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April 16, 2015

Research Notes

New treatments for bowel disease to be studied

Researchers at the School of Medicine will collaborate with Janssen Research & Development on a project to study the effectiveness of potential new therapies for inflammatory bowel disease (IBD).

A research team led by Ian McGowan, faculty member in medicine, will use tissue samples from patients with Crohn’s disease and ulcerative colitis, two types of IBD, as well as from healthy volunteers, to evaluate experimental medicines developed by Janssen.

More than 6,000 IBD patients are seen each year by physicians in the Division of Gastroenterology, Hepatology and Nutrition at Pitt and UPMC.

The project is being coordinated by the University’s pharmaceutical collaborations committee.


Consortium creates art history collaborations

A grant from the Andrew W. Mellon Foundation to the Department of History of Art and Architecture in the Dietrich School of Arts and Sciences is expected to develop stronger partnerships between the department and the Carnegie Museums of Pittsburgh as well as other venues, resulting in more collaborative research and public engagement with Pittsburgh’s collections of art and artifacts.

The $1 million grant will support the formation of the Pittsburgh Constellations Consortium, a group of regional partners who will collaborate with the department to create a mutually beneficial set of college courses, internships, workshops, digital humanities projects, exhibitions and other exchanges. Key to this effort will be the hiring of a lecturer in curatorial studies — a joint appointment between the department and the Carnegie Museums — and the recruitment of an academic curator for the department. These two hires will assist in leading consortium efforts and in the training of a new breed of professionals in art history and curation.

In addition to providing funding for the academic appointments, the foundation grant also will support graduate and undergraduate internships, summer workshops focused on local collections and at least three new Pitt courses.

Said Provost Patricia E. Beeson: “This grant is transformational … The Constellations consortium gives every indication of becoming a national and international model for art historical research, teaching and outreach.”

The consortium will be supported by an advisory committee, which will convene in the fall.

The consortium is an outgrowth of the existing Constellations program within Pitt’s Department of History of Art and Architecture. The program organizes student and faculty work around flexible and changing themes of knowledge in the field, including agency, identity, environment, contemporaneity, visual knowledge and mobility/exchange.

Inspiration for the Pittsburgh Constellations Consortium also came in part from the Configuring Disciplines exhibition hosted at the University Art Gallery last fall. The show emerged from one of the department’s Constellations workshops and involved collaborative research and curatorial work by faculty, graduate and undergraduate students. It also included input from eight arts institutions that contributed artwork, illustrated atlases, treatises and other objects. As an example of the cross-disciplinary and cross-institutional work encouraged by the Constellations program, Configuring Disciplines traced how art, drawings, photographs, maps and other visual materials have shaped disciplinary knowledge in medicine, physics and geography in the modern era.


Nursing researcher wins two awards

Salah Al-Zaiti, School of Nursing faculty member, was awarded a 2014 Emergency Nurses Association/American Nursing Informatics Association research grant for a study titled, “Redefining ECG Interpretation in Emergency Departments: Novel Methods for Real-time Detection of NSTEMI.”

This research aims to identify an electrocardiogram parameter that can improve recognition of non-ST wave elevation cardiac ischemia.

Al-Zaiti also was the winner of the 2014 Martha N. Hill New Investigator Award from the American Heart Association’s Council on Cardiovascular and Stroke Nursing and the Go Red for Women campaign.

He was honored for his work exploring the use of cardiac autonomic function to predict sudden cardiac arrest (SCA). It is a potentially less invasive and less expensive approach to selecting proper candidates for implantable cardioverter-defibrillator therapy.

Said Al-Zaiti: “This work describes a novel pathway linking the autonomic function to regional myocardial sympathetic innervation as a way to support SCA risk stratification. It’s one aspect of my larger research program to help clinicians identify patients with active coronary disease early during care and to recognize who needs more aggressive therapy and follow-up.”


Novel approach taken to outcomes after TBI

Nursing faculty member Yvette Conley and Ava Puccio of the Department of Neurological Surgery in the School of Medicine have received a grant from the National Institute of Nursing Research of the National Institutes of Health (NIH) for the study “Epigenomics of Patient Outcomes after Traumatic Brain Injury.”

Some 5.3 million Americans are living with traumatic brain injury (TBI) currently. They suffer persistent consequences that cause major limitations in daily function and significantly impact quality of life for decades after the injury.

It is completely unknown why some patients fully recover, while others who have the same extent of injury, same care and same demographic factors develop lifelong disabilities. The long-term goal of this research is to identify the biological underpinnings influencing variability in patient outcomes post-TBI and to use this information to develop evidence-based interventions that are tailored to an individual’s risk profile.

Using the methylation status of DNA, a mechanism by which gene regulation in response to the local environment is regulated, the study will characterize serial DNA methylation profiles from DNA representing the daily central nervous system environment post-TBI. Then it will use these data to evaluate if DNA methylation status of genes (nuclear as well as mitochondrial) representing the oxidative phosphorylation (OXPHOS) pathway differentiate patient outcomes post-TBI. The study then will explore the potential impact of DNA methylation across the entire nuclear and mitochondrial genome with patient outcomes post-TBI.

This project represents an opportunity to capitalize on existing DNA samples and extensive longitudinal phenotype data. There is a dearth of projects using genomic/epigenomic tools to understand the biological underpinnings of patient outcomes after TBI and this project represents the first to use a whole nuclear methylome approach as well as a mitochondrial genome methylation approach in serial daily samples of DNA extracted from cerebrospinal fluid.

Data generated from this pilot project will be used to inform a larger study designed to determine the impact of DNA methylation on patient outcomes after TBI and to use those data to identify biological underpinnings involved in variability in patient outcomes after TBI with the intention that a better understanding of these biological underpinnings will lead to development of evidence-based interventions to improve patient outcomes.


Aiming to improve infection control

Ja Hyun Kang, nursing faculty member, was awarded the Association for Professionals in Infection Control and Epidemiology (APIC) Heroes Implementation Research Scholar Award for her “Use of Personal Protective Equipment: Ensuring Safety (UPPEES)” study.

The study will focus on ensuring the use of evidence-based infection control practices in actual health care settings by illustrating behavioral factors of health care providers, elucidating organizational factors such as working environment, policy impact and performance improvement initiatives and, in particular, adopting cost-effectiveness analysis and decision analysis.

The $50,000 grant will be used for research on the use of personal protective equipment (PPE) to ensure safety. Kang noted that “the recent Ebola outbreak reminds us that appropriate use of PPE is very important to protect health care personnel as well as patients. However, very little is known about how health care workers actually use the equipment in their practice.”

She also explained that there are some discrepancies among PPE guidelines provided by agencies such as the Centers for Disease Control and Prevention and the World Health Organization, as well as confusion about how to effectively use such equipment in diverse health care settings.

Given the lack of a highly standardized and clear protocol for PPE use, this study aims to ensure safety for both the health care professionals and patients by providing a standardized best-practice protocol for the optimal use of PPE. Kang also aims to create and optimize an educational intervention across health care facilities as well as professional health schools.


Grant to support PhD researchers in nursing school

The Robert Wood Johnson Foundation has awarded the School of Nursing a $150,000 grant as part of the foundation’s Future of Nursing Scholars program. Under principal investigator and faculty member Susan Cohen, the funds will support two new students in the school’s PhD program.

The goal of the Future of Nursing Scholars program is to develop PhD-prepared nurse leaders who are committed to careers that advance science and discovery, who will enhance and extend nursing education and who will fundamentally change nursing and health care.


Faculty member wins Eli Lilly grant

Nursing faculty member Denise Charron-Prochownik was awarded $65,247 from Eli Lilly and Co. for her project, “Tailoring Preconception Counseling for Hispanic Adolescents With Diabetes.” This year-long grant will help to expand her existing work on the value and promotion of preconception counseling (PC) for young women with diabetes.

Little is known regarding the awareness, attitudes and behaviors related to PC, family planning and contraception vigilance of adolescent Hispanic females with diabetes. Furthermore, for adolescent Hispanics, female members of their social network (such as their mothers) play a key role in providing culturally relevant information on reproductive health practices and should be involved in the formative phases of the intervention.

Charron-Prochownik will explore the understanding of reproductive health and diabetes, PC, risks of unplanned pregnancies, the importance of tight metabolic control and family planning and contraception vigilance among female adolescent Hispanics with diabetes and their mothers. This information will be used to adapt the Reproductive Health Education and Awareness of Diabetes in Youth for Girls (READY-Girls) program to be culturally and linguistically appropriate for this Spanish-speaking group.

The Lilly funding will facilitate the testing and adaptation of the program for 13-21-year-old Hispanic females with type 1 or type 2 diabetes. The American Diabetes Association has adopted the READY-Girls intervention, designed by Charron-Prochownik, as the model PC program for teens with diabetes.


Telerehabilitation research recognized

Ji Yeon Choi, a nursing faculty member, was the recipient of a Rehabilitation Nursing Foundation/American Nurses Foundation Research grant award for her study, “Providing Telerehabilitation at Home for Adult Intensive Care Unit Survivors and Their Family Caregivers.”

This study will provide preliminary data for a full-scale, randomized, controlled trial of her telerehabilitation system, Post-intensive Care Unit Versatile and Integrated System for Telerehabilitation. Choi hopes this system will facilitate family-centered self-management programs for ICU survivors and their families as the patients make the transition to the community.


Nursing researchers win racial justice award from YWCA

The YWCA of Greater Pittsburgh’s annual Racial Justice Award in health care this year went to the School of Nursing ACTS research team. The ACTS (attitude, communication, treatment and support) team has been conducting community-based research for more than a decade on interventions to mitigate the disparity in African-American women’s experience of breast cancer, from screening through end-of-life care.

The team includes faculty member Margaret Rosenzweig and staff members Mary Connolly, Tamami Hamada, Debra Otey, Jacqueline Simon and Howard Stein. This project has received significant funding from the American Cancer Society (2009-15) for the development of regional clinical trials of an intensive psychoeducational intervention that addresses attitudes, communication, treatment and support that will help African-American women to adhere to treatment and, therefore, increase survival rates among this population.


Strategy stimulates heart muscle regeneration in infants, study finds

Surgery often is life-saving for many infants born with heart defects, but one thing that doctors cannot do yet is replace heart muscle that is scarred and dysfunctional. Researchers from the Heart Institute at Children’s Hospital of Pittsburgh of UPMC and Boston Children’s Hospital hope to overcome the challenge by stimulating regeneration of heart tissue. Their findings were described in Science Translational Medicine.

Children born with congenital heart disease are at greater risk of developing heart failure even after surgical correction of the problem. Said lead author Bernhard Kühn, pediatrics faculty member in the School of Medicine and director of research for the Division of Cardiology at Children’s Hospital: “It is not surprising that survivors often develop heart failure later on. But when these patients were given adult medicines in clinical trials, it turned out that they were not effective.”

The researchers examined the potential of recombinant growth factor neuregulin-1 (rNRG1), which stimulates heart regeneration by driving proliferation of heart muscle cells, called cardiomyocytes. They treated newborn mice with injections of rNRG1 at various times after heart injury and found that treatment starting the first day after birth boosted cardiomyocyte cell division and heart function and reduced scarring to a significantly greater degree compared to treatment that began at five days after birth. The growth factor also drove cardiomyocyte proliferation in lab tests of heart muscle samples obtained during surgery from human infants with congenital heart disease.

Pitt collaborators on the study were Balakrishnan Ganapathy and Niyatie Ammanamanchi. Colleagues from Beth Israel Deaconess Medical Center, Bosch Institute and the Institute of Molecular Biotechnology of the Austrian Academy of Sciences also contributed.

The research was supported by NIH, Boston Children’s Hospital and the Richard King Mellon Foundation Institute for Pediatric Research at Children’s Hospital.


New pathway controls how cells make proteins

A serendipitous combination of technology and scientific discovery, coupled with a hunch, allowed University of Pittsburgh Cancer Institute (UPCI) researchers to reveal a previously invisible biological process that may be implicated in the rapid growth of some cancers.

The project, funded by NIH, is described in the Proceedings of the National Academy of Sciences.

Lead author Masahiro Shuda, faculty member in the Department of Microbiology and Molecular Genetics in the School of Medicine, and his colleagues showed that a well-known cancer protein called mTOR, previously thought to be solely responsible for controlling a form of protein production important in cancer cells, called cap-dependent translation, actually can hand its work off to a different protein, CDK1, when cells are dividing. They observed the process while examining a viral oncoprotein that allows a common and usually harmless virus to transform healthy cells into cancer cells.

Merkel cell polyomavirus was discovered in 2008 by Yuan Chang and Patrick S. Moore in the cancer virology program at UPCI. It causes a rare but deadly skin cancer called Merkel cell carcinoma. They later found a viral protein called “small tumor protein,” or sT. It may start a chain reaction that enables tumor growth resistant to cancer drugs that inhibit the protein mTOR.

In studies dating back to the 1960s, scientists had assumed that cap-dependent protein synthesis was turned off during cell division. The new study reveals that this is not necessarily so and that CDK1 can substitute for mTOR. Both mTOR and CDK1 work by inhibiting a gatekeeper protein, called 4E-BP1, that shuts off cap-dependent protein synthesis.

Less than 1 percent of cells are in the active division cycle called mitosis, even in very aggressive cancers, which makes studying cells in mitosis difficult. In addition, a drug traditionally used to arrest the cells during division inhibits protein production by CDK1. This is likely why previous research did not identify the role that CDK1 appears to play.

Shuda used a technology called flow cytometry to identify cells undergoing division. With special fluorescent tags, he was able to see mitotic cells produce fully inactivated 4E-BP1 by CDK1. He also directly measured proteins being made during mitosis.

Sure enough, even when mTOR was knocked out, CDK1 was still present and able to allow protein synthesis needed for cell division to progress.

Said Moore, senior author and faculty member in molecular genetics and biochemistry: “Now, we still can’t say that this process involving CDK1 contributes to cancer — that’s something we’ll tackle with future research. But it does point toward a fundamental control mechanism in cell biology and leads to the interesting possibility that creating or combining cancer drugs, so that they inhibit both mTOR- and CDK1-related protein synthesis, could be a very useful therapy to pursue.”

Additional Pitt researchers were Celestino Velásquez, Erdong Cheng, Daniel G. Cordek and Hyun Jin Kwun.

—Compiled by Marty Levine


The University Times Research Notes column reports on funding awarded to Pitt researchers as well as findings arising from University research.

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