Research News 2021

2018 research news
Xi Chen

NIH Awards Dr. Xi Chen New $425K Exploratory Research Grant

Feb 26, 2021

Millions of people receive palliative care each year in the United States. Many of these individuals can live several years while receiving palliative care.  Although oral health conditions, including dry mouth, infections, and oral pain among others, are extremely prevalent and can significantly affect their quality of life, the great majority of these individuals receive no oral health care prior to death.

Addressing these oral diseases can help maintain dignity and improve quality of life for older adults receiving palliative care. It can also reduce aspiration pneumonia, life-threatening septicemia and other systemic complications. Additionally, preventive care and early treatment are much more cost-effective than reacting to complications resulting from these oral health conditions.

Thus, Dr. Xi Chen and his team of researchers are working to change the paradigm of oral health care for these older adults. Oral health care has not, thus far, been integrated into daily palliative care practices, and physicians often treat oral health as a less important issue for this population, which in turn results in patients and their caregivers not appropriately valuing oral health care.

To begin changing the way that dentists and physicians think about oral health care for this population, the National Institutes of Health awarded Dr. Xi Chen and his research team a $425,000 R21 award.

As a part of the ongoing effort to advance palliative dental education and patient care at University of Iowa, this research builds on Dr. Chen’s early study with palliative care patients and their caregivers to identify barriers and solutions to both personal and professional high-quality oral-health care.

This particular research project will identify patients at the University of Iowa Palliative Care clinic, and conduct oral examinations and perform qualitative interviews with the patients and their caregivers to determine the patient’s oral health care needs, treatment goals, and care preferences. This information will be helpful for developing an intervention designed to increase oral health awareness among palliative care team and increase dental referrals for their patients. The research team will also evaluate the feasibility of integrating a proposed intervention into daily personal palliative care practices over a six-month period.

In addition to this intervention, a palliative dental practice building in the University of Iowa Palliative Care clinic will also be developed to provide on-site assessment and consults for palliative care patients requiring dental referrals.

Dr. Chen’s team including co-investigators Dr. Steven Levy, Department of Preventive and Community Dentistry, Dr. Timothy Thomsen, Department of Internal, Stephanie Gilbertson-White, PhD, APRN-BC and associate professor in the Department of Nursing, and Mary Ellen Macdonald, PhD, at the McGill University Faculty of Dentistry. 

Dr. Xian Jin Xie

Dr. Xian Jin Xie Appointed as New Centenntial Research Professor

Feb 25, 2021

Professor Xian Jin Xie was announced as the next Centennial Research Professor. This professorship recognizes Dr. Xie’s international reputation in research, the impact of his current research for its own sake and for the advancement of the college’s strategic mission in research. Dr. Xie is currently Associate Dean for Research and Director of the Division of Biostatistics and Computational Biology for the University of Iowa College of Dentistry. He also holds a joint appointment in the University of Iowa College of Public Health, and has collaborated with over 100 clinical, translational, and basic science principal investigators, leading the quantitative biomedical research effort on 52 peer-reviewed grants and 32 clinical trials including two NIH Cancer Center Support Grants, SPORE grants (P50) in lung and renal cancer, various single-PI NIH grants, as well as grants from NASA, the Cancer Prevention and Research Institute of Texas (CPRIT), the American Cancer Society, and the US Department of Defense. These awards have provided over $90 million of research funding, and the resulting collaborations have led to 138 articles published in peer-reviewed journals with more than 7000 citations to date.

Dean David Johnsen said of Dr. Xie, "While the numbers are impressive, even more impressive is what a team player Professor Xie is!  He has collaborated with faculty from several colleges on campus as well as graduate and predoctoral students." 

Since Professor Xie assumed the role of associate dean, the college has continued improving its research trajectory with record levels of NIH funding and applications, and securing P3 funds to support an NIH P50 application on oral cancer.  Dr. Xie also initiated a seed grant program with the goal fund innovative projects from early-career investigators or established investigators who are developing a new line of research. The goal of these grants is to encourage research and generate data that will enable the awardees to be competitive for peer-reviewed national funding agencies, such as the National Institutes of Health.

Regarding this professorship, Dr. Xian said, "It is a great honor for me to be nominated for the College of Dentistry’s Centennial Professorship."

He added, "My vision for this professorship is to be a facilitator of others’ scholarship efforts, a discussion leader, and a champion for collaborative research success through serving, collaborating, and empowering others to achieve excellence to make the College of Dentistry a global leader in dental research!"   

Dr. Xie will continue the legacy of excellence exemplified by those who have held this professorship.  

Dr. Eric Van Otterloo

The Genetics of Bone Formation

Feb 19, 2021

As an expert in the genetics of embryonic development, Dr. Eric Van Otterloo has opened a new dimension for understanding craniofacial development, genetics, and bone formation.

Van Otterloo’s most recent line of research began when he identified, in the mouse genome, a mutation in the gene Memo1. The mutation, which removed the Memo1 gene, affected craniofacial bone development. Up until that point, Memo1 was primarily associated with breast cancer. In this context, Memo1 was responsible for cell migration, and thus breast cancer metastasis, but Van Otterloo’s discovery opened a new area of inquiry for this gene.

During embryonic development, the cartilage and bone in the head and the face develops out of a particular kind of cells called the neural crest. Along with the cranial bones and cartilage, neural crest cells contribute to several tissues important for life. Van Otterloo’s discovery, using mice with mutations to the gene Memo1, revealed the MEMO1 protein has a unique role in regulating neural crest derived craniofacial bone.

He and his team began investigating the precise mechanism behind this developmental process. First, they found that deleting Memo1 from the neural crest cells alone resulted in some of the same defects they had observed when Memo1 was removed from the entire mouse embryo. This finding suggested that Memo1 played a role directly within the neural crest cells to regulate craniofacial bone mineralization, rather than having an indirect impact on these cells.

Like the neural crest, the ectoderm also contributes to ameloblasts, the cells that deposit enamel on the outer surface of the teeth. Would MEMO1 also play a role in the mineralization process of these cells? To address this question, the Van Otterloo lab deleted Memo1 specifically from the ameloblasts. They found that deleting Memo1 from these cells resulted in severely compromised tooth enamel, again, suggesting Memo1 was somehow involved in mineralization of another tissue.

These experimental processes have helped Van Otterloo and his team investigate the precise mechanism by which Memo1 is regulating mineralization of distinct tissue types during craniofacial development. Current work in the Van Otterloo lab includes trying to determine exactly how Memo1 is controlling both of these mineralization events, and whether there are any shared feature in these mechanisms.

“Memo1 is still a little bit elusive. In breast cancer, it signals and governs cell migration, and for bone development, it regulates bone mineralization,” Van Otterloo said.

“Being able to understand the mechanism by which Memo1 operates could allow us to enhance bone formation or block bone formation to address developmental defects,” he added.

Van Otterloo is continuing this work with a recent, and he was recently awarded a three-year $700K grant for a project investigation the interactions between Memo1 and Runx2.

Runx2 is a transcription factor for activating genes and a master regulator for bone development. In this research project, Van Otterloo is exploring the precise relationship between Memo1 and Runx2.

“We know that Runx2 is crucial for bone development, but we don’t know whether or how it is related to Memo1,” Van Otterloo explained. “We will determine how central Runx2 is to the expression of Memo1 in gene regulatory networks in bone and enamel development,” Van Otterloo added.

Building on Memo1’s role in communicating and directing other cells, it may be the case that Memo1 plays a coordinating role setting up the cytoskeletal system, which plays an important role in the formation of bone and teeth.

This original research fits well at Iowa.

“Iowa has extensive research on cranial facial anomalies and bone regeneration harnessing genetic research,” Van Otterloo said.

In particular, Van Otterloo said that Memo1 could be a good candidate for the team of researchers at Iowa looking into specific therapeutics regarding bone regeneration, and Memo1 could be used to improve specific bone regeneration strategies. Likewise, researchers at Iowa who specialize in orofacial clefting and human genetics could explore the role of Memo1 in various patient cohorts with orofacial clefting.

These studies into the genetics of embryonic bone formation are not only expanding scientific knowledge in the area, but they are also laying the basic science groundwork necessary to move from the bench to the dental chair.

Liu Hong

Dr. Liu Hong Awarded $125K Supplemental Grant

Feb 12, 2021

Dr. Liu Hong, associate professor in the Iowa Institute for Oral Health Research and the Department of Prosthodontics, was awarded a supplemental $125K subcontract from the National Institutes of Health via the company NaturemiRI. The goal of the project is to help develop a synthetic bone-graft substitute that promotes high-quality bone growth in alveolar ridge of dental patients, thereby offering a new tool in the treatment of craniofacial defects and tooth extractions performed in anticipation of dental implantation

Synthetic bone-graft substitutes are promising alternatives to current standard treatments for oral and craniofacial bone defects. MicroRNAs (miRs) are small, non-coding RNAs that have emerged as critical transcriptional regulators in stem cell differentiation and regeneration. Previous research findings demonstrate that significant potential exists to develop novel therapeutics for bone regeneration of craniofacial and periodontal bone defects by targeting miRs, and miR-200a specifically.

The NaturemiRI, LLC R&D team has developed the Plasmid-based microRNA inhibitor system (PMIS), a non-toxic, nucleic acid-based method of microRNA inhibition. This particular research project is part of an overall series of projects intended to validate and commercialize a PMIS-infused collagen sponge for use in clinical dentistry. Specifically, Dr. Hong’s team expects to show that a PMIS construct inhibiting miR-200a (PMIS-miR-200a) promotes high-quality bone growth in the alveolar ridge of dental patients, thereby offering a new tool in the treatment of craniofacial defects and tooth extractions performed in anticipation of dental implantation.

This project aims to optimize the in vivo osteoinductive capacity and alveolar bone regeneration of PMIS-miR-200a adsorbed in collagen sponges and determine its toxicity risk using an animal model.

Iowa Utility Company

College of Dentistry Awarded $600K+ in P3 Funds to Begin Developing a New Oral Cancer Center of Excellence

Feb 05, 2021

On Thursday, the University of Iowa announced that the first $7.5 million of the investment revenue generated from the public-private partnership (P3) for its utility system would include a $600K+ award for the College of Dentistry. With this support, an interdisciplinary team with over 40-people, including Iowa faculty from the Colleges of Dentistry, Medicine, Pharmacy, and Engineering, will develop the preliminary data and program structure to apply and be competitive for an $11 million grant from the NCI/NIDCR to establish a P50 Specialized Program of Research Excellence in oral cancer. This specialized research program in oral cancer will be the first of its kind in the nation.

Each year, approximately 53,000 people are diagnosed with some form of oral cancer and almost 10,000 die. Early detection, diagnosis, and treatment of oral cancer significantly enhance survival rates and reduce morbidity.

These P3 funds will significantly improve the chances that this interdisciplinary team will be able to secure P50 funds for each of the proposed research projects, and these projects would in turn help fill gaps in knowledge and in clinical translation necessary to substantially improve early detection, diagnosis, and treatment of oral cancer.

More specifically, the P3 funds will enable the team to develop the infrastructure and administrative units for supporting each of the research projects, and it will allow the project teams to generate preliminary data.  

In their award letter, Provost Kevin Kregel and Vice President of Research Martin Scholtz said of the project, "Establishing the nation’s first NCI/NIDCR P50 in Oral Cancer will bring national and international distinction to the University of Iowa. We look forward to seeing the progress towards establishing the support activities necessary to be competitive in the P50 grant submission."

The six projects are as follows:

Project 1: The Oral Microbiome in Oral Squamous Cell Carcinoma (OSCC)

Co-PIs: Jeffrey Banas, PhD; David Drake, PhD; Sukirth Ganesan, BDS, PhD; Co-Is: Emily Lanzel, DDS; John Hellstein, DDS; Xian Jin Xie, PhD; Eric Taylor, PhD; Liu Hong, MD, PhD; Consultant: Kim Brogden, PhD

Project 2: Dissecting the PRMT5 regulatory pathway in oral epithelium differentiation

Co-PIs: Robert Cornell, PhD; Eric Van Otterloo, PhD; Ronald Weigel, MD, PhD; Co-Is: John Hellstein, DDS; Xian Jin Xie, PhD

Project 3: Tissue-Engineered Approaches for Oral Cancer Reconstructive Surgery

Co-PIs: Liu Hong, MD, PhD; Hongli Sun, PhD; Co-Is: Nitin Pagedar, MD; Brad Amendt, PhD; Marisa Buchakjian, MD, PhD; Xuan Song, PhD

Project 4: In situ Immunization with nanoparticles for treating oral squamous cell carcinoma

Co-PIs: Ali Salem, PhD; George Weiner, MD; Co-Is: Douglas Laux, MD; Andrean Simons-Burnett, PhD; Kyungsup Shin, DMD, PhD; Kim Brogden, PhD; Xian Jin Xie, PhD

Project 5: Discovering Genetic Susceptibility to Oral Cancer

Co-PIs: Xian Jin Xie, PhD; Erliang Zeng, PhD; Co-Is: Robert Cornell, PhD; Azeez Butali, DDS, PhD; Ronald Weigel, MD, PhD; Benjamin Darbro, MD, PhD

Project 6: NEK2 in Oral Cancer Biology and Therapy

Co-PIs: Frank Zhan, MD, DDS, PhD; Marisa Buchakjian, MD, PhD; Emily Lanzel, DDS; Co-Is: Carryn Anderson, MD; Veeratrishul Allareddy, BDS

James Wefel

College of Dentistry Announces Inaugural Wefel Research Awards

Jan 22, 2021

Dr. James S. Wefel was a deeply-valued faculty member of the College of Dentistry, who wore many hats in his 40 years of service (1972-2012). He was affiliated with the Department of Pediatric Dentistry and the Dows Institute for Dental Research (now the Iowa Institute for Oral Health Research). He was a well-known professor, researcher, published author, distinguished international speaker, mentor, and innovator. Above all, he was a devoted friend, and he genuinely cared for the College of Dentistry and the people whose lives he touched.

The research award honors the contributions of Dr. Wefel to the College of Dentistry in the fields of Cariology and Dental Sciences. It is intended to encourage and assist promising students in their research endeavors.

The award committee: Dr. Karin Weber-Gasparoni, Dr. Xian Jin Xie, Dr. Jeffrey Banas, Dr. Steven Levy, Dr. Teresa Marshall, and Trudi Westfall are proud to announce the Inaugural James S. Wefel Dental Research Award 2020 recipients:

Chukwuebuka Ogwo (Mentor: Dr. Steven Levy; Department of Preventative and Community Dentistry) Predicting the Risk and Trajectory of Dental Caries Using Machine Learning Algorithm

Olajide Obe (Mentor: Dr. Cristina Vidal; Department of Operative Dentistry) Interaction of Odontoblasts with Products from Bacteria at Different Stages of Lesion Progression Modulate the Protein Expression and Activity of Cathepsins

Yun Jung Kim (Mentor: Dr. Justine Kolker; Department of Operative Dentistry) Evaluation of the effect of fluoride topical agents on the prevention of demineralization adjacent to resin modified glass ionomer restorations in vitro

Congratulations to all students and mentors for receiving such a prestigious award! Their names will be displayed on a new plaque at the entrance of the Iowa Institute for Oral Health Research and we wish them success in their research.

Be advised, the application cycle for the 2021 award begins soon! Applications are due May 15, 2021.  Please contact Mrs. Trudi Westfall in the Department of Pediatric Dentistry for more information.

Dr. Aline Petrin

Dr. Aline Petrin Receives Highest Research Award in Orthodontics

Jan 22, 2021

The American Association of Orthodontics awarded Dr. Aline Petrin, associate research scientist in the Iowa Institute for Oral Health Research, the 2021 Milo Hellman Research Award. This award will be presented during the virtual AAO Excellence in Orthodontics Awards Luncheon at Annual Session.

Dr. Thomas Southard, DEO in the Department of Orthodontics, expressed his congratulations and said of Dr. Petrin receiving the award, “This is the top orthodontic research prize in the world!”

Dr. Petrin was chosen for this prestigious award based on her research project, "Epigenome-wide analysis of DNA methylation in monozygotic twins discordant for orofacial clefts." This project is part of her 5-year career-development K01 NIH grant and draws on a unique and powerful approach to genetic research that uses discordant twins to study key epigenetics factors, which play a causal role in orofacial clefts

"It is an honor to be the recipient of the Milo Hellman Award. This achievement would not have been possible without the support that I receive. I extend my sincere thanks to my mentors, Dr. Moreno, Dr. Murray and Dr. Marazita, to the Department of Orthodontics, to our Division of Biostatistics and Computational Biology, and the College of Dentistry leadership."