My main research interests are molecular processes in organismic development and their malfunction in cancerogenesis.

One major topic of my laboratory is the understanding of signal transduction and gene regulation in cancer, in particular melanoma. Malignant melanoma is one of the most dangerous tumors with an incidence rising faster than any type of cancer worldwide. We use the classical Xiphophorus model system and transgenic medaka that develop different types of pigment cell tumors. With the established tools of biochemistry and molecular genetics as well as high throughput and deep sequencing methods (RNA-seq, CHiP-seq, RAD-tags) we want to better understand the molecular mechanisms that make a normal pigment cell turn into a malignant cancer cells and provide on this basis novel approaches for better diagnoses and therapies.

A second major interest is in the molecular basis and evolution of sex determination. Sex can be determined by a plethora of mechanisms and the different mechanisms do not follow a phylogenetic pattern. Particularly in fish, sex determination is highly variable, sometimes even among closely related species. We want to understand the reasons why this variability exists and what molecular changes are involved. We use a comparative approach studying various fish species. This includes developmental biological studies on the processes that make the decision in the embryo or larvae if the undifferentiated bipotential gonad will develop either as testis or ovary laboratory model fish species. Besides we try to identify the unknown sex determination genes from fish that are representing major branches of the fish tree of life and are of interest because of special ecological, evolutionary or economic features.

Because the function of any gene is shaped by its evolutionary history and its genomic context we are interested in the evolution of genes involved in cancer, pigmentation, sex determination and reproductive development. The opportunities offered by the next generation sequencing technologies allow to obtain the full genome information now also for interesting species besides the mainstream laboratory models, which offers new insights into their evolution and biology.

We are members of several international consortia (some initiated and coordinated by us) for the de-novo sequencing, assembly and annotation of fish genomes, which include our melanoma model organism, the platyfish Xiphophorus maculatus, the Amazon molly, a unisexual clonal fish species, two marine flatfish, two cyprinid species, the coelacanth Latimeria chalumnae, the lungfish and several others. We analyze the genomes with a special attention to the evolution of genes and gene families, which are of our interest from the cancer projects and the evolution of sex determination mechanisms and sex chromosomes. Major focuses are gene and whole genome duplications as important drivers of evolutionary innovations and adaptations. We are also interested how several traits like secondary sex characters, the age of sexual maturation (puberty) or pigmentation patterns evolve and have an impact on speciation.

1. Dodge, TO, Kim, BY, Baczenas, JJ, Banerjee, SM, Gunn, TR, Donny, AE et al.. Structural genomic variation and behavioral interactions underpin a balanced sexual mimicry polymorphism. Curr Biol. 2024;34 (20):4662-4676.e9. doi: 10.1016/j.cub.2024.08.053. PubMed PMID:39326413 .
2. Soria, E, Lu, Q, Boswell, W, Du, K, Xing, Y, Boswell, M et al.. Segregation Between an Ornamental and a Disease Driver Gene Provides Insights Into Pigment Cell Regulation. Pigment Cell Melanoma Res. 2024; :. doi: 10.1111/pcmr.13196. PubMed PMID:39289030 .
3. Preising, GA, Gunn, T, Baczenas, JJ, Powell, DL, Dodge, TO, Sewell, ST et al.. Recurrent evolution of small body size and loss of the sword ornament in Northern swordtail fish. Evolution. 2024; :. doi: 10.1093/evolut/qpae124. PubMed PMID:39252584 .
4. Langdon, QK, Groh, JS, Aguillon, SM, Powell, DL, Gunn, T, Payne, C et al.. Swordtail fish hybrids reveal that genome evolution is surprisingly predictable after initial hybridization. PLoS Biol. 2024;22 (8):e3002742. doi: 10.1371/journal.pbio.3002742. PubMed PMID:39186811 PubMed Central PMC11379403.
5. Schartl, M, Woltering, JM, Irisarri, I, Du, K, Kneitz, S, Pippel, M et al.. The genomes of all lungfish inform on genome expansion and tetrapod evolution. Nature. 2024;634 (8032):96-103. doi: 10.1038/s41586-024-07830-1. PubMed PMID:39143221 PubMed Central PMC11514621.
6. Du, K, Ricci, JMB, Lu, Y, Garcia-Olazabal, M, Walter, RB, Warren, WC et al.. Phylogenomic analyses of all species of swordtail fishes (genus Xiphophorus) show that hybridization preceded speciation. Nat Commun. 2024;15 (1):6609. doi: 10.1038/s41467-024-50852-6. PubMed PMID:39098897 PubMed Central PMC11298535.
7. Garcia-Olazabal, M, Adolfi, MC, Wilde, B, Hufnagel, A, Paudel, R, Lu, Y et al.. Functional Test of a Naturally Occurred Tumor Modifier Gene Provides Insights to Melanoma Development. bioRxiv. 2024; :. doi: 10.1101/2023.11.14.567049. PubMed PMID:38895428 PubMed Central PMC11185518.
8. Kuhl, H, Tan, WH, Klopp, C, Kleiner, W, Koyun, B, Ciorpac, M et al.. A candidate sex determination locus in amphibians which evolved by structural variation between X- and Y-chromosomes. Nat Commun. 2024;15 (1):4781. doi: 10.1038/s41467-024-49025-2. PubMed PMID:38839766 PubMed Central PMC11153619.
9. Soria, E, Lu, Q, Boswell, W, Du, K, Xing, Y, Boswell, M et al.. Segregation between an ornamental and a disease driver gene provides insights into pigment cell regulation. bioRxiv. 2024; :. doi: 10.1101/2024.05.20.595041. PubMed PMID:38826429 PubMed Central PMC11142077.
10. Münch, L, Helmprobst, F, Volff, JN, Chalopin, D, Schartl, M, Kneitz, S et al.. Transposable Element Expression Profiles in Premalignant Pigment Cell Lesions and Melanoma of Xiphophorus. Genes (Basel). 2024;15 (5):. doi: 10.3390/genes15050620. PubMed PMID:38790249 PubMed Central PMC11121471.