Mohamed Elgazzar, PhD, awarded $1,850,000 MIRA/R35
Maximizing Investigators’ Research Award (MIRA) supports the nation’s highly talented investigators through providing research support. This R35 series grant, the Outstanding Investigator Award, was recently awarded to Dr. Mohamed Elgazzar, PhD, on April 1, 2019. This award is described by the National Institute of General Medical Sciences as “funding research programs instead of individual projects” and recognizes Dr. Elgazzar’s career focus on innate immunity, myeloid cell reprogramming, and severe systemic inflammation.
Dr. Elgazzar describes his funded research. “The goal is to identify the signaling and epigenetic reprogramming networks that promote chronic myeloid-derived suppressor cell (MDSC) generation during sepsis. It uses validated biochemical and genetic tools to test the manner in which long non-coding RNAs couple with inflammatory mediators to induce MDSC development. The resultant MDSC presence promotes persistent inflammation and immunosuppression with mounting mortality rates. We will use an animal model of chronic sepsis as well as septic patients in the course of this study.”
The award extends for five years and totals $1,850,000. Dr. Elgazzar is an Associate Professor in the Department of Internal Medicine and is a CIIDI member. Please join us in congratulating him on his award.
Dr. Krishna Singh receives VA grant to study heart failure and treatment
A physiologist at James H. Quillen Veterans Affairs Medical Center, Professor in the Department of Biomedical Sciences (Quillen College of Medicine at East Tennessee State University), and CIIDI member has received a more than $1 million Merit Award from the Department of Veterans Affairs to study the role of a protein called ubiquitin, which has the potential to protect the heart from the damaging effects of heart attack.
Dr. Krishna Singh said that heart attack is a leading cause of death among veterans. It causes damage to the heart muscle and compromises heart function. New and improved therapies are needed to preserve the heart function and enhance the outcome of patients suffering from heart attack. In this study, Singh and her research team will investigate the therapeutic potential of ubiquitin following a heart attack. Ubiquitin is a small, naturally occurring protein found inside cells. The pioneering work investigating the role of ubiquitin in heart attack was started in her VA Medical Center/ETSU laboratory. The team identified that dying heart muscle cells release ubiquitin, which has the potential to protect other cells from dying. The newly funded four-year grant will specifically investigate the role of ubiquitin in cardiac inflammation and extracellular matrix deposition, two important processes involved in healing of the heart following heart attack.
Dr. Singh acknowledges the VA for funding her research efforts on heart failure since 1998. In addition, she has also received multiple funding awards from National Institutes of Health (NHLBI) and American Heart Association. Singh joined the James H. Quillen VA Medical Center and ETSU community in 2002. Her research trajectory includes prestigious institutes such as McGill University (Montreal, Canada), Brigham and Women's Hospital (Harvard Medical School), Boston University School of Medicine, and Boston VA Healthcare System. Singh notes that the award will us to understand the complex processes with the healing of the heart following heart attack. It will also help fund three to four new positions for lab researchers and train future generations of scientists.
Joining Dr. Krishna Singh as Co-Investigators are Drs. Mahipal Singh (Associate Professor, Quillen College of Medicine, Department of Biomedical Sciences), Valentin Yakubenko (Assistant Professor, Quillen College of Medicine, Department Biomedical Sciences), Chuanfu Li (Professor, Quillen College of Medicine, Department of Surgery), and John Kalbfleisch (Professor of Biometry, Quillen College of Medicine and Director of Biometry and Medical Computing). Drs. Yakubenko, Li, and Kalbfleisch are also CIIDI members.
This article and photo used with permission of James H. Quillen Veterans Affairs Medical Center.
Dr. Valentin Yakubenko, graduate student Kui Cui, and team are published in Frontiers of Immunology
Valentin Yakubenko , PhD, Assistant Professor in the Department of Biomedical Sciences
at ETSU’s Quillen College of Medicine, along with his colleagues, was published in
Frontiers of Immunology. The article, “Distinct migratory properties of M1, M2 and resident macrophages are
regulated by αDβ2 and αMβ2 integrin-mediated adhesion,” elucidates their research
showing that “β2 integrin-mediated adhesion may inhibit amoeboid and mesenchymal macrophage
migration or support mesenchymal migration in tissue, and, therefore, represents an
important target to control inflammation.” This finding is particularly important
as “chronic inflammation is an essential mechanism during the development of cardiovascular
and metabolic diseases,” diseases which greatly impact large numbers of individuals
worldwide.
Dr. Yakubenko (above, left) and co-author Kui Cui (above, right), who is a graduate student in the Department of Biomedical Sciences, also utilized CIIDI’s Flow Cytometry Core in the analysis and imaging of cells. Analysis using the Fortessa X-20 and imaging flow cytometry using the Amnis ImageStream Mark II provided striking images found within the article. A link to the article with images can be found at the end of this CIIDI release.
The team’s research has very promising future applications, as well. Dr. Yakubenko comments, “Understanding a mechanism of macrophage migration and accumulation during inflammation is critical for the development of anti-inflammatory treatment. Based on our current data regarding a contribution of integrin αDβ2 to macrophage accumulation in inflamed tissue, we are planning to develop an inhibitor of αDβ2-mediated macrophage adhesion to the extracellular matrix. Such inhibitor might prevent a development of chronic inflammation. This project is currently under development.”
Both the Amnis and Fortessa instruments which were used in this research are available on a fee basis for use by scientists at East Tennessee State University, and both have a wide range of applications. If you would like to explore how these instruments can be of use in your research, please contact Mr. Kenton Hall for more information about the Amnis at hallk@etsu.edu. Dr. Tammy Ozment is the contact for the Fortessa instrument at ozmentsk@etsu.edu.
The authors of the article, in addition to Dr. Yakubenko and Kui Cui, are Chris Ardell, also of the Department of Biomedical Sciences, and Dr. Nataly Podolnikova, Research Assistant Professor at the Center for Metabolic and Vascular Biology, School of Life Sciences, Arizona State University in Tempe, Arizona. Dr. Yakubenko is a member of the Center of Excellence in Inflammation, Infectious Disease, and Immunity. Kui Cui is a CIIDI student member.
https://www.frontiersin.org/articles/10.3389/fimmu.2018.02650/full
