University Of Wisconsin-Madison

NIH Research Projects · FY 2025 · 2001-08

These experiments will further understanding about how and why child adversity leads to a broad range of mental and physical health problems. Although millions of children experience various forms of child adversity each year in the US, little is understood about how this experience influences brain-behavioral development. The General Aim of this research is to determine how environmental experience shapes neural circuitry in ways that lead to child mental health problems, and determine how these systems can be targeted to provide treatments for affected individuals. Here, we will test aspects of learning that might underlie problems in adversity-exposed children by focusing on the way unstable environments influence decision-making. Once we identify a mechanism, we will advance our basic science to a pre-clinical space by determining if these mechanisms are responsive to laboratory manipulations. The Specific Aims are to specify the mechanisms affected by child adversity that lead to developmental changes in systems needed to effectively learn to communicate, interpret, and regulate emotion in the context of social interactions. We will focus on how children learn from these experiences to determine which of these processes are most amenable to change. The proposed experiments combine neuroimaging, behavioral, and computational approaches to examine precise and novel questions about how experiences of child adversity are transformed into disruptions of the brain networks underlying emotional pathologies. This project: (1) Examines developmental change in children ages 9-11 years, covering critical transitions when many mental health problems emerge, (2) Probes discrete developmental mechanisms that can be targeted for intervention, (3) Is amply powered to properly test the hypotheses, (4) Characterizes aspects of relevant brain-behavior relationships are related to both RDoC dimensional constructs and DSM diagnoses, and (5) Employs sophisticated computational rigor to truly interrogate the critical questions under examination. Because child adversity is a powerful determinant of many subsequent mental health problems, the data generated from this project has profound implications for conceptualizing novel and more precise treatments for vulnerable children. It will do so by determining effects of chronic adversity exposure on human neural circuitry early in development, when the brain may be particularly sensitive to environmental influences. The project moves away from description of risk groups to defining and specifying mechanistic ways in which the environment creates long-term effects on brain and behavior. These foci hold tremendous promise for advancement of knowledge and application to improvement of public health.

NIH Research Projects · FY 2025 · 2001-05

PROJECT SUMMARY The number of funded physician-scientists in the United States has decreased steadily since the 1970s and the numbers are most alarming for surgeon-scientists. Currently, only 6% of U.S. surgeons have funding from the National Institutes of Health (NIH)1. From 2006 to 2016, NIH funding for surgery departments decreased by $2.79 million per year and funding success rates for surgeons declined by 0.21% per year2. Contemporaneously, publication impact factors and the career development conversion rate (K to R) for surgeons increased, suggesting the quality of surgical research continues to increase. A recent report from the NIH expressed concerned about the capacity to translate research into clinical care and policy as the number of well-trained individuals who cross the bench to bedside divide drops3. There are two evidence-based interventions that effectively promote surgeon engagement in research. The integration of a two-year research fellowship into general surgery residency increases the likelihood of an academic career. The track record of our training program, which has adhered to this model over the last 20 years, is strong with the majority of our trainees receiving subsequent funding and/or an appointment in an academic department. Recent evidence shows that the presence of PhD-scientists in a department of surgery strongly correlates with increased departmental research productivity as well as increased productivity for individual surgeon-scientists4. We therefore propose the following specific objectives for our training program: 1. To provide training in the conduct of basic, translational, clinical and health services surgical oncology research through a tailored, didactic, postdoctoral research experience; 2. To increase the number of well-trained PhD-scientists with a focus in surgical oncology; 3. To develop scientists and surgeon-scientists as academic leaders with an emphasis on multidisciplinary and translational research as the next generation of surgical researchers in oncology. To meet these objectives, the University of Wisconsin (UW) Surgical Oncology Training (UW-SORT) Program utilizes the extensive resources of the UW Department of Surgery, UW Carbone Cancer Center (UWCCC), the McArdle Laboratory for Cancer Research, the Wisconsin Surgical Outcomes Research Program (WiSOR) and the UW Institute for Clinical and Translational Research (ICTR) to provide world-class, mentored training in the research methodologies necessary to develop productive NIH-funded research programs in surgical oncology. The core of our training program is a strong and diverse pool of experienced, extramurally funded trainers from a variety of surgical oncology-related disciplines. The trainee's practical research experience is supported by appropriate didactics, effective assessment processes, a plan to promote diversity by recruiting and retaining both women and minorities, and a comprehensive plan for training in the responsible conduct of research.

NIH Research Projects · FY 2025 · 2000-08

The Wisconsin Allergy Research Training (WiscART) program aims to provide research training for postdoctoral fellows in Allergy and Immunology to prepare trainees for careers as independent academic research scientists. Objectives to achieve this goal include helping trainees establish a high-quality and productive research project related to allergy/immunology and developing abilities in leadership and education. There are generally 4-6 Allergy/Immunology fellows in the UW program, and four fellows supported by the WiscART program. The post-doctoral trainees are PhDs or MDs who have completed Pediatrics or Internal Medicine residency training. For physicians, the School of Medicine and Public Health and the Departments of Medicine and Pediatrics leverage the T32 funds by providing funds for salary support and stipends for additional training years not covered by WiscART. The WiscART trainers include clinical, translational, and basic scientists, and there are exceptional opportunities for trainee research projects. Training by traditional scientific and career mentorship is supplemented by outstanding educational programs offered by the University of Wisconsin CTSA (Institute for Clinical and Translational Research), including optional advanced degree and certificate programs in clinical and translational research. The program has consistently recruited outstanding trainees with a variety of backgrounds and interests. Overall, 63% of our graduates have pursued academic or research-focused careers upon graduation from WiscART.

NIH Research Projects · FY 2026 · 2000-06

ABSTRACT Cell migration is important in normal development, wound healing and cancer. The long-term goal of this work is to study cell migration in the context of cancer. The most motile, and understudied, population of cells in the tumor microenvironment (TME) are neutrophils, which are primary effector cells of the innate immune response. The presence of chronic neutrophil- mediated inflammation has been associated with the initiation and progression of cancer. However, the role of neutrophils in the tumor microenvironment remains controversial in part because neutrophils can play both pro- and anti-tumor roles. We aim to address this gap by increasing our understanding of how neutrophils are recruited and regulated by the tumor microenvironment during tumor progression. We will test the overall hypotheses that specific signaling pathways induced by transformed cells drive neutrophil recruitment, and that neutrophils “educated” in the tumor microenvironment alter tumor progression. To address these hypotheses, we have developed a robust toolbox using zebrafish to enable in situ imaging of the dynamic behavior of neutrophils, macrophages and cancer cells, in real time, in melanoma and liver cancer models. We take advantage of a new zebrafish model of fibrolamellar carcinoma (FLC), an aggressive early onset cancer that exhibits increased inflammation and early progression, similar to human disease. Here, we propose to examine the role of neutrophils in liver cancer and melanoma inflammation and progression (Aim 1). We will harness TRAPseq findings from neutrophils, macrophages and epithelial cells to probe the role of oncogene-induced genes on neutrophils in the tumor microenvironment and tumorigenesis, including the role of neutrophil intrinsic genes p47phox and the phosphatase ptprja on neutrophil polarization and tumor progression (Aim 2). Finally, we will examine neutrophil-macrophage cross talk in the tumor microenvironment and the role of macrophage polarization on neutrophil inflammation and tumor progression (Aim 3). While there has been substantial interest in manipulating the adaptive immune system to treat cancer, the therapeutic possibilities of the innate immune system remain under-studied. Understanding mechanisms that regulate neutrophils in the tumor microenvironment will enhance basic mechanistic knowledge regarding intercellular interactions, facilitate the design of new strategies to treat cancer and potentially improve the efficacy of cancer immunotherapy.

NIH Research Projects · FY 2026 · 2000-05

Project Summary/Abstract Vocal fold (VF) mucosal injury resulting in scar formation is a debilitating and challenging clinical problem for which there is no uniformly effective treatment. Emerging research, including work completed during our most recent funding cycle, suggests that non-resident, migratory cells may play an important and previously underappreciated role in VF wound healing and tissue remodeling. The migratory cells of particular importance to VF mucosal maintenance and repair are those within the monocyte lineage, a diverse population that arises from myeloid progenitor cells within bone marrow. Based on the scientific premise that bone marrow-derived, monocyte-lineage cells are key effectors of wound healing outcome, we propose a definitive set of experiments that will quantify bone marrow-derived cell migration to normal and injured VF mucosa (Aim 1), identify the functional contribution of monocyte-lineage cells to inflammatory signaling and fibrosis outcome following VF mucosal injury (Aim 2), and determine phonatory outcomes following monocyte-lineage cell neutralization in a humanized rat model of VF mucosal injury (Aim 3). The proposed research will define the relationship between monocyte-lineage cell availability and VF wound healing outcome and, further, provide a foundation for future work in the area of VF scar prophylaxis.

NIH Research Projects · FY 2025 · 2000-02

Project Summary/Abstract Vocal fold (VF) mucosa is critical to vocal quality; poor healing ability and limitations of surgical repair have motivated strategies to engineer living tissue replacements. A lack of fundamental understanding of the complexity of VF mucosa's cellular and spatial heterogeneity is largely responsible for incremental progress being made in VF tissue engineering. The overall objective of this proposal, which is a necessary step towards achieving our long term goal of engineering replacements for VF mucosa, is to link single-cell RNA sequencing and spatial transcriptomics, at exceptional resolution, to characterize VF morphogenesis across time, location and cellular compartments and in response to injury. We will create large-scale single cell spatiotemporal atlases of VF mucosa. In specific aim 1 we will identify and characterize murine VF cell populations and their spatial distribution through embryonic and postnatal development. In specific aim 2 we will identify and characterize human VF cell populations and spatial distribution across the lifespan. Results will provide markers for characterization of proper tissue assembly and maintenance, which can then be applied as design parameters for tissue engineering approaches. Cross-species validation will be a powerful strategy for optimization, to prioritize genes and pathways for further investigation. Work in specific aim 3 will molecularly profile cell subsets involved in VF injury and repair in a murine mucosa injury model. We will identify subpopulations of fibroblasts and epithelial cells that respond to injury. Characterizing the relationship between specific cell subpopulations, their interactions, spatial location and pathways involved in VF injury and repair, will identify therapeutic avenues to mitigate VF scarring. The innovative use of transcriptional profiling as an anchor of our research strategy, will provide differentiation criteria and vital tissue engineering design parameters that can be used for the regeneration of new, normal VF mucosa.

NIH Research Projects · FY 2025 · 1999-08

Project Summary This is a proposal for renewal of the Center for Demography of Health and Aging (CDHA) at the University of Wisconsin-Madison. CDHA supports high-impact, innovative research and the production of multiple shared data resources that benefit the broader scientific community. It also facilitates career development for emerging scholars and enables investigators to pursue new scientific opportunities and collaborations. CDHA’s intellectual community brings together 121 affiliates from 30 departments across the social and health sciences who pursue research in five signature themes: (1) Aging trajectories and health disparities across the life course; (2) Biodemography; (3) Place, health, and aging; (4) Health policy and health services; and (5) Demography of dementia and cognition, a new theme and emerging area of research excellence for CDHA. These themes are a product of our traditional strengths, a growing number of affiliates who bring both breadth and depth of expertise to the study of aging and health, and a vision for impactful future research contributions. CDHA’s research has evolved jointly with the growth of the Wisconsin Longitudinal Study and multiple other locally-led major population-based surveys as well as new studies centering NIH’s Health Disparity Priority Populations. CDHA is an autonomous research unit within the College of Letters & Science. It is supported by a well-developed research infrastructure in administration, computing facilities and data library, and dissemination capacity. CDHA’s Administrative Core (A) provides governance and administrative support and coordination for the Center as a whole. The Program Development Core (B) supports faculty, staff, and research assistants engaged in pilot research projects with a track record of generating substantial subsequent NIA support. It puts a particular emphasis on career development and mentorship for emerging scholars, as well as on supporting innovation in population-based aging research. The Communication and Dissemination Core (C) manages CDHA’s website and multiple digital, print, email and social media platforms to communicate CDHA activities and disseminate research findings and opportunities to internal and external affiliates and diverse audiences in academia, policy, and the public sphere. The External Network Core (D) develops innovative research networks within and beyond CDHA by organizing conferences, workshops, and seminars on critical themes; sponsoring novel modes of local data dissemination and new data user training; and pursuing focused outreach and professional development activities. Finally, the Remote Data Enclave Core (F) supports the analysis of restricted-use data resources under secure conditions and integrates with a state-of-the art Federal Statistical Research Data Center facility on the UW-Madison campus.

NIH Research Projects · FY 2025 · 1998-07

Our training program brings together twenty-three faculty members from ten departments to focus on two areas of broad importance for hematology and human disease: vascular biology/inflammation and hematopoietic stem cell (HSC) biology/bone marrow transplantation (BMT). The primary goal is to train M.D. and Ph.D. scientists in a multi-disciplinary environment to do sustained, independent research in hematology. Two predoctoral positions are requested that will be filled from an outstanding pool of Ph.D. and M.D.-Ph.D. students in the highly competitive graduate programs at the University of Wisconsin (UW). Four postdoctoral positions are requested to train research track candidates from participating clinical (Medicine, Pediatrics, Surgery) and basic science Departments of Biochemistry, Biomolecular Chemistry, Cell & Regenerative Biology, Medical Microbiology & Immunology, Nutritional Sciences, Oncology, and Pathology & Laboratory Medicine. The highly interactive training faculty cluster into two interest groups: vascular biology/inflammation and HSC biology/BMT. Vascular biology expertise includes microfluidics, proteomics, lipidomics and metabolomics; cryo-electron microscopy and structure; neutrophil and innate immune cell biology; zebrafish models of injury/inflammation; in vitro modeling of blood vessels and cell migration; and murine models of aneurysm, hemostasis and thrombosis. HSC biology/BMT expertise includes embryonic, induced pluripotent and mesenchymal stem cell biology; epigenetic regulation of hematopoiesis; genetics of bone marrow failure and cancer predisposition syndromes; metabolomics of normal immune and blood cancer cells, murine and zebrafish models of hematopoiesis and the HSC niche; the innate immune response vs. tumors; human immune xenotransplant models in mice; preclinical models of allogeneic BMT and adoptive cellular therapies; clinical trials and bone marrow imaging. Training opportunities span basic and clinical investigation; including cutting-edge technologies in genomics, proteomics, metabolomics, microfluidics, zebrafish and murine disease models, and stem cell transplantation. A strong emphasis is placed on translational research and multidisciplinary training of clinical investigators. The UW Institute for Clinical and Translational Research offers didactic and degree programs in clinical investigation, career development, and mentoring expertise. Our trainees have an excellent record of establishing research careers. Over the lifespan of the predoctoral program, 19 appointees have completed their Ph.D. degrees. Eight are in academic faculty or scientist positions, eight are industry scientists, one is a chemistry professor at a teaching college, and two are in academic post-doctoral positions. Over the past 15 years, 26 post-doctoral trainees have completed their appointments. These trainees include 14 assistant professors, 4 associate professors, one full professor, 3 academic scientists, 2 industry scientists, and a veterinary pathologist. The large pool of qualified candidates, outstanding mentorship record of our trainers, substantial institutional commitment, and broad range of scientific expertise all contribute to successful careers in science for our trainees.

NIH Research Projects · FY 2025 · 1997-06

Summary/Abstract: The Wisconsin National Primate Research Center (WNPRC) is one of seven federally supported National Primate Research Centers and the only one in the Midwest. WNPRC's mission is to increase the understanding of basic primate biology and to improve human health and quality of life through research. To accomplish this, the WNPRC helps discover treatments, preventions and cures for human disease; generates new knowledge of primate biology, from the molecular and whole animal levels to the understanding of primate ecosystems; facilitates research progress by providing expertise, resources and training to scientists worldwide; and collects primate information and disseminates to the research community and to the public.

NIH Research Projects · FY 2025 · 1997-04

PROJECT SUMMARY/ABSTRACT The University of Wisconsin Carbone Cancer Center (UWCCC) seeks continued funding for years 49-53 to further accelerate its mission to dramatically reduce the burden of cancer within and beyond its catchment – the State of Wisconsin. The UWCCC, which is a matrix center within the University of Wisconsin School of Medicine and Public Health (SMPH), is composed of 218 faculty members from 38 departments and 9 schools of the University of Wisconsin-Madison (UW). Our members pursue cancer care, research, and education through 6 scientific programs (Human Cancer Virology, Cancer Genetic and Epigenetic Mechanisms, Tumor Microenvironment, Imaging and Radiation Sciences, Developmental Therapeutics, and Cancer Prevention and Control) supported by 12 Shared Resources. During the current grant period (2017-2021), leadership has successfully recruited >40 new and more diverse members and strengthened existing or new infrastructure facilitating our membership publishing 3,351 cancer-relevant manuscripts (31% inter- or intra-programmatic, 53% inter-institutional) with a significant increased proportion in high (≥10) impact factor journals (prior grant, 11% compared to current 23%), increasing our NCI research (Direct 2017 $18.6M, 2021 $24.9M) and total research funding (Direct 2017 $70.4M, 2021 $76.3M), obtaining more multi-project awards (P, U), supporting more trainees and supporting communities throughout our expanded catchment. The UWCCC will accomplish this mission through nurturing a diverse and supportive cancer community, reliable infrastructure, and efficient resources. The UWCCC worked to decrease the burden of cancer in our catchment and beyond through prioritized research areas (e.g., innovative therapies and biomarkers, cancer imaging, and expanded population-based cancer research), enhanced research platforms (e.g., improved clinical research infrastructure and shared resources), increased efforts to build mission-related philanthropy, and expanded local- to-global partnerships.

NIH Research Projects · FY 2026 · 1997-02

OVERALL – PROJECT SUMMARY/ABSTRACT Molecular Biology and Genetics of Human Tumor Viruses Paul F. Lambert, PI Viruses cause approximately 15% of human cancers. A viral etiology to a human cancer can have substantive consequences on its treatment and prevention. For example, many virally-caused human cancers express virally encoded products, which are potential targets for anti-viral, tumor-specific therapies. In addition, unique sets of cellular genes and pathways contribute to virally-associated cancers, many of which are currently being pursued as targets for anti-cancer therapies. This program project grant (PPG), now in its 45th year of continual funding, has two major objectives: to use molecular biology and genetics to elucidate the life cycles of and transformation by human tumor viruses and to translate this understanding into the identification of targets for specific anti-viral, anti-tumor therapies. The PPG has seven lead investigators who share these research goals in studying multiple human tumor viruses in two different virus families: papillomaviruses, and herpesviruses. Together, these viruses cause the vast majority of virally-associated human cancers. The PPG has been highly productive over the current funding period with 88 studies published of which 33% involve two or more labs, reflecting on the strong synergies arising from the PPG. Our PPG has a unique organization in which each of four projects have two or more labs working together on a common theme in human tumor virology. Cross-fertilization of ideas and expertise between projects is fostered by having many of the seven investigators participating in multiple projects. This interactive and collaborative organization has been highly fruitful over the current funding period in several regards. Firstly, each project has been productive and has collaborated with other projects. Secondly, innovative new ideas and approaches have arisen, many of which are now being used across multiple projects. Thirdly, the collaborative environment created by this PPG has spawned new interactions that have brought additional expertise to the PPG. The specific themes of this PPG are: 1) Characterize the Mechanism by Which Papillomaviruses Evade Host Immunity; 2) Uncovering Mechanisms of the Lymphoid Oncogenesis of Epstein-Barr Virus and Kaposi’s Sarcoma Herpesvirus; 3) Latent and Lytic EBV Infection in Epithelial Cells; and 4) Defining the Role of EBV in DLBCL Pathogenesis and Identification of Therapeutic Targets. Three cores provide expertise in A) administration, statistics and bioinformatics, B) instrumentation, microscopy and histology, and C) virus engineering and production.

NIH Research Projects · FY 2026 · 1996-07

Cell type-specific mechanisms establish and maintain networks endowing erythroid progenitors with activity to generate billions of erythrocytes physiologically and when conditions demand accelerated output to ensure organ oxygenation and life. Many questions exist regarding essential components and networks, and how inflammation controls small molecules impacting networks governing differentiation and function. Through disruptive actions on erythroid progenitors and non-hematopoietic cells, inflammation instigates anemia of inflammation (AI), which afflicts hundreds of thousands in the USA. Contributions of erythroid-intrinsic versus systemic defects are unresolved. In the prior period, we developed paradigms: 1) mechanisms governing small molecule homeostasis in erythroid cells; 2) ceramide control of human erythroid signaling; 3) inflammation disrupts ceramide homeostasis in erythroid cells; 4) discovered all erythroid progenitor-expressed cytokine/chemokine receptors. AI-linked inflammatory mediators activate progenitor receptors to synergistically impair differentiation; 5) select GATA factor and erythropoietin (Epo) actions are inflammation-sensitive; 6) inflammation disrupts erythroid chromatin and transcriptomes, perturbing small molecule homeostasis. Aim 1: Establish mechanistic intersections between GATA factor and inflammatory mechanisms that control erythropoiesis. Erythroid progenitors express cytokine/chemokine receptors, yet erythroid-autonomous actions of many agonists are unstudied. Inflammatory mediators implicated in AI that activate these receptors synergistically abrogated primary human erythroid progenitor differentiation. We will test the hypothesis that a key sector of GATA-regulated genome is sensitive to inflammation. GATA2 pathogenic germline variant T354M exhibits impaired occupancy and function. We will test if inflammation exacerbates T354M defects. Inflammation erases open chromatin at GATA factor-regulated genes. We will discover inflammation-sensitive, GATA factor- regulated enhancers and mechanisms. Aim 2: Test models for how qualitative, quantitative and temporal changes in inflammatory signaling disrupt human erythroid progenitor genome and differentiation. As certain epigenome attributes are stable, we will test the hypothesis that qualitative, quantitative and temporal parameters of inflammation dictate reversibility vs. irreversibility. Epo induces erythropoiesis, inflammation- induced ceramides suppress Epo signaling, and inflammation represses Epo-induced expression of vital erythroid genes and genes not implicated in erythroid biology. We will establish inflammation-sensitive or - insensitive Epo target genes and dissect mechanisms. Aim 3: Elucidate GATA factor-inflammation mechanism governing BCL11A levels. BCL11A expression is activated by enhancers that are gene-editing targets for human sickle cell disease therapy. Mechanisms governing BCL11A levels/activities are unresolved. We discovered inflammation disrupts BCL11A enhancer chromatin, decreasing expression, and elevating fetal globin. We will dissect mechanisms and devise genomic, epigenomic, and inflammatory principles.

NIH Research Projects · FY 2026 · 1995-09

PROJECT SUMMARY/ABSTRACT Since 1995, the University of Wisconsin-Madison's Waisman Center Postdoctoral Training Program in intellectual and developmental disabilities (IDD) Research has provided inclusive and high-quality training to foster the next generation of leaders in IDD research. The program emphasizes interdisciplinary and translational research on IDD, with a focus on socioemotional, cognitive, motor and communication domains. To date, 57 postdoctoral scholars have completed the program, of whom 40 obtained tenure-track faculty positions, and virtually all others are in research-intensive leadership roles with relevance to advancing IDD science. Our trainees have had tremendous success in authoring high-impact publications and securing NIH and other federally-funded grants in addition to foundations grants. The training program is integrated into the Waisman Center's broader array of interdisciplinary and translational training activities, including those offered through their NICHD-funded Intellectual and Developmental Disabilities Research Center (IDDRC). The 18 program faculty trainers represent eight different departments or schools on UW-Madison's campus. These faculty trainers are committed to promoting a diverse and high-quality training program and serve as the PI or Co-I on 42 active research grants from NIH and other federal agencies. The overarching goal of the program is to provide interdisciplinary biobehavioral and translational research training to foster future IDD research leaders. The program includes a core curriculum and individualized career development activities that provide trainees with a broad foundation of IDD knowledge (e.g., prevalence, etiology, presentation, and social determinants of health) and the skills for engaging in ethical science that is rigorous and replicable. The trainees are also equipped with professional development for publishing, obtaining research funding, managing research projects, and being in leadership positions. By working closely with program faculty trainers, the trainees learn research methods and analytic skills to launch their own independent lines of research. Trainees develop individual development plans and establish specific, measurable, achievable, and time-bound research and professional goals to focus their two years. The program has four learning objectives: 1) Develop a broad interdisciplinary foundation of knowledge on IDD (e.g., prevalence, etiology, presentation and social determinants of health); 2) Gain the needed expertise in an area of IDD research to advance science; 3) Understand key issues of research ethics and the policies and procedures that govern research practices; 4) Obtain the research and professional development skills needed for a research career in IDD including grant writing, manuscript writing, and research management. The program has been successful in creating a diverse training environment and is well-positioned to prepare the next generation of researchers with the skills for addressing the problems of critical importance to the IDD community.

NIH Research Projects · FY 2026 · 1995-01

ABSTRACT This longstanding R01, reviewed for the past 25 years in study section PTHE, has investigated the pathogenesis of blastomycosis with an emphasis on the causative fungus Blastomcyes dermatitidis. While pathogenesis of B. dermatitidis infection is still our focus, we now investigate the immunopathogenesis of B. dermatitidis infection. In the last funding cycle, we uncovered a unique susceptibility to B. dermatitidis infection in the Hmong population of Wisconsin. We discovered that an Interleukin 6 (IL-6) defect in patients underpins their impaired immunity and susceptibility to B. dermatitidis, and we modeled the scenario during murine infection. In patients, we traced the underlying molecular mechanism of this IL-6 defect to polymorphisms in the gene that affect the long non-coding RNA (lncRNA), IL6-AS1. We have now generated compelling preliminary data with induced pluripotent stem cells (iPSC) from patients and healthy control subjects that have been gene-edited. The data support our model that impaired resistance to B. dermatitidis in susceptible hosts like the Hmong population results from altered/im- paired IL6-AS1 lncRNA regulation of IL-6 expression. This defect in turn impairs development of acquired re- sistance to B. dermatitidis mediated by Th17 cells. Here, we propose three aims that will uncover the poorly understood mechanism of action of IL6-AS1 in regulating IL-6 gene expression, decipher how IL6-AS1 polymor- phisms in the Hmong alter the function of IL6-AS1 and expression of IL-6, and analyze the downstream conse- quence on the function, phenotype and gene expression of T cells that help resist B. dermatitidis infection. Our work has implicaitons for understanding the basis of susceptibility to B. dermatifidis and other infectious diseases, including COVID, that hinge on proper regulation and tuning of IL-6 production.

NIH Research Projects · FY 2025 · 1993-04

PROJECT SUMMARY This renewal application seeks continued support for the successful Metabolism and Nutrition Training Program (MANTP). The fundamental rationale is to leverage the unique research and educational resources at the University of Wisconsin-Madison (UW-Madison) to meet the need for the next generation of nutrition scientists and realize the promise of personalized nutrition by recruiting and preparing qualified predoctoral and postdoctoral trainees for biomedical science-related careers that impact the health of the Nation. The specific objectives of the MANTP are to: 1) Create an exceptional training environment that engages and educates predoctoral and postdoctoral trainees (MD and/or PhD) for 2- or 3-year appointments in collaborative, cross- disciplinary research, centering on themes of Digestive Biology, Macro- and micro-nutrient Metabolism, Gut Microbiome, Obesity and Disease, and Systems Biology. Our team of thirty-three well-funded trainers, from various basic, applied, or clinical departments, will provide customized training emphasizing state-of-the-art, integrative approaches to nutrition research. 2) Expand the trainees' knowledge base in multiple disciplines through instruction and discourse between trainees and trainers from diverse backgrounds to bring a broad array of perspectives and expertise to addressing nutrition-related human diseases. We propose a flexible didactic plan that encompasses interdisciplinary breadth and integrative research methods. Trainees will also receive comprehensive training on the rigor and reproducibility in all aspects of research, as well as in the responsible conduct of research. 3) Cultivate physician- and dietitian-scientists for careers in nutrition- related research. Our program will equip them with the skills necessary to conduct basic, applied, or translational hypothesis-based nutrition research through individually designed didactic and mentoring programs. 4) Enhance career competitiveness by providing a range of innovative professional development opportunities, including grant writing, mock study section reviewing proposals, trainee-specific interactions with visiting scientists from across the nation, collaborative retreats with the "Digestive Health Disease and Nutrition" T32 at the University of Chicago, and a “mock interview” program for senior postdocs as they transition to independent careers. These initiatives will increase trainees' exposure to translational research and provide networking opportunities that benefit their research and career advancement. 5) Recruit and retain underrepresented minority (URM) trainees for successful careers in nutrition-research. MANTP is committed to institutional, departmental, and programmatic efforts to recruit URM trainees and create inclusive climate that allow trainees of diverse backgrounds to thrive. With renewed support from the NIH, the MANTP will continue to expand and refine its mission in producing expertly trained scientists with PhD, MD, RDN/PhD and MD/PhD degrees who will make significant contributions as leaders in reducing the incidence of diet- related diseases.

NIH Research Projects · FY 2025 · 1992-07

7. Project Summary/Abstract Parasitic diseases caused by protozoans, helminths, and arthropod-vectored infectious diseases continue to plague much of the developing world. Even in industrialized nations, poorer communities are deeply affected by parasitology and arthropod-vectored infectious diseases, especially in the southern Gulf Coast region of the United States. What is needed to combat these devastating infections is a new generation of researchers focused on parasitology and arthropod-vectored infectious diseases; however, there are only a few NIH T32s focused on parasitology and vector-borne infectious diseases. One of these T32s is the Parasitology and Vector Biology (PVB) Training Program at the University of Wisconsin-Madison. The PVB training program aims to attract and train the next generation of parasitology/vector biology investigators by providing opportunities to study significant, cutting-edge research problems associated with these important neglected tropical diseases. This goal will be accomplished by trainees acquiring a solid foundation of advanced knowledge through coursework and seminars, and then combining this knowledge with the latest technologies available in the laboratories of our 16 faculty trainers. Funding for this renewal is requested for 5 years to support 4 predoctoral trainees per year. After matriculating into one of three main graduate degree programs and successfully completing the first year of graduate school, PVB trainees will be appointed for 2 years. In addition to meeting their degree program requirements, trainees are required to complete courses in research ethics, rigor and reproducibility, and general parasitology, as well as complete an individual development plan, update it yearly, and present their research annually in the PVB seminar series. In an effort to increase the diversity of graduate students seeking advanced degrees in parasitology and vector biology, plans are described to identify and recruit under-represented minority (URM) students. This plan has been successfully active during the last two cycles of the PVB and has increased our number of URMs trainees in the program. Providing cutting-edge and well-rounded training in molecular parasitology and arthropod-vectored infectious diseases for predoctoral trainees has been and will continue to be our mission. Given the worldwide need to combat these infections, we must train the next generation to think broadly about parasite and arthropod-vectored diseases so that novel solutions to these devastating problems they cause can be found.

NIH Research Projects · FY 2025 · 1992-07

ABSTRACT This request is for five years of continuing support for the Symposium on Research in Child Language Disorders (SRCLD) held annually at the Monona Terrace Convention Center in Madison, Wisconsin. This symposium is sponsored by the Department of Communication Sciences and Disorders, University of Wisconsin-Madison and by NIDCD/NICHD, as well as funds obtained through registration fees. SRCLD is the only national conference devoted solely to research on child language disorders. Over the past 45 years this meeting has achieved the distinction among child language researchers as a high-quality scientific meeting which fosters the exchange of theoretical, experimental, and methodological advances among professional researchers and doctoral students in training. Past programs have been uniformly of high quality, featuring multiple invited plenary presentations by prominent researchers from the field of communication sciences and disorders and related fields and a steady number of research papers submitted for poster presentations or short oral presentations. The impact of the SRCLD conference has been documented in several areas including its unique focus, program growth and quality, and the extent of student participation in all aspects of the conference. NIH funds are requested to provide travel and per diem for invited speakers, travel support for students, partial support for an administrative coordinator, and website improvements and management. Progress since the last grant began in 2020 includes: 1) a vibrant and diverse annual program comprised of 4 invited plenary talks, nine submitted short oral presentations, and an average of 110 poster presentations; 2) support of a minimum of 20 students through NIH student travel funds and private donations, with student travel award recipients consisting of 59% under-represented minorities; 3) expansion of mentoring activities to include a formal round-table mentoring session; 4) continued advances in the website which features an online poster attendance planner, expanded abstract archives, and online evaluations; and 5) sustained international participation. Over the next five years we intend to: 1) Highlight cutting edge and emerging topics in child language disorders through invited talks, tutorials, submitted oral presentations, and posters; 2) Engage predoctoral and postdoctoral students in all aspects of the conference, with an emphasis on inclusion of under-represented minority students; 3) Expand mentoring and networking opportunities for early-career scholars, with a concerted effort to support scholars from under-represented groups; and 4) Expand dissemination of the results of the conference through social media.

NIH Research Projects · FY 2026 · 1992-01

PROJECT SUMMARY/ABSTRACT The main objective of the proposed experimental program is to address questions of mechanotransducer (MET) channel structure and function employing a combination of electrophysiological and genetic techniques. Experiments will focus on the attributes and molecular composition of the hair cell MET channel complex, gathering more evidence that transmembrane channel-like protein isoform TMC1 forms a central component of the channel and dictates its biophysical properties. Hair cell responses will be measured in acutely isolated cochleae of wild-type and mutant mice. Specific aims are: (1) to record and characterize the conductance and ionic properties of MET channels in cochlear hair cells of different mice, each with a distinct Tmc1 missense mutation. The site of the mutations will be selected to define the location of the channel pore, the residues differing between TMC1 and TMC2, and those determining channel block by Ca2+. (2) Using mutations of the accessory protein LHFPL5 to define its contribution to channel conductance, gating and adaptation. One hypothesis is that LHFPL5 provides force transmission between the tip link and the MET channel. (3) To investigate the time course of loss of MET currents and transduction in Tmc1 mutants during the third postnatal week and explore underlying mechanisms. All mutants display MET currents up to postnatal day 12 but lose them over the subsequent five to ten days depending on the mutant. One hypothesis to be tested is that decreased Ca2+ entry into the hair bundle is a major determinant of loss of transduction and that differences between mutants reflect differences in steady Ca2+ influx. The connection between reduced hair bundle Ca2+, lipid scrambling, and hair cell death will also be explored. (4) Determine the origin of a new type of Ca2+ dependent force generation that we previously observed in gecko hair cells. It is hypothesized that this same process exists in mammalian vestibular hair cells. The roles in the process of the kinocilium and non-muscle myosins NMIIB and NMIIC at the endolymphatic surface of the hair cell around the cuticular plate will be studied. It is hoped that the results will supply evidence on the molecular makeup of the hair cell transduction apparatus and yield information about proteins that are mutated in certain forms of human genetic deafness.

NIH Research Projects · FY 2025 · 1991-07

Project Summary Funded by NIA since 1991, this application seeks the 7th competitive renewal for a highly successful T32 program at the University of Wisconsin-Madison (UW). It requests support for 4 predoctoral and 4 postdoctoral trainees in aging biology and translational gerontology research. The major mission of this T32 is to provide interdisciplinary, state-of-the-art training to talented pre- and post-doctoral fellows in basic biological and translational/clinical research in aging and related diseases. In keeping with our track record, it is projected that the majority of trainees in the next funding cycle will pursue successful academic careers, and lead prominent programs in aging research across the country. This application builds upon the remarkable resources of UW in gerontology research and includes 39 (20 women and 19 men) faculty mentors with acknowledged expertise in aging research. Notably, the mentors are balanced across the three faculty ranks of Professor (20), Associate Professor (12) and Assistant Professor (7), and each mentor has a celebrated history of conducting NIH- or other peer-reviewed source-funded cutting-edge research in aging and training successful scientists in gerontology. For over 32 years, this T32 has received substantial institutional commitment. The present application includes significant financial commitments, including support for a (i.e., 5th position) predoctoral position each year, funds to cover 10% effort for both the Program Director and Co-Director annually, and salary support to cover 25% effort for a T32 Administrator. Additional strengths of this application include: 1) inclusion of 14 (36%) new faculty mentors representing emerging areas in aging and translational research; 2) balanced distribution of mentors between early-stage, mid-career, and established faculty ranks; 3) history of over 87% of T32 trainees supported over the past 15 years pursuing successful research-related careers; 4) notable accomplishments by trainees with each publishing peer-reviewed papers, presenting preliminary findings at local or national meetings, and attending courses as necessary; 5) enhanced efforts to increase recruitment and retention of trainees from underrepresented groups; and 6) inclusion of an outstanding training curriculum in both basic biological and clinical research with the addition of new teaching programs. Overall, the present T32 will continue to provide outstanding training to talented young scientists in both laboratory-based and clinical/translational research in aging and related diseases, and help them launch successful, independently funded academic careers in gerontology.

NIH Research Projects · FY 2025 · 1990-07

PROJECT SUMMARY – New treatments for anxiety disorders are critically needed as numerous individuals fail to respond to current treatments. A more complete understanding of pathological anxiety at the molecular, cellular and circuit levels will provide a foundation for new treatment development. In this regard, nonhuman primate (NHP) models are invaluable for understanding mechanisms underlying maladaptive anxiety relevant to stress-related psychopathology. An important recent advance is the use of chemogenetic methods to modulate the primate amygdala. This work serves as an initial foundation for treatment development directed at the regulation of subcortical regions relevant to the pathophysiology of psychiatric disorders. As a translational bridge, our laboratory employs methods that provide an in-depth mechanistic understanding of brain alterations associated with extreme anxiety, including behavioral phenotyping, functional and structural neuroimaging, RNA sequencing and viral vector-mediated gene delivery. Findings from our chemogenetic studies using Designer Receptors Exclusively Activation by Designer Drugs (DREADDs) point to basolateral amygdala (BLA) neurons as potential treatment targets. The BLA processes threat-related information received from cortical and subcortical sources and transmits this information to the extended amygdala (central nucleus of the amygdala (Ce) and bed nucleus of the stria terminalis), which activates threat- related responses via its downstream targets. Within the BLA, inhibitory interneurons modulate the function and output of longer-range projecting excitatory neurons, which project to the Ce, other subcortical structures, and posterior orbitofrontal cortex (pOFC). The overall aims of this proposal are to further understand the implications of amygdala modulation in relation to treatment development focusing on BLA neurons. Neuroimaging and RNA sequencing (RNA-Seq) will provide insights into mechanisms related to therapeutic efficacy. Additionally, these studies will serve as a proof-of-concept to understand the feasibility of developing chemogenetic approaches for the future treatment of severe and refractory psychiatric disorders.

NIH Research Projects · FY 2025 · 1989-07

This application seeks five additional years of support for the training grant on emotion research at the University of Wisconsin-Madison. This training program continues to focus on four specific themes: 1. Personality, temperament, and individual and cultural differences: Lifespan developmental, genetic, cognitive and biological approaches, and human-computer interaction; 2. Affective neuroscience; 3. Emotion, health, and wellbeing; and 4. Emotion and psychopathology. In this renewal, funds are requested for 4 pre-doctoral and 3 post-doctoral stipends/year, the same as our current funding. At the time of the last competing continuation, this training grant provided support for 5 pre-doctoral and 3 post-doctoral stipends/year. Since the time of the last competitive renewal, several additional faculty with research interests centrally in emotion have been added; the brain imaging facility has been strengthened—the Waisman Center Laboratory for Brain Imaging and Behavior—that is focused principally on affective neuroscience; the innovative Center for Healthy Minds, which focuses on contemplative neuroscience and its impact on positive affect, has continued to expand; and several major collaborative projects focused on emotion in aging, various areas of affective neuroscience, and affective development have begun. There are now 19 program faculty, drawn from nine academic units, with Psychology as the lead department. Pre-doctoral trainees will be supported for two years and post-doctoral trainees will be offered up to three years of support but will be encouraged to write their own post-doctoral training proposals during their initial year in the program to help leverage the funds we request from this T32. Major elements of the training program include: a new 15-week Seminar in Emotion course coordinated by Pollak and held in Fall of odd-number years, providing an overview of the range of thinking, methods, and approaches to the study of emotion reflected among the T32 Emotion Research Training Grant faculty, focusing primarily on the four themes upon which the program is based; a Spring seminar each year associated with the Wisconsin Symposium on Emotion, an annual event at the University of Wisconsin- Madison that brings 5-6 outside speakers to campus for a meeting on a specific topic in emotion research; participation in a seminar series devoted to ethical issues in research; and participation in monthly emotion groups held on a video-conferencing platform each month. We believe this program is unique and provides an extraordinary opportunity for interdisciplinary training in emotion research.

NIH Research Projects · FY 2025 · 1987-07

Project Summary/Abstract The long-term goal of this project is to define the interactions within transcription elongation complexes and with regulators that cause and control pausing and termination by RNA polymerase. Pausing and premature termination underlie many aspects of gene regulation in diverse prokaryotes and eukaryotes, including transcription through chromatin and linkages to RNA maturation and translation. Both the basic mechanisms of pausing and termination and the mechanisms by which regulators control pausing and termination depend on poorly understood changes to interactions within the elongation complex. Many of these interactions modulate conformational changes in RNA polymerase involving mobile modules including the clamp, trigger loop, and lineage-specific insertions that must achieve particular conformations for efficient transcription. Understanding how regulators promote or inhibit these different conformations in diverse bacteria will provide key basic knowledge essential to guide the rational manipulation of regulators for antimicrobials or genetic therapies. Knowledge gained about diverse bacterial systems also helps define highly conserved mechanisms of transcription in humans. Additionally, bacterial RNA polymerases are known target of antibiotics, and knowledge about their functional mechanisms will aid in identifying and characterizing new antibiotics. A combination of structural, biochemical, and genetic approaches will be used to characterize the interac- tions in the elongation complex that mediate regulation. New methods for transcription assay by cryo-electron microscopy, for single-molecule assay of RNA polymerase interactions with RNA structures, regulators, and ribosomes, and for genome-scale analysis of chromatin structure and elongation complex regulation will be developed. This combination of approaches will be used to understand connections among progress of the elongation complex during transcription, the structure of bacterial chromatin, RNA folding, and RNA translation. The work builds on recent discoveries of the structural basis by which RNA polymerase pauses, of the role of H-NS family nucleoprotein filaments in stimulating pausing and termination during transcriptional silencing, and of the different actions of the only universal transcription elongation regulator, NusG. The specific aims of the project are to (i) integrate models of pausing and termination mechanisms across diverse bacterial lineages; (ii) elucidate the molecular basis of pro- vs. anti-pausing and recruitment for NusGs and paralogs; and (iii) link genome-scale regulation in vivo to the molecular basis of elongation complex structural changes. This integrated research will help build a new understanding of transcriptional regulation by defining how pause and termination signals change elongation complex structure and activity dynamically across evolutionarily diverse microbes. The impact of these studies will be an improved understanding of elongation complex regulation, with broad applications to biotechnology, human medicine, and both prokaryotic and eukaryotic molecular biology.

NIH Research Projects · FY 2025 · 1986-07

Abstract We propose to continue and improve the NIA training program on “Population, Life Course and Aging” located in the Center for Demography of Health and Aging (CDHA) at the University of Wisconsin-Madison (UW). The training program builds on the resources of CDHA to form a long-standing, highly-visible core of research and training in population aging and health at UW. The program draws from a large pool of talented and highly qualified students in the social sciences and public health, and benefits from the rich interdisciplinary environment that integrates research and teaching across the departments of Sociology, Economics, and Population Health Sciences, as well as the La Follette School of Public Affairs, Alzheimer’s Disease Research Center, the Institute on Aging, the Center for Demography and Ecology, and other centers and programs at UW. The goal of the CDHA training program is to recruit, develop, support and place productive and innovative researchers with expertise in demographic methods and statistical analysis who approach the study of aging from a life course perspective. The current emphases of the program reflect the research strengths of our faculty: biodemography; the lifetime determinants of cognitive health; and the role of social, economic, geographic, environmental, and institutional factors in shaping health and health disparities in later life. The training program also capitalizes on several locally-designed large-scale surveys that combine innovative biological and social measurements and provide opportunities for training at multiple forefronts of research on population, aging, and health across the life course. Our program cultivates trainees’ professional skills, including the conceptualization, execution, presentation, publication, and critique of research via a (1) rigorous methodological and substantive coursework, (2) research apprenticeships that allow trainees to begin collaborative research and publication from the start of the program; (3) specialized interdisciplinary research working groups; (4) professional development seminars ongoing support for developing individual research agendas, presenting at conferences, publishing papers, and developing grant proposals; (5) close mentoring relationships between trainees and preceptors; and (6) access to local and national workshops and professional meetings. We request support for 4 predoctoral trainees (who will generally be supported for 3 years) and 1 postdoctoral trainee (who will generally be supported for 2 years), a level equal to our current number of positions. This support is essential for sustaining a critical mass of trainees and training-related research activity. Our students have an excellent record and graduates embark on careers that contribute substantially to research, education, and public service in the areas of population aging and health.

NIH Research Projects · FY 2025 · 1978-08

ABSTRACT This training program prepares pre-doctoral & post-doctoral trainees for careers where they will invent the physics and engineering of new tools and techniques that will lead to discoveries in cancer research and in the management of cancer patients. The research specializations cover a broad range of technologies in disease diagnosis, personalized treatment and delivery assessment, with the core focus being applied medical physics research in cancer. The 34 faculty mentors with another 22 participating faculty in the core departments include Medical Physics, Radiology, Human Oncology (Radiation Oncology), Physics and Electrical Engineering faculty, who have a broad spectrum of collaborations with other clinical and basic science researchers. Translational, team-driven research includes traditional x-ray, CT, MRI, ultrasound, optical and PET/SPECT imaging with the Department of Radiology, and radiation physics, radiation biology, and radiation therapy with the Department of Human Oncology. Trainees are intimate participants in these research programs as collaborators, publishing joint research articles, and learning the skill to apply for extramurally funded grants and contracts. Extensive faculty contact provides leadership and supervision, including weekly lunch visits with visiting colloquia faculty. Pre-doctoral trainees in Medical Physics take two years of didactic medical physics training progressively oriented towards their research specialization, and are typically voted into this training program after passing their oral qualifier, with a preliminary research plan related to cancer. This design has significantly increased the likelihood of their remaining in cancer-related research and shortens their typical time in the NRSA position to 2 years, funded both before and after by their primary advisor. Post-doctoral trainees are encouraged to broaden and deepen their academic training by auditing appropriate courses, and their appointments are typically 2 years. Both predoctoral and postdoctoral trainees must take or audit additional research ethics courses, take cancer- specific courses, attend relevant cancer grand rounds presentations, and must participate in a newly created course on the PhD Scientist Profession, including instruction on patenting, business startups, grant writing, career guidance and one-on-one mentoring. Trainees give seminars, attend colloquia, present research results at local, national, and international meetings, and co-author articles and reports. An annual Training Grant Symposium provides additional opportunity for trainees to present research results to the Medical Physics and collaborating faculty. Additionally, a newly created biennial Symposium/Workshop on Emerging Leaders of Academic Medical Physics includes their participation with networking, diversity building and ideation of research vision. The program benefits from an external advisory board of T32 directors in medical imaging and cancer, as well as active participation by 16 physician-scientists. Trainees in the program are exceptionally well prepared to assume leadership positions as visionary researchers and academics in the application of physics to cancer prevention, diagnosis, and treatment.

NIH Research Projects · FY 2025 · 1975-07

The Molecular and Environmental Toxicology T32 (MET-T32) involves dozens of mentors, each with outstanding training records and well-funded research programs. These trainers cover a variety of environmental health science research areas and employ tools, such as data sciences, bioinformatics, developmental biology, epidemiology, structural biology, high throughput technology, stem cell biology, mammalian genetics, molecular biology, and biochemistry. Predoctoral trainees are supported for two years, early in their graduate study. After three laboratory rotations funded by the University of Wisconsin, the trainees are selected for the MET-T32 and complete several “challenges” that prime their ability to understand, develop and generate high content and “omic” data. Among these challenges is a Biotechnology Scholar/Intern (BSI) program that integrates each trainee into a state-of-the-art facility applying cutting edge technologies to current biological problems (NexGen sequencing, Mass Spectroscopy, Gene Editing, etc.). This is followed by additional challenges in short workshops in “Data and Software Carpentry, and Genomic Analysis.” Additional challenges provide the underpinnings and formal training to support their success in the environmental health sciences and provide opportunities to present scientific information in a rigorous and clear manner. In parallel, trainees, begin molecular toxicology research in laboratories from investigators from dozens of unique departments housed in multiple colleges on the UW Campus. The selection of trainees and oversight of the grant will be carried out by the Training Grant Leadership (TGL) which consists of the director, the deputy director, and one additional trainer. In addition, a number of subcommittees monitor progress of the trainee. These include, Trainee Tracking and Achievement Committee (TAC), Curriculum Committee (CC), Candidate Review Committee (CRC), Network Committee (NC), Trainee Liaison Committee (TLC), and Thesis Committee. This proposal seeks support for twelve predoctoral trainees. All trainees are also required to attend a weekly environmental health research seminar, a yearly symposia/retreat, and complete any additional courses required by their graduate program. Everyone will be trained as a lifelong learner through their participation in multiple continuing education courses and in scientific symposia related to environmental health. To aid our trainees in important careers choices, a practicum opportunity is offered in teaching, providing independent funding in later years and an opportunity to experience first-hand the roles and responsibilities of a classroom educator. The recruitment of underrepresented populations to this MET-T32 is given high priority and is facilitated by a NIEHS-funded Summer Minority Research Program for undergraduates (SROP). Upon completion of the MET-T32 training program, graduates usually undertake a period of additional postdoctoral training, or assume responsible career positions in toxicology in academic, governmental, or other public or private research institutions, or industrial laboratories.