News Archive

2009

Sulfolobus islandicus holds clues to evolution

Sulfolobus islandicus, a microbe that can live in boiling acid, is offering up its secrets to researchers hardy enough to capture it from the volcanic hot springs where it thrives. In a new study, which has received international attention, a team of researchers led by Microbiology Professor report that populations of S. islandicus are more diverse than previously thought, and that their diversity is driven largely by geographic isolation.

redOrbit
University of Illinois News Bureau
Science Daily
UPI     
Posted June 08, 2009
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Edwin Goldberg, M.D. (1923-2009)

Dr. Goldberg (affectionately known as "Dr. Ed") obtained his M. D. degree in 1949 and subsequently completed internal medicine residencies at North Cambridgeshire Hospital in Cambridge, England and at Cook County Hospital in Chicago, IL, where he served as the chief medical resident. He then joined the Air Force, holding the rank as captain, and he served for two years as the Chief of Medical Service for the 6604th USAF Hospital at Pepperrell Air Force Base in St. John's, Newfoundland, Canada.

After his military service, he moved to Decatur, IL and practiced internal medicine there until 1986. During his years in Decatur, Dr. Ed received an appointment as a Clinical Professor of Medicine at the University of Illinois School of Medicine at Urbana-Champaign. He enjoyed teaching the medical students and visited the UIUC campus regularly to lecture on various medical topics. His quick wit, personal warmth and charm, and his willingness to share his extensive medical knowledge made him a favorite among the students.

Drs. Ed and Jeanne supported the Medical Scholars Program at the University of Illinois Urbana-Champaign School of Medicine and endowed three separate professorial chairs in their names and in the names of Jeanne's parents in the Department of Molecular and Integrative Physiology, School of Molecular and Cellular Biology, and the school of Integrative Biology. They received the University of Illinois College of Liberal Arts & Sciences Dean's Quadrangle Award in 2001, served as members of the President's Council at UIUC, and were invited to speak at the Department of Molecular & Integrative Physiology Retreats in Illinois on two occasions.

Dr. Ed was a man of many talents and will be missed for his kindness, spirit, vitality, intelligence, wit and charm.

Naples Daily News     
Posted June 16, 2009
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Gene Robinson, Martha Gillette awarded Center for Advanced Study Professorships

Beckman faculty members Martha Gillette and Gene Robinson have been awarded Center for Advanced Study (CAS) Professorships pending approval by the Board of Trustees.

Gillette and Robinson are both members of the NeuroTech group at the Institute.

The mission of CAS, according to its Web site, is to bring together “scholars from diverse disciplines and backgrounds, encouraging and rewarding excellence in all areas of academic inquiry.”

The CAS offers University of Illinois faculty a chance to take time off to pursue research or creative projects, and the opportunity to help shape campus research programs by advising campus leaders on topics.

Gene Robinson received his Ph.D. from Cornell University in 1986. He is a professor in the University of Illinois Department of Entomology and an affiliate member in the Beckman Institute NeuroTech group. He is director of the Neuroscience Program at Illinois and an affiliate of the Department of Cell & Developmental Biology; Department of Animal Biology (UIUC); Department of Political Science; Center for Economic Entomology, Illinois Natural History Survey; and the Biotechnology Center.

Beckman Institute
UI News Bureau     
Posted June 16, 2009
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Xiang Makes Nanoneedle

Yang Xiang and his partners have developed a nanoneedle capable of delivering molecules directly into living cells. This tool promises to be of vital importance in future cellular research.

UI News Bureau     
Posted May 04, 2009
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Kemper Published in Genes and Development

Jongsook Kim Kemper, Associate Professor of Molecular and Integrative Physiology, authored a study about cholesterol regulation published in the most recent issue of Genes and Development.

The Kemper lab and its partners have detailed how the activity of a small protein, named Small Heterodimer Partner (SHP), is controlled to modulate the conversion of cholesterol to bile acids.

Cholesterol is an important constituent of cell membranes and is used by the liver to make bile acids.

Bile acids play important dietary roles in the body, including the absorption of fat-soluble nutrients during digestion and regulating fat and glucose metabolism.  Excessive amounts of cholesterol and bile acids, however, can lead to cardiovascular disease and metabolic ailments.

When bile acid levels are too high, SHP is made to stop the conversion of cholesterol into new bile acid.

The Kemper Lab found when bile acid levels are low, SHP is rapidly broken down in liver cells to allow for the production of more bile acids.  Then, when bile acid levels increase, SHP remains stable and can halt the conversion of cholesterol into new bile acids.

In another interesting discovery, obese mice were found to have very stable SHP compared to their non-obese counterparts.  Mice fed a chronic western diet had more than twice the levels of stable SHP than those that had normal diets.

 “Abnormal stabilization of SHP may be associated with metabolic disorders, including obesity and diabetes,” according to the paper. “The mechanism underlying elevated SHP stability in these obese mice is not clear, but these intriguing results provide a potential link between abnormally elevated SHP stability and metabolic disease.”

Genes and Development     
Posted April 27, 2009
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James Slauch appears in PLoS ONE

For decades, microbiologists assumed that macrophages, immune cells that can engulf and poison bacteria and other pathogens, killed microbes by damaging their DNA. A new study from the University of Illinois disproves that.

The study, published in the journal PLoS One, shows that macrophages focus their most potent poisons, known as reactive oxygen species (ROS), on targets outside the cytoplasm.

-from the University of Illinois News Bureau

News Bureau
PLOS ONE     
Posted March 23, 2009
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Imlay featured in ASBMB Today

Professor of microbiology James Imlay is featured in the latest issue of ASBMB Today for his work on the mechanisms of oxidative damage.

ASBMB Today     
Posted March 16, 2009
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Chen Finds Molecular Pathway

Assistant Professor of Biochemistry Lin-Feng Chen and his colleagues discovered a novel way inflammation is regulated.

The University of Illinois News Bureau     
Posted March 11, 2009
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Woese to Recieve Achievement Award

Professor of Microbiology Carl Woese will be honored this year with the Abbott-ASM Lifetime Achievement Award for his work on microbe diversity.

American Society of Microbiologists     
Posted February 23, 2009
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Prasanth Published in Science

Supriya Prasanth

Cell and developmental biology assistant professor Supriya Prasanth is the coauthor of a manuscript that reveals a new role for Orc1, a protein essential for DNA replication in animal cells. 

A cell must replicate its DNA to provide a copy of genetic material for future generations.  Orc1 is an important subunit of the Origin Recognition Complex (ORC), a group of proteins that work together to start DNA replication before a cell divides.

A complex known as the centrosome organizes cellular machinery responsible for segregating that replicated DNA during cell division. Poor DNA replication or segregation can lead to numerous problems, including cell death or cancer.

Professor Prasanth’s research has helped show that not only is Orc1 essential to DNA replication, its traditional role, but also regulates how many centrosomes are found in a cell.

Increased numbers of centrosomes have been associated with cancer, and Prasanth’s team noticed cells lacking the Orc1 protein contained more centrosomes than a normal cell.  This suggests Orc1 is responsible for controlling the number of centrosomes found in a cell, and therefore may play an important role in avoiding uncontrolled cell division such as cancer.

The team’s paper is published in the February 6th issue of Science.  A full electronic text is available.

Science     
Posted February 11, 2009
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Dr. Robert Gennis Invested as Harry E. Preble Endowed Professor

Dr. Robert Gennis (Biochemistry) will be one of four individuals invested as a Harry E. Preble Endowed Professor, along with Dean Ruth Watkins, Dr. Don Wuebbles (Atmospheric Sciences) and Dr. Brigit Kelly (English). A celebratory event will be held on Monday, September 21, and is tentatively scheduled to include a 4:00 p.m. ceremony, with a 5:00 p.m. reception and 6:30 p.m. celebratory dinner, at the Spurlock Museum. Posted June 18, 2009
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Neural Systems Modeling, by Thomas Anastasio

From the publisher's website:

Neural systems models are elegant conceptual tools that provide satisfying insight into brain function. The goal of this new book is to make these tools accessible. It is written specifically for students in neuroscience, cognitive science, and related areas who want to learn about neural systems modeling but lack extensive background in mathematics and computer programming.

The book opens with an introduction to computer programming. Each of twelve subsequent chapters presents a different modeling paradigm by describing its basic structure and showing how it can be applied in understanding brain function. The text guides the reader through short, simple computer programs—printed in the book and available by download at the companion website—that implement the paradigms and simulate real neural systems. Motivation for the simulations is provided in the form of a narrative that places specific aspects of neural system behavior in the context of more general brain function. The narrative integrates instruction for using the programs with description of neural system function, and readers can actively experience the fun and excitement of doing the simulations themselves. Designed as a hands-on tutorial for students, this book also serves instructors as both a teaching tool and a source of examples and exercises that provide convenient starting points for more in-depth exploration of topics of their own specific interest.

The distinguishing pedagogical feature of this book is its computer programs, written in MATLAB, that help readers develop basic skill in the area of neural systems modeling. Actual data on real neural systems is presented in the book for comparison with the results of the simulations. Also included are asides (“Math Boxes”) that present mathematical material that is relevant but not essential to running the programs. Exercises and references at the end of each chapter invite readers to explore each topic area on their own.

Sinauer Associates, Inc.     
Posted June 17, 2009
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MCB Professors Discover Unusual Chemical Reaction

With the help of X-ray crystallography, researchers have identified and structurally analyzed an iron-containing enzyme that carries out a tricky bond-breaking reaction. The findings could inspire versatile new catalysts.

Bacteria make phosphinothricin, a natural product widely used as a weed killer, with several unusual steps. One includes the cleavage of a very poorly activated carbon-carbon bond in 2-hydroxyethylphosphonate (HEP), a phosphinothricin precursor.

Because unactivated C–C bonds are tough to break with the known synthetic tool kit, scientists want to understand how this transformation takes place, says chemist Wilfred A. van der Donk of the University of Illinois, Urbana-Champaign, who has been working to understand phosphinothricin biosynthesis. But until now his team "didn't know what kind of enzyme did the job and whether cofactors were required for it to work," he says.

So van der Donk's group joined forces with structural biologist Satish K. Nair and microbiologist William W. Metcalf, both at Illinois. The team has now solved the enzyme's X-ray structure and identified it as a nonheme iron-containing oxygenase (Nature, DOI: 10.1038/nature07972). The enzyme, hydroxyethylphosphonate dioxygenase (HEPD), uses molecular oxygen to cleave the poorly activated C–C bond in HEP. -from Chemical and Engineering News

C&EN
UPI
Chemistry World
Nature     
Posted June 17, 2009
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Carl Woese receives Distinguished Service Medallion

The UI Board of Trustees voted March 11 to present its highest honor, the Distinguished Service Medallion, to Carl R. Woese, the Stanley O. Ikenberry Endowed Chair and Center for Advanced Study Professor of Microbiology.

The award was created to recognize individuals whose contributions to the growth and development of the UI, through extraordinary service or benefaction, has been of unusual significance.

Woese, a faculty member since 1964, describes himself as a molecular biologist turned evolutionist. He received the 2003 Crafoord Prize in Biosciences from the Royal Swedish Academy of Science for the 1977 discovery of a third domain of life known as Archaea. The Crafoord Prize is presented by the Royal Swedish Academy of Sciences in recognition of accomplishments in scientific fields not covered by the Nobel Prize, which the academy also selects.

Woese won the John D. and Catherine T. MacArthur Award, known as the “genius award,” in 1984. He was the 12th recipient of the Leeuwenhoek Medal, microbiology’s highest honor given each decade, by the Dutch Royal Academy of Science in 1992 and the National Medal of Science in 2000. He is a member of the National Academy of Sciences, the American Academy of Arts and Sciences, the American Philosophical Society and a foreign associate of the Royal Society (U.K.). Posted March 24, 2009
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Salyers Receives ASM Award

Professor of Microbiology Abigail Salyers has been given the American Society for Microbiology Graduate MicrobiologyTeaching Award. The honor is given to an individual for distinguished teaching at the graduate level and outstanding mentoring of graduate and postgraduate students.

Salyers is well known for her commitment to microbiology instruction at both the graduate and undergraduate levels. Unsatisfied with the course material available to her students, Salyers co-authored multiple text books and developed the microbiology curriculum for first-year medical students. She has been with the University of Illinois for over 30 years, and was awarded the All-Campus Award for Excellence in Teaching by the University of Illinois College Of Medicine.

Salyers has received international recognition for her research on the spread of antibiotic resistance and is currently researching bacteria found in the human colon. She has mentored over 30 Ph.D. students, over two dozen undergraduates, and continues to run a renowned microbiology laboratory in the School of Molecular and Cellular Biology.

Salyers was nominated for the ASM award by one of her former Ph.D. students, Dr. Thomas Zahrt, who is now an Associate Professor at the Medical College of Wisconsin, Milwaukee. Posted January 24, 2009
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Deborah Paul Creates Endowment at UIUC for AIDS Research

Deborah Paul (M.S. biology 1979) was one of the first AIDS researchers to develop a method for detecting HIV in the blood. She was also part of the team that developed Norvir, a drug used in AIDS treatment. She recently created an endowment at the U of I to fund immunological research.

LAS News     
Posted June 24, 2009
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Novel toxin receptor discovered for ulcer-causing stomach pathogen

Steven Blanke, a University of Illinois professor in the department of microbiology and Institute for Genomic Biology, has helped discover how the bacterium Helicobacter pylori is able to get into cells in the acidic, inhospitable human stomach.

UI News Bureau     
Posted May 24, 2009
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David Clayton Appointed Fellow of Canadian Institute for Advanced Research

Professor of Cell and Developmental Biology David Clayton has been appointed a Fellow of the Canadian Institute for Advanced Research. As a member of the Experience-Based Brain and Biological Development Program, he will work with a distinguished collective of international researchers to consider how early social experiences change neural, endocrine, and immunological systems.

CIFAR     
Posted June 23, 2009
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David Clayton Discovers Genetic Basis of Songbird Memory

Professor of Cell and Developmental Biology David Clayton and colleagues have discovered that the gene expression of a zebra finch is altered when the bird hears a new song by a bird of the same species. The researchers have shown that the auditory forebrain of the finch responds to a new song by switching on and off thousands of genes. Twenty-four hours later, a third pattern of gene expression is present, showing the bird's efforts to process its new memory.

University News Bureau
PNAS
Science Daily
Wall Street Journal     
Posted June 26, 2009
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Brian Freeman Receives 2009 Educator's Award

Assistant Professor of Cell and Developmental Biology Brian Freeman received the 2009 Educator’s Award from the UI Alumni Association in April. He was nominated by Joyce Woo, a graduating senior who entered the U of I at age 14. “As a student, there are few ways I can thank an individual who has served as a leader, role model and mentor,” Woo wrote, saying she considered it “an honor to have studied under a brilliant scientist and great person.”

UI Alumni Association     
Posted July 06, 2009
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New Estrogen Source Discovered

A new discovery in the newly created Center for Research in Reproduction and Infertility has revealed a previously unknown site of estrogen synthesis. Though the ovaries produce estrogen, research showed that embryos in mice with the ovaries removed still implanted successfully, suggesting the presence of estrogen produced in a different site. Looking for another source of estrogen, the researchers found an enzyme, P450 aromatase, in uterine tissues that converts testosterone to estrogen. Inhibiting this enzyme prevented implantation and blocked the critical differentiation and remodeling of uterine cells as well as vessel development. This newly discovered source of estrogen as a critical control mechanism explains several phenomena, including the inability of mice missing the aromatase gene to become pregnant even when supplied extra estrogen. The findings, published by lead author Amrita Das, a graduate student in Vet Biosciences, appear in the Proceedings of the National Academy of Sciences.

PNAS
First Science
Science Daily
Science Centric     
Posted July 21, 2009
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Welcoming Susan Martinis

Effective July 16, Dr. Susan Martinis was appointed as Interim Department Head for Biochemistry upon the departure of Dr. Colin Wraight after more than five years of extraordinary service to the Department of Biochemistry and School of Molecular and Cellular Biology. A search for a new Department Head will begin during the fall semester. Professor Martinis earned her Ph.D. on this campus in 1990, and completed postdoctoral work at the Massachusetts Institute of Technology. Her central research interests include RNA structure and function and tRNA synthetases. Posted July 21, 2009
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Martha Gillette cited by NIH

Alumni Professor of Cell and Developmental Biology Martha Gillette is cited in an article about circadian rhythms published by NIH News in Health, a publication of the National Institutes of Health.

NIH News in Health     
Posted August 06, 2009
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Carl Woese named in Science

In the eighth essay in Science’s series in honor of the Year of Darwin, Carl Zimmer describes one of the most important transitions in the history of life: the origin of cells with a nucleus, which gave rise to every multicellular form of life. In the 1970s, U. of I. microbiologist Carl Woese and his colleagues discovered archaea, a third branch on the evolutionary tree.

Science     
Posted August 07, 2009
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Welcoming Dr. Eric Bolton and Dr. Hee Jung Chung

Dr. Eric Bolton and Dr. Hee Jung Chung have accepted offers to join the MCB faculty in the Department of Molecular and Integrative Physiology. They arrive and begin work in early January. Posted August 11, 2009
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John Gerlt receives Arthur C. Cope Scholar Award

Gutgsell Endowed Professor of Biochemistry John Gerlt has been selected by the American Chemical Society as an ACS 2010 Award Winner. Dr. Gerlt was one of ten national candidates to receive an Arthur C. Cope Scholar Award sponsored by the Arthur C. Cope Fund.

ACS     
Posted September 03, 2009
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Maria Spies receives Margaret Oakley Dayhoff Award

Assistant Professor of Biochemistry and Biophysics Maria Spies has received the 2010 Margaret Oakley Dayhoff Award from the Biophysical Society. This prestigious award honors Spies's impressive achievements in biophysical research at the early stages of her academic career. It also recognizes her promise as an emerging leader in the scientific community. According to the Biophysical Society, Spies was selected for "her exemplary research into the mechanisms of DNA repair and the cell cycle maintenance machinery."

Dr. Spies and her work will be featured at the Awards Symposium during the 54th Annual Meeting of the Biophysics Society in San Francisco this coming February, 2010.

Earlier this year, Dr. Spies received a Howard Hughes Medical Institute (HHMI) Early Career Scientist Award.

Biophysical Society     
Posted September 03, 2009
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Differential Effect of ssDNA-Binding Proteins on DNA Translocation

Biochemistry professor Maria Spies and biochemistry affiliate Taekjip Ha are contributing authors of an article newly published in Molecular Cell: "Single-Molecule Analysis Reveals Differential Effect of ssDNA-Binding Proteins on DNA Translocation by XPD Helicase." The issue also includes a preview article that attempts to introduce their findings using a metaphor nonscientists can understand.

Molecular Cell article
Molecular Cell preview     
Posted September 17, 2009
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Steven Blanke Published in Science

Although once thought to be largely irrelevant in the biological world, new and unexpected functions for D-amino acids continue to emerge, microbiology professor Steven R. Blanke says in a “Perspective” essay in this week's issue of Science.

Science     
Posted September 18, 2009
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Colin Wraight Granted 2009 MCB Faculty Excellence Award

Colin Wraight, former head of the Department of Biochemistry, is the recipient of the 2009 MCB Faculty Excellence Award. This award is made to recognize outstanding contribution to the instructional and research missions of the School of Molecular and Cellular Biology and the University of Illinois. In addition to a prominent plaque display, a reception will be held next year to celebrate his receipt of this award as well as to thank Colin for his service as Department Head in Biochemistry. Posted September 22, 2009
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Raven Huang Discovers First Bacterial RNA Repair Mechanism

In new papers appearing in October in Science and the Proceedings of the National Academy of Sciences (PNAS), University of Illinois biochemistry professor Raven H. Huang and his colleagues describe the first RNA repair system to be discovered in bacteria. This is only the second RNA repair system discovered to date (with two proteins from T4 phage, a virus that attacks bacteria, as the first). The novelty of the newly discovered bacterial RNA repair system is that, before the damaged RNA is sealed, a methyl group is added to the two-prime hydroxyl group at the cleavage site of the damaged RNA, making it impossible to cleave the site again. Thus, the repaired RNA is “better than new.”

This discovery has implications for protecting cells against ribotoxins, a class of toxins that kills cells by cleaving essential RNAs involved in protein translation. Because the enzyme responsible for methylation in the newly-discovered RNA repair system is the Hen1 homolog in bacteria, the discovery has also implications for the understanding of RNA interference and gene expression in plants, animals, and other eukaryotes. The eukaryotic Hen1 is one of three enzymes (along with Dicer and Argonaute) essential for the generation of small non-coding RNAs of 19-30 nucleotides in RNA interference.

While the Science paper describes the mechanism of the entire RNA repair process, the article in PNAS focuses on the chemistry of methylation reaction, specifically the crystal structure of the methyltransferase domain of bacterial Hen1. Because the eukaryotic Hen1 carries out the same chemical reaction, the study should further understanding of RNA interference in eukaryotic organisms.

According to Professor Huang, “Hen1 is one of three essential enzymes in generating small noncoding RNAs for RNA interference in eukaryotes. We found out that Hen1 homologs exists in bacteria, but bacteria have no RNA interference. Therefore, we were very curious to find out what bacterial Hen1 is used for.”

“Our studies demonstrated that bacterial Hen1 carries out the same chemical reaction as its counterpart in eukaryotes, which was not surprising. What surprised us was that, instead of involvement in RNA interference, the bacterial Hen1 is part of a RNA repair and modification system. And Hen1 is responsible for producing the repaired RNA that is ‘better than new.’”

Science
PNAS
News Medical
Red Orbit
e! Science News
Medical News
Genetic Engineering and Biotechnology News     
Posted October 12, 2009
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Richard Gumport (1937-2009)

Richard I. Gumport, Ph.D., 72, professor emeritus of biochemistry, retired associate dean of the College of Medicine, and a native of Pocatello, Idaho, died Oct. 13, 2009, at his home in Chicago.

Dr. Gumport had a particular interest in learning how enzymes and proteins interacted with DNA sequences. As professor emeritus, he continued to publish articles and mentor undergraduates.

He was preceded in death by his wife Roberta. Posted October 19, 2009
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MCB Third Most Popular Major

In a news story published October 17th, Molecular and Cellular Biology was identified as the third most popular major among undergraduates at the University of Illinois.

MCB was narrowly edged out by Electrical Engineering, and placed third behind psychology. MCB is one of the largest schools in the College of Liberal Arts and Sciences, which claims three of the top four majors.

Daily Illini     
Posted October 20, 2009
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Benita Katzenellenbogen Receives 2009 Komen Brinker Award

Swanlund Professor of Cell and Developmental Biology and Molecular and Integrative Physiology Benita Katzenellenbogen has received the 2009 Susan G. Komen for the Cure Brinker Award for Scientific Distinction in basic science and clinical research for her work investigating breast cancer treatments.

This is the highest award of merit given by the nation’s leading breast cancer advocacy organization.

Katzenellenbogen is being honored for pivotal laboratory work that led to a better understanding of how drugs like tamoxifen and raloxifene work on a molecular level to fight and prevent certain breast cancers.

These drugs fight the hormone sensitive breast cancers that account for 70 percent of all breast cancers. The survival rates for all breast cancers is now 89 percent, largely due to the successful use of these hormone therapies before and after surgery.

Katzenenellenbogen, along with the other two honorees, will deliver a keynote lecture and be honored at the 32nd annual San Antonio Breast Cancer Symposium, a major international gathering of breast cancer researchers, clinicians and patient advocacy organizations. She will receive a cash award of $25,000.

Benita S. Katzenellenbogen is a Fellow of the American Academy of Arts and Sciences and recently served as president of The Endocrine Society, the world's largest professional society representing approximately 10,000 endocrinologists. She has published more than 270 research articles and co-edited a book on “Hormone-Dependent Cancer.” During her career she has received 5 different Komen grants.

The Brinker Award for Scientific Distinction was established in 1992 to recognize the efforts of pioneers in two critically important areas of the fight to end breast cancer: clinical research and basic science. Nancy G. Brinker promised her dying sister, Susan G. Komen, she would do everything in her power to end breast cancer forever. In 1982, that promise became Susan G. Komen for the Cure and launched the global breast cancer movement. Today, Komen for the Cure is the world's largest grassroots network of breast cancer survivors and activists fighting to save lives, empower people, ensure quality care for all and energize science to find the cures.

Susan G. Komen for the Cure
Benita Katzenellenbogen's faculty profile
Reuters     
Posted October 27, 2009
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Associate Professor Jonsook Kim Kemper Published in Cell Metabolism

Associate Professor of Molecular and Integrative Physiology Jongsook Kim Kemper is the lead author on a paper published in Cell Metabolism: "FXR Acetylation Is Normally Dynamically Regulated by p300 and SIRT1 but Constitutively Elevated in Metabolic Disease States."

From the abstract:

The nuclear bile acid receptor FXR is critical for regulation of lipid and glucose metabolism. Here, we report that FXR is a target of SIRT1, a deacetylase that mediates nutritional and hormonal modulation of hepatic metabolism. Lysine 217 of FXR is the major acetylation site targeted by p300 and SIRT1. Acetylation of FXR increases its stability but inhibits heterodimerization with RXRα, DNA binding, and transactivation activity. Downregulation of hepatic SIRT1 increased FXR acetylation with deleterious metabolic outcomes. Surprisingly, in mouse models of metabolic disease, FXR interaction with SIRT1 and p300 was dramatically altered, FXR acetylation levels were elevated, and overexpression of SIRT1 or resveratrol treatment reduced acetylated FXR levels. Our data demonstrate that FXR acetylation is normally dynamically regulated by p300 and SIRT1 but is constitutively elevated in metabolic disease states. Small molecules that inhibit FXR acetylation by targeting SIRT1 or p300 may be promising therapeutic agents for metabolic disorders.

Cell Metabolism     
Posted November 03, 2009
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Carvedilol Shown to have Unique Characteristics Among Beta Blockers

In a new study, Kevin Xiang and colleagues report that a class of heart medications called beta-blockers can have a helpful, or harmful, effect on the heart, depending on their molecular activity.

The study, which appears in the journal Circulation Research, and which has been selected for comment by Faculty of 1000 Biology, found that beta-blockers that target both the alpha- and beta-receptors on the heart muscle offer the most benefit to cardiac patients, while those that target only the beta-receptors can actually undermine the structure and function of the heart.

Circulation Research is published by the American Heart Association.

Heart disease is the leading cause of death in the United States. Patients with heart disease usually have higher levels of catecholamines – hormones that activate the beta-adrenergic receptors to stimulate cardiac muscle contraction. In this process, the heart initially grows to become a more efficient pump. Unfortunately, the researchers found, this growth also predisposes the heart to eventual failure.

Traditionally, beta-blockers targeting the beta-adrenergic receptors have been utilized as a long-term therapy for heart failure.

Interestingly, blocking adrenergic receptors has been widely used clinically for nearly 50 years without a full understanding of the molecular consequences of these drugs, said co-author and graduate student David Cervantes. Kevin Xiang, a professor of molecular and integrative physiology at the University of Illinois led the study. The research team also included researcher Catherine Crosby.

A previous study in 2003 showed that the beta-blocker carvedilol produced a greater survival benefit than another drug, metoprolol tartrate. Carvedilol targets both the beta- and alpha-adrenergic receptors.

The new study unveiled an elegant intracellular signaling system in which beta-receptor activation modulates alpha-adrenergic signaling. It showed that blocking the beta-receptor alone promotes cardiac remodeling via growth of cardiac fibroblasts induced by alpha-adrenergic receptor signaling. The growth of fibroblasts in the heart further damages the integrity and function of the heart.

This observation suggests that the use of carvedilol in combination with inhibitors of angiotensin-converting enzyme (ACE inhibitors) may be of the greatest benefit to cardiac patients, and has significant clinical implications on which beta-blockers patients should take.

"I think this is really good stuff," Xiang says. "It's a surprise project. It's not what we initially intended looking into. But it's a very nice, elegant study and a very beautiful cellular mechanism. It definitely will help people along the way to understand how to further manipulate this system. Beta blockers are still the most commonly used drug for heart disease."

Circulation Research
Faculty of 1000     
Posted November 19, 2009
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Morrissey and Colleagues Further Unravel Mysteries of Thrombosis

In a new study published in Cell, and rated "exceptional" by the Faculty of 1000 Biology, Professor of Biochemistry Jim Morrissey and colleagues have determined that polyphosphate, an inorganic polymer of phosphate secreted by human platelets, is an important link in thrombotic diseases and inflammation.

The three authors of the study from Dr. James Morrissey’s group at the University of Illinois had previously demonstrated, in a paper appearing in The Proceedings of the National Academy of Sciences (PNAS) in 2006, that polyphosphate triggers blood clotting via the contact pathway, one of two known pathways for initiating clotting. The contact pathway is dispensable for hemostasis, the normal clotting process that stops bleeding following injury. On the other hand, the contact pathway was recently shown to play an essential role in thrombosis, the formation of clots inside rather than outside a blood vessel, and also in stroke, in papers published in the Journal of Experimental Medicine in 2005 and 2006 by Dr. Thomas Renné and colleagues.

Said Dr. Morrissey, “I met Dr. Renné over a lobster dinner in a chance meeting at a Gordon conference on hemostasis. We were excited by one another’s research and the connections between our work. His studies in vivo related strongly to our own experiments in vitro. We decided to work together to investigate more closely the relationships between the contact pathway, polyphosphates, and platelets.”

This international collaboration has resulted in new findings appearing in the journal Cell. The paper shows, via a study involving several labs, that polyphosphate is also important in thrombotic diseases—abnormal processes in which unwanted blood clots block arteries or veins, causing often life-threatening tissue damage—and in platelet-driven inflammatory processes.

For many decades, it has been known that the contact pathway of blood clotting can be triggered when blood is mixed with materials such as glass or clay, substances that blood would not normally come into contact with, even in disease states. This is the underlying principle for a widely used diagnostic blood clotting test termed aPTT. The present study indicates that polyphosphate may represent the long-sought "foreign" substance that triggers blood clotting by activated platelets, certain types of tissue damage, and infectious organisms.

“The data obtained in an international collaboration with British, Swedish, Dutch, German and American universities indicate that polyphosphate initiates blood clotting on platelets with critical importance for thrombotic diseases,” said Dr. Renné from the Karolinska Institute, Stockholm.

The new study, suggesting that polyphosphate may represent a new target for interrupting thrombotic and inflammatory processes in multiple diseases, has myriad implications for new medical treatments of major diseases.

Cell
Faculty of 1000 Biology     
Posted December 10, 2009
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