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Research Matters

By Terry Magnuson, January 3, 2022

December’s Research Matters focused on how Carolina’s research programs have persevered during the pandemic. Several accomplishments were highlighted that related to Initiative 4: Discover of the university’s strategic plan, Carolina Next: Innovations for Public Good. None of these accomplishments would have been achieved without the incredible effort of staff to ensure that our research operations continued.

On the heels of the significant disruptions of 2020, followed by unique challenges of 2021, and now a looming threat of yet another Sars-CoV-2 variant at the start of 2022, our research support offices have remained operational through it all. We know that the fluid nature of the pandemic is personally taxing, and we are so appreciative that our workforce has remained dedicated through all these trials.

Although certainly not an exhaustive list, the examples highlighted below capture the essence of the incredible work our research support offices accomplished this past year:

  • The Office of Clinical Trials (OCT) and the Office of Research Information Systems launched the OnCore clinical trials management system. They began expanding the systems to units beyond Lineberger Comprehensive Cancer Center. OCT also launched the new Billing Coverage Analysis
  • The OVCR Research Administration Service Center expanded to serve more units. The Office of Sponsored Research launched its updated Subrecipient Initiation Portal and continued to expand the Carolina Rapids training program for the campus. OSR also negotiated a rate extension for our F&A return, keeping it at the critical 55.5% level.
  • The Office of Animal Care and Use and the Division of Comparative Medicine successfully achieved reaccreditation from AAALAC and a flawless inspection by the USDA. This accomplishment is unique for institutions across the country as complex as Carolina and was achieved by hard work and concern for the care of animals.
  • The Office of Human Research Ethics successfully supported the campus COVID-19 research efforts, where they saw a 33% increase in the number of IRB submissions during 2021.
  • The Office of Research Development (ORD) celebrated the success of the Creativity Hubs program, which continued its supports of innovative new research such as:
    • chemical and molecular designs that desalinate and capture heavy metals from water;
    • data collection and integration of extreme storms and flooding to aid in predicting impacts of future storms on coastal habitats and their inhabitants;
    • discovery and development of antiviral therapeutics using new methods targeting a person’s cellular machinery; and
    • use of AI technology to identify novel matter for solar fuels and develop robotics to automate chemical synthesis and characterization.
  • ORD also supported large grant proposals through team building, project management, and grant writing support. They led a substantial increase in the total number of limited submissions from federal and private sponsors and supported several key collaborative efforts in arts and humanities.
  • The Office of Postdoctoral Affairs provided career counseling for postdoctoral fellows affiliated with over 50 departments. The Carolina Postdoctoral Program for Faculty Diversity successfully recruits talented, diverse researchers to the Carolina faculty. For the 2021 cohort, scholars have accepted faculty positions at Carolina in history, health behavior, and in the schools of Nursing and Government.
  • The OVCR managed the Pinnacle Hill collaboration with Deerfield to develop therapeutics for commercial interests. Another avenue for corporate sponsorship opportunities, the Advance Therapeutics Initiative (AdvanTx) is advancing the discovery and development of therapeutics at UNC.
  • The Office of Partnerships and Research Impact worked with North Carolina’s Office of Strategic Partnerships, facilitating new pathways for centers and institutes to engage with state agencies and provide those agencies with expertise to better serve the people of the state.
  • The Office of Research Communications coalesced stories, messaging, and branding for the OVCR around the phrase” “Research Perseveres,” highlighting perseverance at the bench, in the field, in the classroom, and in the offices that support research infrastructure. They also led this year’s University Research Week, which was the largest and most successful iteration of that event yet, with over 66 events and nearly 3,000 participants. Perseverance was also highlighted in this year’s Endeavors The magazine is an incredible showcase of tenacity and persistence of researchers at all stages and across many different disciplines.

Research at Carolina is at the most successful place it has ever been. While there is much to celebrate on that front, we know that this growth requires great effort from UNC’s research support offices. The work of those that support the research mission has not gone unnoticed. Their contributions are meaningful, essential, and truly matter to the university, the state, and citizens of North Carolina.

As we look to the new year, the take-away message is one of optimism. We have a new state budget for the first time in three years. We have had another record-breaking year for research awards, which subsequently puts us on track for continued success. Although we do face challenges, overall, the university research support infrastructure is outstanding. We will mitigate challenges as quickly as possible, and we will continue to look for ways to provide the resources needed to equip these offices.

2022 will be a better year, and I look forward to working alongside our staff as we continue to provide our world-class researchers world-class support.

Permalink: World-Class Support for World-Class Researchers

By Terry Magnuson, December 1, 2021

As 2021 comes to an end, Associate Vice Chancellor for Research Joyce Tan and I want to reflect on progress of Initiative 4: Discover, the research framework for the University’s strategic plan Carolina Next: Innovations for Public Good. Discover is one of eight initiatives representing core areas of focus and targeted investments by UNC.

Carolina Next is not a comprehensive list of university priorities. Rather, it is a document that evolves as new opportunities and challenges present themselves. The connection among Discover, Serve to Benefit Society (initiative 6) and Globalize (initiative 7) became abundantly clear as work during the year showed how Carolina’s research not only enhances the scholarly mission, but impacts innovation throughout North Carolina and the world beyond.

The Gillings School of Public Health and the School of Medicine’s Marsico Lung Institute collaborated this year to demonstrate how an oral antiviral drug for treatment of COVID-19 blocked virus transmission and reduced lung damage. The School of Medicine and the Institute for Global Health and Infectious Disease led a Phase 2 clinical trial of molnupravir and the results led industry partners Merck and Ridgeback Biotherapeutics to seek emergency-use authorization.

The Rapidly Emerging Antiviral Drug Development Initiative, READDI, grew out of the Infectious Disease Drug Discovery Program Creativity Hub. READDI is developing a global partnership among academia, industry, and foundations to develop antiviral drugs against future emerging pandemics. The focus is to study the host cellular impact of antiviral families most likely to cause a pandemic by developing therapeutics that target the viruses themselves, as well as highly conserved host proteins needed for viral replication.

The Lineberger Comprehensive Cancer Center has developed a personalized immunotherapy program for therapies that modulate a cancer patient’s immune system. The patient’s immune cells are removed, manipulated in vitro, and then placed back into the patient to target and kill cancer cells. This treatment protocol requires a specialized Good Manufacturing Process facility, which Lineberger has constructed. Several active clinical trials are ongoing.

Research for service and policy is a key component of Discover. Jonas Monast in the Law School collaborated with the Institute for the Environment on a report based on a year-long project analyzing our state’s policy options to decarbonize the electricity sector. The NC State Environmental Management Commission relied on the report to shape new policy. This work also has potential for global impact as illustrated by policies discussed at the November Glasgow COP26 climate conference.

Center for Health Promotion and Disease Prevention Director Alice Ammerman and the Sheps Center’s Seth Berkowitz and Darren DeWalt joined with Blue Cross NC to address food insecurity through better nutrition. The study is addressing health outcomes through non-medical drivers of health, namely food, and the results have global implications for using nutrition to treat chronic conditions.

To promote artistic and humanist teams, the Office of Research Development identified a funding opportunity focused on music therapy sponsored by the NIH Institute of Integrative and Complementary Medicine. The College of Arts & Sciences partnered with the School of Medicine’s Department of Allied Health Sciences and clinical and Appalachian State University’s music therapy program. They’re currently concepting a rehabilitative breathing program for long COVID patients using operatic breathing techniques.

Our office also partnered with the Institute of Arts and Humanities to encourage artistic practice by providing pilot grants. Examples of such work include Mohamed Mwamzandi’s digitization of Pulaar Islamic texts in Senegal and Mali to preserve a vital language from extinction. Angela Stuesse’s research on immigration policy, homophobia, racism, and family separation impacts on the life experience of an undocumented youth was also funded by this program. Her studies blend ethnography and cultural analysis to cultivate empathy and understanding.

Research Perseveres was the theme for this year’s University Research Week, which was held last month. The theme was chosen to illustrate how research at Carolina progressed during the challenges of the pandemic, civil rights protests, and other unprecedented events of the last year. Amongst the more than 60 events featured during the week, the signature event — The Health of Our State and Beyond series — highlighted winning Creativity Hubs teams who provided overviews of the challenges they are working to eradicate around the world, despite the pandemic.

UNC’s research and innovation pipeline came together with the official launch of the Institute for Convergent Science (ICS) this year. While research encompasses fundamental investigation, discovery, and pre-development, the ICS covers the pre-commercial environment with technical and product de-risking and development. Along with Innovate Carolina, this pipeline establishes a comprehensive innovation ecosystem supported by the Advance Therapeutics Initiative (AdvanTx) — which brings together scientific expertise to organize and advocate for funding to develop a commercialization strategy. Currently, the AdvanTx team has vetted more than 30 projects and is actively working to advance several more.

UNC’s gene therapy investments have propelled Research Triangle Park as a go-to place for corporate expansion of gene therapy manufacturing. The NC VVIRAL project represents an academic-industrial partnership focused on developing next-generation biomanufacturing processes for gene therapy products and the development of tailored curricula to train the biomanufacturing workforce.

These examples are just a few of many scholarly advances that have been made this year. Many more stories can be found in Endeavors, which is the publication that showcases Carolina’s best science and artistic discovery. Three series within the Endeavors publication include:

  • Foundations, which uncovers the nature of basic science and its potential to shape the world;
  • Research Uncovered, a biweekly series that showcases researchers at all career levels and highlights what inspires them, how they overcome obstacles, and a little about their lives outside labs and offices; and
  • Time & Tenacity, which focuses on Carolina discoveries and inventions since the founding of the university.

I’d like to emphasize again that Carolina Next is a living and dynamic process. Under the Discover initiative, we are continuously planning, evaluating, and changing to meet the problems of the day. This process involves the OVCR interacting biweekly with UNC’s research deans and pan-campus centers and institutes directors. This group is now diving into research at the College, the schools, and our centers and institutes to create individual strategic plans that guide the Discover objectives.

Research has persevered at Carolina during the challenges of the last few years thanks to the dedication of our faculty, staff, and trainees. Our research enterprise is one of the best in the country — one that we can take pride in.

Permalink: Carolina’s Research Perseveres through the Pandemic — and Beyond

By Terry Magnuson, November 3, 2021

Last monthʼs Research Matters focused on the benefits of international scientific collaboration. Collaboration incentivizes open science, which is a topic of interest in the research community today. One definition of open science is “the idea that scientific knowledge of all kinds should be openly shared as early as is practical in the discovery process.” The National Academies of Science, Engineering, and Medicine slightly expands that definition to reflect that open science is “an effort that aims to ensure the free availability and usability of scholarly publications, the data that result from scholarly research, and the methodologies, including code or algorithms that were used to generate those data.”

The Pew Research Center survey conducted in 2019 found that U.S. adults trust scientific research findings more if researchers make their data publicly available, which allows for independent review and corroboration.

One particularly potent example of publicly available data is The Cancer Genome Atlas , a landmark open-science program that characterized over 20,000 primary cancer and matched normal samples spanning 33 cancer types. This remarkable program was a joint effort between the National Cancer Institute and the National Human Genome Research Institute that brought together international researchers from diverse disciplines and multiple institutions. The program has a Genomic Data Commons Portal, which harmonizes cancer datasets available to the research community worldwide. In addition, investigators developed computational tools for data analysis and the technologies utilized to generate data that are available to everyone.

Another amazing example of open science is the NIH All of Us research program. The program is recruiting one million people across the U.S. to build a diverse health database for researchers to learn how biology, lifestyle, and environment affect health. The All of Us Research Hub allows investigators to view data and methods of data curation and access a workbench platform with a suite of custom tools.

The Open Research Area was established to strengthen international co-operation in the social sciences. It is a joint agreement between France, Germany, the United Kingdom, and the Netherlands to promote international collaboration, improve coordination between teams of researchers from different European states, and enable research collaboration with major and emerging research nations beyond Europe.

The Open Library of Humanities facilitates the open-access publication of all humanities disciplines. This international consortium of libraries funds open access publication of scholarly work with no author-facing article processing charges.

The UNC Health Sciences Library has an Open Access and Scholarly Communications portal that defines open access as “free, online availability of scholarly content that is free from most copyright and licensing restrictions.” This portal is an important guide for faculty to navigate open access publishing.

Examples like these inspired the National Academies to establish a roundtable forum focused on aligning incentives for open science. The roundtable has been convening two times per year exchanging ideas and strategies amongst stakeholders, including universities, funding agencies, societies, philanthropies, and industry.

In 2020, the forum held a workshop called Developing a Toolkit for Fostering Open Science Practices. One goal of the workshop was to reimagine the credit and reward systems for academic appointments, tenure, and promotion (APT) and grants in a manner that would incentivize open science practices. The workshop emphasized how academic research environments previously incentivized competition between individual researchers for hiring and promotion.

The increasing technical sophistication of research and the use of data in all disciplines makes it impossible for a single individual or lab to work alone. Success requires teams of researchers with diverse knowledge and skills to facilitate ongoing discovery, which means the APT process in academia is changing to account for scholarly contribution rather than order of authorship. Iʼm encouraged that Carolinaʼs recently revised APT guidelines align with collaborative and open research.

Permalink: Open Science Fuels Collaboration

By Terry Magnuson, October 6, 2021

Although international collaborations present significant research opportunities, challenges face U.S.-based institutions working across national borders. Enhancing international collaboration requires recognition of differences in culture, legitimate national security needs, and critical needs in education and training. To address these matters, in 2011 the National Academies held the Examining Core Elements of International Research Collaboration workshop. They concluded that the globalization of science, engineering, and medical research is proceeding rapidly.

In 2019, the Federation of American Societies for Experimental Biology (FASEB), which represents 30 U.S. scientific societies, reaffirmed the importance that international collaborations have on discovery and innovation. Such collaborations play critical roles in biological research, ranging from deciphering the human genome to stemming the spread of infectious diseases, such as Ebola, Zika, and now COVID-19. FASEB emphasized the delicate balance between fostering an environment of open scientific collaboration while protecting U.S. investments and discoveries. Policies that confirm appropriate utilization of critical resources and discoveries are needed to ensure continued engagement of international scholars in U.S. research endeavors.

Most recently, the American Academy of Arts and Sciences undertook an initiative called the Challenges for International Scientific Partnerships (CISP) to assess the importance and the complexities of international scientific collaborations. In their report “America and the International Future of Science,”  the Academy highlighted the importance of worldwide science by quoting President Harry Truman: “When more of the peoples of the world have learned the ways of thought of the scientist, we shall have better reason to expect lasting peace and a fuller life for all.”

The CISP initiative outlined several recommendations to address the challenges of international scientific collaboration:

  • Any restrictions on international collaborations involving federally supported research should be well-justified and carefully/narrowly defined. Large-scale scientific endeavors are an important component of our nation’s overall science and technology enterprise. The United States must be prepared to contribute support for operations outside the United States. Scientific talent arises across the globe at an increasing rate as many countries invest in building a more robust science and technology enterprise.
  • Many of the most pressing scientific questions are not defined by national boundaries and require global collaboration for advancement. Both fundamental questions and those related to broad societal problems frequently involve people with different capabilities, perspectives, and access to resources. Forming teams with the best skills to address a research challenge increasingly draws on international collaborators.
  • To maintain leadership in fundamental research, it is essential that the United States continues to have an academic education and research system that is open, strong, and attractive and welcoming to international students. In 1960, federal funding represented 45% of all global R&D, while today it accounts for less than 10%. Our country should examine investing in R&D and approving policies that facilitate, support, and foster its scientists in collaborating internationally.
  • The United States must engage with the broader scientific community if America is to be among the world leaders across all scientific fields. Scientific partnerships are an important element of foreign policy and international relationships and necessitates cooperation.
  • The United States must look not only to those nations that are presently strong, but also to those that are emerging, as scientific partners. Without support and commitment to collaboration from the U.S. government, U.S. scientists may be excluded from some of the world’s leading scientific projects and associated technological advances, especially as multinational funders promote increasingly large international projects.
  • Most importantly, the United States must be engaged in the development of global ethical frameworks for research. As discoveries and technological capacities increase, ethical questions are becoming more complex.

The scientific community certainly understands the benefits of international scientific collaboration. However, risks of such collaboration to U.S. national security are now at the forefront of debate. Those risks must be acknowledged along with the benefits from scientific collaboration with countries that are potential adversaries.

Permalink: The U.S. and International Science

By Terry Magnuson, September 1, 2021

A recent Science Focus article discussed theories of why giraffes have long necks. The most obvious suggested that their length, which can reach up to 6 feet, evolved because it gives the animal access to the topmost leaves of trees, eliminating competition for food. Another theory is that the long neck is used as a weapon, wielded in fights between males. Male giraffes indulge in bouts of “neck fighting” to gain access to females, swinging their necks at each other and using their thick, heavy heads to break vertebrae. The males that reproduce most successfully do have the longest necks.

If sexual selection is the cause, males should have noticeably longer necks than females — but the difference is too small to be explained by sexual selection alone. Another theory is that the long neck helps the animal spot predators, or maybe the large surface area assists in regulating body temperature. It might also have evolved in response to giraffes’ legs getting longer, ensuring that they could continue to drink at waterholes.

Whatever the reason for the long neck, it creates a physiological engineering problem as described in a recent Science Advances article, which was summarized in a Science commentary. Researchers from China, Norway, and Denmark compared gene variants of a male giraffe with those of other mammals, including the giraffe’s closest relative: the short-necked, zebra-sized okapi. These animals diverged about 11.5 million years ago. The data identified 490 genes with unique adaptations in the giraffe. Many of the DNA variants were in genes linked to cardiovascular features, bone growth, and the sensory system.

A giraffe’s heart must pump blood at a pressure that is approximately 2.5 times higher than humans. DNA sequencing of the giraffe genome found seven unique DNA variants in the gene Fgrl1 (Fibroblast Growth Factor Receptor Like 1).

The researchers used CRISPR gene editing techniques to insert the giraffe variants into the Fgrl1 gene of mice. Not surprisingly, the mice did not grow long necks, and they did not show any obvious change in their cardiovascular system. However, when the researchers gave the modified mice a drug to induce high blood pressure, they stayed healthy, and their blood pressure rose only slightly. The unmodified control mice developed hypertension and associated kidney and heart damage.

The Fgfrl1 giraffe variant does something to the cardiovascular system that counteracts the effects of hypertension in mice, but the mechanisms are not known. There is not yet any evidence that Fgrl1 is one of the genes that causes hypertension in humans, but studying how the giraffe variants do protect mice from hypertension could lead to important new cardiovascular pathways for therapeutic investigations.

The study also highlights other DNA variants unique to the giraffe. Previous research has shown that giraffes have the best vision of all hoofed mammals, which — with their height — allows them to scan the horizon more effectively than other animals. The study also shows that the giraffe lost at least 53 olfactory genes compared with the okapi. So it traded its sense of smell, which is not as important given how far off the ground their head is, for improved eyesight — a definite benefit for their height. The team also found variants in genes that regulate sleep patterns. These findings could explain why giraffes only sleep 40 minutes per day and about three to five minutes at a time.

I use giraffes to illustrate the importance of genomic variants in health. We now know that DNA differences in the gene have profound physiological differences across all mammals. How is this example tied to UNC Research’s priorities? One of our seven research priorities is “Precision Health and Society,” which is focused on tailoring health care practice, delivery, and therapeutics to unique individual circumstances, using factors from genetics to social and environmental influences.

Francis Collins, director of the National Institutes of Health, has declared precision health a priority initiative for the agency as well.

“Precision medicine is really an effort to capture all of the specifics about an individual’s health from their environmental exposures, health behaviors, various aspects of their physiology, their metabolism, as well as genetic information through a variety of genomic loci,” Collins recently shared.

Just as giraffes’ necks allow them to reach great heights, the expertise of UNC researchers allows them to do the same across fields. I look forward to sharing more regarding Carolina’s unique contributions to precision health and society later this year.

Permalink: Giraffes, Genomics, and Physiology