"What Matters" - 2015 Commencement address delivered by alumna, Dr. Tamara Helfer
Dr. Tamara Helfer, center, with Brad Mehrtens, Tina Knox, Stephen Sligar, and one of Dr. Helfer’s special deliveries on the left, the mini Mehrtens.
Dr. Tamara Helfer practices Obstetrics and Gynecology with Christie Clinic in Champaign, IL. A graduate of the University of Illinois, Dr. Helfer earned her BS in Microbiology and MBA from the University of Illinois at Urbana-Champaign. She earned her medical degree at the University of Illinois College of Medicine in Peoria, IL and completed her residency at the University of Missouri Hospital in Columbia, MO.
Dr. Helfer reminded graduates that “what matters” are the people and the process, not necessarily the outcome. And though graduates will soon get caught up in the frenzy of work life or further studies, Dr. Helfer reminded all to listen, be present, embrace failure, and be passionate. Her advice for new professionals: be humble; believe in people and trust; stay true to yourself; and say yes to life, love, and opportunity.
Dr. Helfer has served on multiple committees for The American Congress of Obstetricians and Gynecologist, ACOG, including the Coding and Health Economics, the Practice Management and the Industrial Exhibits Committee. She has been ACOG’s District VI Young Physician for the past 7 years, and is the Past President of the Champaign County Medical Society. Dr. Helfer enjoys having undergraduates, midlevel care providers, and medical students from the University of Illinois shadow her Practice. Once a semester, she is a guest lecturer to undergraduates and speaks on Ethics in Medicine.
Posted June 30, 2015
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Kevin Yum’s outstanding undergraduate career
His undergraduate research focused on understanding the pathogenesis of Myotonic Dystrophy type 1 (DM1), an autosomal dominant neuromuscular disease that affects 1 in 8,000 individuals worldwide. As an undergraduate researcher, Kevin investigated the role of muscleblind-like splicing factor 1 (MBNL1) and its implications in DM1 liver pathology and misregulation of alternative splicing.
“I enjoyed working with Dr. Kalsotra on the DM1 project, since it is a rare disease caused by toxic RNA gain-of-function that sequesters an essential splicing factor MBNL1. Fully elucidating the mechanism of this disease will not only lead us to devise new therapeutic approaches to treat DM1 patients but also discover other RNA-mediated disease-causing mechanisms and revolutionize the way we think about current diseases.” said Kevin.
Kevin also commented that his research experience at Illinois was truly amazing. He not only learned about the most cutting edge techniques in biochemistry and molecular biology but was able to apply many of those techniques in actual research.
“Since there are such diverse research areas covered by the distinguished MCB/Biochemistry faculty members on our campus, it was easy for me to find the lab that sparked my interest and advanced my understanding of basic science,” he said. “I was able to benefit from attending weekly seminars hosted by the school of MCB, where both graduate and undergraduate students can participate to explore current topics and latest research in the field.”
In addition to receiving the departmental awards, Kevin also won the Outstanding Oral Presentation Award during the campus-wide Undergraduate Research Week as well as the James Scholar Preble Research Scholarship. He believes that these accomplishments could not have been made without the invaluable skills in grant writing and research presentation he obtained from taking senior seminar courses.
Kevin plans to continue working in the Kalsotra lab for the next two years before pursuing a combined MD/PhD degree. His long-term goal is to seek a career in academia in order to teach and motivate the next-generation of students to become scientists.
Posted June 26, 2015
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Biochemistry graduate student wins NSF pre-doctoral fellowship
Livezey is currently working on two projects with Professor Shapiro, whose focus is on the discovery and use of novel small molecule biomodulators to identify and analyze interactions and pathways important in cancer and in the development of these small molecules as potential anticancer drugs.
Livezey’s first project is working on getting a new anti-cancer drug, BHPI, ready for clinical trials by figuring out how exactly the drug is so successful at shrinking tumors.
Her second project explores the pathway by which estrogen is protective in neurodegenerative diseases, such as Parkinson’s and Alzheimer’s.
Livezey says that her interest in these projects and the Shapiro Lab is not just because the science is so fascinating but also because the experience of disease in her own family has motivated her to search for cures. “I understand what the possible impacts are, and that is why science is so great.”
A first-year graduate student, Livezey chose the University of Illinois’s Biochemistry department because of the variety of biochemical research being done, including structural biology using crystallography; the physiology-related work; and the connection with the Chemical Biology department.
She applied for the fellowship during her second rotation with Biochemistry Affiliate Dr. Jefferson Chan, who, along with Dr. Auinash Kalsotra (Assistant Professor in Biochemistry), Livezey credits for providing significant feedback on her research statement and application.
The NSF Graduate Research Fellowship Program (GRFP) is awarded yearly to ensure the vitality and diversity of the scientific and engineering workforce of the United States. The program recognizes and supports outstanding graduate students who are pursuing research-based master's and doctoral degrees in science and engineering. The GRFP provides three years of support for the graduate education of individuals who have demonstrated their potential for significant achievements in science and engineering.
Posted May 06, 2015
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A new RNA repair complex employing a “one-stop shopping” repair mechanism
To fight for a limited resource of nutrition in the wildness, microbes release toxins to kill their neighbors to increase their share of nutrition. A majority of toxins are ribotoxins that cleave essential RNAs involved in protein translation, which are conserved in and required for all organisms to live. To counter the damage inflicted by ribotoxins, organisms employ protein enzymes to repair the damaged RNA for survival. Over the past several years, the Huang group has been engaged in discovery, biochemical and structural characterization of RNA repair systems. Significant research includes the discovery of a Pnkp–Hen1 RNA repair complex that carries out RNA repair with immunity. In the present study, published in the journal Nature Communications, Huang and coworkers described the discovery and characterization of a new bacterial RNA repair complex. The approach involved bioinformatic analyses to reveal the presence of a new putative RNA repair system in certain bacteria. The genes encoding three proteins (named Pnkp1, Rnl, and Hen1) that constitute the putative new RNA repair system were then cloned into expression vectors. All three proteins were overexpressed in E. coli and purified to homogeneity. In vitro reconstitution using the purified recombinant proteins and a ribotoxin-cleaved RNA substrate demonstrated that RNA repair requires the presence of all three proteins. Furthermore, the three proteins were shown to form a heterohexamer in vitro. Huang and coworkers were able to crystallize and solve the structure of the Pnkp–Rnl–Hen1 heterohexamer. The structure revealed the molecular architecture of the heterohexamer as two ring structures of Pnkp1–Rnl–Hen1 heterotrimer fused at the Pnkp1 dimer interface. The four active sites required for RNA repair are located on the inner rim of each ring, reminiscent of architectures of shopping malls. This particular arrangement of the four active sites suggests that RNA repair might be carried out via a “one-stop shopping” mechanism. Unlike the Pnkp–Hen1 RNA repair complex, which is present in many bacteria, the newly discovered Pnkp1–Rnl–Hen1 RNA repair complex is only found in ten bacterial species so far. Interestingly, the majority of the bacteria possessing the newly discovered RNA repair complex live in gingival plaques of human mouth. Huang hypothesized that the unique RNA repair carried out by the Pnkp1–Rnl–Hen1 complex in these bacteria might provide them with a heightened ability to survive. If this hypothesis proves to be correct, inhibiting RNA repair might provide a vehicle to reduce the population of these bacteria, which are linked to human dental and gum diseases. Development of small-molecule inhibitors of the new RNA repair complex is currently underway in Huang laboratory to test this possibility.
Microbes Scared to Death by Virus Presence
University of Illinois researchers found that Sulfolobus islandicus can go dormant, ceasing to grow and reproduce, in order to protect themselves from infection by Sulfolobus spindle-shaped virus 9 (SSV9). The dormant microbes are able to recover if the virus goes away within 24 to 48 hours—otherwise they die. “The microbe is hedging its bet,” said Associate Professor of Microbiology Rachel Whitaker, who led the research at the Carl R. Woese Institute for Genomic Biology. “If they go dormant, they might die, but we think this must be better than getting infected and passing it on.” Sulfolobus is a species of archaea (a domain of single-celled organisms distinct from bacteria) found in acidic hot springs all over the world, where free viruses are not as common as in other environments. These microbes will go dormant in the presence of just a few viruses, whether active or inactive. While inactivated virus particles cannot infect a host, Whitaker’s lab found they could still cause dormancy, and ultimately, death in Sulfolobus. “People thought these inactivated viruses were just an accident, that they were just mispackaged,” Whitaker said. “Now we know they are being sensed by the host so they are having an effect. People are starting to think that it is adaptive for the virus to produce inactivated virus particles.” Sulfolobus have an adaptive immune system found in archaea and bacteria that allows the microbe to encode a specific piece of DNA that matches the viral DNA, causing it to target the viral DNA and degrade it thus preventing the virus from propagating, or reproducing. Cultures with immunity to SSV9 recover from dormancy and grow normally once the virus is removed from the culture. Microbes without this immunity are susceptible to infection and eventually kill their neighbors by maintaining viral particles in the environment. The researchers do not know exactly what is going on while the microbes are dormant, only that the microbes look drastically different in that state. More research is needed to better understand these new interactions between microbes and viruses. Incorporating these findings into models will show the true ecological impact of viruses in the microbial world, Whitaker said. “We really don’t understand the way that viruses affect microbes,” Whitaker said. “There is a lot to learn. These communities are usually modeled where a virus will either kill the microbe or the microbe is resistant. But actually there are all these other subtleties going on, like dormancy, that are having a bigger impact than we understand.” Dormant microbes are found everywhere, in water, soil, and even the human gut, said Maria Bautista, a graduate student in Whitaker’s lab, who led the research. “Many microbes go dormant when they face environmental stress such as a change in pH or temperature ” Bautista said. “Maybe virus-induced dormancy is something that doesn’t just happen in Sulfolobus; it may be a widespread response to viruses in other environments. We don’t know.” The NSF supported this work. The paper, “Virus-Induced Dormancy in Archaeon Sulfolobus islandicus,” is available online (doi:10.1128/mBio.02565-14). Article by Claire Sturgeon and photo by Kathryn Coulter, Carl R. Woese Institute for Genomic Biology
New drug stalls estrogen receptor-positive cancer cells and shrinks tumors
An experimental drug rapidly shrinks most tumors in a mouse model of human breast cancer, researchers report in the Proceedings of the National Academy of Sciences. When mice were treated with the experimental drug, BHPI, “the tumors immediately stopped growing and began shrinking rapidly,” said University of Illinois biochemistry professor and senior author David Shapiro. “In just 10 days, 48 out of the 52 tumors stopped growing, and most shrank 30 to 50 percent.” The key to the drug’s potency lies in its unusual mode of action, Shapiro said. “BHPI works through the estrogen receptor protein, but in a way that is different than estrogenic hormones,” he said. “The drug hyperactivates a pathway called the unfolded protein response, which estrogens normally use to protect cells from stress and help them grow.” Rather than blocking the stress response, BHPI kicks the UPR into overdrive, said M.D./Ph.D. student and lead author Neal Andruska. “This drives the cancer cells from using the UPR in a protective way into making it a lethal pathway,” Andruska said. “In this way, it stops growth and eventually kills many types of breast, ovarian and endometrial cancer cells that contain estrogen receptor.” BHPI shuts down the production of new proteins, including proteins that normally keep the stress response pathway in check, Andruska said. “Eventually, many cancer cells die – in part because they can’t make any new proteins,” he said. BHPI spurs a number of events in the cell, including the opening of calcium channels in the endoplasmic reticulum, a special intracellular compartment. The influx of calcium into the cytoplasm sets off a cascade of events that prepare the cell to deal with stress. The cells try to pump the calcium back into its compartment, but BHPI keeps the calcium channels open, allowing the calcium to flow back into the cytoplasm. After about 30 minutes of this “futile cycle,” the cells run low on energy. (Watch a movie of cancer cells responding to estrogen and BHPI: Anticancer Drug BHPI Hyperactivates a Cell Stress Response to Kill Cancer Cells) “Without enough energy, cancer cells don’t grow,” Shapiro said. The cascade initiated by BHPI eventually turns on four pathways, “each of which could potentially contribute to the death of the cancer cells,” he said. Because the UPR pathway is overexpressed in therapy-resistant cancer cells, the drug is especially effective in targeting estrogen receptor-positive cells that are resistant to tamoxifen and other anti-cancer drugs, the researchers report. “BHPI works equally well in the presence or absence of estrogen,” Shapiro said. The mice that received the drug tolerated it well, with no weight loss or other negative side effects, the researchers said. “It’s still in the early days for this drug, and there are many hurdles to overcome to bring BHPI to the clinic,” Shapiro said. “But so far, it’s been clearing the hurdles by a wide margin.” The study team also includes researchers from the U. of I. department of food science and human nutrition, the department of molecular and integrative physiology, the College of Medicine and the U. of I. Cancer Center. The National Institute of Diabetes and Digestive and Kidney Diseases at the National Institutes of Health and the Department of Defense Breast Cancer Research Program funded this research. Article by Diana Yates, News Bureau Photo by L. Brian Stauffer, News Bureau
Read coverage of the research in the News-Gazette.
Read the full PNAS article here.
Posted April 06, 2015
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A new hat for Aip1: Uncovering new roles for Aip1 in the disassembly of filamentous actin
Disassembly of actin filaments is important for many processes that involve rapid reorganization of cell shape such as cell movement and division. Cofilin is a vital disassembly protein however one limitation of cofilin is that it can stabilize filaments at saturating concentrations. Nadkarni and Brieher showed that the amount of cofilin in thymus extract is too high to allow disassembly of single actin filaments in solution. They discovered that Aip1 is able to disassemble filaments even in the presence of stabilizing concentrations of cofilin. In the presence of Aip1, stable filaments underwent increased severing and disassembly at filament ends. This indicated that Aip1 could act all along the sides of cofilin-decorated actin filaments. However, previous work had shown that Aip1 was a capping factor that acted at filament ends. Nadkarni and Brieher went on to show that Aip1 acts differently than a well-characterized capping factor CapZ, and does not behave like a capping factor. This led to a revision of the view of Aip1's mode of action on actin filaments.
Professor Phillip Newmark elected Fellow of the American Association for the Advancement of Science (AAAS).
Newmark was cited for his work in developmental biology, with particular emphasis on regeneration and germ cell development in flatworms, which carry profound implications for the field of regenerative medicine by their ability to regenerate from just a small sample of tissue. Newmark studies how their stem cells contribute to regeneration and tissue maintenance. He earned his PhD from the University of Colorado at Boulder in 1994 and joined the U of I faculty in 2001. Newmark is also an investigator of the Howard Hughes Medical Institute, and the recipient of a CAREER Award from National Science Foundation, and a Damon Runyon Scholar Award from the Damon Runyon Cancer Research Foundation. He has been named a University Scholar. The AAAS, the world’s largest general scientific society, was founded in 1848. Fellows have been elected to the organization since 1874. The organization’s stated goal is to “advance science, engineering, and innovation throughout the world for the benefit of all people.”
Posted December 18, 2014
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Jongsook Kim Kemper’s lab discovers that elevated acetylation of FXR in obesity promotes hepatic inflammation, published in the EMBO Journal
Posttranslational acetylation of transcriptional regulators is often persistently elevated in nutrient-excessive obesity conditions. In this study, we investigated the functional consequences of such elevated acetylation of the key metabolic regulator and bile acid nuclear receptor FXR. Proteomic studies identified Lys-217 as the FXR acetylation site in diet-induced obese mice. In vivo studies utilizing acetylation-mimic and acetylation-defective Lys-217 mutants and gene expression profiling revealed that FXR acetylation increased proinflammatory gene expression, inflammatory responses, and liver fat levels, and impaired insulin sensitivity. Mechanistically, agonist-activated FXR is SUMO2-modified at lysine 277 by the PIASy SUMO E3 ligase. SUMOylation of FXR inhibits inflammatory gene expression in response to inflammatory signaling. Selective transrepression of inflammatory genes results from increased interaction of SUMO-FXR with NF-kB. In obese mice, FXR acetylation at lysine 217 inhibits its SUMOylation and diminishes SUMO2-dependent FXR anti-inflammatory action. There are several important aspects to this study. First, although posttranslational modifications (PTMs) of proteins have been extensively studied, there is little evidence establishing the physiological/pathological relevance of PTMs and the mechanisms underlying PTM-mediated selective gene regulation. The present study, for the first time, demonstrates the relevance in vivo of a functional antagonism between acetylation and SUMOylation of FXR in diet-induced obese mice. Second, agonist-activated SUMOylated FXR selectively trans-represses NF-κB target inflammatory genes without transcriptionally regulating conventional FXR/RXRα target genes and further, the results indicate that the underlying mechanism is the selective interaction of SUMO2-FXR with NF-κB and not with RXRα. Third, since FXR is expressed in many non-hepatic tissues, including intestine, kidney, endothelial cells, and macrophages, the dysregulated acetyl/SUMO switch identified for liver FXR in obesity may also play a role in the pathogenesis of inflammatory diseases in other tissues, such as inflammatory bowel disease and atherosclerosis, as well as, liver steatohepatitis. Targeting the dysregulated acetyl/SUMO switch of FXR may provide novel therapeutic options and diagnostic markers for obesity-related inflammatory and metabolic disorders. This study was supported by grants from National Institutes of Health to Professor Kemper and a post-doctoral fellowship from America Heart Association to Dong-Hyun Kim.
Professor Tajkhorshid Awarded Supercomputing Capacity at DOE National Laboratory
The U.S. Department of Energy Office of Science selected Professor Emad Tajkhorshid’s project for a 2015 Innovative and Novel Computational Impact on Theory and Experiment (INCITE) award. The award provides 96 million hours of massive supercomputing at a Leadership Computing Facility that focuses only on the most ambitious research projects with the potential for major breakthroughs. Tajkhorshid’s lab has been exploring the precise way in which nutrient molecules enter cells and waste molecules leave cells. Proteins known as membrane transporters undergo structural changes to allow a unidirectional transfer of molecules, functioning as active pumps, but just how the pumps work is unknown. “The Holy Grail of structural biology of membrane transporters is to describe this whole transition. Right now we only have the initial and final structures,” said Professor Tajkhorshid. Understanding the transition could allow drug developers to design more targeted drugs for major pathophysiological conditions such as psychological disorders, cancer, and multi-drug resistance. Tajkhorshid’s project, which has been developed and tested in his lab, will study the transition between structural intermediates of a number of transporters using a novel combination of several replica-based techniques coupling a massive array of all-atom molecular dynamics simulations, which are only possible with this type of supercomputing capacity. The goal of the project is to develop an atomistic view of membrane transporter transitions and to understand the ways in which the membrane transporters use energy to function as one-way pumps. The Department of Energy accords supercomputing hours to a small number of projects every year through the INCITE program, which aims to accelerate scientific discoveries and technological innovations to projects that address “grand challenges” in science and engineering. Tajkhorshid’s INCITE award is a two-year grant with the possibility of renewal, and uniquely, the award includes a staff liaison for scientific support. Dr. Tajkhorshid is a professor of biochemistry, pharmacology, and biophysics and computational biology and an affiliate of the Beckman Institute. “This award is order of magnitude larger than anything else we have had in the past. I am very pleased (actually honored) that our project was selected,” he said. To learn more about the fundamental questions involved in this research, watch Dancing Proteins: Cell Membrane Transporter Motion May Revolutionize Drug Therapies. Video courtesy of The Beckman Institute.
Read the press release from the US Department of Energy.
Posted November 19, 2014
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Professor Jongsook Kim Kemper and collaborators discover FXR and CREB as key physiological regulators of autophagy, published in the journal Nature.
Lysosomal degradation of cytoplasmic components by autophagy is essential for cellular survival and energy homeostasis under nutrient-deprived conditions. Acute regulation of autophagy by nutrient-sensing kinases, such as mTOR and AMPK, is well defined, but longer-term transcriptional regulation is not. In this study, Sunmi Seok and Ting Fu (co-first authors) in the Jongsook Kim Kemper lab in the Department of Molecular and Integrative Physiology and collaborators, including Jian Ma’s group in the Department of Bioengineering, have identified the feeding-activated nuclear receptor FXR and the fasting-activated transcriptional factor CREB as key physiological regulators of autophagy. There are several important aspects to this study. First, it was believed that autophagy occurs only under extremely stressful nutrient-deprived conditions but we show that it actually occurs physiologically during feeding/fasting. Second, autophagy does have important metabolic functions, for example lipophagy is dynamically regulated by the FXR/CREB axis. Third, this is the first report that FXR and CREB are transcriptional regulators of the autophagy gene network. Fourth, defective autophagy has been implicated in many diseases but excess autophagy is also harmful because it promotes cell death and also may provide a favorable microenvironment for tumor growth. The team's discovery that the FXR/CREB axis tightly regulates the autophagy gene network reveals potential new targets for developing new drugs to treat human diseases associated with autophagy dysfunction, including metabolic disorders, neurodegenerative disease, and cancer. This study was supported by grants from National Institutes of Health to Professor Kemper.
Scientists engineer human T cell receptors against cancer antigens
T cell receptors are found on the surface of T cells, where they bind to antigens such as those on cancer cells. After activation by the binding of the receptor, the T cell destroys the cancer cell. One of the problems associated with cancer is that a patient’s own T cells may not have the proper T cell receptors that can bind to such antigens. Over the past 15 years, the Kranz group has developed various strategies to attempt to engineer receptors that can serve these purposes, by taking a single receptor from a known T cell clone and improving its affinity for an antigen. In the present study, published in the journal Nature Communications , the scientists showed that it was possible to take a T cell receptor against one antigen (Figure) and using entirely in vitro, directed evolution techniques, to convert this receptor to a completely different specificity. The strategy could thus allow the development of specific receptors, at will, against a large array of known cancer antigens. The approach involved computational analyses to guide the design of “libraries” that contain millions of mutated T cell receptors. The mutants are each displayed on the surface of a yeast cell, and then high-speed instruments called fluorescence activated cell sorters could be used to select only those yeast cells displaying a T cell receptor that binds to the antigen of interest. In the present study, the antigen of interest was derived from human melanoma (Target B in Figure), and the original T cell receptor had been derived from a T cell clone that recognized a viral antigen (Target A in Figure). Various mutational approaches, and molecular dynamics simulations by the Tajkhorshid group, provided insight into how the specific mutations found in the selected T cell receptors allowed binding only to the melanoma antigen. A major implication of the study is that the design approach could be extended to other target antigens providing a platform to rapidly discover T cell receptors against many antigens. Current methods have required that each engineered T cell receptor be generated from human T cell clone, which can take years to produce. Engineered T cell receptors have already reached clinical trials in various therapeutic formats. The present approach provides an additional discovery strategy for their use in the treatment and detection of cancer, viral diseases, and autoimmune diseases, depending on the target antigen chosen for the specific T cell receptor.
Scientists discover a new role for estrogen in the pathology of breast cancer
Scientists have discovered a previously unknown mechanism by which estrogen prepares cells to divide, grow and, in the case of estrogen-positive breast cancers, resist cancer drugs. The researchers say the work reveals new targets for breast cancer therapy and will help doctors predict which patients need the most aggressive treatment. The University of Illinois team reports its findings in the journal Oncogene. Estrogen pre-activates the unfolded-protein response (UPR), a pathway that normally protects cells from stress, the researchers report. The UPR spurs the production of molecular chaperones that prepare cells to divide and grow. Without chaperone proteins to do the work of folding and packaging other proteins, cells – including cancer cells – cannot divide. For this reason, chaperones are a popular target for new cancer therapies. Activation of the UPR is known as a normal response to stress – when a cell lacks adequate oxygen or nutrients, for example, or is exposed to cancer-killing drugs. UPR activation prepares the cell for major changes associated with cell growth, division and survival under stress. It wasn’t known before this study, however, that estrogen initiates this pathway before such stresses appear, said University of Illinois biochemistry professor David Shapiro, who led the new analysis with lead author, M.D.-Ph.D.-student Neal Andruska. “This is a new role for estrogen in the pathology of cancer,” Shapiro said. “Others have shown that stress activates this pathway, helping to protect some tumors. What is new is our finding that estrogen can pre-activate this pathway to protect tumors.” When estrogen binds to its receptor it sparks a cascade of molecular events in the cell. A key event occurs when a channel opens in the membrane of a compartment that stockpiles calcium, and calcium floods into the cell. “That’s a signal to activate the UPR pathway, the stress pathway,” Shapiro said. “It’s also a signal that many researchers think has something to do with cell proliferation. The calcium itself may be a proliferation signal.” The stress-response pathway induces the production of chaperone proteins. “I like to think of this pathway as an assembly line,” Shapiro said. “In order for cells to divide, you’re going to have to produce a lot more proteins. The chaperones help you to package, fold up and ship all these proteins.” The UPR also is a mediator of cell death. If a normal cell is exposed to too much stress, the stress response spurs apoptosis, a kind of cellular suicide. In cancer, however, mild activation of the UPR by estrogen blunts this cell-death pathway, allowing cancer cells to survive and even resist drugs, the researchers found. The team also looked at the expression of UPR-related genes in publicly available data from samples of breast tumors obtained from women who had been diagnosed up to 15 years prior. “Andruska, who spearheaded the research and carried out the computer analysis of the breast cancer data, found that UPR activation is a very powerful prognostic marker of the course of a woman’s disease,” Shapiro said. The analysis revealed that among women with estrogen-receptor-positive breast cancer who underwent tamoxifen therapy, breast cancer was 3.7 times more likely to recur in those overexpressing the UPR. Ten years after a breast cancer diagnosis, only 15 percent of those with the highest level of UPR-gene expression were disease-free, compared with 80 percent of women with minimal UPR expression. “Our marker helps identify breast cancers that are likely to be highly aggressive and therefore require intensive therapy,” Shapiro said. U. of I. graduate student Xiaobin Zheng, postdoctoral researcher Xujuan Yang and food science and human nutrition professor William Helferich contributed to the research. The National Institute of Diabetes and Digestive and Kidney Diseases at the National Institutes of Health funded the research. Written by: Diana Yates, News Bureau Life Sciences Editor