Andrew Tsin - US grants

The location of retinyl palmitate hydrolase in the eye will be determined by immunohistochemical techniques. The retinyl palmitate hydrolase will first be purified to homogeneity from bovine tissue. Rabbit will be used to produce antibody against this enzyme. Sections of the bovine eye will be incubated with antiserum specific to the retinyl palmitate hydrolase. The location of the antigen-antibody complex will be visualized by specific staining and reveals whether this enzyme is found in the photoreceptors, Muller cells, other cells of the retina and/or in the cells of the retinal pigment epithelium. The results of this project will provide information important to our current understanding on the origin of retinoids to form visual pigments in the eye.

The Minorities in Research and Science Achievement (MIRASA) Program at The University of Texas at San Antonio is intended to (1) enhance the biomedical research capabilities of science faculty at the University, (2) provide research opportunities for students at the undergraduate and graduate levels, and (3) expose minority science students to a variety of scientists and their research. To achieve these ends, 13 principal investigators, 4 co- principal investigators, and 2 associate investigators will provide research opportunities and guidance in specific biomedical research projects. The 15 research projects will include (1) the genetic control of filarial development, (2) trimethytlin-induced alterations of hippocampal physiology, (3) lipid requirements of calcium and magnesium-dependent ATPase in bovine brain, (4) structural changes in adult mammalian neurons, (5) biochemical indicators for aquatic toxicity testing, (6) photoacoustic and fluorescence characterization of melanin in retina pigment epithelium, (7) circular dichroism in the asymmetric synthesis of amino acids, (8) role of cell surface in expression of multicell spheroid phenotype, (9) biochemistry of the purple membrane proton pump, (10) regulation and neuronendocine modulation of anti-red cell autoantibody responses, (11) the biosynthesis of rhodopsin-retinoid utilization and glycosylation, (12) bio-cultural comparisons in Mexican American health beliefs and practices, (13) synthesis and interaction of cholchicine ligands with renal tubulin, (14) the development of video-based optical imaging from salivary glands, and (15) hypothalamic-olfactory interactions in the control of ingestion. The students' research potential will be enhanced by exposing them to sophisticated equipment and modern techniques employed in biochemistry, bioorganic and organic chemistry, bio-physics, genetics, medical anthropology, microbiology, and environmental, neuro- and vision physiology. Likewise, all students will interact with several regional and national scientists actively involved in biomedical research. Institutional seminars will be conducted with outstanding scientists and in cooperation with other institutions. Attendance at regional and national professional meetings will also be strongly encouraged.

minority institution research support; secondary schools;

The focus of our research is to augment current concepts and theories of retinyl ester utilization in mammalian visual systems. In particular, we propose to conduct detailed biochemical analyses of a visual system hydrolase which, despite its potential physiological significance, remains largely uncharacterized. The 11-cis-retinyl ester hydrolase catalyzes the hydrolysis of 11-cis-retinyl esters stored in the retinal pigment epithelium of the eye. Thus, we believe that it must participate in the biosynthesis of 11-cis-retinal, the visual chromophore of rhodopsin. 11-cis-retinoids in-vivo can only be synthesized in the visual system and are, therefore, not normal dietary constituents. Investigation of 11-cis-retinyl ester utilization in the visual cycle may provide information vital to our understanding of various ocular disorders characterized by reduced flow of retinoids through the visual system and hence reducing the production of visual chromophore. Only limited information is available with regard to hydrolysis of 11-cis- retinyl esters in mammalian visual systems. In contrast, a complete representation of vitamin A synthase, isomerase, and dehydrogenase is given in the literature. In fact, purification procedures have been initiated or completed on all of the enzymes which are thought to play a role in the metabolism of vitamin A in the visual cycle, with the exception of the vitamin A ester hydrolases. Ultimately, a comprehensive understanding of the metabolism of vitamin A in the visual system will be contingent upon purification and detailed biochemical characterization of visual system retinyl ester hydrolase(s), specifically, the 11-cis- retinyl ester hydrolase.

Background: Current concept of the visual pathway involves the formation of 11-cis retinol from all-trans retinyl esters by an isomerohydrolase. Both 11-cis retinal and 11-cis retinyl esters are derived from this 11-cis retinol and this branch point of the visual pathway is known. Although the fate of 11-cis retinal to serve as visual chromophore has been well studied, exactly how 11-cis retinyl esters are used to supply retinal chromophores for pigment regeneration is not known. Preliminary Studies: Previous studies conducted in our laboratory established the presence of an 11-cis retinyl ester hydrolase (REH) activity in the bovine retinal pigment epithelium (RPE) microsomes. Subcellular fractionation by sucrose and Percol gradients showed that 11- cis retinyl esters and hydrolase enzyme activity are co-localized at the plasma membrane (PM). Hypothesis: These data support the hypothesis that in the RPE PM, there is an 11-cis REH enzyme. This enzyme may control a novel, unexplored branch of the visual pathway to supply visual chromosomes for visual pigment regeneration. Methods: We propose to extend our current research to include complete purification and biochemical characterization of this 11-cis REH enzyme. When a sufficient amount of this protein is available, polyclonal antibody will be raised and immunofluorescence method will be used to study the localization of this enzyme in the RPE. Biomedical Relevance: This research is important because details of this branch of the visual pathway is completely lacking. Results from studies on the control of 11-cis retinyl ester hydrolysis could provide rationale for understanding those ocular diseases associated with a reduction of visual sensitivity and/or delays in the time course of bleaching recovery.

Current concept of the visual pathway involves the formation of 11-cis retinol from all-trans retinyl esters by an isomerohydrolase. Both 11- cis retinal and 11-cis retinyl esters are derived from this 11-cis retinol and this branch point of the visual pathway is known. Although the fate of 11-cis retinal to serve as visual chromophore has been well studied, exactly how 11-cis retinyl esters are used to supply retinal chromophores for pigment regeneration is not known. Previous studies conducted in our laboratory established the presence of an 11-cis retinyl ester hydrolase activity in the bovine retinal pigment epithelium (RPE) microsomes. Our current research focused on the purification and biochemical characterization of this 11-cis retinyl ester hydrolase enzyme. In this faculty development project, we propose to expand the focus of our current biochemistry research to cover molecular biology. The applicant will work full-time for five consecutive summers in the laboratory of Dr. John Lee at the Department of Biochemistry at the University of Texas Health Science Center in San Antonio to clone and to sequence the gene encoding this protein. Expression of the gene encoding this enzyme will also be studied in bovine retinal pigment epithelial primary cell cultures. This research is important because an understanding of the details of this branch of the visual pathway is lacking. In addition, this faculty development program will also expand the applicant's current teaching and research focus from biochemistry to molecular biology. This is supportive of his department's new focus in the area of cellular and molecular neurobiology. This expansion of the applicant's teaching and research programs will also bring modern biology concepts and techniques to minority and non-minority students at The University of Texas at San Antonio.

The UTSA MBRS SCORE Program is designed to provide support for innovative, cutting-edge biomedical research projects and to enhance the research capabilities of the faculty and institution. The overall goals of the UTSA SCORE Program are to increase the research productivity and competitiveness of the faculty as well as significantly increase the number of minority faculty and students engaged in and pursuing biomedical research careers. The proposed research projects will provide an environment where MBRS faculty and students can actively engage in exciting and challenging biomedical research. UTSA has a proven commitment to the hiring and advancement of minority faculty. Moreover, UTSA enrolls a large, growing number of under-represented minority students (primarily Hispanic 7,797 or 42.4%), and has developed a number of active, federally-supported minority enhancement programs in one of the nation's top five Hispanic education universities. In addition, the UTSA is ranked second in the nation in the number of undergraduate degrees awarded to Hispanics in the Life Sciences. Continued funding of the UTSA MBRS Program will allow UTSA to develop and support 21 basic biomedical research laboratories, providing essential support for research activities, and excellent mentoring and training opportunities for under-represented undergraduate and graduate minority students. This research opportunities will be supported by many existing, shared institutional and divisional resources. MBRS SCORE research will be conducted in state-of-the-art research laboratories in the new Biosciences Building which opened this past Spring (98). This $17.2 million dollar, 3-story, 62,000 square feet research facility has been fully dedicated to research and research training. MBRS SCORE Projects and Principal Investigators include the following: 1) Dr. E. Barea-Rodriguez "Agrin and Integrin Expression in Learning and LTP"; 2) Dr. A. Cassill Derrick "Novelty-Induced Facilitation of Hippocampal LTP; 5) Dr. M. Gdovin "Neurobiology of Respiration in the Developing Amphibian"; 6) Dr. W. Gorski "Enzyme Electrodes Based on Chitosan Scaffolding"; 7) Dr. L. Haro "Biological Significance of 45 kDa Human Growth Hormone Variant"; 8) Dr. H. Heidner "Characterization of the Mosquito Furin Endoprotease"; Dr. R. Lebaron "Functional Properties of Human p68 (BIG-H3) Protein in Cornea"; 1) Dr. A. Martinez "Role of ApoE Isoforms in Development of AD-Like Pathology in Transgenic Mice"; 12) Dr. J. McClusky "Development of Polyurethanes with Enhanced Biostability; 13) Dr. G. Negrete "Conformationally Promoted Degradation of BPDE- DNA Adducts"; 14) Dr. R. Renthal "Membrane Protein Folding"; 15) Dr. A. Tsin "11-cis Retinyl Ester Hydrolase in the Eye"; 16) Dr. J. Walmsley "Metal-Mediated Molecular Aggregates of Guanine and Adenine Nucleotides"; 17) Dr. E. Wheeler "Developing Muscle and Aberrant Trk B Receptor Expression"; Media Exposure and Psychological and Physical Well-being.

minority institution research support;

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. A. SPECIFIC AIMS The Specific Aims have not changed. B. PROGRESS THIS YEAR The RCMI Program has generated a significant and widening impact on the University of Texas at San Antonio's (UTSA) expansion of biomedical research capabilities as it strives to become a premier research institution. During the past year, UTSA's RCMI Program made progress in the areas of PROGRAM LEADERSHIP, RECRUITMENT, submission of the COMPETITIVE RENEWAL APPLICATION, RESEARCH PRODUCTIVITY, GRANT FUNDING, and FACULTY DEVELOPMENT. The CAJAL NEUROSCIENCE RESEARCH CENTER, created through RCMI support during the first funding cycle, developed into the Cajal Neuroscience Institute and in 2008, its name was officially changed to the UTSA NEUROSCIENCES INSTITUTE (NI). The NI has become one of the most dynamic and productive groups of collaborative researchers at UTSA. Dr. Charles Wilson, Director, was an RCMI faculty hire during the first funding cycle and is the Principal Investigator of the RCMI Advanced Imaging Core established during the current funding cycle. Recently, Dr. Wilson submitted and UTSA was awarded the $5.4 million SPECIALIZED NEUROSCIENCES RESEARCH PROGRAM (SNRP) project grant (NIH U54 NS060658-A01) that highly leverages the RCMI core research facilities and established two new research cores (SNRP Image Analysis Core and the SNRP Neurostatistics Core). In 2009, a reciprocity agreement was established that allows RCMI and SNRP investigators to share access to both sets of research core facilities. PROGRAM LEADERSHIP The Administrative Core obtained new organizational leadership that now includes the highest levels of UTSA's administration. President Ricardo Romo became the new Principal Investigator (PI) and as planned, in August 2008, Dr. Matthew Gdovin stepped down as Interim Program Director and he now serves as a member of UTSA's RCMI Internal Advisory Committee. The new Program Director (PD), Dr. Andrew Tsin, is an accomplished biochemist and Associate Dean of Research in the College of Sciences.

UTSA's proposed RCMI Center for Interdisciplinary Health Research (CIHR) will expand research infrastructure and expertise to establish a program of excellence in basic and translational health research that will advance both the strategic goals of UTSA and RCMI/NCRR. The RCMI CIHR is greatly needed for UTSA to develop present areas of scientific strength into competitive health research programs to advance our strategic mission. The proposed program will foster and guide the development of UTSA faculty whose research has great relevance to human health and will support translational research projects. The Administrative Core will provide leadership and support for activities to advance the center's mission, develop research cores, and provide administrative and academic support for investigators. It will coordinate the IAC/EAC, establish intra- and inter-institutional collaborations, and execute a Faculty Development Plan and Evaluation Program. A Biophotonics Core will acquire cutting-edge imaging technologies to study biological processes at the molecular level in live cells with exceptional detail. A Computational Systems Biology Core will build high-performance computing infrastructure for simulation of biological systems, livecell imaging, and protein biomarker research. A Protein Biomarkers Core will build infrastructure for protein biomarkers discovery for disease diagnosis and targeted therapy, including biomarkers that are specific to minority populations. A Nanotechnology and Human Health Core will build infrastructure to synthesize nanomaterials for diagnostics, drug/gene delivery, tissue engineering, and for use with electron microscopy to produce 3-D structural information at the finest level. Five pilot project PIs will also be developed. Dr Lorenzo Brancaleon: Photo-induced unfolding of cancer-specific membrane receptors; Dr Thomas Forsthuber: Biomarker discovery in glucocorticoid resistance in experimental autoimmune encephalomyelitis; Dr Fidel Santamaria:Structural basis of biochemical information processing in neurons; Dr Tao Wei: Molecular mechanisms of A. baumannii biofilm formation; and Dr Jianqiu Michelle Zhang:Advanced Data Processing for Capillary LC/MS data.

Dr. Andrew Tsin is Professor of Biochemistry and Physiology and Associate Vice President for Health Research at the University of Texas at San Antonio (UTSA). Through his innovative, comprehensive mentoring methods tailored specifically for underrepresented groups, 100% of his undergraduate and graduate students completed their degrees. Since 1981, Dr. Tsin has personally mentored 119 students in his research laboratory, of whom 93% are from underrepresented minority groups (i.e., Hispanic, African American, and American Indian) or are female. In addition to his faculty duties, Dr. Tsin serves as associate dean of research in the UTSA College of Sciences, director of UTSA's major National Institutes of Health programs, and as Director of the UTSA Center for Research and Training in the Sciences (CRTS). Dr. Tsin has received numerous awards for excellence in mentoring, research, and teaching and he has published 57 peer-reviewed publications co-authored by students from underrepresented groups.

The University of Texas Rio Grande Valley (UTRGV), the second largest Hispanic-serving institution in the nation, has a special focus on health disparities. The UTRGV founded the School of Medicine (SOM) in 2015 to serve as an educational, clinical, and research facility for the highly underserved populations along the US- Mexico border. As part of its mission, in 2017 the SOM began hosting an annual Research Symposium on health disparities, the first of its kind in the Rio Grande Valley and one in which over half the participants are minorities and women. Considering enthusiastic participation from US and Mexico border institutions, the UTRGV-SOM plans to host the ?International Conference on Cancer Health Disparities? in September 2020. This International Conference will be expanded to take advantage of the opportunity for continued medical education for our diverse populations and to continue emphasis on minority health and cancer health disparities in US-Mexico border areas. This conference complements well the mission of the AACR Annual and AACR cancer health disparity meetings. To date, UTRGV has successfully held three research symposia with 300 attendees each year. Meetings include a nationally known keynote speaker, six plenary sessions, abstracts and posters presented by students, researchers, fellows, faculty and their colleagues from neighboring border institutions. UTRGV-SOM respectfully requests support from the NIH NCI for the 4th Annual Research Symposium entitled ?International Conference on Cancer Health Disparities,? to be held from September 11-12, 2020. NIH funds will be used to invite topnotch cancer health disparity researchers and young scientists (competitive basis) from national and international institutions, including third-world countries. Funds will also be used to successfully implement our scientific agenda over two days, showcasing collaborative community-engaged research where researchers, practitioners, and community partners address global cancer health disparities in underserved populations. This International Conference also closely aligns with the mission of the NCI (NCI Global Health Center) and NIMHD, that is, to support global cancer research and cancer health disparity research to advance scientific knowledge and help all people live longer and maintain a high-quality lifestyle. This International Conference will have a strong emphasis on how the scientific and medical research community can interact with community health organizations/workers to inform the design and implementation of community intervention programs, the integration of behavioral health care in primary health clinics to address global cancer health disparities in health care utilization, as well as the study of cancer associated-etiological factors in underserved minority populations. The potential impact of this conference will be multi fold: 1) a global platform for the participation of basic scientists, clinicians, and community health workers (including third-world countries), 2) foster global crosstalk between academia, research, and clinics to encourage multimodal collaborations and vital community engagement, and 3) understand local & global cancer health disparity issues including US-Mexico border areas.