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https://engineering.wustl.edu/news/Pages/2-6-million-to-build-versatile-genetic-toolkit-for-studying-animal-behavior.aspx693$2.6 million to build genetic toolkit for studying animal behavior<p>​On Aug. 1, the National Science Foundation announced <a href="https://nsf.gov/awardsearch/showAward?AWD_ID=1707221">17 Next Generation Networks for Neuroscience (NeuroNex) awards</a> for projects that will yield innovative ways to tackle the mysteries of the brain.<br/></p><img alt="" src="/news/PublishingImages/Collecting_bees2-760x570.jpg?RenditionID=1" style="BORDER:0px solid;" /><p>​A team from Washington University in St. Louis and the University of Illinois at Urbana-Champaign was awarded $2.6 million to develop a simplified genetic toolkit that will allow scientists who study animal behavior to test hypotheses about its neural underpinnings. The Washington University award is intended to establish a NeuroNex Technology Hub that will develop and disseminate innovative neurotechnology.</p><p><a href="https://source.wustl.edu/experts/yehuda-ben-sharar/">Yehuda Ben-Shahar</a>, the project’s principal investigator and associate professor of biology in Arts & Sciences, said much of what we know about the connections between behavior and the brain is derived from work with just four species: the fruit fly, mouse, roundworm and zebrafish.</p><p>As science has progressed, hard core neuroscience and ethology (the study of animal behavior) have drifted apart. “Fewer scientists trained as ethologists would consider testing a hypothesis or model by genetic manipulation,” Ben-Shahar said, “because they’re not trained in the techniques, and there are all sorts of real and imaginary barriers to adopting them.”</p><p>So the goal of his team is to devise a simple approach that can be used to produce animal lines that would readily accept transgenes (foreign genes) and to teach organismal biologists how to use it.</p><p>In proof-of-principle demonstrations, his team will insert a gene into the olfactory neurons of locusts and honey bees that will allow researchers to watch the response to odors. Although they are starting with insects, the ultimate goal, Ben-Shahar said, is a flexible set of tools that scientists can easily tailor for any purpose and any animal.</p><p>Working with Ben-Shahar will be <a href="/Profiles/Pages/Barani-Raman.aspx">Barani Raman</a>, associate professor of biomedical engineering in the School of Engineering & Applied Science at Washington University; Gene Robinson, director of the Carl R. Woese Institute for Genomic Biology at the University of Illinois at Urbana-Champaign; and <a href="https://wubio.wustl.edu/duncan">Ian Duncan</a>, professor of biology in Arts & Sciences at Washington University.</p><p>Raman maintains a breeding facility for the locust Schistocerca americana and Robinson for the honeybee Apis mellifera. Duncan studies the gene expression in fruit flies as they develop from larva to pupa to fly.</p><h3>A sampling problem</h3><p>Ben-Shahar has nothing against model organisms. In fact, his desk is covered with small flasks of fruit flies stoppered with cotton balls. “Some were different species of Drosophila, he said. “Others were various transgenic animals for one of my side projects. I like to keep them on my desk so I don’t forget to take care of them.”</p><p>Still, he points out that the number of species we study with modern neuroscience tools has been steadily shrinking. Many breakthroughs in the neurosciences were made with species that are now rare in the lab. For example, the action potential, or nerve impulse, was originally characterized in the squid, which happened to have a giant axon, or nerve projection, so that it could contract the muscles needed to jet away from danger as quickly as possible. Yet, squids are rarely used in neuroscience research nowadays.</p><p>Gradually, the animals used for basic neuroscience have been reduced to a few whose genomes have been completely sequenced. The tools for neural imaging and optogenetics (the manipulation of genes with light) exist primarily for these chosen few, so the gap between canonical model organisms and species not considered genetically tractable is rapidly widening.</p><p>Given the accidental way model organisms were chosen, it is highly unlikely that they are the best or the only model organisms we will need to understand the brain. “The brain is a noisy organ,” Ben-Shahar said. “Sometimes there’s no easy way to start understanding how something works in a human or a mouse, but you might be able to make a start on a nervous system that is a bit simpler, simple enough that you can see a signal in the noise.”</p><h3>Insert cassette, press play</h3><p>So how does the team propose to turn neurogenetics into a turnkey operation? To create transgenic animals, they need to be able to control the location where the foreign gene is inserted and the efficiency with which the swap is made. The scientists propose to achieve both goals with the help of a two-step process.</p><p>The first step relies on the CRISPR/Cas9 genome editing to substitute DNA “landing sites” for a foreign gene (a transgene) for a gene called white that is found in similar or identical form in most insects.</p><p>When there is a mutation in white, insects’ eyes, which are typically bright red, turn white. White was one of the first genes identified in T.H. Morgan’s fly room at Columbia University because the white-eyed flies were so easy to spot among their red-eyed siblings.</p><p>CRISPR/Cas9 is a homing device (the CRISPR part) that guides molecular scissors (the Cas9 enzyme). The scientists plan to use CRISPR/Cas9 to cut a section out of white that is then replaced with a foreign piece of DNA that codes for red fluorescent protein and for “landing sites” for the enzyme used in the next step.</p><p>This first step produces stable insect lines prepped for the insertion of any additional pieces of foreign DNA and which can be easily identified by their white eyes or, under the right light, glowing red eyes.</p><p>In the second step, the transgene of a scientist’s choosing will be inserted into the “landing site” by a second, highly efficient reaction that replaces the red fluorescent protein. If the integration is successful, the insect’s eyes will remain white, but the fluorescent proteins will be lost and the eyes will no longer glow.</p><p>The reason for the two step process, Ben-Shahar explains, is that CRISPR/Cas9, while precise, is not efficient, meaning that most of the time the effort to insert the DNA cassette in the white gene will fail. But the second step makes use of an enzyme that is highly specific, fast and efficient.</p><p>“That’s the trick,” Ben-Shahar said. “We take a first step that is low efficiency and we generate a line that can be used to construct many different transgenic animals with very high efficiency.”</p><h3>Taking it for a spin</h3><p>The scientists will beta test their toolkit by generating honey bee and locust lines that express a reporter for neural activity in olfactory (smell) neurons.</p><p>This reporter, called GCaMP, is a genetically encoded protein, which acts as a fluorescent indicator for levels of calcium ions in neurons. The more active a neuron, the higher its calcium levels, so bright fluorescent GCaMP signals indicate nerves are firing.<br/></p><p>The Raman lab has been studying the olfactory system of the locust for a long time, Ben-Shahar said, but they’ve been using the traditional method of recording neuronal activity by directly measuring the electrical activity of neurons. “That gives you very high temporal resolution,” he said, “but you can only record activity in a few neurons.”</p><p>“What we’re going to try to do is to generate grasshoppers with calcium reporters in larger populations of neurons — tens to hundreds of neurons. The idea is to do the same experiments they’ve done already to see if the activity in whole regions of the brain or subpopulations of neurons differs from the electrophysiological data they have on individual neurons.</p><p>“We’ll try something very similar with the honeybee,” he said, “again inserting a calcium reporter in areas of the brain thought to be important for olfaction. One interesting question we could address is how olfaction changes as bees age into different roles in the hive.”</p><p>As workers get older, he explains, their roles change from nursing and cleaning the hive to guarding and foraging. “Nurse bees are attentive to olfactory cues released by the larvae  to which foragers pay no attention,” he said. “How does that work? The foragers used to be nurses, after all. What changes in a bee’s sensory system when it suddenly commits to a different task?</p><p>“There are many models for how this might work,” Ben-Shahar said, “but now we can generate tools that will allow us to directly test experimental predictions from these models and either prove or disprove them.</p><p>“We didn’t invent anything here,” he said. “We’re really just taking bits and pieces that people have used in different contexts and putting them together in a user-friendly system. The innovative aspect of this is making these tools accessible to a whole community that wasn’t able to take advantage of them before.”<br/></p><p>​<br/></p><p><br/></p><p><br/></p> <span> <div class="cstm-section"><h3>Media Coverage<br/></h3><div> <strong>St. Louis Business Journal: </strong><a href="https://www.bizjournals.com/stlouis/news/2017/08/08/washington-university-awarded-2-6-million-for.html">Washington University awarded $2.6 million for neurotechnology research</a><br/></div></div></span>Scientists at Washington University in St. Louis are working on a simplified toolkit that will allow scientists who study animal behavior to manipulate the genomes of many other animals. Diana Lutzhttps://source.wustl.edu/2017/08/2-6-million-build-versatile-genetic-toolkit-studying-animal-behavior/2017-08-02T05:00:00ZScientists at Washington University in St. Louis are working on a simplified toolkit that will allow scientists who study animal behavior to manipulate the genomes of many other animals.<p>​Looking beyond the mouse, fruit fly and roundworm for the neural underpinnings of behavior<br/></p>
https://engineering.wustl.edu/news/Pages/Testing-begins-for-student-created-app-to-aid-Alzheimers-diagnosis.aspx692Testing begins for student-created app to aid Alzheimer’s diagnosis<p>​In the hectic, tightly scheduled day at a memory clinic, doctors set aside blocks of time to meet with new patients suspected of having dementia. But much of that time is taken up gathering information needed to make a diagnosis, leaving little time for doctors to discuss the condition’s life-changing implications with patients and their families.<br/></p><img alt="" src="/news/PublishingImages/Memory-v2-760-600x400.jpg?RenditionID=2" style="BORDER:0px solid;" /><div id="__publishingReusableFragmentIdSection"><a href="/ReusableContent/36_.000">a</a></div><p>​With the aim of streamlining the diagnosis of Alzheimer’s disease, a student-led team has designed an online app to help doctors more quickly evaluate patients. The app is being tested at Washington University School of Medicine in St. Louis.</p><p>“This app is not meant to replace the visit with the physician,” said MD/PhD student Robert Chen, who co-leads the student group known as Memento that designed the app. “It is meant to help physicians have more information about the patient before they are evaluated in person. With additional reliable and clinically relevant information in the hands of physicians beforehand, the hope is that physicians can make a diagnosis more quickly and confidently, and spend the extra time building a treatment plan and answering questions from patients and caregivers in the face of a devastating diagnosis.”</p><p>The app represents a collaboration between students at the Schools of Medicine, Arts & Sciences, and Engineering & Applied Science. It consists of 60 to 100 questions for a patient’s caregiver to answer on an iPad before the patient sees a dementia specialist. Once the questionnaire is complete, the app will generate a report with the information handily organized into categories that fit with the Clinical Dementia Rating Scale (CDR).</p><p>Developed at the School of Medicine, the CDR is the most commonly used tool for diagnosing dementia. It breaks down the patient’s symptoms into six domains – memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care – and provides a score for each.</p><p>“Having all the intake information from the patient and family summarized in alignment with the CDR could be really helpful,” said <a href="https://neuro.wustl.edu/about-us/physician-faculty-directory/nupur-ghoshal-md-phd/">Nupur Ghoshal, MD, PhD</a>, an assistant professor of neurology and of psychiatry, and the faculty mentor on the project. “It wouldn’t make the diagnosis for us, but it could feed into the thought processes that we go through as we evaluate each patient.”</p><p>The students have launched a six-month trial of the new app at the School of Medicine’s <a href="http://memoryloss.wustl.edu/">Memory Diagnostic Center</a>. The caregiver of each new patient arriving for a dementia evaluation will be asked to use the app and answer the questions in the waiting room. Then, a doctor will examine the patient and make a diagnosis as usual.</p><p>Without seeing the patient, another doctor in the clinic will review the app’s report and make a diagnosis as well. With feedback from the physicians, the students will apply machine-learning techniques to identify which questions provided helpful information that led to an accurate diagnosis.</p><blockquote> “We will determine which questions were most indicative, which were the least indicative and, at any given point, what’s the next best question to ask,” said Allen Osgood, who co-leads the Memento team and earned bachelor’s and master’s degrees in computer science from the School of Engineering & Applied Science in May.</blockquote> <p>The doctors also will note how long it takes them to read and digest the report, so the students can estimate how much time the app saves.</p><p>Building the app required not just an understanding of how Alzheimer’s disease is diagnosed and treated, but programming and design, as well.</p><p>“One of the students, Jenny Liu, really helped make the app appealing and intuitive,” Ghoshal said. “It doesn’t look like your standard questionnaire. We hope that a warmer design will help caregivers feel more comfortable answering these questions.”</p><blockquote>The student group was brought together by <a href="http://slinghealth.org/">Sling Health Network</a>, a student-run biotechnology incubator that provides resources, training and mentorship to teams of students tackling clinical problems by developing innovative solutions. </blockquote><p>Along with Chen and Osgood, the team includes: Jenny Liu, who earned a bachelor’s degree in biology in 2016; Morgan Redding, who earned a bachelor’s degree in computer science with a second major in mathematics in May; and Stolovitz, who earned a bachelor’s degree in computer science with minors in design and physics, also in May.</p><p>If the trial is successful, the team plans to work with the Alzheimer’s Association to launch the app at other St. Louis-area neurology clinics in the future. Last summer, <a href="/news/pages/student-team-wins-10000-for-alzheimers-disease-diagnostic-tool.aspx">the team won $10,000</a> as a finalist for the Student Technology Prize for Primary Healthcare from the Gelfand Family Charitable Trust.</p><p>“Having the chance to build things from the ground up in an environment where there is no clear answer is definitely a testament to the education we’ve received at Washington University,” Osgood said. “Having the ability to go in and work with professionals to learn HIPAA compliance and systems security and all the different things we need to implement this on the user and technical side has been instrumental to the success of the project.”<br/></p><div class="boilerplate" style="box-sizing: inherit; color: #3c3d3d; font-family: "source sans pro", "helvetica neue", helvetica, arial, sans-serif; font-size: 19.2px;"><h5 style="box-sizing: inherit; color: #2f3030;">Memento is supported by Sling Health, formerly Idea Labs, which has paid for two interns; the James M. McKelvey Undergraduate Research Scholar program; and the Alzheimer’s Association of St. Louis.</h5></div><div class="bio-wrapper" style="box-sizing: inherit; color: #3c3d3d; font-family: "source sans pro", "helvetica neue", helvetica, arial, sans-serif; font-size: 19.2px;"> <strong style="box-sizing: inherit;"><a href="https://medicine.wustl.edu/news/testing-begins-student-created-app-aid-alzheimers-diagnosis/" style="box-sizing: inherit; color: #a51417;">Originally published by the School of Medicine</a></strong></div><p> <br/> </p> <SPAN ID="__publishingReusableFragment"></SPAN><br/>​​​​​<div><br/></div><div><br/> <div>​​<br/> <div class="cstm-section"><h3>Entrepr​​eneurship at WashU</h3><ul><li> <a href="/our-school/initiatives/Pages/entrepreneurship.aspx">WashU engineers </a>are engaged in St. Louis' startup community and contribute to more than 20 accelerators and incubators.</li><li> <a href="http://fuse.wustl.edu/">WashU Fuse</a> - igniting innovation and connecting entrepreneurs​<br/></li></ul></div>​​​</div><br/></div>To streamline diagnoses of Alzheimer’s disease, a student-led team has designed an online app to help doctors more quickly evaluate patients. (Image: Robert Chen) Tamara Bhandari and Beth Millerhttps://source.wustl.edu/2017/07/testing-begins-student-created-app-aid-alzheimers-diagnosis/2017-07-31T05:00:00ZWith the aim of streamlining the diagnosis of Alzheimer’s disease, a Washington University student-led team has designed an online app to help doctors more quickly evaluate patients. The app is being tested at the School of Medicine.<p>​By speeding detection, app aims to free doctors to discuss treatment, implications with patients<br/></p>
https://engineering.wustl.edu/news/Pages/Klein-named-vice-provost-and-associate-dean-for-graduate-education.aspx687Klein named vice provost and associate dean for graduate education<p>​<a href="http://dbbs.wustl.edu/faculty/Pages/faculty_bio.aspx?SID=5865">Robyn S. Klein, MD, PhD</a>, a physician-scientist recognized internationally for her work on the brain’s immune system, has been named vice provost and associate dean for graduate education for the <a href="http://dbbs.wustl.edu/Pages/index.aspx">Division of Biology & Biomedical Sciences</a> (DBBS) at Washington University in St. Louis. She will begin her new post Jan. 1.<br/></p><img alt="" src="/news/PublishingImages/Klein-Robyn-photo-760x535.jpg?RenditionID=1" style="BORDER:0px solid;" /><p>“The Division of Biology & Biomedical Sciences is an integral part of the university’s collaborative research and education enterprise,” said Provost Holden Thorp. “We are exceptionally fortunate to have such an accomplished scientist and leader as Robyn Klein to step into the role of vice provost and associate dean. Under her direction, the division will undoubtedly further its success in bringing together faculty and graduate students across disciplines to seek solutions to today’s most critical challenges in biomedical research. I look forward to working with her in her new role.”</p><p>Klein succeeds <a href="http://devbio.wustl.edu/faculty/faculty-members/john-russell">John H. Russell</a>, who is retiring but will retain an appointment in developmental biology. He plans to focus on revitalizing the <a href="http://dbbs.wustl.edu/PostDocs/Pages/PostDocs.aspx">Office of Postdoctoral Affairs</a>.</p><p>Widely emulated for its interdisciplinary and collaborative approach to training PhD scientists, DBBS crosses both the Danforth and Medical campuses. It brings together about 525 faculty members from 37 departments in the <a href="https://medicine.wustl.edu/">School of Medicine</a>, <a href="https://artsci.wustl.edu/">Arts & Sciences</a>, and the <a href="/Pages/home.aspx">School of Engineering & Applied Science</a> who teach and mentor some 500 graduate students, making it the largest PhD program at the university.</p><p>As associate dean, Klein will set the direction of graduate education at DBBS. She also will be the first associate dean of graduate education to hold the title of vice provost, a change in governance that recognizes the status of DBBS as a universitywide academic endeavor. Klein intends to build on the division’s strength in training young scientists, and to prepare students for scientific careers that are interdisciplinary and extend beyond academic domains.</p><p>“We have a fantastic graduate program, and our faculty provide first-rate scientific training,” said Klein, a professor of medicine, of neuroscience, and of pathology and immunology. “We have to provide the best training and experience for our graduate students so they will be prepared for top positions, whether they go into academia, industry, science policy, scientific publishing or any other field.”</p><p>The national search for a DBBS leader came after an extensive review of the program, led by Thorp, Barbara A. Schaal, dean of the faculty of Arts & Sciences, and the current and former deans of the School of Medicine, David H. Perlmutter, MD, and Larry J. Shapiro, MD, respectively. Additionally, internal and external experts worked together in a multistage process to make a set of recommendations aimed at ensuring that DBBS remains a leader in the field of graduate training in the basic sciences. Based on the review and recommendations for moving DBBS forward, the university has updated the leadership structure of the program.</p><p>As part of her responsibilities, Klein will evaluate new programs and educational approaches and experiences to keep DBBS at the forefront of graduate education. Such enhancements will be aimed at preserving and strengthening the legacy created when Chancellor Emeritus William H.  Danforth, MD, and P. Roy Vagelos, MD, former head of the Department of Biological Chemistry, founded DBBS in 1973. Their pioneering vision — a program in which cross-departmental intellectual pollination would benefit students and mentors while promoting innovation and cutting-edge research — continues to guide DBBS today.</p><p>DBBS has an important role in promoting diversity and inclusion at Washington University, and Klein plans to lead new efforts in this area, among students, faculty and staff. She believes increased diversity will enhance the quality of education and research at the university. She plans to focus on new ways to increase recruitment of students from underrepresented minority groups.</p><p>“There are a lot of excellent underrepresented minority students who do not necessarily consider our program when they are looking at graduate training,” Klein said. “I am looking for ways to identify such students and encourage them to come to St. Louis.”</p><p>Klein, who joined the faculty in 2003, is the founding director of the university’s <a href="https://cnnd.wustl.edu/">Center for Neuroimmunology and Neuroinfectious Diseases</a>. Much of her work has focused on how the barrier between the brain and the rest of the body changes when the brain is infected or inflamed and, more recently, on how infections alter cognitive function. Her past studies have shed light on why women are much more likely than men to develop multiple sclerosis, and how viral infections such as West Nile and Zika damage the brain.</p><p>Klein is an elected member of the International Advisory Board of the International Society of Neuroimmunology and a recipient of the Dana Foundation Award for Neuroimmunology. She is a founding member of the International Society for Neurovirology and a member of the American College of Physicians, the American Society for Microbiology, the American Society for Immunology and the International Society for Neuroimmunology.</p><p>She is also president of the Academic Women’s Network at the School of Medicine. In that role, she promotes career development and mentorship for women in science and medicine.</p><p>After earning a bachelor’s degree in biology at Barnard College in 1985, Klein earned a master’s degree in neuroscience in 1990 and a doctorate in neuroscience and a medical degree in 1993 from the Albert Einstein College of Medicine. She completed her internship and residency at Brigham & Women’s Hospital in Boston, followed by a fellowship in infectious diseases at Massachusetts General Hospital and a fellowship in immunology at Harvard Medical School.<br/></p>Robyn S. Klein, MD, PhD, has been named vice provost and associate dean for graduate education for the Division of Biology & Biomedical Sciences at Washington University in St. Louis. She will begin her new post Jan. 1. (Photo: James Byard)Tamara Bhandari and Julia Evangelou Straithttps://source.wustl.edu/2017/07/klein-named-vice-provost-associate-dean-graduate-education/2017-07-24T05:00:00ZRobyn S. Klein, MD, PhD, a physician-scientist recognized internationally for her work on the brain’s immune system, has been named vice provost and associate dean for graduate education for the Division of Biology & Biomedical Sciences.<p>​Physician-scientist to lead Division of Biology & Biomedical Sciences<br/></p>
https://engineering.wustl.edu/news/Pages/WashU-biomedical-engineer-combines-data-algorithms-to-understand-HER2-breast-cancer-gene.aspx686WashU biomedical engineer combines data, algorithms to understand HER2 breast cancer gene<p>​In American women, breast cancer is the second most common cancer and the second leading cause of cancer death. Using data, algorithms and lab experimentation, a biomedical engineer at Washington University in St. Louis is studying breast cancer at the most basic level – the cells – to look for clues about how the cancerous cells metastasize.<br/></p><img alt="" src="/news/PublishingImages/Kristen%20Naegle%20cell%20image%20WashU%20engineering.png?RenditionID=1" style="BORDER:0px solid;" /><div id="__publishingReusableFragmentIdSection"><a href="/ReusableContent/News/34_.000">a</a></div><p> <a href="/Profiles/Pages/Kristen-Naegle.aspx">Kristen Naegle</a>, assistant professor of biomedical engineering in the School of Engineering & Applied Science, applied her unique computational skills to look at the HER2 gene. HER2-positive breast cancers are aggressive and spread faster than other types. Researchers have found that too much protein is made from the HER2 gene — called overexpression — in 20 percent of all breast cancers, making HER2 a valuable target for potential personalized treatment methods for this type of breast cancer.</p><p style="color: #000000; font-family: "times new roman"; font-size: medium;"></p><p>To determine why HER2-positive cancers are more aggressive, Naegle analyzed measurements from a previous study that isolated signaling molecules in a HER2-overexpressing breast cell line and a normal breast cell.</p><p style="color: #000000; font-family: "times new roman"; font-size: medium;"></p><p>“We use mathematical approaches to find similarities in the data,” Naegle said. “For this dataset, we looked at how signaling molecules are most related to each other in the normal cells, compared to how they are related to each other in the HER2-overexpressing cells. We looked for relationships that are drastically different in the two cell types to understand how signaling is altered. Despite the fact that individual molecules are highly similar to each other across cell types, we found that small changes in signaling dynamics led to very large changes in the relationships uncovered between groups of signaling molecules.”</p><p style="color: #000000; font-family: "times new roman"; font-size: medium;"></p><p>One of these big changes they found involves a protein that regulates how cells are connected.</p><p style="color: #000000; font-family: "times new roman"; font-size: medium;"></p><blockquote>“One of the things that decreases metastatic behavior is that the cells stick tightly together through cell-cell junctions,” Naegle said. “That told us that if there are signaling alterations happening at the cell junctions, then maybe that’s why these cells are more metastatic.”</blockquote> <p style="color: #000000; font-family: "times new roman"; font-size: medium;"></p><p>Naegle and members of her lab tested the hypothesis that interactions with this cell junction protein were altered according to the differences in the signaling relationships they saw from their analysis. They found that interactions with the cell junction protein were very different between the two cell types, and the interaction dynamics matched the dynamics of the signaling that uncovered the relationship.</p><p style="color: #000000; font-family: "times new roman"; font-size: medium;"></p><p>“This is exciting, because it’s been proposed that testing for interactions in a cancer biopsy may be a better predictor of how a cancer will respond to a treatment,” Naegle said. “Given that some HER2-positive breast cancer patients don’t respond to HER2 therapy, maybe this protein interaction could help us identify patients who will respond well to therapy and those who will not gain additional benefits.”</p><p style="color: #000000; font-family: "times new roman"; font-size: medium;"></p><p>Additionally, with Venktesh Shirure, a former research scientists in biomedical engineering, the team conducted a series of experiments to test whether cell junctions were altered in the conditions that correspond with the most aggressive cell type. Their experiments revealed that the cell junctions in with high HER2 expression break down and become “leaky” in response to the growth factor, which may be related to how HER2-postive cancers metastasize.</p><p>“This study shows that by using a different mathematical interpretation of the data, even a decade after its first publication, we can still find new nuggets of information hidden in these high-throughput, systems-level measurements of early signaling dynamics and identify novel, unknown findings,” Naegle said.<br/></p><p style="color: #000000; font-family: "times new roman"; font-size: medium;"></p><p>“My lab believes that disease is a context shift, so what we should fundamentally understand is how context shapes cell decisions and then understanding disease becomes relatively trivial,” Naegle said. “It’s a bottom-up approach where we look to understand the basic mechanisms of the interactions in the cell to find the outcomes. There still remains a wealth of hypotheses from this analysis that may continue to help us understand how HER2 drives metastasis.”</p><p style="color: #000000; font-family: "times new roman"; font-size: medium;"></p><p style="color: #000000; font-family: "times new roman"; font-size: medium;"></p> <span><hr/></span> <p>Schaberg K, Shirure V, Worley E, George S, Naegle K. “Ensemble clustering of phosphoproteomic data identifies differences in protein interactions and cell-cell junction integrity of HER2-overexpressing cells.” Integrative Biology, April 28, 2017. 2017, 9, 539. DOI: 10.1029/c7ib00054e.<br/></p> <SPAN ID="__publishingReusableFragment"></SPAN><br/>​<br/><br/><br/> <div><div class="cstm-section"><h3>Kristen Naegle<br/></h3><div style="text-align: center;"> <strong> <a href="/Profiles/Pages/Kristen-Naegle.aspx"> <img src="/Profiles/PublishingImages/Naegle_Kristen.jpg?RenditionID=3" alt="Kristen Naegle" style="margin: 5px;"/></a> <br/> </strong> </div><div style="text-align: center;"> <span style="font-size: 12px;">Assistant Professor<br/>Biomedical Engineering<br/><a href="/Profiles/Pages/Kristen-Naegle.aspx">>> View Bio</a></span></div></div></div> <br/> Kristen Naegle's research combines computational mining and modeling techniques with experimental molecular biology approaches to understand the function of post-translational modifications in regulatory networks of the cell.Beth Miller2017-07-21T05:00:00ZAssistant Professor Kristen Naegle is studying breast cancer at the most basic level – the cells – to look for clues about how the cancerous cells metastasize.
https://engineering.wustl.edu/news/Pages/A-sodium-surprise.aspx683A sodium surprise<p>​Irregular heartbeat — or arrhythmia — can have sudden and often fatal consequences. A biomedical engineering team at Washington University in St. Louis examining molecular behavior in cardiac tissue recently made a surprising discovery that could someday impact treatment of the life-threatening condition.<br/></p><img alt="" src="/news/PublishingImages/WashU%20engineers%20Jon%20Silva%20Sodium%20Research%20Cardiac.jpg?RenditionID=1" style="BORDER:0px solid;" /><div id="__publishingReusableFragmentIdSection"><a href="/ReusableContent/News/34_.000">a</a></div><p>“It was a fun finding, not at all what we expected to see,” said <a href="/Profiles/Pages/Jonathan-Silva.aspx">Jonathan Silva</a>, assistant professor of biomedical engineering at the School of Engineering & Applied Science.</p><p>Silva and his team study sodium ion channels — tiny proteins in cardiac muscle that electrically control a heartbeat — and how they interact with molecules which could affect their performance. In new research, recently published by the <a href="http://jgp.rupress.org/content/early/2017/07/17/jgp.201711802">Journal of General Physiology</a>, Silva worked with collaborators to take a closer look at the sodium ion channels responsible for creating the electrical signal that makes the heartbeat: Zoltan Varga at the University of Debrecen in Hungary; and <a href="http://devbio.wustl.edu/faculty/faculty-members/jeanne-nerbonne">Jeanne M. Nerbonne</a>, Alumni Endowed Professor of Molecular Biology and Pharmacology and Director of the Center for Cardiovascular Research at Washington University’s School of Medicine.</p><p>“Sodium channels aren’t made out of just one part,” Silva said. “The main portion is a really big protein made up of more than 2,000 amino acids, and then there are smaller proteins called beta subunits that attach to it. We wanted to understand what the differences were in how the beta subunits controlled the channel.”</p><blockquote>Using an imaging technique called voltage-clamp fluorometry, Silva and his team observed that two different  beta subunits  worked on the channel in very different ways. The results were unexpected.<br/></blockquote><p>“Most people believe that these subunits attach to the same place on the main protein,” Silva explained. “But what we found was, they attached to different places and they have different effects. We think those different effects are going to change how patients respond to drug therapies, how those different subunits control the channel, and therefore the heartbeat.”</p><div style="font-style: italic; font-size: 0.9em; color: #555555; max-width: 300px; float: left; margin: 0px 10px 10px 0px;"> <img src="/news/PublishingImages/WashU%20engineering%20Jon%20Silva.jpg" alt="" style="padding-bottom: 5px;"/> <br/> Silva and his colleagues found certain sodium subunits attached to the main protein in different places. It was an unexpected result that could lead to better drug delivery and efficacy for patients with heart arrhythmia. </div><p>Silva says this new information is another piece in a vast puzzle: As researchers obtain better information on exactly how sodium ion channels work to keep a strong, steady heartbeat, they can work toward developing therapies specific to an individual’s exact needs.</p><p>“It’s gaining the mechanistic insight that we need to perform precision, molecularly-driven medicine,” Silva said.<br/></p><p>This research was funded by a Burroughs Wellcome Fund Career Award at the Scientific Interface (1010299), the National Institutes of Health (R01 HL136553), the American Heart Association (15PRE25080073), the Bolyai Fellowship and the National Heart, Lung, and Blood Institute of the National Institutes of Health (HL-034161)<br/></p> <SPAN ID="__publishingReusableFragment"></SPAN> <p> <br/> </p>​<br/><br/><br/> <div><div class="cstm-section"><h3>Jonathan Silva<br/></h3><div style="text-align: center;"> <strong><a href="/Profiles/Pages/Jonathan-Silva.aspx"><img src="/Profiles/PublishingImages/Silva_Jon.jpg?RenditionID=3" alt="Jonathan Silva" style="margin: 5px;"/></a><br/> </strong> </div><div style="text-align: center;"> <span style="font-size: 12px;">Assistant Professor<br/>Biomedical Engineering<br/><a href="/Profiles/Pages/Jonathan-Silva.aspx">>> View Bio</a></span></div></div></div> <br/> <span> <div class="cstm-section"><h3>Media Coverage<br/></h3><div> <strong>Scicasts: </strong> <a href="https://scicasts.com/channels/cell-biology/2089-cellular-processes/12743-engineers-make-unexpected-finding-during-cardiac-research/">Engineers Make Unexpected Discovery During Cardiac Research</a><br/><br/><strong>Bioscience Technology:</strong> <a href="https://www.biosciencetechnology.com/news/2017/07/sodium-surprise">A Sodium Suprise</a><br/></div></div></span><br/><br/>Engineers at Washington University in St. Louis have discovered something new about how sodium ions act in cardiac muscle, a finding that could someday help inform treatment of heart arrhythmia.Erika Ebsworth-Gooldhttps://source.wustl.edu/2017/07/a-sodium-surprise/2017-07-20T05:00:00ZA biomedical engineering team at Washington University in St. Louis examining molecular behavior in cardiac tissue recently made a surprising discovery that could someday impact treatment of the life-threatening condition.<p>​Engineers find unexpected result during cardiac research<br/></p>

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