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Xiphophorus Research Group


WELCOME TO THE XIPHOPHORUS RESEARCH GROUP  


Dr. Manfred Schartl

Dr. Manfred Schartl

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Co-PI for the Xiphophorus Genetic Stock Center

Dr. Schartl's main research interests are the molecular processes in organismic development and their malfunction in cancerogenesis. One major topic is signal transduction and gene regulation in melanoma. He uses the Xiphophorus model system and transgenic medaka that develop different types of pigment cell tumors. Besides classical tools for biochemical characterization of signal transduction and transcriptional regulation, he uses genome sequencing and RNA-Seq transcriptomics in a comparative approach of fish models with human data to identify new melanoma genes and small non-coding RNAs that are involved in the transition from a benign pigmentary lesion to malignant melanoma. 

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Dr. Yuan Lu

Dr. Yuan Lu

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Co-PI for the Xiphophorus Genetic Stock Center

Dr. Lu's research focuses on using the Xiphophorus model system to identify an endogenous EGFR regulator utilizing transcriptomics and genome wide association studies. In addition, his research characterizes the light-induced genetic response in several aquatic model systems, including Xiphophorus, medaka, zebrafish and using Xiphophorus interspecies hybrid, and allele specific gene expression to identify key genetic responses to environmental cues such as light.

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Dr. Caitlin Gabor

Dr. Caitlin Gabor

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Co-PI for the Xiphophorus Genetic Stock Center

Dr. Gabor's research program spans population level questions using conservation physiology and behavioral and evolutionary ecology with fish and amphibians as model organisms. Her lab studies the historical forces of natural and sexual selection on speciation in a unisexual-bisexual species complex of live bearing fish from a population, behavioral, genetic and physiological standpoint.

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Dr. Carolyn Chang

Dr. Carolyn Chang

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South Texas Bridge Program Coordinator

Dr. Chang has been with the XGSC since 2019. She currently serves as the Program Coordinator for the South Texas Bridges to Biomedicine program in addition to conducting independent research with the XGSC.

Mrs. Mikki Boswell

Mikki Boswell

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Program Coordinator

Ms. Boswell has a M.S. degree in biochemistry and has served in the Program Coordinator position for the past 9 years. She has been instrumental in the success of the research program and is extremely experienced in all Center matters.

Mr. William Boswell

William Boswell

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Laboratory Manager

Mr. Boswell has two M.S. degrees in Microbiology and Infectious Disease. He has served in the Research Scientist role and as the Laboratory Manager in the XGSC for the past 8 years. He is an all-purpose expert that is essential to XGSC research and proper operation/maintenance of the Center.

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Current Research

 SF424-OD011120 (Genetic Effects of Light Exposure on Pregnant Fish)

Human health effects due to increasing exposure to artificial lighting have been shown to be significant and quantifiable. Both the amount of light and spectral composition of artificial lighting are important parameters associated with human health. In addition, pregnancy is associated with a plethora of varied skin diseases that may affect quality of life. Baseline comparisons of pregnant to non-pregnant females are needed to better understand the effect of pregnancy on skin disorders, but few tractable animals exist to perform such studies at the molecular genetic level.

Xiphophorus is live bearing, genetically tractable model that has been used in studies characterizing light-incited genetic response. Sex-specific responses to several varied types of light have also been shown using this model. Based on previous observations, we hypothesize that females and males respond to different wavelengths of light by modifying different sets of genes and/or pathways that result in sex specific genetic outcomes.

Considering the important pathways we have previously shown to be affected by various types of complex light, we propose in this supplement to accomplish two goals: (1) to identify sets of genes of female Xiphophorus maculatus that are transcriptionally responsive to successive 50 nm wavelength intervals (i.e., waveband) between 300 to 600 nm, and determine waveband(s) that produce significantly different genetic pathway responses in skin, brain and liver of highly inbred females, and compare the finding in females to the male responses we have previously analyzed; and (2) to compare the genetic differences between non-pregnant and pregnant female in response to fluorescent light and 50nm wavebands to identify lighting conditions that result in differential responses.

The proposed study will provide critical information in regard to understanding differences in the genetic response between male and female vertebrates exposed to the same light sources and deconvolute these responses to particular wavebands. More importantly, these studies will document, for the first time, how light stimulus may alter genetic baselines during pregnancy. These novel data will position us to seek future support to study the effect of pregnancy on the female genetic response to light and specific light wavelengths in this tractable genetic model. Such studies will be novel in taking advantage of the unique biology and genetic power of the Xiphophorus experimental system to explore a pertinent human health issue during pregnancy.

Specific Aim 1: Identify sets of genes in the skin, brain and liver of female X. maculatus that are responsive to FL and 50 nm wavelength regions between 300 to 600 nm and determine waveband(s) that lead to the largest and the smallest genetic response differences between females and males. 

Specific Aim 2: Identify sets of genes in skin, brain and liver of pregnant female X. maculatus that are responsive to FL and to 50 nm wavebands between 300 to 600 nm and characterize functions that involve waveband-responsive genes. 

SF424-OD011120 (Effects of Diet on Fish growth, fecundity and overall animal well-being)

As shown by numerous presentations at a recent NIH workshop entitled “Defined Reference Diets for Zebrafish and Other Aquatic Biomedical Research Models: Needs and Challenges Workshop” (https://orip.nih.gov/about-orip/workshop-reports), differences in diet are known variables in animal studies. Use of different diets among laboratories using the same model may lead to lack of reproducibility and confounded study outcomes. Similar to zebrafish, researchers utilizing medaka (i.e., Japanese rice fish), and Xiphophorus species (i.e., platyfish and swordtails) still use a wide variety of commercial and “home-made” diets. Both animal models are used intensively in genetic studies. Inconsistency in animal diet may lead to misinterpretation of particular genetically controlled trait to be controlled by both genetic background and environment, or vice versa. Therefore, it is important to standardize diet in these aquatic model systems to minimize the environmental (e.g., diet) influence in genetic studies. This proposal is part of a multi-laboratory approach to study the same diet among different aquatic models (i.e., zebrafish, medaka, and Xiphophorus). In concert with our colleagues, we propose to investigate the influence of different diet on medaka and Xiphophorus growth, fecundity and overall animal well-being.

Specific Aim 1: Compare the effects of different diets on performance of medaka and Xiphophorus fishes in growth, fecundity, body fat content, and microbiome composition.

Specific Aim 2: Compare the histology of several organs of medaka and Xiphophorus fed by different diets and determine histological baselines for each diet as a reference for differential animal housing.

R15 (Characterize the R(Diff) Locus)

The epidermal growth factor receptor (EGFR) is a leading oncogene firmly associated with many types of cancer. Both anti-EGFR small molecules and monoclonal antibodies have been developed to block its kinase activity for cancer treatment. However, innate and acquired resistance are frequently observed in clinical application. Such observations significantly limit anti-EGFR medicines usage, and also challenge current knowledge of EGFR-driver cancer. Therefore, it is necessary to study the relationship between EGFR and cancer from a different angle, with different research strategy.

Xiphophorus maculatus encodes a mutant, autonomous, dysregulated and oncogenic EGFR, named xmrk. However, carcinogenesis is only observed in backcross interspecies hybrid between xmrk positive and xmrk-null Xiphophorus species, or when xmrk is ectopically expressed in non-Xiphophorus model system (e.g., medaka, murine). These suggest that X. maculatus genome also encode a regulator gene that may co-evolved with xmrk and is able to suppressing its oncogenic activity. Therefore, characterizing how the regulator, termed R(Diff) inhibit xmrk, may lead to novel therapeutic strategy in controlling EGFR.   

Our recent study has defined the R(Diff) tumor regulatory locus to a 101.7 kbp locus on chromosome 5. This small candidate size and low candidate gene number enables functional and mechanistic studies are impractical. Therefore, this proposal is designed to final determine the R(Diff) locus by examining the following aims:

Specific Aim 1: Characterize all expressed but unannotated genetic elements, in addition to the known coding genes, in the 101.7 Kbp candidate R(Diff) locus, to fully annotate the R(Diff) locus.

Specific Aim 2: Determine the gene/element(s) carrying R(Diff) activity by performing gene knock-out screens in non-tumor-bearing Xiphophorus fish, tumor-bearing hybrids, and xmrk-transgenic medaka.

Specific Aim 3: Profile xmrk and R(Diff) candidates, as well as phenotypes of several hybrids between Xiphophorus species, to define R(Diff) by association of candidate sequence with varied phenotypes of additional hybrids.