University Of Iowa

NIH Research Projects · FY 2026 · 1998-09

Project Summary The central objective of this Molecular Virology and Viral Pathogenesis Training Grant is to train predoctoral students in virology so that they can become productive members of the research community. The importance of virology has been highlighted by reports of the morbidity and mortality caused by viruses long known to infect humans as well as the emergence of zoonotic virus infections. Thus, there is an urgent need to continue producing young scientists who are expert in virology. This training grant, which has trained students for 27 years, consists of trainers with interests in a variety of viruses and who are both junior and senior. There are 19 trainers from a number of departments and interdisciplinary programs who serve as faculty on this training grant. Our focus is on understanding fundamental aspects of human virology, with an emphasis on emerging virus infections and viral pathogenesis. The training grant program is rigorous and consists of a mixture of didactic courses, seminars, seminar courses which emphasize critical reading of the literature and data presentation, and teaching opportunities. Trainees are provided feedback in several venues to hone their presentation and laboratory skills. Its interdisciplinary nature promotes interaction among students and faculty interested in virology across the University of Iowa. By providing stipend support and travel funds for graduate students, the training grant also facilitates exposure of our students to the national and international virology community. Students selected for support by the training grant have extra opportunities to teach classes and to receive funding to attend off-campus courses in a cutting-edge technology, such as bioinformatics. Through the T32 program, our trainees participate in career symposia, seminars discussing cutting edge technology and are able to interact with visiting virologists. Issues of scientific integrity and data reproducibility are also emphasized as part of the virology training grant. Career outcomes of our T32 trainees have been impressive. To date, students appointed to the training grant have uniformly completed their Ph.D.s and obtained post-graduate positions in the life sciences. One-third of our former trainees now hold a faculty position at a R1 institution, whereas many of our other former trainees have senior positions in biotech. In short, this training grant has had many years of success, and we will build upon this success. We continue to request funds for three predoctoral graduate students per year, with support generally provided for two years between their second and fourth years of study.

NIH Research Projects · FY 2025 · 1998-08

PROJECT SUMMARY and ABSTRACT The vast majority of biological functions use membrane-embedded proteins. Controlling the quality and quantity of these membrane proteins is critical for these processes to work normally, and defects in the ability to destroy misfolded proteins or getting rid of membrane proteins that are no longer needed cause a plethora of human diseases. A central mechanism used to specify which proteins undergo degradation is attaching ubiquitin to them. Ubiquitin is a small protein that is extremely well-conserved across the entire kingdom of eukaryotic organisms. When ubiquitin is chemically linked to a membrane protein, it causes that protein to be degradaded by cellular machinery that can recognize ubiquitin. Ubiquitin can also be linked to another ubiquitin, forming polyubiquitin chains. Different polyubiquitin chains are made by changing how one ubiquitin is linked to another, and different ubiquitin chains are used by different degradation machines. One machine sorts membrane proteins to the interior of lysosomes by first sorting them into intralumenal vesicles that accumulate within multivesicular endosomes/bodies (MVB). MVB sorting primarily uses ubiquitin chains that are linked via lysine-63 of ubiquitin, which binds to a number of endosomal proteins that cluster and sort ubiquitinated membrane proteins into intralumenal vesicles. These intralumenal vesicles can either be delivered to the interior Lysosomes and be degraded, or they can be secreted as extracellular vesicles/exosomes, that carry and delivery contents to other cells to elicit a range biological effects. Many critical questions remain outstanding about how proteins are sorted into endosomal intralumenal vesicles and what differentiates how they are sorted to Lysosomes versus being sorted into exosomes. Aim1 will address these questions by examining the molecular mechanisms that two homologous sorting proteins use to differentially sort proteins into intralumenal vesicles that go to Lysosomes or become exosomes. Additional questions remain about whether ubiquitin attachment to membrane proteins in the trans­ Golgi Network, Endosomes, and cell surface that have made it through their initial synthesis in the endoplasmic reticulum (so-called 'post-ER' proteins) exclusively sends them through the MVB pathway as their mode of degradation. We found that post-ER proteins modified with a different type of polyubiquitin chain are sent along a different pathway for degradation. Aim2 will study the molecular features of this pathway and assess how this pathway may contribute to controlling the quality and quantity of membrane proteins.

NIH Research Projects · FY 2026 · 1997-04

The Environmental Health Sciences Research Center (EHSRC) will advance and translate research that addresses environmental health problems across the urban-rural continuum. Rural America faces unique environmental challenges from exposure to farm chemicals, air and water pollution from livestock and agricultural production, rural manufacturing, and the green energy economy. The EHSRC is at the forefront of research in rural environmental health, determining the role of innate immunity and the inflammasome in lung disease; the role of the microbiome in health and disease; state-of-the-art biomedical imaging with advanced computational modeling to assess the effect of inhaled toxicants; and applications for distributed sensor networks and data analytics for exposure monitoring. The Center applies innovations, for example, in advanced -omics technologies, population-based animal models, and advanced lung imaging, to advance this research. The EHSRC vision is to be the primary environmental health sciences (EHS) resource for improving the health of rural residents in the Midwest by stimulating and translating innovative environmental health sciences research. This is accomplished by enhancing the careers of Center investigators and through our translational research vision to translate new insights from rural exposures; population health; individual susceptibilities; and pathways of toxicity, disease, and repair to enhance environmental health literacy, public health practice, regulatory policy, new clinical treatments, and precision environmental health. Center goals are to: 1) enhance the effectiveness of environmental health sciences research and extend the focus of research in five Thematic Areas, including Inflammation and Innate Immunity, Nanoscience, Population Health, Systemic and Redox Toxicology, and Water Quality; 2) recruit, mentor, and nurture a broad group of investigators interested in the environmental health sciences, with an emphasis on recruiting and grooming future leaders in the field; and 3) engage with communities and other audiences to translate research knowledge toward improving the health and environment of rural people in the Midwest and the nation. The interdisciplinary research of the EHSRC is organized around its Thematic Areas and supported by three facilities, the Integrated Health Sciences Facility Core (IHSFC), Exposure Science Facility (ESF), and Pulmonary Toxicology Facility (PTF). These facilities provide cost-effective and cutting-edge services and state-of-the-art equipment. An Administrative Core provides transformative leadership, leverages institutional support, and manages highly effective Pilot Grant and Career Enhancement Programs that provide resources and mentoring to advance the careers of promising early-stage investigators. The Community Engagement Core engages the Center’s audiences to ensure the relevance of EHSRC research and, in collaboration with the IHSFC, translates research to environmental public health

NIH Research Projects · FY 2025 · 1996-08

ABSTRACT The Mechanisms of Parasitism training program has been an ongoing program at the University of Iowa for 24 sequential years. The program unites scientists working on different microbial systems and methods, but addressing similar questions about “Parasitism”, i.e. the pathogenesis of microbial diseases. Our underlying hypothesis is that protozoal, helminthic, bacterial, and viral pathogens face similar obstacles in overcoming mammalian antimicrobial defenses, establishing a niche in which they coexist asymptomatic in their host, or lead to pathologic conditions (i.e., disease). Our premise is that the mechanisms through which one pathogen evades killing within the host provides insights into means through which other pathogens survive in their unique host niche. Most definitely the methods used to investigate host interactions with different hosts overlap. There is a long history of collaborative research and training among many laboratories at the University of Iowa, and specifically particularly between members of this Parasitism program. With this new application, we have expanded our horizons to meet the growing need for collaborative expertise in applying rigorous approaches to the study of host and pathogen genomes, transcriptomes, proteomes, metabolomes, microbiomes, and phageomes, drawing upon analyses of these massive data sets to generate hypotheses that address the common and unique mechanisms through which different microbes establish parasitism. This interdepartmental, interdisciplinary program draws upon faculty members in eight departments and four interdisciplinary programs with homes in four Colleges (Medicine, Public Health, Engineering, Liberal Arts) at the University of Iowa. Our activities are aimed at inspiring and enhancing not only training of our students and postdoctoral scholars, but also enriching the collaborative interactions between faculty members with different areas of expertise. In this submission, we now add faculty with expertise in Metabolomics, Phylogenetics, Bioinformatics, and Epidemiology to the faculty. Our current faculty members already have considerable depth in mechanisms of microbial virulence and host innate and adaptive immune responses. We aim to adopt, and by default, have our trainees adopt a more comprehensive view of the intricate relationships between host, microbe, and environment that contributed to parasitism. Our prior trainees have been highly successful; 100% of those who are done with training have assumed positions in the biomedical sciences or related fields, with 54% holding tenure track university positions and 39% performing research in industry. In this application we propose an enhanced approach to helping trainees develop their careers. We have been successful at recruiting minority candidates and propose means to enhance that even further. Overall, we view this as a comprehensive program to train graduate students and postdoctoral scholars in diverse aspects of parasitism, and to prepare them for productive careers in education, industry scientific policy or biomedical research.

NIH Research Projects · FY 2025 · 1995-08

Studies of the immune system over the last hundred+ years have demonstrated its critical importance to defense against pathogens and toxins; its role in asthma, allergy and autoimmunity; and more recently how it can be harnessed in the treatment of cancer. The routine appearance of viral, bacterial, and parasitic outbreaks all point to the need for the development of new or better immune-based vaccines and a need for better understanding of how the immune system controls or contributes to disease. Likewise, recent work in Immunology has increased our understanding of how the microbiome can contribute to or regulate autoimmune as well as infectious disease, how immunoparalysis alters long-term outcomes after sepsis and other diseases, and how manipulation of immune checkpoints can boost the immune response. Collectively these and other immune based studies have had a major impact on human health and led to the discovery of new therapies and vaccines. Thus, in order to continue recent advancements, discover new therapies, prepare for future pathogen outbreaks, and educate both medical professionals as well as the public, there is a distinct need to continue to train the next generation of immunologists. The overall goal of the University of Iowa Predoctoral Training Program in Immunology is to educate, train, and produce a new generation of excellent young immunologists, well-prepared to advance the science of immunology and their own independent careers in academic, educational, and industrial settings. This is a competitive renewal application for years 26-30 of a training program supporting students pursuing doctoral studies in basic and translational immunology at The University of Iowa. Thirty-one training faculty members provide intensive laboratory research training and effective, relevant classroom instruction leading to the Ph.D. or the combined M.D. Ph.D. degree in Immunology. The diversity of faculty research expertise within the discipline of immunology is a strength of the training opportunities provided, and is complemented by a network of frequent and successful collaborations in funding, publication, and student training. We continue to revise and optimize our Program to best meet the needs of trainee scientific careers and the diverse scientific workforce of the future. This program fills a critical need to support our continuing efforts in training predoctoral students from diverse backgrounds for independent careers as immunologists.

NIH Research Projects · FY 2026 · 1995-01

Project summary/Abstract The long-term goal of this research program is to elucidate the molecular mechanisms underlying the function and regulation of cGMP-phosphodiesterases (PDE6) in rod and cone photoreceptor cells. As a central effector enzyme in the phototransduction cascade, PDE6 is critical to photoreceptor cell physiology and survival. Severe retinal diseases including retinitis pigmentosa, achromatopsia, and Leber congenital amaurosis result from pathogenic mutations in genes that encode PDE6 subunits or aryl hydrocarbon receptor- interacting protein-like 1 (AIPL1), a specialized PDE6 chaperone. Despite our advanced understanding of the PDE6 regulation in phototransduction, little is known about the folding and maturation of this enzyme, and the proposed research aims to fill this gap. Our evidence suggests that AIPL1 forms a complex with ubiquitous chaperone HSP90 that is absolutely required for maturation of PDE6 into a functional enzyme. We will define the protein-protein interfaces and the structure of the HSP90/AIPL1 complex in solution to gain mechanistic insights into how this chaperone complex interacts with PDE6. Based on our preliminary studies, we hypothesize that nascent PDE6 assumes a closed nonfunctional state, and the HSP90/AIPL1 complex and the regulatory P-subunit of PDE6 induce and/or catalyze the transition of PDE6 from the closed state to the functional open state via an intermediate state. We propose a detailed model as to how HSP90, AIPL1 and P facilitate the maturation of PDE6 and will rigorously interrogate this model by leveraging our heterologous expression system for cone PDE6C in HEK293T cells, and rod PDEAB in the Pde6g-/-/Pde6ccpfl1 mouse model. In addition, we will use the HSP90 knockout mouse, which highlights the importance of HSP90 in photoreceptor cells because of its rapid retinal degeneration phenotype, to test our hypothesis that defects in PDE6 maturation are the key cause of the degenerative phenotype. Elucidation of the molecular mechanisms of PDE6 maturation will have important implications for retinal diseases and the design of new therapeutic strategies.

NIH Research Projects · FY 2025 · 1993-07

This application requests continued support for a research training program in Otolaryngology to provide two-year translational and clinical research training opportunities for physicians pursuing an academic career in Otolaryngology-Head and Neck Surgery. Research training in neurosciences, molecular genetics, molecular biology, bioengineering, and epidemiology promotes the long-term goal of increasing the number and quality of Otolaryngology surgeons capable of being key members of research teams that studying the underlying mechanisms, diagnostic criteria, and therapeutic approaches of the impaired auditory and other communicative systems. A multidisciplinary educational environment is created through the interaction of twenty-four clinicians and basic scientists from the departments and programs of Otolaryngology-Head and Neck Surgery, Hearing Sciences, Speech Science, Neuroscience, Internal Medicine, Pediatric Genetics, Microbiology, Molecular Biology, Physiology, Radiation Oncology and Free Radical Biology, and The Colleges of Pharmacy, Engineering, Public Health, and Business. A wide assortment of research training opportunities are available, ranging from basic research in electrophysiology and molecular biology of the auditory system, neuroanatomy, molecular genetics of deafness, free radical biology, biomaterial engineering, and molecular biology of craniofacial deformities to clinical investigations involving epidemiologic study of hearing loss, head and neck cancer, speech disorders, and clinical trials study of hearing loss, head and neck cancer, speech disorders and clinical trials methodology. Trainees will be enrolled in didactic courses in their area of interest throughout the two-year training period. The application requests two postgraduate training positions a year (ten over five years) for physicians completing at least one year of clinical training. Emphasis is placed on multi-disciplinary research teams and training. Trainees will devote 100% of their effort to research training for two consecutive years, to be followed by completion of a four-year clinical residency in Otolaryngology-Head and Neck Surgery. Trainees will have two additional 3-month research blocks during the PGY3 and PGY4 years, supported by the Department of Otolaryngology-Head and Neck Surgery, providing at least 2.5 years of an intensive research training experience. The proposed research training program will expand the research training opportunities available to future academic otolaryngologists, foster interaction among clinical and basic scientists, and provide physicians with tools to become function as key members of research teams that translate basic discovery into improved clinical care.

NIH Research Projects · FY 2026 · 1991-09

This application requests continuation of funding for a successful and long-standing training program (dating back to 1991). This program was rebranded 5 years ago as the Iowa Neuroscience Specialty Program In Research Education (INSPIRE) to integrate training in Translational Neuroscience relevant to psychiatry with an emphasis on a lifespan trajectory perspective. Research opportunities are unified through a focus on the critical framework for Translational Neuroscience, the NIMH’s Research Domain Criteria (RDoC) project which focuses on mechanisms of psychopathology within functional dimensions rather than diagnostic criteria. INSPIRE is now training young investigators who have a high level of sophistication in thinking about and interrogating the complexities of the human brain’s functional domains, the change of these systems over time, and how discovery of mechanisms of pathologic functioning are translated to clinical diagnosis and treatment. The Co-PIs are Peg Nopoulos, an alumnus of this T32 program herself and a national leader in research training and neuroimaging, and John Wemmie, a translational psychiatry investigator with long-term federal research funding across multiple domains. The Co-PIs have retained the solid foundation of this program put in place by Nancy Andreasen, a pioneer in neuroimaging and psychosis. The reframed program started 5 years ago has two core areas: 1) a highly structured curriculum emphasizing Translational Neuroscience, and 2) a focus on the study of neurobiologic mechanisms of psychiatric illness across the lifespan. The content of the program expanded into multiple areas of Translational Neuroscience by partnering with the Molecular and Computational Psychiatry division and the Iowa Neuroscience Institute (INI). MD/PhD and PhD mentors with strong training records are newly recruited to the program due to a focus on Translational Neuroscience or through recent INI recruitment. Accordingly, the program has a diverse, interdisciplinary group of trainees with basic science PhDs, MDs, and MD/PhDs all building a Translational Neuroscience identity. Matching funds that support additional trainees help to form a cohesive cohort. This mix of types of trainees adds an additional layer of exposure to translational research with a strong emphasis on team science. Central to the training is the Master’s in Translational Biomedicine (TBM) program through our Institute for Clinical and Translational Sciences (ICTS). This program is designed to be individualized and flexible. The INSPIRE program recruits fellows to fill 4 positions each year for two years of postdoctoral training. Each fellow is ‘matched’ with an outstanding mentor and mentor team to oversee the primary activity of mentored research. A weekly seminar encompasses essential skills including presenting, writing, and networking with faculty in Translational Neuroscience. In addition, each fellow develops a program through the TBM that suits their needs while fulfilling requirements (such as Training in Responsible Conduct in Research), utilizing formal didactics and career development activities. A degree (certificate or Master’s) is an option, but not required.

NIH Research Projects · FY 2025 · 1988-07

This application requests continued funding for a postdoctoral research training program in hematology that has been successful in attracting young scientists and physician-scientists into academic careers in hematology. The program has as its primary objective to prepare MD, MD/PhD, and PhD postdoctoral fellows for productive careers in the hematology research workforce. We are requesting support for four postdoctoral trainees per year (two PhD trainees and two MD or MD/PhD trainees), which is unchanged from the previous grant period. Under the leadership of MPIs Steven Lentz and Anil Chauhan, the training will be carried out in an enriched environment of active basic, translational and clinical investigation at an institution that emphasizes the career development and collaborative science. We aim to recruit outstanding postdoctoral trainees who wish to obtain comprehensive knowledge of the principles and techniques of basic and translational research related to hematology, blood cells, vascular biology, coagulation, hematopoiesis, and immunobiology, and prepare them for successful careers as independent investigators or related scientific positions. We have defined six specific objectives for trainees that are linked to measurable outputs in our evidenced-based evaluation process. Upon completion of the program, trainees will be able to: (1) Integrate knowledge of basic mechanisms, research methods, and clinical hematology to identify the most significant and impactful research questions; (2) Demonstrate critical thinking and reasoning in the conduct of research; (3) Demonstrate integrity and rigor in the conduct of research; (4) Demonstrate skills in oral and written communication, including grant applications and publications; (5) Demonstrate skills in leadership and mentoring. Several new initiatives have been instituted, including expansion of the clinical hematology fellowship and creation of an advanced hematology fellowship track, closer partnership with the PSTP (a robust pipeline for physician-scientist trainees), a new scientific focus on thrombo-inflammation and stroke, and implementation of structured individualized career mentoring. The curriculum includes core lectures in clinical hematology, research methods, RCR, rigor and reproducibility, and grant writing. Mentoring committees and individual development plans are required for all trainees. The foundation of training continues to be centered on the individual mentored research project, marked by a period of intensive, sustained research under the guidance of an established, dedicated mentor. The rich training environment provided by experienced faculty, extensive laboratory, clinical, and core facilities, and strong institutional support should ensure continued success in attracting and preparing highly qualified postdoctoral trainees for careers in hematology research.

NIH Research Projects · FY 2024 · 1988-07

Program Summary This application proposes continuation of a highly successful interdisciplinary training program in infectious diseases research that is based on the tenet that both MD and PhD postdoctoral research trainees benefit enormously from exposure to faculty and trainees from both backgrounds. The program, whose research emphasis is on the interface between human host and microbial (bacterial and viral) pathogens and their epidemiological spread and prevention, provides an intense mentored research experience for MD and PhD postdoctoral trainees in infectious diseases. This occurs in conjunction with an individualized curriculum of didactic courses, seminars and journal clubs designed to encourage substantive interactions between MDs and PhDs. A short- term 3-month research experience for medical students is also offered. Most faculty are drawn from 1 basic science and 2 clinical departments, as well as 2 interdisciplinary PhD programs. Collaboration among program faculty is high. Research facilities are superb. The scientific program centers around three major areas: 1) Host Defense, emphasizing innate immunity; 2) Microbial Pathogenesis; and 3) Epidemiology and Healthcare Infections. Faculty are divided into: 1) full members; and 2) associate members on the basis of their extramural research support and their experience both as an independent investigator and research mentor. Primary research mentors come from faculty meeting the criteria for full membership. An important aspect of the 3-year research experience for MD postdoctoral trainees with minimal prior research experience is an intensive exposure to a broad spectrum of graduate level basic science courses. All postdoctoral trainees establish a Research Advisory Committee. All trainees attend a research conference, as well as a seminar/ journal club designed to encourage cross-fertilization of ideas and scientific approaches between clinical medicine and basic science. They will interact with outstanding visiting scientists, attend scientific meetings, learn scientific writing and grant preparation skills, and complete a course in research and biomedical ethics. Recruitment of trainees in underrepresented minority groups has been strong, and plans to expand efforts are in place. In summary, this proposal requests continuation of an ongoing training program with an excellent training record which will provide a coordinated and integrated training experience for postdoctoral MD and PhD trainees in infectious diseases research related to the microbial pathogenesis of bacterial and viral infections of humans.

NIH Research Projects · FY 2026 · 1985-09

Program Director/Principal Investigator (Last, First, Middle): Gantz, Bruce J. PROJECT SUMMARY - OVERVIEW Cochlear implants (CI) have become the standard of care for managing profound sensorineural hearing loss. These devices provide significant improvement in word understanding in quiet but have limitations in noisy backgrounds. Difficulty understanding speech perception in noise (SiN) in real-world environments is one of the most common complaints of people with any type of hearing impairment who are seeking hearing rehabilitation. We believe that the ability to understand SiN is a product of the auditory periphery as well as plasticity afforded by cortical and cognitive processes. At the level of cortical and cognitive processing, our prior work has identified a suite of cognitive mechanisms, including figure/ground separation and changes in lexical processing that interact with the signal quality to impact SiN outcomes. Upon this progress, we now must expand investigations to better understand the influence of other important factors, such as higher order cognitive processes (e.g., working memory and executive functioning), with high potential to assist improvement in SiN abilities among individuals with hearing loss. Furthermore, understanding the effect of these abilities on communication and socialization in real-world settings and its influence on psychosocial well- being could have long-term impact on cognitive stability. This grant incorporates a multi-pronged approach to parse the critical issues at all auditory system levels and as it relates to understanding in real-world listening. Through utilization of a variety of CI users (e.g., SSD, Bilateral, A+E), we can expand our understanding of: 1) mechanisms involved in loss of residual acoustic hearing and how those can facilitate better preservation outcomes; 2) how listeners adapt to and fuse the A+E information to improve hearing in real-world challenging situations; and 3) whether an individual’s cognitive functioning assist the integration of A+E processing. Furthermore, we recognize that communication difficulties transcend SiN performance; we will investigate mechanisms involved with listening in rapid, quiet, or accented speech, reverberant environments, and missing cues (e.g., wearing face masks). The Iowa Cochlear Implant Clinical Research Center requests competitive renewal of funding. Four research projects and two cores are proposed in this application. We will leverage the unique structure of the P50 and our large cohort of CI subjects from our patient registry to develop predictive models at the group and individual levels incorporating peripheral, cortical, cognitive, and language processing insights to predict outcomes in real-world challenging listening environments (i.e., natural listening environments). The four research projects are highly integrated and depend on data from each other to answer the experimental questions proposed.

Other NSERC · FY 2024

hyperpolarized gas MRI, CT, radiation therapy, radiation induced lung injury, cancer, algorithm, artificial intelligence