tag:transgene.nd.edu,2005:/news-events/newsW.M. Keck Center for Transgene Research | News2024-01-11T16:13:00-05:00tag:transgene.nd.edu,2005:News/1591502024-01-11T16:13:00-05:002024-01-11T16:21:20-05:00Bradley 5 Charitable Donation <div> <figure class="image image-right"><img src="https://transgene.nd.edu/assets/553605/screenshot_2024_01_11_at_4.06.56_pm.png" alt="Screenshot 2024 01 11 At 4"></figure> The Bradley 5 Charitable Fund came to W.M. Keck Center to make a donation. They have set up a fellowship for future use for blood coagulation research.…</div><div>
<figure class="image image-right"><img src="https://transgene.nd.edu/assets/553605/screenshot_2024_01_11_at_4.06.56_pm.png" alt="Screenshot 2024 01 11 At 4"></figure>
The Bradley 5 Charitable Fund came to W.M. Keck Center to make a donation. They have set up a fellowship for future use for blood coagulation research. Thank you for you continued support.</div>
<div>WNDU and WSBT came to document the presentation of the gift and to spread the story of the Bradley 5's fund.</div>
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<div><a href="https://www.wndu.com/2024/01/05/bradley-5-charitable-fund-donates-more-than-20k-towards-blood-disorder-research/">https://www.wndu.com/2024/01/05/bradley-5-charitable-fund-donates-more-than-20k-towards-blood-disorder-research/</a></div>
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<div><a href="https://wsbt.com/news/local/nappanee-family-funds-blood-clot-research-project-their-son-died-one-check-future-legacy-foundation-notre-dame-south-bend-indiana#">https://wsbt.com/news/local/nappanee-family-funds-blood-clot-research-project-their-son-died-one-check-future-legacy-foundation-notre-dame-south-bend-indiana#</a></div>
<p><span style="color: #888888;">--</span></p>Deborah Donahuetag:transgene.nd.edu,2005:News/1528032023-04-26T10:00:00-04:002023-04-26T09:33:58-04:00Opportunities to Support Research on Notre Dame Day<p>Notre Dame Day, the University's annual day of giving, is celebrating its 10th anniversary this year. From April 25th to 26th, alumni, parents, students, and friends of Notre Dame will have the chance to support the causes, clubs, and residence halls that inspire them—including the University’s research…</p><p>Notre Dame Day, the University's annual day of giving, is celebrating its 10th anniversary this year. From April 25th to 26th, alumni, parents, students, and friends of Notre Dame will have the chance to support the causes, clubs, and residence halls that inspire them—including the University’s research centers and facilities.</p>
<p>As part of this year's Notre Dame Day celebration, Notre Dame Research (NDR) is proud to showcase the research and innovation efforts that align with our mission to advance human understanding through research, scholarship, and creative endeavor. Your support helps researchers foster knowledge and innovation to address some of the world's most pressing challenges.</p>
<p>Several of NDR’s reporting units can be supported during Notre Dame Day, and each has a unique focus and expertise. Gifts to these units can help support cutting-edge research and provide valuable resources for Notre Dame's researchers, faculty, and students. Below is a list of the units that can be supported:</p>
<ul>
<li><a href="https://notredameday.nd.edu/organizations/analytical-sciences-and-engineering-at-notre-dame-asend" target="_blank">Analytical Sciences and Engineering at Notre Dame (ASEND)</a></li>
<li><a href="https://notredameday.nd.edu/organizations/institute-for-precision-health" target="_blank">Berthiaume Institute for Precision Health (BIPH)</a></li>
<li><a href="https://notredameday.nd.edu/organizations/center-for-research-computing" target="_blank">Center for Research Computing (CRC)</a></li>
<li><a href="https://notredameday.nd.edu/organizations/eck-institute-for-global-health" target="_blank">Eck Institute for Global Health (EIGH)</a></li>
<li><a href="https://notredameday.nd.edu/organizations/environmental-research-center-underc" target="_blank">University of Notre Dame Environmental Research Center (UNDERC)</a></li>
<li><a href="https://notredameday.nd.edu/organizations/harper-cancer-research-institute" target="_blank">Harper Cancer Research Center (HRCI)</a></li>
<li><a href="https://notredameday.nd.edu/organizations/institute-for-advanced-study" target="_blank">Notre Dame Institute for Advanced Study (NDIAS)</a></li>
<li><a href="https://notredameday.nd.edu/organizations/notre-dame-energy" target="_blank">Notre Dame Energy (NDE)</a></li>
<li><a href="https://notredameday.nd.edu/organizations/notre-dame-integrated-imaging-facility" target="_blank">Notre Dame Integrated Imaging Facility (ND-IIF)</a></li>
<li><a href="https://notredameday.nd.edu/organizations/ndnano-center-for-nano-science-technology" target="_blank">Notre Dame Nanoscience and Technology (NDnano)</a></li>
<li><a href="https://notredameday.nd.edu/organizations/notre-dame-radiation-laboratory" target="_blank">Notre Dame Radiation Laboratory (NDRL)</a></li>
<li><a href="https://notredameday.nd.edu/organizations/notre-dame-turbomachinery-laboratory" target="_blank">NDTL Propulsion & Power (Notre Dame Turbomachinery Laboratory)</a></li>
<li><a href="https://notredameday.nd.edu/organizations/w-m-keck-center-for-transgene-research" target="_blank">W.M Keck Center for Transgene Research</a></li>
</ul>
<p>To contribute, please visit the <a href="https://notredameday.nd.edu/" target="_blank">Notre Dame Day website</a> and donate to the specific research unit they wish to support. Donors can also track progress on the Notre Dame Day website and social media pages, and participate in various events and activities related to the days of giving.</p>
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<p><strong>About Notre Dame Research:</strong></p>
<p>The University of Notre Dame is a private research and teaching university inspired by its Catholic mission. Located in South Bend, Indiana, its researchers are advancing human understanding through research, scholarship, education, and creative endeavor in order to be a repository for knowledge and a powerful means for doing good in the world. For more information, please see <a href="http://research.nd.edu">research.nd.edu</a> or <a href="https://twitter.com/UNDResearch">@UNDResearch</a>.</p>
<p class="attribution">Originally published by <span class="rel-author">Courtney Sniadecki</span> at <span class="rel-source"><a href="https://research.nd.edu/news-and-events/news/opportunities-to-support-research-on-notre-dame-day/">research.nd.edu</a></span> on <span class="rel-pubdate">April 25, 2023</span>.</p>Courtney Sniadeckitag:transgene.nd.edu,2005:News/1402022021-09-17T09:00:00-04:002021-09-17T09:52:59-04:00Bradley 5 Charitable Fund Makes Donation<p>The Bradley 5 Foundation visited the W.M. Keck Center on Sept 16, 2021 and presented Dr. Francis Castellino with a check to help continue our research on blood clotting. Please visit <a href="https://bradleyfive.org">https://bradleyfive.org</a> to learn more about this local family's mission to help…</p><p>The Bradley 5 Foundation visited the W.M. Keck Center on Sept 16, 2021 and presented Dr. Francis Castellino with a check to help continue our research on blood clotting. Please visit <a href="https://bradleyfive.org">https://bradleyfive.org</a> to learn more about this local family's mission to help fund research. Everyone at the Keck Center thanks you for your support.</p>Deborah Donahuetag:transgene.nd.edu,2005:News/1276322020-07-17T12:00:00-04:002020-07-17T12:58:33-04:00Francis Castellino receives 2020 ISTH Esteemed Career Award<p>Francis J. Castellino, Kleiderer-Pezold Professor of Biochemistry and director of the W.M. Keck Center for Transgene Research, has been selected as a recipient of the 2020 International Society on Thrombosis and Haemostasis (ISTH) Esteemed Career Award. <br />
.</p><figure class="image-left"><img alt="Castellino1" src="https://chemistry.nd.edu/assets/281821/300x/castellino1.jpg"></figure>
<p><a href="https://chemistry.nd.edu/people/francis-j-castellino/">Francis J. Castellino</a>, Kleiderer-Pezold Professor of Biochemistry and Director of the <a href="https://transgene.nd.edu/">W.M. Keck Center for Transgene Research</a>, has been selected as a recipient of the <a href="https://www.isth.org/news/516978/ISTH-Presents-2020-Esteemed-Career-Awards.htm">2020 International Society on Thrombosis and Haemostasis (ISTH) Esteemed Career Award</a>. This prestigious award is given to those who “have made significant contributions to the understanding, treatment and diagnosis, research and education in the thrombosis and hemostasis field.” Five recipients are selected annually.</p>
<p>The general theme of Castellino’s research program during his 50-year tenure at Notre Dame involves the complex physiological process known as hemostasis--the tenuous molecular interplay between mechanisms of blood clot formation and dissolution. Numerous acute and chronic conditions can arise from the disruption of normal hemostatic processes, including stroke, heart attack, and hemophilia. Additionally, an imbalance of specific hemostatic proteins can contribute to the progression of a number of diseases <em>i.e.,</em> cancer, bacterial infection, asthma, and atherosclerosis. Castellino’s work in hemostasis is remarkably diverse and extends from studies conducted at the most basic molecular level to <em>in vivo </em>analyses of transgenic mice.</p>
<p>Castellino’s research career at Notre Dame began with a focus on the molecular mechanisms governing the activation of plasmin, the major blood clot-dissolving enzyme of the fibrinolytic system, from its dormant precursor, plasminogen. This work has informed the clinical use of life-saving plasminogen activators such as streptokinase, urokinase and tissue plasminogen activator (tPA). His work in this vein continues and has been supported by the NIH since 1972, making it among the longest of that agency’s continuously supported grants.</p>
<p>Castellino’s initial studies on plasmin and other components of the hemostatic system were constrained to those enzymes isolated from mammalian plasma sources. In the late 1980’s, his group pivoted to the use of recombinant DNA technology to express a variety of blood factors and their site-specific mutants, helping to rapidly advance our understanding of structure-function relationships in these biomolecules. Over the years, his group succeeded in identifying a host of specific amino acid residues in the kringle domains of plasminogen that contribute to its activation through ligand-induced conformational changes. Mutational studies focused on the N-terminal gamma-carboxyglutamic acid domains of Protein C and Factor IX yielded a wealth of information on amino acid residues and structural motifs that are crucial for the Ca<sup>2+</sup>-induced, biologically-relevant structures of these molecules. In the early 1990’s, Castellino recognized that targeted gene replacement, or transgenesis, represented the wave of the future in terms of generating animal models of human disease. In 1996, he successfully competed for start-up funds from the W.M. Keck Foundation, and established the W.M. Keck Center for Transgene Research at Notre Dame. It continues to this day as one of the premier facilities of its type. Using gene-targeting technology, Castellino and associates have determined how certain blood factor deficiencies influence phenotypes in transgenic mice including atherosclerosis, asthmatic responses, sepsis, tumorigenesis, and bacterial infectivity.</p>
<p>Trained as a biophysicist, Castellino has extensively employed NMR spectroscopy, crystallography, calorimetry, fluorimetry, electrophysiology, and hydrodynamic techniques in efforts to relate structure to function for the broad array of biomolecules he studies. Noteworthy in this regard is his extensive biophysical characterization of small gamma-carboxyglutamic acid -containing peptides from marine cone snails that target the brain NMDA receptor. These peptides inhibit Ca<sup>2+ </sup>flow into neuronal cells and have the potential to abate pathologies resulting from Ca<sup>2+</sup>-induced neurotoxicity in the wake of stroke, epilepsy, Alzheimer’s Disease, and head trauma.</p>
<p>More recently, Castellino has worked extensively with local physicians to conduct translational research for improving treatment of trauma patients. He has developed models for use with thromboelastogram (TEG) equipment to determine the most effective blood product replacements for patients. Expanding these efforts to traumatic brain injury, the team achieved groundbreaking results that showed that patients may incur lung injury following brain trauma because of biological events including the release of tissue factor, a protein that triggers blood clotting.</p>
<p>Castellino received his B.S. from the University of Scranton, his Ph.D. from the University of Iowa, and was an NIH postdoctoral fellow at Duke University. After arriving at Notre Dame in 1970, he quickly rose through the ranks, becoming Dean of the College of Science in 1979, a position he held for a remarkable 23 years. He has authored more than 450 journal articles and given countless invited seminars.</p>
<p class="attribution">Originally published by <span class="rel-author">Mary Prorok</span> at <span class="rel-source"><a href="https://chemistry.nd.edu/news/francis-castellino-receives-2020-isth-esteemed-career-award/">chemistry.nd.edu</a></span> on <span class="rel-pubdate">July 16, 2020</span>.</p>Mary Proroktag:transgene.nd.edu,2005:News/1250382020-04-22T16:45:00-04:002020-04-22T16:45:09-04:00Former Dean Castellino celebrates 50 years at the University of Notre Dame<p>Castellino, who has no immediate plans for retirement, remembers highlights from his research, teaching, and University culture during the past 50 years.</p><p><span style="font-variant:normal; font-weight:400; white-space:pre-wrap"><span style="font-style:normal">When <a href="https://chemistry.nd.edu/people/francis-j-castellino/" target="_blank">Francis Castellino</a> attended scientific conferences</span></span><span style="font-variant:normal; font-weight:400; white-space:pre-wrap"><span style="font-style:normal"> </span></span><span style="font-variant:normal; font-weight:400; white-space:pre-wrap"><span style="font-style:normal">during his early days at the University of Notre Dame, his colleagues primarily wanted to talk about just one topic.</span></span></p>
<p><span style="font-variant:normal; font-weight:400; white-space:pre-wrap"><span style="font-style:normal">The football team.</span></span></p>
<figure class="image-right"><img alt="Frank Castellino" src="https://science.nd.edu/assets/281151/castellino1.jpg"></figure>
<p><span style="font-variant:normal; font-weight:400; white-space:pre-wrap"><span style="font-style:normal">“Not the academic accomplishments of the University,” said Castellino, a biochemist who has been at the University of Notre Dame for 50 years and is currently the director of the <a href="https://research.nd.edu/our-research/facilities-and-resources/w-m-keck-center-for-transgene-research/" target="_blank">W.M. Keck Center for Transgene Research</a>. “But the football program is really important to this place, and it makes a huge difference in terms of the university being known all over the country, having alumni coming together for certain activities, and generating loyalty in those who follow us. “</span></span></p>
<p><span style="font-variant:normal; font-weight:400; white-space:pre-wrap"><span style="font-style:normal">He’s thankful that he doesn’t get asked exclusively about the football program anymore, but added, “that ‘community’ does lead to academic excellence.”</span></span></p>
<p><span style="font-variant:normal; font-weight:400; white-space:pre-wrap"><span style="font-style:normal">That community of alumni, however, wouldn’t have formed without the dedication of professors including Castellino, according to <a href="https://chemistry.nd.edu/people/victoria-ploplis/" target="_blank">Victoria Ploplis</a>, a research professor and associate director of the W.M. Keck Center for Transgene Research. She was one of his graduate students in the 1970s, when Castellino did rounds in the lab, talking every day to all</span></span><span style="font-variant:normal; font-weight:400; white-space:pre-wrap"><span style="font-style:normal"> </span></span><span style="font-variant:normal; font-weight:400; white-space:pre-wrap"><span style="font-style:normal">the investigators and students about current experiments.</span></span></p>
<p><span style="font-variant:normal; font-weight:400; white-space:pre-wrap"><span style="font-style:normal">“He was on top of everyone’s research, and still does that to this day,” she said. “Asking, ‘What’s the science?’”</span></span></p>
<p><span style="font-variant:normal; font-weight:400; white-space:pre-wrap"><span style="font-style:normal">Castellino has watched that academic excellence unfold since his early days. He joined the University of Notre Dame in February 1970, and recounted many of the highlights that range from University-wide academics, to his time as Dean of the College of Science, to presidential candidates and other notable people he’s met, and beyond.</span></span></p>
<p><span style="font-variant:normal; font-weight:400; white-space:pre-wrap"><span style="font-style:normal">He researches the structure, function, an activation of proteins that participate in blood coagulation, blood clot dissolution, inflammation and infection. Although there was no official form of “biochemistry” when he arrived, he landed a research grant in 1975 through the National Institutes of Health that has been continuously renewed through today. His most important discovery is understanding the interconnections of the hemostasis system in inflammatory diseases.</span></span></p>
<p><span style="font-variant:normal; font-weight:400; white-space:pre-wrap"><span style="font-style:normal">He became the founding director of the then-Center for Transgene Research in 1996, which developed mouse models with designed gene alterations. This allowed researchers to study functions of components of the hemostasis system, which is the process that stops blood loss from a damaged blood vessel. Today, the W.M. Keck Center for Transgene Research maintains among the world’s largest collection of models with modified hemostatic systems in the world, and consists of several complementary research programs. Its translational program collaborates with Memorial Hospital trauma and emergency room physicians in developing models of traumatic brain injury, to further characterize how blood coagulates after those injuries.</span></span></p>
<p><span style="font-variant:normal; font-weight:400; white-space:pre-wrap"><span style="font-style:normal">“When I came in 1970, I was just a naïve kid. And in 1978, I went through the ranks of promotion, and I was appointed chair of chemistry,” he said. “But I only lasted a month, because then I was appointed dean.” He went on to be the longest-running dean of the College of Science, serving in that role from 1979 to 2003.</span></span></p>
<p><span style="font-variant:normal; font-weight:400; white-space:pre-wrap"><span style="font-style:normal">He vigorously</span></span><span style="font-variant:normal; font-weight:400; white-space:pre-wrap"><span style="font-style:normal"> </span></span><span style="font-variant:normal; font-weight:400; white-space:pre-wrap"><span style="font-style:normal">maintained his laboratory while working as dean, and still teaches courses to graduate students. He’s an adjunct professor at the Indiana School of Medicine-South Bend, and enjoys and works hard at</span></span><span style="font-variant:normal; font-weight:400; white-space:pre-wrap"><span style="font-style:normal"> </span></span><span style="font-variant:normal; font-weight:400; white-space:pre-wrap"><span style="font-style:normal">teaching.. </span></span></p>
<p><span style="font-variant:normal; font-weight:400; white-space:pre-wrap"><span style="font-style:normal">“I think I’m viewed as a very good teacher, but my biggest disaster was trying to teach a new course in chemical biology to first year students,</span></span><span style="font-variant:normal; font-weight:400; white-space:pre-wrap"><span style="font-style:normal"> </span></span><span style="font-variant:normal; font-weight:400; white-space:pre-wrap"><span style="font-style:normal">and I had a huge class at the time. Let’s just say it didn’t go well,” he joked. “Sometimes, my wife tells me my expectations of them were too high. I asked her if she wanted me to lower my expectations? And she said, ‘no.’”</span></span></p>
<p><span style="font-variant:normal; font-weight:400; white-space:pre-wrap"><span style="font-style:normal">Castellino’s greatest legacy so far, according to <a href="https://chemistry.nd.edu/people/a-graham-lappin/" target="_blank">A. Graham Lappin</a>, professor of chemistry who was hired by him in 1982, is the quality of professors retained during his tenure as dean. </span></span></p>
<p><span style="font-variant:normal; font-weight:400; white-space:pre-wrap"><span style="font-style:normal">“Frank was a master at figuring out how to marshal the resources required to hire leading faculty,” Lappin said. “Whether it was by offering spousal hiring or unique facilities, Frank found a way.”</span></span></p>
<p><span style="font-variant:normal; font-weight:400; white-space:pre-wrap"><span style="font-style:normal">Though he has been successful in the lab, in his establishment of core facilities, and persistence in getting an undergraduate laboratory building planned and constructed</span></span><span style="font-variant:normal; font-weight:400; white-space:pre-wrap"><span style="font-style:normal">—</span></span><span style="font-variant:normal; font-weight:400; white-space:pre-wrap"><span style="font-style:normal">Jordan Hall of Science opened in 2006, three years after he stepped down as dean</span></span><span style="font-variant:normal; font-weight:400; white-space:pre-wrap"><span style="font-style:normal">—</span></span><span style="font-variant:normal; font-weight:400; white-space:pre-wrap"><span style="font-style:normal">some of Castellino’s best memories are centered around University culture.</span></span><span style="font-variant:normal; font-weight:400; white-space:pre-wrap"><span style="font-style:normal"> </span></span><span style="font-variant:normal; font-weight:400; white-space:pre-wrap"><span style="font-style:normal">He fondly recalls working with former Notre Dame President Theodore Hesburgh, C.S.C., and former Provost Timothy O’Meara when, in his words, “everything was on the table, and all we discussed was how to achieve excellence.”</span></span></p>
<p><span style="font-variant:normal; font-weight:400; white-space:pre-wrap"><span style="font-style:normal">He met five United States presidents</span></span><span style="font-variant:normal; font-weight:400; white-space:pre-wrap"><span style="font-style:normal">—</span></span><span style="font-variant:normal; font-weight:400; white-space:pre-wrap"><span style="font-style:normal">Gerald Ford, Jimmy Carter, George H. Bush, George H.W. Bush, and Ronald Reagan</span></span><span style="font-variant:normal; font-weight:400; white-space:pre-wrap"><span style="font-style:normal">—</span></span><span style="font-variant:normal; font-weight:400; white-space:pre-wrap"><span style="font-style:normal">during his years as dean, as well as global dignitaries. Castellino, who grew up in Pittston, a blue-collar northeastern Pennsylvania coal town made infamous in the recent movie “The Irishman,” felt it was remarkable to be put in situations where he could meet high-ranking public officials. </span></span></p>
<p><span style="font-variant:normal; font-weight:400; white-space:pre-wrap"><span style="font-style:normal">“Particularly special was one commencement when both Stephen Hawking and Lech Walesa were honorary degree recipients,” he said. Walesa was the leader of the Solidarity movement, who later was awarded the Nobel Peace Prize and elected president of Poland. Because he was imprisoned during the time of the commencement, there was the flag of Poland draped over an empty chair.</span></span></p>
<p><span style="font-variant:normal; font-weight:400; white-space:pre-wrap"><span style="font-style:normal">“It was a very emotional commencement and when Provost O’Meara read the citation</span></span><span style="font-variant:normal; font-weight:400; white-space:pre-wrap"><span style="font-style:normal">—</span></span><span style="font-variant:normal; font-weight:400; white-space:pre-wrap"><span style="font-style:normal">I almost cried. It was unbelievable,” he said. “I am still moved by it.” This was, at the time, the only honorary degree awarded by Notre Dame </span></span><span style="font-variant:normal; font-weight:400; white-space:pre-wrap"><em style="font-style:italic">in absentia. </em></span></p>
<p><span style="font-variant:normal; font-weight:400; white-space:pre-wrap"><span style="font-style:normal">Castellino has always enjoyed his research, starting from his days in graduate school. </span></span><span style="font-variant:normal; font-weight:400; white-space:pre-wrap"><span style="font-style:normal">After earning his Master of Science in 1966 and a doctoral degree in 1968 from the University of Iowa, Castellino completed a National Institutes of Health Postdoctoral Fellowship at Duke University, before joining the Notre Dame faculty.</span></span></p>
<p><span style="font-variant:normal; font-weight:400; white-space:pre-wrap"><span style="font-style:normal">Castellino’s lab is currently doing research to understand Group A streptococcus, on a molecular and cellular level, as well as on an evolutionary basis. </span></span></p>
<p><span style="font-variant:normal; font-weight:400; white-space:pre-wrap"><span style="font-style:normal">“His research relied on keeping abreast of the development at the forefront of biochemistry to provide a vision of how these might affect his own work,” Lappin said, adding that </span></span><span style="font-variant:normal; font-weight:400; white-space:pre-wrap"><span style="font-style:normal">the rise of molecular biology in the 1980s provided a challenge to put in place key personnel to develop expertise on the faculty at Notre Dame.</span></span></p>
<p><span style="font-variant:normal; font-weight:400; white-space:pre-wrap"><span style="font-style:normal">Castellino quickly moved to expand these efforts to work with the </span></span><span style="font-variant:normal; font-weight:400; white-space:pre-wrap"><span style="font-style:normal">latest molecular biology and immunology studies. </span></span></p>
<p><span style="font-variant:normal; font-weight:400; white-space:pre-wrap"><span style="font-style:normal">“Advances in cancer research and other important areas followed these fundamental developments,” Lappin said.</span></span></p>
<p><span style="font-variant:normal; font-weight:400; white-space:pre-wrap"><span style="font-style:normal">With the importance of balancing both research and teaching, Castellino advises new professors to concentrate on teaching, but also to make sure they can develop notable research programs. </span></span></p>
<p><span style="font-variant:normal; font-weight:400; white-space:pre-wrap"><span style="font-style:normal">“Teach well, but know that teaching involves many things, including how well you run your research lab,” he said. “A student can’t define what good teaching is, but they know when they’ve had a good teacher, because they learn something.” </span></span></p>
<p><span style="font-variant:normal; font-weight:400; white-space:pre-wrap"><span style="font-style:normal">Castellino’s passion for mentoring has continued during his career, and last year he nominated <a href="https://biology.nd.edu/people/ana-lidia-flores-mireles/" target="_blank">Ana Lidia Flores-Mireles</a>, Hawk Assistant Professor in the Department of Biological Sciences, to give a talk in California in February at the Gordon Research Conference on Plasminogenic Activation and Extracellular Proteolysis, which, “for a junior investigator, this is a big deal,” she said.</span></span></p>
<p><span style="font-variant:normal; font-weight:400; white-space:pre-wrap"><span style="font-style:normal">“My participation in that conference opened the door for me to new collaborations, and to enter into a new scientific field,” Flores-Mireles said, praising his generosity and collaborative spirit. “I cannot thank him enough for his support and guidance — scientifically and personally.”</span></span></p>
<p><span style="font-variant:normal; font-weight:400; white-space:pre-wrap"><span style="font-style:normal">Castellino and his wife, Mary, raised three children, all of whom graduated from Notre Dame as undergraduates, and one who also received a law degree from the University. And though he’s been at the University for 50 years, he’s not looking to retire soon. He’s in good health, he’s active, he still runs an active research laboratory, and he publishes frequently. </span></span></p>
<p><span style="font-variant:normal; font-weight:400; white-space:pre-wrap"><span style="font-style:normal">“My wife says that if I retire, I better have something else to do, and I don’t,” he said, adding that he doesn’t foresee himself thinking about retirement within the next five years, and he and his wife have already traveled the globe. </span></span></p>
<p><span style="font-variant:normal; font-weight:400; white-space:pre-wrap"><span style="font-style:normal">“Of course, God is going to make that decision for me to retire someday, but I’m not quite ready yet,” he said. “My only need is to be part of something bigger. If I were to wake up in the morning and nobody gave a darn about what I was doing, that would kill me. Basically, I have to think about retirement because of my age, but I don’t want to have to think about it because I don’t want to think about what happens if I’m not being useful anymore.”</span></span></p>
<p><span style="font-variant:normal; font-weight:400; white-space:pre-wrap"><span style="font-style:normal">As Castellino continues his research into blood clotting disorders, he appreciates how far research has come across the University. Now that Notre Dame has become more well-known for its research, Castellino doesn’t hear the questions about football nearly as often at academic conferences.</span></span></p>
<p><span style="font-variant:normal; font-weight:400; white-space:pre-wrap"><span style="font-style:normal">“I’ve seen unbelievable progress in 50 years,” he said.</span></span></p>
<p> </p>
<p class="attribution">Originally published by <span class="rel-author">Deanna Csomo McCool</span> at <span class="rel-source"><a href="https://science.nd.edu/news/ormer-dean-castellino-celebrates-50-years-at-the-university-of-notre-dame/">science.nd.edu</a></span> on <span class="rel-pubdate">April 06, 2020</span>.</p>Deanna Csomo McCooltag:transgene.nd.edu,2005:News/1082192019-04-08T15:00:00-04:002020-02-25T15:18:02-05:00W.M. Keck Center Undergraduates earn Science Fellowships<p>Congratulations to the W.M. Keck Center for Transgene Research’s three undergraduates for earning summer fellowships. The 2019 College of Science Summer Fellowships were awarded to Muqsit Buchh ’21, Sydnye Nosbusch ’20, and Michael Seraphin ’20. Musquit is a dual major neuroscience and behavior and…</p><p>Congratulations to the W.M. Keck Center for Transgene Research’s three undergraduates for earning summer fellowships. The 2019 College of Science Summer Fellowships were awarded to Muqsit Buchh ’21, Sydnye Nosbusch ’20, and Michael Seraphin ’20. Musquit is a dual major neuroscience and behavior and applied and computational mathematics and statistics. Sydnye is working toward a major in neuroscience and behavior and a minor in collaborative innovation. Michael is pursing a major in biochemisty and theology.</p>Deborah Donahuetag:transgene.nd.edu,2005:News/1082222018-12-06T15:00:00-05:002020-02-25T15:22:31-05:00Bradley 5 Charitable Fund donates to W.M. Keck Center<p>The Bradley 5 Charitable Fund has generously donated to the W.M. Keck Center for Transgene Research. This is the second time the organization has donated to research at the Center.  </p> <p>Learn more: <a href="http://www.abc57.com/news/bradley-five-charitable-fund-donates-17k-to-w-m-keck-center">http://www.abc57.com/news/bradley-five-charitable-fund-donates-17k-to-w-m-keck-center</a></p><p>The Bradley 5 Charitable Fund has generously donated to the W.M. Keck Center for Transgene Research. This is the second time the organization has donated to research at the Center. </p>
<p>Learn more: <a href="http://www.abc57.com/news/bradley-five-charitable-fund-donates-17k-to-w-m-keck-center">http://www.abc57.com/news/bradley-five-charitable-fund-donates-17k-to-w-m-keck-center</a></p>Deborah Donahuetag:transgene.nd.edu,2005:News/1082232018-07-12T15:15:00-04:002020-02-25T15:16:14-05:00Community research collaboration creates better system for treating trauma patients<p>Since 2009, Francis J. Castellino, Kleiderer-Pezold Professor of Biochemistry and director of the Keck Center, has worked with a team of doctors at Memorial Hospital in South Bend to find new methods for treating trauma patients.</p><p>Trauma, or any kind of severe physical injury, continues to be today’s leading cause of death for people 46 and younger in the United States. In 2007, doctors <a href="https://transgene.nd.edu/people/scott-thomas-md-facs/">Scott Thomas</a> and <a href="https://transgene.nd.edu/people/mark-walsh-md-facep/">Mark Walsh</a> of Memorial Hospital in South Bend were looking for a better way to treat trauma patients who arrived in the emergency room with excessive bleeding. Their search eventually led to a translational research collaboration with the <a href="https://transgene.nd.edu/">W. M. Keck Center for Transgene Research</a> at the University of Notre Dame and the development of a new method for treating trauma patients.</p>
<p>Upon arrival to an ER, about 25 percent to 35 percent of seriously injured trauma patients have excessive bleeding, or coagulopathy, without clotting. Traditionally, coagulopathy could be treated with fluid resuscitation, but Thomas, chief of trauma services for Beacon Health Systems, and Walsh, an ER physician, knew that a blood replacement product – like platelets, plasma or cryoprecipitate – would be a better treatment option. </p>
<p>However, each patient has individual blood replacement product needs, and there was no standard method for determining those needs in a trauma setting. After speaking with other medical professionals, they realized a machine called the thromboelastogram or <span class="caps">TEG</span>, used to test the efficiency of blood coagulation for transplant and cardiac surgery patients, could be used in the ER to look at coagulation profiles. </p>
<p>“This had never been done before,” said Walsh. “From that point, we began to consider how that work could be translated in different ways, but knew we would need a research arm to support this effort.”</p>
<p>Walsh and Thomas reached out to <a href="https://chemistry.nd.edu/people/francis-j-castellino/">Francis J. Castellino</a>, Kleiderer-Pezold Professor of Biochemistry and <a href="https://transgene.nd.edu/people/francis-j-castellino-phd/">director of the Keck Center</a>, who they knew studied the functions of components of the hemostasis system – or the process that causes bleeding to stop – in a variety of genetic diseases. Castellino worked to develop a model for Thomas and Walsh that helped determine which replacement blood product was needed for treating a trauma patient who wasn’t clotting properly.</p>
<p>Eventually, the team received a research grant from Memorial Hospital, and Haemonetics Corp. donated <span class="caps">TEG</span> machines for the project. With data from Col. John Holcomb, one of the military’s top medical surgeons who met with the research team in 2009, the team found that the TEG’s ability to map platelets allows any given trauma team the ability to more effectively manage blood products for resuscitation of patients who are bleeding out. </p>
<p>“When our initial studies were being published in 2011, most trauma centers had not yet adopted the use of <span class="caps">TEG</span> machine analysis,” said Thomas. “However, because of this collaboration with Dr. Castellino and his team, we were better prepared here in South Bend than many other trauma centers in the country with this technique.” </p>
<p><iframe allowfullscreen="" frameborder="0" height="360" src="https://www.youtube.com/embed/jGYmC8BlU4U?rel=0" width="640"></iframe></p>
<p>From here, the collaboration expanded to other areas of trauma care and blood coagulation. For example, Castellino developed models for a number of studies including one for analyzing <a href="https://transgene.nd.edu/research/traumatic-brain-injury/">blunt traumatic brain injury</a> (<span class="caps">TBI</span>) that represented coagulopathy. <span class="caps">TBI</span> is a contributing factor to a third of all injury-related deaths in the U.S., and acute coagulopathy is a serious complication for this injury.</p>
<p>“Our goal was to develop a model of <span class="caps">TBI</span> that mimicked the condition observed in people so that a procedure for treating patients with <span class="caps">TBI</span> would be readily understood,” said Castellino. “This is just one example of how Dr. Thomas, Dr. Walsh and I were able to establish a translational research collaboration, and because of the partnership with Memorial Hospital, which is nationally recognized for providing a high level of trauma and surgical care as well as being a leader in innovation, we get to see how this research directly and positively impacts the community.”</p>
<p>This <span class="caps">TBI</span> research also led to an <a href="https://www.physiology.org/doi/abs/10.1152/ajplung.00429.2015">additional study</a> funded by the Indiana State Department of Health and the National Heart, Lung, and Blood Institute and published in the American Journal of Physiology in 2016. The groundbreaking results showed that patients may incur lung injury following <span class="caps">TBI</span> because of biological events including the release of tissue factor, a protein that triggers blood clotting. Together, the research team has published about 15 papers on the topic of blood coagulation, resuscitation and the use of <span class="caps">TEG</span> in successful trauma care. Now, Thomas and Walsh are working on establishing guidelines and protocols for transfusing patients and for using the <span class="caps">TEG</span> machine to treat trauma patients with their established, goal-directed model.</p>
<p>“There were a lot of factors that fell in to place and allowed this collaboration to work, but it has given Dr. Thomas and myself an opportunity to have a greater impact in our field and all over the world,” said Walsh. “Without the advantage of Notre Dame’s research infrastructure, the ‘right size’ of the local community, and Castellino’s expertise and team, we wouldn’t be where we are today.”</p>
<p>The W. M. Keck Center for Transgene Research at the University of Notre Dame develops models as well as uses gene-targeting technology to investigate the roles of genes for blood coagulation for embryonic development, cancer, stroke, infection and more. To learn more about the center, visit <a href="https://transgene.nd.edu/">transgene.nd.edu</a>. </p>
<p>Memorial Hospital provides the highest level of newborn and pediatric care, cancer care, trauma care, surgical care and rehabilitation care in the region. Memorial Hospital of South Bend is a community-owned, not-for-profit corporation governed by volunteer representatives of the community guided by a mission to improve the quality of life for the people of our community. To learn more, visit <a href="https://www.beaconhealthsystem.org/">https://www.beaconhealthsystem.org</a>.</p>
<p><em><strong>Contact:</strong> Brandi R. Klingerman, Notre Dame Research, <a href="mailto:bklinger@nd.edu">bklinger@nd.edu</a>, 574-631-8183; <a href="https://twitter.com/UNDResearch">@UNDResearch</a></em></p>
<p class="attribution"><em>Originally published by <span class="rel-author">Brandi Klingerman</span> at <span class="rel-source"><a href="https://research.nd.edu/news/community-research-collaboration-creates-better-system-for-treating-trauma-patients/">research.nd.edu</a></span> on <span class="rel-pubdate">July 11</span>.</em></p>Brandi Klingermantag:transgene.nd.edu,2005:News/1082242018-03-20T15:00:00-04:002020-02-25T15:17:24-05:00Natural bacterial proteins may prove viable alternatives to antibiotics<p class="image-left"><img alt="Fields 250" src="https://science.nd.edu/assets/269602/fields_250.jpg" /></p>
<p>Tiny proteins found in the genomes of some types of bacteria are effective weapons against a wide range of other bacteria, opening the door for the development of new therapies in the age of antibiotic resistance, according to new research at the University of Notre Dame.</p><p dir="ltr">Tiny proteins found in the genomes of some types of bacteria are effective weapons against a wide range of other bacteria, opening the door for the development of new therapies in the age of antibiotic resistance, according to new research at the University of Notre Dame.</p>
<p dir="ltr">Francisco “Pancho” Fields, a fourth-year graduate student in the <a href="https://biology.nd.edu/" target="_blank">Department of Biological Sciences</a>, studied some of the antimicrobial peptides, known as bacteriocins, inside bacteria found in mungbean seeds. Fields, the lead author on the <a href="https://www.nature.com/articles/s41429-018-0032-4" target="_blank">paper published in February 2018</a> in The Journal of Antibiotics, completed his research with other colleagues in the lab of <a href="https://biology.nd.edu/people/shaun-w-lee/" target="_blank">Shaun Lee,</a> the Monahan Family Associate Professor of Rare and Neglected Diseases in the Department of Biological Sciences and the <a href="https://globalhealth.nd.edu/" target="_blank">Eck Institute for Global Health</a>.</p>
<p dir="ltr">The team sequenced the genome of a bacterial species isolated from the seed and discovered a portion of one bacteriocin, AS-48, would interact with the membranes of certain types of bacteria like E. coli. The researchers decided to capitalize on the characteristics that would initiate the interaction, then created 96 different variations of the peptide. Nine of those variations were more effective against a wide array of bacteria than the others.</p>
<p class="image-right"><img alt="Fields 250" src="https://science.nd.edu/assets/269602/fields_250.jpg"></p>
<p dir="ltr">“It caused the bacteria to develop these little holes, and they started leaking their cellular content until they died,” Fields said, likening the cell death process to air leaking out of a balloon that had been stuck with a pin.</p>
<p dir="ltr">Though many different types of antimicrobial peptides have been explained in scientific literature, Fields’ and Lee’s study is novel because it was the first time that a library of peptides was designed from a circular bacteriocin, rather than from a straight chain. In nature, many of these proteins exist as circular forms, so using this approach assured that the team optimized the peptides to the point where they’re as effective as their natural counterparts.</p>
<p dir="ltr">Fields expects future antibiotic alternatives developed from their discovery could be used topically. For instance, burn wounds often become infected with Pseudomonas bacteria, which can be fought with this natural bacteriocin compound.</p>
<p dir="ltr">“We’re also excited about the potential of these optimized bacteriocins for agriculture,” Lee said. “Jeanne Romero-Severson [professor in the Department of Biological Sciences] and I originally found this bacterium in a foodsafe source of mungbean seeds. Because this was derived from a commensal bacterium in a plant source, it may have application as an agricultural product to prevent bacterial infection in plants and crops.”</p>
<p dir="ltr">In addition to Fields and Lee, the research team included Katelyn E. Carothers and Rashna D. Balsara, as well as Victoria Ploplis, research director and associate director of the <a href="https://transgene.nd.edu/" target="_blank">W.M. Keck Center for Transgene Research</a>, and Francis Castellino, director of the W.M. Keck Center for Transgene Research and Kleiderer/Pezold Professor of Biochemistry.</p>
<p>The research was funded with an <a href="https://www.nsf.gov/" target="_blank">National Science Foundation</a> Graduate Research Fellowship and a <a href="http://www.gemfellowship.org/students/gem-fellowship-program/" target="_blank">National <span class="caps">GEM</span> Consortium Fellowship</a> to Francisco Fields, as well as an <a href="https://www.nih.gov/" target="_blank">National Institutes of Health</a> Innovator Grant to Lee.</p>
<p class="attribution">Originally published by <span class="rel-author">Deanna Csomo McCool</span> at <span class="rel-source"><a href="https://science.nd.edu/news/natural-bacterial-proteins-may-prove-viable-alternatives-to-antibiotics/">science.nd.edu</a></span> on <span class="rel-pubdate">March 20, 2018</span>.</p>Deanna Csomo McCooltag:transgene.nd.edu,2005:News/1082272018-01-28T15:00:00-05:002020-02-25T15:27:47-05:00New avenues found for treatment of pathogen behind diseases including fasciitis, toxic shock syndrome<p class="image-left"><img alt="Scanning electron micrograph of red blood cell hemolysis by the Streptolysin S producing Group A Streptococcus. Credit: Shaun Lee, Dustin Higashi" src="http://news.nd.edu/assets/188709/200x/shaun_lee_gas.jpg" title="Scanning electron micrograph of red blood cell hemolysis by the Streptolysin S producing Group A Streptococcus. Credit: Shaun Lee, Dustin Higashi" /></p>
<p>One bacterial pathogen is responsible for a range of diseases, from pharyngitis and impetigo to more severe diagnoses such as toxic shock syndrome and necrotizing fasciitis (flesh eating disease), a serious bacterial skin infection that spreads quickly and kills the body’s soft tissue. The pathogen, known as Group A Streptococcus, remains a global health burden with an estimated 700 million cases reported annually, and more than half a million deaths due to severe infections.</p><p class="image-right"><img alt="Scanning electron micrograph of red blood cell hemolysis by the Streptolysin S producing Group A Streptococcus. Credit: Shaun Lee, Dustin Higashi" src="http://news.nd.edu/assets/188709/300x/shaun_lee_gas.jpg" title="Scanning electron micrograph of red blood cell hemolysis by the Streptolysin S producing Group A Streptococcus. Credit: Shaun Lee, Dustin Higashi"> Scanning electron micrograph of red blood cell hemolysis by the Streptolysin S producing Group A Streptococcus. Credit: Shaun Lee, Dustin Higashi</p>
<p>One bacterial pathogen is responsible for a range of diseases, from pharyngitis and impetigo to more severe diagnoses such as toxic shock syndrome and necrotizing fasciitis (flesh eating disease), a serious bacterial skin infection that spreads quickly and kills the body’s soft tissue. The pathogen, known as Group A Streptococcus, remains a global health burden with an estimated 700 million cases reported annually, and more than half a million deaths due to severe infections.</p>
<p>The ability of Group A Streptococcus (<span class="caps">GAS</span>) to induce rapid destruction of red blood cells has been observed for more than a century and remains a clinical hallmark of <span class="caps">GAS</span> diagnosis. This destruction is due to the production of a small peptide toxin by <span class="caps">GAS</span> known as Streptolysin S (<span class="caps">SLS</span>).</p>
<p>Although it has been widely held that <span class="caps">SLS</span> exerts its lytic activity — the excessive destruction of red blood cells — through membrane disruption, its exact mode of action has remained unknown.</p>
<p>“Recent molecular studies by our lab and others have demonstrated that <span class="caps">SLS</span> is a peptide toxin linked to a broad class of bacterially produced compounds known as bacteriocins,” <a href="http://biology.nd.edu/people/shaun-w-lee/">Shaun Lee</a>, an associate professor of <a href="http://biology.nd.edu/">biological sciences</a> at the University of Notre Dame, said. “Many of these related bacteriocins have defined cellular targets and have not been shown to function as general lytic agents of cellular membranes.”</p>
<p>In a <a href="http://www.nature.com/nmicrobiol/">new study</a>, Lee’s research group provides the first real-time, high-resolution observation of Group A streptoccocal red cell destruction, also called beta-hemolysis.</p>
<p>“We demonstrate that the long-observed red blood cell hemolysis by <span class="caps">SLS</span> is not caused by general destruction of the red blood cell membrane, as has been previously thought, but rather that the action is due to the ability of the <span class="caps">SLS</span> toxin to directly target a specific outer membrane protein on the surface of the red blood cell, the major erythrocyte anion exchange protein Band 3.”</p>
<p>Importantly, chemical inhibition of Band 3 function completely blocked the hemolytic activity of <span class="caps">SLS</span>, and significantly altered the pathology induced by <span class="caps">GAS</span> in an in vivo skin infection model.</p>
<p>“Our studies provide the first mechanistic look into the longstanding question of <span class="caps">SLS</span> function and, importantly, open new therapeutic avenues for the treatment of severe <span class="caps">GAS</span> disease,” Lee said.</p>
<p>“This was a wonderful collaborative effort led by Dustin Higashi, a senior researcher in my lab, to try to answer the longstanding mystery of how this very powerful toxin known as Streptolysin S lyses red blood cells to contribute to invasive human disease caused by the Group A Streptococcus,” he said.</p>
<p>“Findings critical to the support of our hypothesis were provided by in vivo studies performed at the <a href="http://transgene.nd.edu/">W.M. Keck Center for Transgene Research</a>, under the direction of Francis Castellino and Victoria Ploplis. Using humanized mouse models, Keck scientists Deborah Donahue and Jeff Mayfield demonstrated that by blocking the action of <span class="caps">SLS</span> toxin during a <span class="caps">GAS</span> infection, the pathology at the site of the infection could be drastically reduced. These findings have tremendous potential for developing novel therapeutics to treat severe diseases caused by Group A Streptococcus.”</p>
<p>The study was supported by an <span class="caps">NIH</span> Innovator Grant awarded to Lee and appears in the journal Nature Microbiology. It can be found here: <a href="http://www.nature.com/nmicrobiol/">http://www.nature.com/nmicrobiol/</a>.</p>
<p><em><strong>Contact</strong>: Shaun Lee, 574-631-7197, <a href="mailto:lee.310@nd.edu">lee.310@nd.edu</a></em></p>
<p class="attribution">Originally published by <span class="rel-author">William G. Gilroy</span> at <span class="rel-source"><a href="https://science.nd.edu/news/new-avenues-found-for-treatment-of-pathogen-behind-diseases-including-fasciitis-toxic-shock-syndrome/">ibms.nd.edu</a></span> on <span class="rel-pubdate">January 29, 2016</span>.</p>William G. Gilroytag:transgene.nd.edu,2005:News/1082252017-11-15T15:00:00-05:002020-02-25T15:21:33-05:00Bradley 5 Charitable Fund donation to W.M. Keck Center<p>On behalf of the Bradley 5 Charitable Fund, Dawn and Dana Hollar with their family, came to the W. M. Keck Center on November 13, 2017 to present a check for $15,000. The money was raised in memory of their late son, Bradley Hollar and will to support Center research.</p> <p class="image-right"><img>…</p><p>On behalf of the Bradley 5 Charitable Fund, Dawn and Dana Hollar with their family, came to the W. M. Keck Center on November 13, 2017 to present a check for $15,000. The money was raised in memory of their late son, Bradley Hollar and will to support Center research.</p>
<p class="image-right"><img alt="Hollar" src="https://transgene.nd.edu/assets/257510/hollar_.png"></p>
<p>Learn more: <a href="http://www.wndu.com/content/news/Michiana-couple-fights-genetic-disorder-that--457117793.html">http://www.wndu.com/content/news/Michiana-couple-fights-genetic-disorder-that—457117793.html</a></p>Deborah Donahuetag:transgene.nd.edu,2005:News/1082262017-08-31T15:00:00-04:002020-02-25T15:25:10-05:00Researchers and family hope to learn more about genetic blood disorders<p>Researchers at the University of Notre Dame are learning more about genetic blood disorders that can lead to serious health concerns.</p> <p>They use mice with genetic defects to understand how blood clots happen in humans.</p> <p>A large part of their research focuses on how proteins are involved…</p><p>Researchers at the University of Notre Dame are learning more about genetic blood disorders that can lead to serious health concerns.</p>
<p>They use mice with genetic defects to understand how blood clots happen in humans.</p>
<p>A large part of their research focuses on how proteins are involved in clot formation and clot dissolution.</p>
<p>View full story at WSBT: <a href="https://wsbt.com/news/health/researchers-and-family-hope-to-learn-more-about-genetic-blood-disorders">https://wsbt.com/news/health/researchers-and-family-hope-to-learn-more-about-genetic-blood-disorders</a></p>Caroline Torietag:transgene.nd.edu,2005:News/1082322014-01-16T15:00:00-05:002020-02-25T15:29:35-05:00Castellino earns Distinguished Alumnus Award from the University of Iowa<p class="image-left"><img alt="Frank Castellino" src="https://science.nd.edu/assets/122181/frank_castellino250.jpg" title="Frank Castellino" /></p>
<p><a href="http://chemistry.nd.edu/people/francis-j-castellino/" target="_blank">Francis Castellino</a>, Kleiderer-Pezold Professor of Biochemistry, has been selected to receive the University of Iowa Carver College of Medicine Distinguished Alumnus Award for Achievement. He was selected for his career of service leadership and contributions to medicine and will be formally recognized by the university in June 2014.</p><p class="image-right"><img alt="Frank Castellino" src="https://science.nd.edu/assets/122180/frank_castellino.jpg" title="Frank Castellino"></p>
<p><a href="http://chemistry.nd.edu/people/francis-j-castellino/" target="_blank">Francis Castellino</a>, Kleiderer-Pezold Professor of Biochemistry, has been selected to receive the University of Iowa Carver College of Medicine Distinguished Alumnus Award for Achievement. He was selected for his career of service leadership and contributions to medicine and will be formally recognized by the university in June 2014. </p>
<p>After earning a Master of Science in 1966 and a Ph.D. in 1968 from the University of Iowa, Castellino completed a National Institutes of Health Postdoctoral Fellowship at Duke University. He joined the Notre Dame faculty in 1970 and served as dean of the College of Science from 1979-2002. Currently, Castellino is the director for the <a href="http://transgene.nd.edu/" target="_blank">W.M. Keck Center for Transgene Research</a> and an adjunct professor of biochemistry and molecular biology at Indiana University School of Medicine – South Bend. </p>
<p>Castellino’s research interests include the structure, function, and activation of proteins that participate in blood coagulation, blood clot dissolution, inflammation, and infection. By studying the biological functions of coagulation and clot-dissolving genes and proteins in conditions such as cancer, sepsis, wound healing, atherosclerosis, bacterial infections, and head trauma, his research group has produced important information regarding the development and progression of these disease states.</p>
<p>A highly accomplished researcher and teacher, Castellino has earned several prestigious recognitions throughout his career. In 2008, he earned a Wyeth-<span class="caps">ISPF</span> Research Prize. He is a Fellow in several prestigious organizations, which include the American Heart Association and the Council on Arteriosclerosis, Thrombosis, and Vascular Biology; the American Association for the Advancement of Science (<span class="caps">AAAS</span>); and Sigma Xi. He earned the University of Notre Dame Annual Faculty Award in 2003 and was named a Fellow of the <a href="http://reilly.nd.edu/" target="_blank">Reilly Center</a> for Science, Technology, and Values in 2006. Castellino also holds honorary degrees from the University of Scranton, his undergraduate alma mater, and Waterloo University in Canada, where he presented the commencement address in 1993.</p>
<p class="attribution">Originally published by <span class="rel-author">Stephanie Healey</span> at <span class="rel-source"><a href="https://science.nd.edu/news/castellino-earns-distinguished-alumnus-award-from-the-university-of-iowa/">science.nd.edu</a></span> on <span class="rel-pubdate">January 16, 2014</span>.</p>Stephanie Healeytag:transgene.nd.edu,2005:News/1082342011-10-28T15:35:00-04:002020-02-25T15:35:32-05:00New technology helps ER doctors make critical decisions <p class="image-right"><img alt="Emergency room" src="https://news.nd.edu/assets/52646/emergency_room.jpg" title="Emergency room" /></p>
<p>Researchers from the University of Notre Dame’s <a href="http://www.nd.edu/~transgen/">Keck Center for Transgene Research</a> and trauma physicians at South Bend’s Memorial Hospital are joining forces to use a new medical technology to help save the lives of trauma patients.</p>
<p>Researchers at the Keck Center investigate how the genes involved in blood clotting processes function in inflammatory diseases like sepsis, atherosclerosis and asthma. In particular, the Center’s Thromboelastographic Study Group focuses on the coagulopathy (clotting disorder or bleeding disorder) of trauma.</p><p class="image-right"><img alt="Emergency room" src="https://news.nd.edu/assets/52646/emergency_room.jpg" title="Emergency room"></p>
<p>Researchers from the University of Notre Dame’s <a href="http://www.nd.edu/~transgen/">Keck Center for Transgene Research</a> and trauma physicians at South Bend’s Memorial Hospital are joining forces to use a new medical technology to help save the lives of trauma patients.</p>
<p>Researchers at the Keck Center investigate how the genes involved in blood clotting processes function in inflammatory diseases like sepsis, atherosclerosis and asthma. In particular, the Center’s Thromboelastographic Study Group focuses on the coagulopathy (clotting disorder or bleeding disorder) of trauma.</p>
<p>The Keck Center, as well as Memorial Hospital, recently obtained a new piece of medical technology called a thromboelastograph (<span class="caps">TEG</span>) analyzer for use on trauma patients suffering from acute traumatic coagulopathy. Memorial trauma physicians Scott Thomas and Mark Walsh and Keck Center director <a href="http://www.nd.edu/~transgen/biographies/administration/castellino.html">Frank Castellino</a> have formed a unique partnership to use the <span class="caps">TEG</span> analyzer in groundbreaking ways.</p>
<p>Patients arriving at a trauma center following automobile accidents, falls, shootings and other acts of violence often are experiencing significant blood loss.</p>
<p class="image-left"><img alt="Frank Castellino" src="https://news.nd.edu/assets/9116/castellino_frank_web.jpg" title="Frank Castellino"></p>
<p>“The goal of trauma physicians is to first stop the blood loss and stabilize the patient. The aim of the current work between the Keck Center and Memorial Hospital is to employ real time thrombus measurements, combined with platelet functional analysis, which will engage the expertise of the trauma physician, researcher and perfusionist to make rapid point of care decisions as to which blood products the patient requires," Castellino said. “This will allow specific transfusion protocols to be used and save precious blood products and unnecessary expense to the patients, while at the same time providing state-of-the-art patient care.</p>
<p>“The testing requires a small sample of the patient’s blood to determine its ability to form stable clots with use of <span class="caps">TEG</span> measurements. Complex transfusion decisions can then be made in a very short time with the maximal amount of data.”</p>
<p>Castellino notes that this close collaboration between scientific researchers and physicians is both unique and highly productive. Keck researchers are doing fundamental work in molecular medicine which is being employed by the the Memorial Trauma Center for patient care in a model of translational research.</p>
<p>The result means a state-of-the-art level of trauma care for residents of northern Indiana and a model for national care in this area.</p>
<p><em><strong>Contact</strong>: Frank Castellino, 574-631-8996, <a href="mailto:facstell@nd.edu">fcastell@nd.edu</a></em></p>
<p class="attribution">Originally published by <span class="rel-author">William G. Gilroy</span> at <span class="rel-source"><a href="https://news.nd.edu/news/university-of-notre-dame-researchers-and-memorial-hospital-trauma-physicians-combine-forces-to-help-save-patient-lives/">news.nd.edu</a></span> on <span class="rel-pubdate">October 28, 2011</span>.</p>William G. Gilroytag:transgene.nd.edu,2005:News/1082332007-10-07T15:00:00-04:002020-02-25T15:34:14-05:00W.M. Keck Center: Battling diseases to save lives<p>Everyone knows that inflammation signals infection or injury, like smoke does a fire. But researchers have learned that it can be an underlying cause of disease as well. p. Chronic inflammation has been linked to cancer in the colon, asthma in the airways and atherosclerosis in the arteries, setting…</p><p class="image-right"><img alt="Frank_Castellino_rel.jpg" src="https://news.nd.edu/assets/7202/Frank_Castellino_rel.jpg" title="Frank_Castellino_rel.jpg"></p>
<p>Everyone knows that inflammation signals infection or injury, like smoke does a fire. But researchers have learned that it can be an underlying cause of disease as well.</p>
<p>Chronic inflammation has been linked to cancer in the colon, asthma in the airways and atherosclerosis in the arteries, setting the stage for heart attacks and strokes. <img alt="" src="https://news.nd.edu/assets/Keck_text-box.jpg"></p>
<p>And a major killer called sepsis is nothing less than inflammation run amok.</p>
<p>I can think of no disease that does not involve inflammation, said Francis J. Castellino, director of the Notre Dames W.M. Keck Center for Transgene Research.</p>
<p>Its also hard to imagine a research center better equipped and staffed to sort out the inner workings of inflammation than the Keck Center.</p>
<p>Located in Raclin-Carmichael Hall, the center is a world-class facility focused on the study of proteins involved in inflammation and the related process of hemostasis, the body's way of balancing blood flow and clotting.</p>
<p>Research into blood proteins has been growing steadily more sophisticated at Notre Dame for more three decades under Castellino's direction, spurred by technological advances that have made it possible to study the structure and function of hemostasis-related proteins in ever more detail.</p>
<p>But two relatively recent milestones have really helped.</p>
<p>In 2004, Keck Center scientists were awarded $9 million in grants from the National Institutes of Health to study inflammation in sepsis, the genetics of colon cancer and the role of homeostasis following artery damage.</p>
<p>Then, in 2005, the center joined the Indiana University School of Medicine-South Bend as primary occupants of Raclin-Carmichael Hall, the new academic building just outside the University's main gate on Notre Dame Avenue.</p>
<p>The Keck Centers move to Raclin-Carmichael Hall consolidated an operation that had been spread over nine spaces in four campus buildings, assistant director Melanie DeFord said. That's created a more cohesive work atmosphere for the centers staff of 35 scientists, technicians and students. The centers new labs, besides being about 20 percent larger overall, employ an impressive array of state-of-the-art equipment, like a laser knife so precise it can cut out individual colon cancer cells for genetic analysis.</p>
<p>None of it would be possible, however, without the mice that live in the basement.</p>
<p>* <em>Keys to discovery</em> *</p>
<p>A colony of 6,000 specially engineered, transgenic mice is the engine that drives the flow of discoveries from the Keck Center. Experts at the center have created more than 50 different strains of mice, with each strain having its own strategically chosen gene alterations.</p>
<p>Because genes are templates for production of proteins, adding or subtracting them from the genome produces mice that have excesses or deficiencies of the blood proteins that Keck scientists want to study, Castellino explained.</p>
<p>Studying proteins in live animals is a huge advance over the technology available to Castellino when he began studying blood proteins in the early 1970s. Back then, researchers had to tediously extract the selected protein from blood, he says. Experiments involved mixing two different proteins in test tubes to see the reaction.</p>
<p>But when you alter a gene in an intact animal, you're looking at everything (in a living system), starting with, ‘Does it live for long? Castellino explained.</p>
<p>The care, feeding and breeding of these special mice, who reside in about 1,500 cages, is itself a big operation requiring special technical expertise and upwards of $150,000 a year to cover costs.</p>
<p>We have five or six people working downstairs on the colony alone, Castellino says.</p>
<p>The breeding pairs in the colony are giving birth to about 1,000pupseach month, DeFord said. They must each be genotyped to determine which genes they inherited from their parents, who are heterozygous for the mutations. That means that the breeding mice, for the sake of hardiness, do not themselves have highly abnormal protein. But a certain percentage of their offspring do. Genotyping determines which offspring are suitable for experiments.</p>
<p>Every year, Keck scientists create three to four new strains with unique alterations as new research identifies new proteins that might be relevant to disease processes in humans, DeFord said. The center has to be selective, as the expense of engineering a new mouse is so high two years of work and up to $100,000, according to Castellino.</p>
<p>We have to ask, ‘Why do we want to make this mouse?There has to be a hypothesis,he said.</p>
<p>To aid those decisions, the Keck Center has laboratory resources capable of synthesizing any protein molecule that scientists can think of. Its done in sophisticated machines that exploit the protein-producing power of <span class="caps">DNA</span> in a variety of cells, including yeast, insect and mammalian. Candidate proteins are studied extensively in vitro before the decision is made to transect them into a mouse model.</p>
<p>But cooking up proteins and genetically customizing mice, impressive as it is, is not the point of the research, DeFord said. The real purpose of the center is to lay the groundwork for medical breakthroughs that battle disease and save lives.</p>
<p>Were not trying to make healthier mice,she said.</p>
<p>* <em>From mice to people</em> *</p>
<p>In Keck Center experiments, the genetically altered mice provide models of disease processes that occur in people. If researchers can figure exactly out how a disease starts or progresses in a mouse, that will provide clues about how to stop that disease in people.</p>
<p>Seeing what happens to the health of altered mouse is a start. But the researchers want to know much more than whether a mouse with a particular gene defect died or not, Castellino said. They also want to figure out exactly why.</p>
<p>To that end, the Keck Center has medical equipment and expertise found in hospitals that is, if mice had their own hospitals.</p>
<p>A tiny endoscope, for example, is used to visualize tumor growth and progression in the colons of mice genetically disposed to develop colon cancer, DeFord said. In asthma-related studies, specially equipped chambers called plethysmographs are able to measure the respiratory function of mice in reaction to irritants sprayed into the chamber. The mice move about freely in the plethysmographs during these measurements.</p>
<p>An equally ingenious device provides a more accurate way to measure blood pressure and heart rate in mice. Instead of the old way, putting a cuff on the mouses tail, an electronic probe is surgically implanted in its carotid artery, a feat requiring remarkable surgical dexterity. Other surgeries involve taking a vein from one mouse and grafting into another.</p>
<p>We have some talented people here, Castellino explains.Were talking about doing this on a mouse, for Gods sake.</p>
<p>Naturally, there's also the equivalent of a pathology lab at Keck to analyze tissue from autopsied mice. This includes an in-house histology lab where researchers examine cells from mouse tissues under microscopes. A device called a micro dissector allows researchers to probe even deeper. It can excise individual cells from a colon cancer tumor for <span class="caps">DNA</span> micro-array analysis to determine which proteins are up-regulated and down-regulated, DeFord explained. Running the same test on nearby normal cells is yielding clues about what causes benign polyps to become cancerous.</p>
<p>* <em>Whats at stake</em> *</p>
<p>Colon cancer, atherosclerosis, asthma and sepsis the diseases that Keck Center researchers have targeted take an enormous human toll. The American Cancer Society estimates that colorectal cancer killed 55,000 people in 2006. Heart attacks, a result of arterial plaques in atherosclerosis, cause about 450,000 deaths annually in the U.S., according to the American Heart Association. Asthma afflicts 20 million Americans, including 9 million children, and causes about 4,000 deaths annually.</p>
<p>The least familiar of Keck's target diseases, sepsis, is a major health problem that occurs when an infection overwhelms the system. The body's responses including out-of-control inflammation and blood clotting lead to organ failure.</p>
<p>Doctors don't understand exactly what sets off sepsis, and they do not have a good medicine to stop it once it gets rolling. About 750,000 people go into septic shock each year, and an estimated 28 percent of them die.</p>
<p>While thousands of researchers around the world are studying these diseases, DeFord said the Keck Center is unique in its focus on homeostasis-related blood proteins and its capacity to study them at all levels, from molecules to cells to whole animals.</p>
<p>No other place can synthesize a protein, evaluate it, put it in a living mouse and then analyze the results in such detail.</p>
<p>I think that makes us special, she said.</p>
<p class="attribution">Originally published by <span class="rel-author">Dave Rumbach</span> at <span class="rel-source"><a href="https://news.nd.edu/news/keck-center-battling-diseases-to-save-lives/">news.nd.edu</a></span> on <span class="rel-pubdate">October 07, 2007</span>.</p>Dave Rumbachtag:transgene.nd.edu,2005:News/1082352004-05-04T15:00:00-04:002020-02-25T15:39:32-05:00$9 million NIH grant heightens Keck research profile<p>Scientists from the University of Notre Dame’s W.M. Keck Center for Transgene Research have received a $9 million, five-year Program Project Grant (<span class="caps">PPG</span>) from the National Institutes of Health (<span class="caps">NIH</span>) that will advance the Universitys contribution to hemostasis research. Hemostasis is the collection of processes regulating bleeding, clotting and the…</p><p class="image-right"><img alt="castellino2big.jpg" src="https://news.nd.edu/assets/5596/castellino2big.jpg" title="castellino2big.jpg"></p>
<p>Scientists from the University of Notre Dame’s W.M. Keck Center for Transgene Research have received a $9 million, five-year Program Project Grant (<span class="caps">PPG</span>) from the National Institutes of Health (<span class="caps">NIH</span>) that will advance the Universitys contribution to hemostasis research. Hemostasis is the collection of processes regulating bleeding, clotting and the emergence of new blood vessels.</p>
<p>The grant, from the NIH’S National Heart, Lung, and Blood Institute, will fund three medically relevant areas of research:•</p>
<ul>
<li>Relationships between hemostasis, inflammation and sepis (Francis J. Castellino, director of the Keck Center and Keiderer-Pezold Professof of Biochemistry)</li>
<li>Genetic basis of colon cancer (Victoria A. Ploplis, associate director of the Keck Center and research professor in chemistry and biochemistry)</li>
<li>Rescue strategies for genetically deficient mice (Elliot D. Rosen, formerly of the Keck Center and now assistant professor in the Division of Molecular Genetics and Gene Therapy at Indiana University)</li>
</ul>
<p>The grant also will help support an administrative infrastructure and enhance the University’s existing Keck Center histology and animal husbandry efforts. Moreover, it solidifies Notre Dames standing as a transgene research center with a primary focus on determining how proteins, traditionally associated with blood coagulation, anticoagulation and clot dissolution, contribute to other pathologies.</p>
<p>“It is rare for a university without a medical school to receive a highly sought <span class="caps">PPG</span> from the <span class="caps">NIH</span> of this magnitude in molecular medicine,” Castellino, the program director of the grant, said. "The competition for these grants is very heavy. We competed with the best medical schools for this program grant and its success demonstrates that Notre Dame can succeed in well-thought out areas of molecular medicine."</p>
<p> This is the second <span class="caps">PPG</span> that Notre Dame researchers have received from the <span class="caps">NIH</span>. Frank Collins, George and Winifred Clark Professor of Biological Sciences, received a $9 million award from NIH’s National Institute of Allergy and Infectious Diseases (<span class="caps">NIAID</span>) in 2001 to help reveal the genetic secrets of malaria.</p>
<p>“We are delighted to be among the select group of universities receiving <span class="caps">PPG</span> grants from <span class="caps">NIH</span>,” said Jeffrey C. Kantor, the University’s vice president for graduate studies and research. “Because these grants are so competitive, the fact that we have received two of them is testament to the quality of work being done by our researchers.”</p>
<p>The Keck Center long has focused on identifying and characterizing genes involved in hemostasis as they relate to regulation of blood coagulation and other diverse physiologies and pathologies. A primary focus has been on inflammation, which is closely tied to the blood coagulation process. Inflammation is a natural defense response to tissue damage and infection. Scientists also are finding increasing linkages of acute and chronic inflammation with heart disease, atherosclerosis, cancer, asthma, and a number of other pathologies, according to Castellino.</p>
<p>The Keck Center conducts whole mouse research and has more than 50 different strains of mice with altered expression of a number of genes.</p>
<p>“One line of mice has a genetic defect that causes the animal to first develop intestinal polyps, which transform into an invasive carcinoma,” Castellino said. "Another mouse strain spontaneously develops atherosclerosis.</p>
<p>“We ‘chip’ out a gene or make changes and reinsert it into the genome and then observe the animal’s response to that deletion or change in order to determine the role of that gene in normal physiology or pathology. If you are performing these studies in a test tube, you only see what you’re specifically testing for. In the whole animal, you see everything, even unanticipated effects, such as its role in pregnancy maintenance.”</p>
<p>Notre Dame’s potential as a leading research center in transgenic research related to hemostasis became apparent in 1997, when its scientists produced a mouse with a genetic deficient for a protein involved in blood coagulation, one of the first in the world. This research, and the establishment of the Keck Center, drew the attention of the Walther Cancer Center in Indianapolis, ultimately resulting in a Walther Cancer Center site at the University. This center oversees interdisciplinary projects involving 25 Notre Dame faculty members in chemistry and biochemistry, biological sciences and preprofessional studies in the College of Science. A number of the center’s research projects involve inter-university collaborations with Indiana and Purdue Universities and the University of Michigan.</p>
<p><strong>Contact:</strong> Francis J. Castellino, director of the Keck Center and Kleiderer-Pezold Professor of Biochemistry, 574-631-9152</p>
<p class="attribution">Originally published by <span class="rel-author">William G. Gilroy</span> at <span class="rel-source"><a href="https://news.nd.edu/news/9-million-nih-grant-heightens-keck-research-profile/">news.nd.edu</a></span> on <span class="rel-pubdate">May 03, 2004</span>.</p>William G. Gilroytag:transgene.nd.edu,2005:News/1082412003-01-21T15:40:00-05:002020-02-25T15:41:53-05:00Novel approach to cellular transplantation may be helpful with hemophilia<p>A team of researchers from the University of Notre Dame’s W.M. Keck Center for Transgene Research and Department of Chemistry and Biochemistry has developed a novel cellular transplantation technique that may alleviate immune responses complicating treatments for hemophiliacs. The technique is described in a paper in this month’s inaugural…</p><p>A team of researchers from the University of Notre Dame’s W.M. Keck Center for Transgene Research and Department of Chemistry and Biochemistry has developed a novel cellular transplantation technique that may alleviate immune responses complicating treatments for hemophiliacs. The technique is described in a paper in this month’s inaugural issue of the Journal of Thrombosis and Haemostasis.</p>
<p>Led by Elliot D. Rosen, associate director of the Keck Center, the Notre Dame researchers studied mice that lacked the gene for Factor X, an essential clotting protein. Approximately 30 percent of Factor X-deficient embryos die before term and the remaining animals survive to term but die shortly after birth due to abdominal or brain hemorrhage. In humans, Factor X-deficiency is an inherited disorder that causes abnormal bleeding due to a lack of the protein.</p>
<p>Since Factor X— as well as several other coagulation proteins— is made by the liver, the Notre Dame scientists explored the possibility of transplanting normal liver cells to correct the defect. Using an in utero transplantation approach, the researchers isolated fetal liver cells from embryonic mice that synthesized Factor X. These cells were transplanted into the peritoneal cavities of the Factor X-deficient fetuses. The donor cells were found in approximately 50 percent of the livers of mice who received the transplants in utero.</p>
<p>Most importantly, unlike untreated Factor X-deficient mice that died shortly after birth, those mice that incorporated the donor cells were rescued and survived long term. The transplanted liver cells were detected in 47 percent of the livers of adult mice and were also recovered in the bone marrow, spleen, lung and, occasionally, in the brain and testis.</p>
<p>In utero cell transplantation could potentially offer an effective therapeutic strategy for treating hemophilia. Hemophilia is a group of hereditary bleeding disorders in which patients fail to produce a functional, or sufficient, quantity of at least one essential blood clotting protein. The disorder results in spontaneous bleeding, particularly in joints, muscles and internal organs.</p>
<p>Historically, hemophilia has been linked to royalty. However, one in 10,000 male births worldwide is hemophilic.</p>
<p> The treatment of hemophilia and related clotting disorders has been largely based on replacing the missing clotting factor with a substitute, typically obtained from human plasma or, more recently, recombinant, or genetically engineered, preparations. However, because they are foreign proteins, more than 15 percent of patients develop antibodies or “inhibitors” to the clotting factor substitutes and become resistant to further treatment.</p>
<p> The Notre Dame scientists reasoned that by implanting the fetal liver cells into the embryo before the development of the mouse’s immune system, the Factor X made by the donor cells would be recognized by the mouse as its own and would not trigger an immune reaction. Furthermore, the donor cells continuously produce the missing coagulation factor and should eliminate the need to continually inject the therapeutic protein.</p>
<p class="attribution">Originally published by <span class="rel-author">William G. Gilroy</span> at <span class="rel-source"><a href="https://news.nd.edu/news/novel-approach-to-cellular-transplantation-may-be-helpful-with-hemophilia/">news.nd.edu</a></span> on <span class="rel-pubdate">January 21, 2003</span>.</p>William G. Gilroy