The address is set for 4 p.m. Wednesday, October 29 at the UAB Alumni House.
During this year’s annual State of the University Address, hosted by the UAB Faculty Senate, President Ray L. Watts, M.D., will highlight UAB’s achievements during the past year and the ongoing strategic planning process.

The address is set for 4 p.m. Wednesday, October 29 at the UAB Alumni House.

Faculty News

Resolvin D1 reduces post-heart-attack heart failure
Resolvin D1 reduces post-heart-attack heart failure
The protective effect is achieved by reducing acute inflammation in the spleen and the left ventricle of the heart.

ganash halade wGanesh HaladeChronic inflammation provokes a downward spiral in many diseases, including congestive heart failure, atherosclerosis and peripheral artery disease. A University of Alabama at Birmingham-led research team has now found that mice that are given the lipid “Resolvin D1” after experimental heart attacks have substantially reduced amounts of inflammation and heart failure.

“Thus, Resolvin D1 has the potential to delay heart failure but still requires long-term studies in order to prove its utilization in chronic heart failure management,” Ganesh Halade, Ph.D., and his study co-authors concluded in a Journal of Molecular and Cellular Cardiology article recently published online. “This paper is the first to show resolvin’s effect on heart failure,” said Halade, an assistant professor in the Division of Cardiovascular Disease, UAB Department of Medicine.

About 5.1 million people in the United States have heart failure, according to the Centers for Disease Control and Prevention. Heart failure contributes to one in nine deaths, and half of those with heart failure die within five years of diagnosis. The annual cost for health care, medications and missed work is about $32 billion.

Inflammation is the body’s immune system response to injury, such as the muscle cells that die in a heart attack. The early acute inflammation response is beneficial, removing dead cells and beginning repairs in the injured area. Lingering, ungoverned chronic inflammation, however, is harmful.

Resolvin D1 is naturally produced in the body as a metabolite of one omega-3 fatty acid that is especially present in fish oil. It and other resolvins have potent anti-inflammatory effects; the term was coined by one of the co-authors, Charles Serhan, Ph.D., of Brigham and Women’s Hospital, Boston. Resolvins are natural signaling lipids in the body; but in the mouse experiments, Halade and colleagues boosted the amount of Resolvin D1 by an injection three hours after experimental myocardial infarction.

About 5.1 million people in the United States have heart failure, according to the Centers for Disease Control and Prevention. Heart failure contributes to one in nine deaths, and half of those with heart failure die within five years of diagnosis.

They found that the heart-attack mice that were given Resolvin D1, or a more stable Resolvin D1 protected inside liposomes, had less left ventricle enlargement, an improved left ventricle function, less lung edema and a reduced collagen deposition, as compared with heart-attack mice that received only saline.

All of these indicated reduced heart failure in the Resolvin D1-treated mice.

Besides this bottom-line proof of concept, Halade and colleagues did detailed experiments to find where and how the Resolvin D1 was working. “This is basic research to understand the mechanism of how the resolvin acts to change immune cell kinetics,” Halade said.

This included looking not only at the left ventricle — the major pumping chamber of the heart — but also at the spleen. One of the co-authors, Sumanth Prabhu, M.D., director of the UAB Division of Cardiovascular Disease, last year published a key Circulation Research paper showing that splenocytes — the immune cells stored in the spleen as part of the body’s early defense system — are intricately involved in the heart failure that follows an infarction, a blockage of the blood supply that kills heart muscle cells, in a mouse model. One of Prabhu’s lines of evidence was that adoptive transfer of the heart-failure splenocytes into healthy mice led to systolic dysfunction and heart “remodeling,” the cardiovascular disease term for harmful changes in shape, size and function.

Among the details in the Halade paper, the researchers found that Resolvin D1: 1) prevented early changes in the splenic reservoir, 2) reduced neutrophil density in the spleen and stopped neutrophil recruitment in the left ventricle, 3) increased the spleen levels of various resolving lipid mediators that help resolve inflammation, 4) stimulated macrophage clearance from the left ventricle to promote early resolution of inflammation, 5) stimulated the 5-lipoxygenase and lipoxin A4 receptor genes that aid wound healing after a heart attack, and 6) reduced extracellular matrix gene expression in the left ventricle.

Besides Halade, Serhan and Prabhu, co-authors are Vasundhara Kain, Ph.D., and Kevin A. Ingle, UAB Division of Cardiovascular Disease; Romain A. Colas, Ph.D., and Jesmond Dalli, Ph.D., Brigham and Women’s Hospital, Boston; and Medha Joshi, Ph.D., Midwestern University. 

New mechanism triggers endothelial permeability in vivo
New mechanism triggers endothelial permeability in vivo
UAB discovery gives better understanding of and potential therapies for septic shock and reperfusion injuries.

amit gaggarAmit GaggarA single layer of endothelial cells and extracellular matrix lines the inside of blood vessels, like the inner tube inside a bicycle tire. Injury and inflammation can damage this thin layer, allowing a dangerous leakage of fluid from blood vessels to tissues. When this happens in the lung it can lead to acute respiratory distress syndrome, or ARDS, a major cause of death in hospital intensive-care units.

In a paper published today in Science Advances, University of Alabama at Birmingham researchers identify for the first time a new mechanism for this increased permeability, and they also show the ability to block it in cell culture, animal disease models, and in human specimens from patients with ARDS.

In the future, this discovery could lead to therapy to target ARDS, and also other human diseases that have extracellular matrix turnover and blood vessel leakage, including reperfusion of organs after they have been cut off from oxygen, lung vascular disease, kidney injury and heart attacks. In all of these, the critical biological function of the endothelium is altered by inflammation or disease.

Key to this new mechanism of blood vessel permeability is a small peptide called “acetylated proline-glycine-proline” (N-α-PGP). The UAB researchers have discovered that N-α-PGP is a critical regulator of endothelial permeability, and its signal couples extracellular matrix fragmentation to that leakage.

When tissue is damaged or infected, part of the inflammatory response is the release and activation of proteases that degrade the collagen of the extracellular matrix; the matrix is made up of secreted molecules that help glue endothelial cells together. One of these degradation products is N-α-PGP.

N-α-PGP has long been known to act as a signal that attracts neutrophils — the white blood cells that are the first line of defense to engulf infecting bacteria or respond to injury — thanks to seminal work conducted by Roswell Pfister, M.D., and J. Edwin Blalock, Ph.D., at UAB. The N-α-PGP acts on the neutrophil’s CXC chemokine receptor 2 (CXCR2). Since endothelial cells also have those receptors, the senior co-authors — Rakesh Patel, Ph.D., UAB Department of Pathology, and Amit Gaggar, M.D., Ph.D., UAB Department of Medicine — decided to test whether N-α-PGP might also act as a signal upon endothelial cells. Now, they and colleagues report the first evidence that N-α-PGP acts on the endothelial cell CXCR2 receptors and activates the downstream signaling that is seen for other pathogenic factors that disrupt vascular permeability.

This discovery could lead to therapy to target ARDS, and also other human diseases that have extracellular matrix turnover and blood vessel leakage, including reperfusion of organs after they have been cut off from oxygen, lung vascular disease, kidney injury and heart attacks. In all of these, the critical biological function of the endothelium is altered by inflammation or disease.

Several of their experiments had vivid results. The endotoxin LPS (lipopolysaccharide) is a potent mediator of septic shock, but it does not act directly on the CXCR2 receptor. In mouse models, the local administration of N-α-PGP caused a vascular leakage, and the systemic administration of N-α-PGP caused increased lung permeability — both similar to the effects of local or systemic LPS. When the researchers gave the mice a combination of LPS and the peptide RTR (arginine-threonine-arginine), which inactivates N-α-PGP through binding, the RTR blocked the LPS-induced blood vessel permeability.

This showed a role for N-α-PGP as a novel effector of endotoxin-induced injury.

“LPS is a very generic sledgehammer,” Gaggar said. “The fact that you could attenuate that was eye-opening.”

This first example of RTR’s targeting endothelial permeability in vivo suggests that endogenous bioactive PGP-containing peptides help mediate lung fluid accumulation in ARDS.

“That tells us that this is important in vivo,” Patel said.

The other vivid experiment was in cell cultures with ARDS patient samples. The research team showed that blood plasma from ARDS patients increased the permeability of endothelial cells in vitro; but if RTR was added to the plasma, it blocked about 15-20 percent of that increased permeability — presumably by acting on N-α-PGP.

“As a clinician,” said Gaggar, a pulmonologist who cares for patients in the ICU setting, “I find it very exciting to think there is something that is targetable that might become a therapy for ARDS.”

The title of the paper is “The matrikine N-α-PGP couples extracellular matrix fragmentation to endothelial permeability.”

The first three authors of the paper contributed equally. The first two are Cornelia S. Hahn, M.D., Ph.D., and David W. Scott, Ph.D., who did the research as a UAB Department of Medicine internal medicine resident and a UAB Department of Pathology graduate student, respectively, and are now both at the University of North Carolina-Chapel Hill. The third author is Xin Xu, M.D., Ph.D., UAB Department of Medicine. The other authors are Mojtaba Abdul Roda, Pharm.D., Gregory A. Payne, M.D., J. Michael Wells, M.D., Liliana Viera, Ph.D., Preston Bratcher, Ph.D., Patricia L. Jackson, Ph.D., and J. Edwin Blalock, Ph.D., UAB Department of Medicine; Colleen J. Winstead, Ph.D., UAB Department of Pathology; and Rolf W. Sparidans, Ph.D., Frank A. Redegeld, Ph.D., and Gert Folkerts, Ph.D., Utrecht University, the Netherlands.

UAB’s College of Arts and Sciences aims to grow enrollment, undergrad programs, students’ global awareness and success
UAB’s College of Arts and Sciences aims to grow enrollment, undergrad programs, students’ global awareness and success
As UAB’s strategic planning process continues, top CAS priorities include undergraduate program development, and recruitment, retention and graduation; building a new College of Arts and Sciences building and renovating Campbell Hall; and growing leadership and personnel.

heritage hallHeritage HallNearly two years into the college’s strategic planning process, University of Alabama at Birmingham College of Arts and Sciences Dean Robert E. Palazzo has updated campus leaders on his plans and progress on topmost goals, which include preparing students to succeed in a new global environment, offering them an immersive, interdisciplinary educational experience, and ensuring each student obtains the tools he or she needs to succeed.

Every undergraduate student who enters the university will pass through the College of Arts and Sciences, Palazzo says. The college is dedicated to helping them develop ethical and moral reasoning, the scientific method, communication and cultural competence skills, and confidence in the face of complexity.

“We strive to help students grow through a rigorous curriculum grounded in formal instruction in the liberal arts and sciences. We will prepare students to operate and succeed and help them to become self-aware, culturally nimble and confident,” Palazzo said. “We are responsible for ensuring that all students develop expertise in a chosen discipline, while providing opportunities for personal maturation and character development.”

The college’s strategic planning process began two years ago and was completed in September 2013. The results of that work are now part of the university’s largest, most comprehensive, institutionwide strategic plan initiative.

The College of Arts and Sciences is home to strong academic programs, outstanding teaching and a diverse student body. With 19 departments — home to more than 300 faculty and offering more than 30 baccalaureate, master’s and doctoral degrees — it is the most diverse UAB academic enterprise. CAS is home to research centers and community outreach programs and is engaged in numerous campuswide interdisciplinary initiatives.

Top priorities for CAS are undergraduate program development with continued focus on freshman enrollment and overall student retention and graduation; improving infrastructure by building a new CAS administrative and classroom building and renovating laboratories, offices and educational facilities in Campbell Hall; and growing leadership and personnel with ongoing recruitment.

The College of Arts and Sciences is home to strong academic programs, outstanding teaching and a diverse student body. With 19 departments — home to more than 300 faculty and offering more than 30 baccalaureate, master’s and doctoral degrees — it is the most diverse UAB academic enterprise. CAS is home to research centers and community outreach programs and is engaged in numerous campuswide interdisciplinary initiatives.

Five new department chairs have been recruited in the past two years, and four new chairs will join the college this summer: Julian Arribas, Ph.D., in the Department of Foreign Languages and Literatures; Patrick Evans, DMA, in the Department of Music; Timothy Levine, Ph.D., in the Department of Communication Studies; and Yuliang Zheng, Ph.D., in the Department of Computer and Information Sciences. More appointments are expected by fall. More than 60 new faculty have been recruited to the college in the past two years.

The College of Arts and Sciences has developed five strategic priorities to ensure that each student graduates with the knowledge he or she needs to compete and thrive in an expanding and complex global future: globalization, undergraduate education, research and graduate education, diversity, and entrepreneurship and innovation.

The goal of globalization is to increase the college’s international profile and enhance students’ global perspective. The CAS English Language Institute is growing, from 30 students in 2009 to 81 in 2015. Scholarships to support international travel for students are being increased, as well as partnerships with international universities to boost student enrollment.

For undergraduate education, the college will strive to double the number of student applications within five years and increase student enrollment by 30 percent in seven years. That will be accomplished by collaborating with campus partners to offer novel interdisciplinary programs and course offerings, recruiting and retaining a world-class faculty and body of students, enhancing advising and mentoring, and improving technology and facilities.

Among the college’s achievements rank Rhodes, Truman, Fulbright and Critical Language scholarship winners; nine students out of 17 total Clinton Global Initiative scholars; Guggenheim and Humboldt prizes awarded to two faculty in 2014; a new Bachelor of Fine Arts degree in musical theater; the launch of UABTeach to increase STEM educators in Alabama in 2014; and the SACS re-accreditation in 2015.

Among the college’s achievements rank Rhodes, Truman, Fulbright and Critical Language scholarship winners; nine students out of 17 total Clinton Global Initiative scholars; Guggenheim and Humboldt prizes awarded to two faculty in 2014; a new Bachelor of Fine Arts degree in musical theater; the launch of UABTeach to increase STEM educators in Alabama in 2014; and the SACS re-accreditation in 2015. CAS developed and taught 21 honors-designated sections in fall 2014 and 18 in spring 2015. Advising last year grew from 15 to 19 advisers, for a ratio of 350:1, with more than 35,000 logged contacts with students. Instructional Technology Services has been restructured, developing online master’s programs and growing by 150 percent since 2010.

Grants awarded in research and graduate education have increased by nearly 16 percent in the last fiscal year. More than $1.7 million has been redirected to develop competitive Ph.D. programs, and UAB is one of nine universities chosen by The MITRE Corporation to serve on the Academic Affiliates Council, solely dedicated to enhancing the security of the nation’s information systems. More detailed information on CAS achievements is available online.

To foster a diverse community, CAS created an Institute for Human Rights to raise awareness and understanding of human rights issues; a search for a director is underway. UAB is nationally ranked for diversity, so recruiting and retaining a faculty that reflects society, including adding more women and underrepresented minorities in leadership positions, is a priority. Scholarships available to students from underrepresented groups have been increased, and faculty from historically black colleges and universities have partnered with their CAS peers on various interdisciplinary projects. Of faculty hired since October 2012, 56 percent have been women and 26 percent from an underrepresented minority. Partnerships are in discussion with the Birmingham Civil Rights Institute and Birmingham Area Consortium of Higher Education.

To further a culture of creativity, innovation and entrepreneurship, CAS wants to offer opportunities at every level of the college experience. That means providing faculty and students with resources and chances to explore solutions to real-world challenges; partnering with corporations, industry and other academic institutions to pursue areas of mutual interest; encouraging faculty to submit large-scale interdisciplinary grant proposals focused on forging academic-industrial partnerships; and bringing entrepreneurs and innovators to campus for inspiration. Among achievements in the realm of innovation and entrepreneurship are four CAS junior faculty NSF Early Career awards totaling $2.61 million, an NSF Partnership for Innovation Award of $600,000 and NIH Innovation Corps award of $25,000, and five graduate entrepreneurship awards of $10,000 each for students to pursue commercialization efforts with faculty and industry mentors.

“The College of Arts and Sciences continues to make tremendous progress under Dean Palazzo’s leadership,” said UAB President Ray L. Watts. “With a lot of positive momentum, CAS faculty, staff, students and supporters are rallying around a clear and ambitious vision that continues to build on a strong foundation.”

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