patients, they found 99 non-synonymous mutations.

In particular, 19 percent of the individuals had mutations affecting ERBB4 (also known as HER4), while ten percent carried PTK2B or FLT3 mutations.

Of these, the ERBB4 appeared to be the most severely mutated. As such, the team decided to investigate whether mutations in that gene influenced melanoma growth and/or treatment response, focusing on seven different missense mutations in ERBB4.

The researchers found that the growth of melanoma cell lines containing ERBB4 mutations was curbed when they knocked down the mutated form of the gene using small interfering RNA.

The team was also able to slow the growth of the melanoma cell lines by treating them with the ERBB4-inhibiting drug lapatinib, sold as Tykerb by GlaxoSmithKline.

"We have found what appears to be an Achilles' heel of a sizable share of melanomas," senior author Yardena Samuels, a researcher with the National Human Genome Research Institute's Cancer Genetics Branch, said in a statement.

The team plans to do a clinical trial looking at whether lapatinib is effective for treating melanoma in patients who carry ERBB4 mutations. Steven Rosenberg, chief of surgery at the National Cancer Institute and a researcher with the NIH's clinical center will reportedly head the trial.

"We envision a day when each cancer patient will have therapies tailored to the specific genetic profile of his or her tumor," NHGRI Director Eric Green, said in a statement. "Ultimately, this should lead to more effective and less toxic approaches to cancer care." Green was not directly involved in the current study, but heads the NIH sequencing center that generated the sequence data.

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