Molecular Biosciences Research Group
WELCOME TO THE MOLECULAR BIOSCIENCES RESEARCH GROUP
Ronald B. Walter, PhD
From top left: Angel Sandoval, Yuan Lu, Markita Savage, Christina Mendoza.
MBRG: Recent Areas of Research
Development of Xiphophorus genomics capabilities
Beginning with classical genetic mapping in Xiphophorus interspecies backcross hybrids, moving through BAC library assembly, and now genome sequencing, the Walter lab has been enhancing Xiphophorus genomic capabilities for over 20 years. In 2009, the XGSC/MBRG spearheaded the first Xiphophorus genome project as part of a collaborative team between laboratories headed by Dr. Walter (Texas State University), Prof. Manfred Schartl (Univ. of Wurzburg), Dr. Wes Warren (Washington University-Genome Sequencing Center), and Dr. John Postlethwait (University of Oregon). This X. maculatus Jp 163 A genome assembly was published in 2013 and was followed by correlation of the genome assembly with the meiotic Rad-Tag gene map. This investigative team produced one of the first vertebrate genomes to have the de novo assembly contigs aligned with an independently produced (16,411 markers) Rad-Tag meiotic map and is one of most highly marked genetic maps among vertebrates. Recently, this collaborative group also sequenced and assembled three other Xiphophorus genomes (X. hellerii, X. couchianus, and X. montezumae) and a manuscript detailing these genomes has been published (2015). The four Xiphophorus genomes allow both chromosome structural comparison and allele specific expression analysis among interspecies hybrids genetically predisposed to induced carcinogenesis.
Walter, R.B., Rains, J.D., Russell, J.E., Guerra, T.M., Daniels, C., Johnston, D.A., Kumar, J., Wheeler, A., Kelnar, K., Khanolkar, V.A., Williams, E.L., Hornecker, J.L., Hollek, L., Mamerow, M., Pedroza, A., and S. Kazianis (2004). "A Microsatellite Genetic Linkage Map for Xiphophorus." Genetics, 168:363-372.
Schartl, M., Walter, R. B., Shen. Y., Garcia, T., Catchen, J., Amores. A., Braasch. I., Chapolin D., Volff, J-N., Lesch, K-P., Bisazza, A., Minx P., Wilson. R.K., Fuerstenberg, S., Boore, J., Postlethwait, J. H. and W.C. Warren. (2013). The genome of the platyfish, Xiphophorus maculatus, Nature Genetics, 45(5):567-572.
Amores, A., Catchen, C., Nanda, I., Warren, W., Walter, R.B., and M. Schartl and J.H. Postlethwait (2014). A Rad-tag genetic map for the playtfish (Xiphophorus maculatus) reveals mechanisms of karyotype evolution among teleost fish. Genetics, 197(2):625-641.
Yingjia Shen, Domitille Chalopin, Tzintzuni Garcia, Mikki Boswell, William Boswell, Sergey A. Shiryev, Richa Agarwala, Jean-Nicolas Volff, John H. Postlethwait, Manfred Schartl, Patrick Minx, Wesley C. Warren and Ronald B. Walter. (2016). X. couchianus and X. hellerii genome models provide genomic variation insight among Xiphophorus species. BMC Genomics 17:37. DOI 10.1186/s12864-015-2361-z
Genetic determinants of carcinogenesis using Xiphophorus interspecies hybrids and models
Studies in the Walter laboratory have historically focused on the molecular determinants of carcinogenesis using Xiphophorus interspecies hybrids for spontaneous and inducible melanoma models. With the sequence assemblies of four Xiphophorus species, we have more recently been performing RNA-Seq style global gene expression analyses to assess biochemical pathway modulation in various tissues upon exposure to select environmental agents. We are able to follow the expression of each parental allele within the interspecies hybrid genetic background to quantitatively assess the contribution of each allele to the development of complex traits. This genetic power is only now being realized and holds tremendous promise for producing new fundamental discoveries of gene interactions leading to the tumor predisposition.
Nairn, R.S., Kazianis, S., McEntire, B., Della Coletta, L, Walter, R.B., and D.C. Morizot (1996) "A CDKN2-like Polymorphism in Xiphophorus LG V is Associated with UV-induced Melanoma Formation in Platyfish-swordtail hybrids." Proc. of the National Academy of Sciences (USA) 93: 13042-13047
Kazianis, S, Gimenez-Conti, I., Setlow, R.B., Woodhead, A.D., Harshbarger, J.C., Trono, D., Ledesma, M., Nairn, R.S., and R.B. Walter (2001) "MNU Induction of Neoplasia in a Novel Fish Model." Laboratory Investigation, 81(9): 1191-1198. (Cover photo.)
Wood, S.R., Berwick, M., Ley, R.D., Walter, R.B., and G.S. Timmins (2006) "UV Causation of melanoma in Xiphophorus Is Dominated by Melanin Photosensitized Oxidant Production." Proc. of the National Academy of Sciences (USA), 103 (11):4111-4115.
Perez, A.N., Oehlers, L., Heater, S.J., Booth, R.E., Walter, R.B., and W.M. David (2012). Proteomic Analyses of the Xiphophorus Gordon-Kosswig Melanoma Model. Comparative Biochem. & Physiol., Part C, 81-88.
Yang, K., Boswell, M., Walter, D.J., Downs, K., Gaston-Pravia, Garcia, T., Shen, Y. Mitchell, D.L. and R.B. Walter (2014). UVB-induced Gene Expression in the Skin of Xiphophorus maculatus Jp163 B. Comparative Biochem. & Physiol., Part C, 163:86-94.
Schartl, M., Shen, Y., Maurus, K., Walter, R., Tomlinson, C., Wilson, R.K., Postlethwait, J., Warren, W.C. (2015). Whole Body Melanoma Transcriptome Response in Medaka. Plos One doi:10.1371/journal.pone.0143057
Lu, Y., Boswell, M., Boswell, W., Yang, K., Schartl, M., Walter, R.B. (2015) Molecular genetic response of Xiphophorus maculatus-X. couchianus interspecies hybrid skin to UVB exposure. Comp Biochem Physiol C Toxicol Pharmacol., 178:86-92. doi: 10.1016/j.cbpc.2015.07.011 PMID: 26254713
Walter, R.B., Walter, D.J., Boswell, W.T., Caballero, K.L., Boswell, M., Lu, Y., Chang, J., Savage, M.G. (2015) Exposure to fluorescent light triggers down regulation of genes involved with mitotic progression in Xiphophorus skin. Comp Biochem Physiol C Toxicol Pharmacol., 178:93-103. doi: 10.1016/j.cbpc.2015.08.006
Chang, J., Lu, Y., Boswell, W.T., Boswell, M., Caballero, K.L., Walter, R.B. (2015) Molecular genetic response to varied wavelengths of light in Xiphophorus maculatus skin. Comp Biochem Physiol C Toxicol Pharmacol., 178:104-15. doi: 10.1016/j.cbpc.2015.10.002. PMID: 26460196
Promotion of of transcriptomics in aquatic models for biomedical research
The Walter lab organized and hosted the first biannual "Aquatic Models of Human Disease Conference” (AQMHD) in 2000. This conference has become a premier gathering for those working with the myriad of different aquatic models being applied to biomedical questions. In Fall 2015, we hosted the 7th AQMHD conference in Austin, TX. The Walter lab has made scientific contributions utilizing many varied aquatic models such as Xiphophorus, medaka, zebrafish, Fundulus, and whales, and recently, developed contemporary genomic and transcriptomic resources for aquatic models research. We have organized NIH workshops on “Realizing the Scientific Potential of Transcriptomics in Aquatic Models" (2010), and recently “The Medaka Model for Comparative Assessment of Human Disease Mechanisms" (2015).
Walter, R.B. (2001) "Introduction" to a special edition of Marine Biotechnology dedicated to aquaria fish models of human disease. Marine Biotech. 3(S1): 1-3.
Ju, Z., Wells, M.C., and R.B. Walter (2007) "Multiple Tissue Gene Expression Analyses in Japanese Medaka (Oryzias latipes) Exposed to Hypoxia." Comparative Biochem. & Physiol., Part C., 145(1): 134-144.
Boswell, M.G., Wells, M., Kirk, L.M., Ju, Z., Zhang, Z., Booth, R., and R. B. Walter (2009). Comparison of gene expression responses to hypoxia in viviparous (Xiphophorus) and oviparous (Oryzias) fishes using a medaka mcroarray. Comparative Biochem. & Physiol., Part C., 149:258-265.
Whitehead, A., Dubansky, B., Bodiner, C., Garcia, T., Miles, S., Pilley, C., Raghunathan, V., Roach, J., Walker, N., Walter, R.B., Rice, C.D., and F. Glavez (2012). Genomic and Physiological Footprint of the Deepwater Horizon Oil Spill on Resident Marsh Fishes. Proc. of the National Academy of Sciences (USA), 109(50): 20298-20302.
Garcia, T.I., Shen, Y., Whitehead, A., Oleksiak, M., Crawford, D.C., and R.B. Walter (2012). RNA-Seq reveals complex genetic response to Deepwater Horizon oil release in Fundulus grandis. BMC Genomics, 13:474-483. 13:474-483.
Pabuwal, V., Boswell, M., Pasquali, A., Wise, S.S., Kumar, S., Shen, Y., Garcia, T., LaCerte, C., Wise, J.P. Jr, Wise, J.P. Sr., Warren, W., and R. B. Walter. (2013). Transcriptomic Analysis of Cultured Whale Skin Cells Exposed to Hexavalent Chromium [Cr(VI)], Aquatic Toxicology, 134-135:74-81.
Garcia T.I., Matos I., Shen, Y., Pabuwal V., Coelho, M.M., Wakamatsu, Y., Schartl, M., and R.B. Walter (2014). Novel Method for Analysis of Allele Specific Expression in Triploid Oryzias latipes Reveals Consistent Pattern of Allele Exclusion. PLOS ONE 9(6): e100250.
Walter, R.B., and T. Obara (2015). Workshop Report: The Medaka Model for Comparative Assessment of Human Disease Mechanisms, Aquatic Animal Models of Human Disease: Selected Papers and Recommendations form the 7th Conference. Comparative Biochem. & Physiol., Part C, 178: 156-162.
Boswell, W., Boswell, M., Titus, J., Savage, M., Lu, Y., Shen, J., Walter, R.B. (2015) Sex-specific molecular genetic response to UVB exposure in Xiphophorus maculatus skin. Comp Biochem Physiol C Toxicol Pharmacol., 178:76-85. doi: 10.1016/j.cbpc.2015.07.007. PMID: 26256120
Undergraduate and graduate science education
Dr. Walter has spent his 28-year academic career at a primarily undergraduate campus that has just recently been designated an “Emerging Research Institution.” He has served in the Department of Biology (9 years) and then moved to the Department of Chemistry & Biochemistry to assist in development of a Biochemistry undergraduate program. Dr. Walter developed partnership grant proposals aimed towards providing scholarships for student groups that are underrepresented in the sciences (URM). In Fall 2013, he was awarded a Bridges to Biomedicine (B2B) grant wherein Texas State University is partnering with two Alamo Community College campuses to establish a program focused on increasing success of URM students in the biomedical sciences upon transfer to the baccalaureate institution. The B2B program addresses the most important obstacles to upper-division degree completion experienced by students showing an early commitment to a biomedical career. Additionally, Dr. Walter serves as Co-PI for the South Texas Doctoral Bridge Program (STDBP). The STDBP is aimed at student matriculation from the MS degree into highly competitive doctoral programs. The STDBP is established between the Univ. of Texas Health Science Center at San Antonio (UTHSCSA, medical school) and Texas State University. The STDBP is designed to provide a combination of mentoring and student development activities as well as enhance didactics and research training during a thesis-based M.S. degree in Biochemistry.
X. couchianus and X. hellerii genome models provide genomic variation insight among Xiphophorus species (PDF)
Yingjia Shen, Domitille Chalopin, Tzintzuni Garcia, Mikki Boswell, William Boswell, Sergey A. Shiryev, Richa Agarwala, Jean-Nicolas Volff, John H. Postlethwait, Manfred Schartl, Patrick Minx, Wesley C. Warren and Ronald B. Walter. (2016). BMC Genomics 17:37. DOI 10.1186/s12864-015-2361-z
Manfred Schartl, Yingjia Shen, Katja Maurus, Ron Walter, Chad Tomlinson, Richard K. Wilson, John Postlethwait, Wesley C. Warren. (2015). PLOS One DOI:10.1371/journal.pone.0143057