Alison K. Hall - US grants

9310511 Hall The nervous system is composed of two major cell types, neurons and glia. Glial cells have many important roles that allow the neurons to function. Different types of glial cells have different functions and are needed in different parts of the nervous system. Little is known about how the different glial cell types arise during development of the nervous system. This study will define how neurons alter glial cells during the development, and will establish the similarities and differences between two types of glial cells, those of nerves and those of ganglia. The hypothesis to be tested is that glial cell precursors divide and mature into either of these two types of glia in response to factors from the neurons. A cell culture system has been developed that will allow this hypothesis to be tested. Information from these studies will lead to a greater understanding of how cell-cell interactions influence development in the normal nervous system. *** 9310511 Hall The nervous system is composed of two major cell types, neurons and glia. Glial cells have many important roles T Y ! ! F ( Times New Roman Symbol & Arial " h C ? ? hall William Proctor, IBN William Proctor, IBN

DESCRIPTION(Verbatim from applicant's abstract): Regulated development of the sensory nervous system results in the ability to feel pain and to sense body position. A major challenge has been to understand how neural crest precursor differentiation is controlled during development and how appropriate neurons are matched with target tissues in the periphery. This application focuses on the developmental regulation of the pain-sensing, calcitonin gene related peptide (CGRP)-containing sensory neurons in the dorsal root ganglion (DRG). CGRP-containing sensory neurons contact skin and gut peripheral target tissues and play pivotal roles in mediating pain sensation and local skin inflammation. This project is based on our novel observation that members of the transforming growth factor beta family -- including activins and bone morphogenetic proteins (BMPs) -- induce the pain sensing phenotype that includes CGRP expression in vitro. We hypothesize that specific TGFb family ligands from skin, blood vessel and gut target tissues induce the pain-sensing phenotype in sensory neurons during development. Studies in this application will test this hypothesis using both in vitro and in vivo functional assays. Noggin and follistatin will be used to identify classes of ligands that underlie CGRP induction by skin cell line factors. Native skin and gut will be assayed for biological activity and ligands in vitro, using assays developed with cell lines. The spatial and temporal localization of ligands and inhibitors will be carried out at critical periods of target contact to learn where and when bioactive factors are present. The role of TGFb family ligands in vivo will be tested by viral misexpression of ligand, inhibitor or BMP receptor. The long term objective of these studies is to understand the mechanisms that regulate neuronal differentiation. Even within the DRG, where relatively few neuronal types arise, little is known about what regulates how different types of neurons are generated from neural crest cells. The completion of the proposed studies will advance our understanding of the importance of target derived growth factors, and in particular the TGFb family ligands activin and bone morphogenetic proteins, in specifying sensory neuronal types from embryonic precursors.

DESCRIPTION (provided by applicant): A major challenge for the scientific community is to increase the participation of underrepresented minority students in biomedical research and subsequent leadership in the professoriate. For example, less than 10% of students in Case SOM biomedical PhD programs come from underrepresented minorities (URMs), and 2% of our full time faculty are URM. To address this need, this proposal is designed to prepare underrepresented minority students who hold a recent baccalaureate degree with additional research training, coursework and student development to successfully transition into biomedical doctoral programs. This proposal requests funds to support 12 students per year (six in the first year) to engage in research in biochemistry, genetics, molecular biology and microbiology, neuroscience, nutrition, pathology, pharmacology or physiology and biophysics. The program will coordinate the expertise of the faculty in an integrated postgraduate training program. Participating faculty mentors all have active and well-funded research programs that contribute to a lively and stimulating scientific environment. In addition to one-two years laboratory experience, students will complete academic coursework to augment their quantitative and biomedical foundation and acquire professional presentation skills. Further, students will have direct tutoring in standardized test preparation and assistance in the preparation of graduate school applications. The participating mentors are located at Case School of Medicine and already interact in the training of graduate students throughout our interdisciplinary PhD programs. The Institution has demonstrated continued success in attracting underrepresented minority students into our medical programs, and will focus that experience now in increasing minority matriculation into graduate programs. Students will be recruited from a national pool of applicants using comprehensive recruitment strategies. Each aim is associated with measurable outcomes that assay science interest, matriculation into graduate and other programs, changes in standardized tests as well as information about program efficacy. This combination of interventions is designed to convey the excitement and culture of scientific research along with the academic and programmatic preparation to students and prepare them to transition to graduate school and a biomedical research career.

DESCRIPTION (provided by applicant): This research education program offers short-term support to underrepresented or disadvantaged undergraduate and medical school students to provide them with career opportunities in cardiovascular, pulmonary, hematologic or sleep research. The research activity will expose trainees to the excitement, challenges and rewards of a career in biomedical research that are not otherwise available in their regular course of study. The Case short term HLB program will provide mentored research training with outstanding investigators in these four areas to 12 undergraduates and 8 medical students each year. The overall goal of this training program is to increase diversity among students who pursue academic careers in medicine and science, particularly in cardiovascular, pulmonary, hematologic and sleep research. This goal will be pursued by 1) helping trainees develop research skills, identity with the scientific profession and confidence in a research environment through well structured, mentored short term experiences that lay the foundation for biomedical research in clinical and bench settings, 2) providing exposure to other areas and leaders in research with guest lectures, student presentations and social activities. Undergraduates from around the nation will be selected from more than 100 or more online applications each year after competitive review, and matched in researchers for 2-3 months on a full time basis as summer research trainees. Medical students largely from this institution will be selected on the basis of the quality of the research proposal, the strength of the advisor as a research mentor and role model and the potential for a positive research experience and spend 2-3 consecutive full time months during the summer. Both groups of trainees will attend common weekly sessions and interact to build a community of peers. Our faculty lead outstanding programs that encompass basic, translational, clinical, population-based research programs in cardiovascular, pulmonary, hematologic and sleep research, and each has an outstanding training record and strong interest in working with students. Our evaluation system allows us to continuously improve our training program, and our database and tracking plan highlights the achievements and career outcomes of our trainees. PUBLIC HEALTH RELEVANCE: The CWRU Short-Term Heart Lung and Blood Research Opportunities program will provide key support for underrepresented minority and disadvantaged undergraduate and medical students in research education in order to expose students to biomedical challenges in cardiovascular, pulmonary, hematologic and sleep research. This experience, coupled with additional activities will strengthen their confidence as researchers, bolster their competiveness for subsequent graduate and medical programs, and encourage students to continue academic research. (End of Abstract)

DESCRIPTION (provided by applicant): A major challenge for the scientific community is to increase diversity in the biomedical workforce and subsequent leadership in the professoriate. To address this need, we propose interventions in the Case PREP to prepare recent college graduates in natural sciences to be successful in doctoral study in the biomedical sciences. This proposal requests support for 8 Scholars per year to engage in research in biochemistry, biomedical engineering, genetics, molecular biology and microbiology, neuroscience, nutrition, pathology, pharmacology or physiology and biophysics within in an integrated postgraduate training program. Participating faculty mentors all have active and well-funded research programs and strong training experience. The participating mentors are located at Case Western Reserve University School of Medicine (CWRU SOM) and already interact in the training of graduate students through our interdisciplinary PhD programs. In addition to a full year as a laboratory apprentice, scholars will complete graduate academic coursework to augment their quantitative skills and to explore biomedical research areas. Scholars will have direct tutoring in standardized test content and strategies, and assistance in the preparation of graduate school applications. Scholars will be recruited from a national pool of applicants using existing relationships and comprehensive recruitment strategies. Measurable outcomes that assay student research skill development, matriculation into graduate programs, changes in standardized test performance, and science attitudes will be evaluated. This combination of interventions is designed to convey the excitement and culture of scientific research along with the academic and programmatic skill development to prepare Scholars to transition to doctoral study and a biomedical research career. Public Health Relevance Statement: The biomedical workforce at CWRU SOM and other research-intensive institutions nationally is not as diverse as the public at large or even as diverse as baccalaureate earners in Biology, and reflects academic and social factors that must be overcome. We propose that a postbaccalaureate program with extensive research experience in modern, competitive research laboratories, coupled with individualized coursework and professional development will help recent college graduates in natural sciences become fully qualified for doctoral study.