Xiphophorus Genetic Stock Center

Dr. Manfred Schartl

Co-PI for the XGSC

My 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. I use 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, I use 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. For functional studies we have set up various cell culture systems from fish, mouse and human melanoma to measure the readouts of single malignant transformation parameters. This is complemented by studies with transgenic and CRISPR/Cas9 knockout fish. My team has pioneered the use of small aquarium fish models for cancer research. After isolating the first melanoma oncogene from a model organism our research has uncovered the importance of Ras/Raf/MAPK signaling for melanoma formation, which today is recognized to be responsible for more than 60% of human melanomas. Although my research is rooted in basic science to understand the genetic, molecular and cellular basis of cancer formation, I have always paid keen attention on the translational aspect of my results. I have set up assistant and associate professor teams at my chair that work on mouse models and human cancer cell lines and have frequently collaborated with clinical scientist. Comparative studies have resulted in the characterization of molecules and cellular processes first detected in fish models that show relevance for diagnostics and therapy of the human disease. At the Medical school of my university I have initiated the use of next generation sequencing in cancer patient diagnosis. I developed with my colleagues from Dermatology a targeted sequencing genetic diagnosis for melanoma patients, which is now adapted to new technological development. This program was so successful that other clinical units of the Comprehensive Cancer Center have quickly also adopted this methodology for their patients. In our NIH funded project together with my colleagues at Texas State University, I have developed a new screening system based on transcriptome changes in melanoma developing fish for detection of anti-cancer drugs from high-throughput testing of chemical libraries.

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Dr. Yuan Lu

Co-PI for the XGSC

Research Interests

I am interested in studying mechanisms that various species adapted to cope with or repress disease, or disease causal mutations that are similar to human condition, to better understand disease etiology and develop novel strategies in controlling human disease. Specifically, my research program studies genetics and molecular mechanisms that account for tumorigenic negative epistasis of select Xiphophorus interspecies hybrids [i.e., X. hellerii x (X. maculatus x X. hellerii)]. Tumor development is a result of segregation between a X. maculatus specific mutant copy of epidermal growth factor receptor (egfr) and co-evolved regulator gene named R(Diff). We recently identified the genetic location and discovered the identity of the R(Diff) . My current research focus is to elucidate mechanisms of egfr suppression by R(Diff). As an oncogene, EGFR mutation and overexpression are present in a majority of human cancers. However, EGFR-targeted cancer therapies suffer from low-response rate and resistance. Characterizing R(Diff) regulation on egfr may lead to novel therapeutic strategies in controlling EGFR-driven cancer. 

NCBI 

Dr. Caitlin Gabor

Co-PI for the XGSC

Research Interests

My research program spans population level questions using conservation physiology and behavioral and evolutionary ecology with fish and amphibians as model organisms. My 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. Currently, our work focuses on the consequences of anthropogenic stressors on live-bearing fish and amphibian declines using a holistic framework that evaluates mechanisms (e.g., genetic and physiology) through function (e.g., evolutionary and conservation implications). Specifically, we have been focusing on the consequences of land use conversion on multiple measures of physiological health, life history traits, and fitness of mosquitofish, Gambusia affinis, and multiple species of amphibians to explore evolutionary questions about population persistence in the face of change. We propose to extend our work to include cognition, community ecology, additional physiological measures, microbiome, and population genetic question with collaborators. As multi-PI for the Xiphophorus Genetic Stock Center I will help maintain the current successful research and I propose to bridge my research program with the current research programs. I see important links between life-history evolution, cognition and behavior, stress physiology, gene expression, microbiome, ecotoxicology and broad population genetic and evolutionary questions. I think taking a population level perspective using model fish at the Xiphophorus Genetic Stock Center will help expand our understanding of how anthropogenic change affects organismal fitness, such as via affecting rates of cancers, changes in cognitive function, stress levels, reproduction and behavior. These studies could also aid in understanding human responses to change.

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