Kellee R. Siegfried

ORCID: 0000-0002-7951-392X
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About
Contact & Profiles
Research Areas
  • Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
  • Sperm and Testicular Function
  • Reproductive biology and impacts on aquatic species
  • Reproductive Biology and Fertility
  • Animal Genetics and Reproduction
  • Epigenetics and DNA Methylation
  • Prostate Cancer Treatment and Research
  • Cancer-related gene regulation
  • Ubiquitin and proteasome pathways
  • Chromosomal and Genetic Variations
  • RNA modifications and cancer
  • Genomics and Chromatin Dynamics
  • RNA Research and Splicing
  • Sexual Differentiation and Disorders
  • CRISPR and Genetic Engineering
  • Genetics, Aging, and Longevity in Model Organisms
  • Zebrafish Biomedical Research Applications
  • Fish biology, ecology, and behavior
  • Plant Molecular Biology Research
  • MicroRNA in disease regulation
  • Microtubule and mitosis dynamics
  • DNA Repair Mechanisms
  • FOXO transcription factor regulation
  • Memory and Neural Mechanisms
  • Cholinesterase and Neurodegenerative Diseases

University of Massachusetts Boston
2015-2025

Center of Advanced European Studies and Research
2015

Stanford University
2015

Max Planck Institute for Developmental Biology
2011-2012

Massachusetts General Hospital
2011

Boston Children's Hospital
2011

Max Planck Society
2008-2010

Klinikum Frankfurt Höchst
2009

University of Wisconsin–Madison
2004-2005

Laboratory of Molecular Genetics
2002

ABSTRACT Lateral organs produced by shoot apical and flower meristems exhibit a fundamental abaxial-adaxial asymmetry. We describe three members of the YABBY gene family, FILAMENTOUS FLOWER, YABBY2 YABBY3, isolated on basis homology to CRABS CLAW. Each these genes is expressed in polar manner all lateral organ primordia from meristems. The expression precisely correlated with abaxial cell fate mutants which fates are found ectopically, reduced or eliminated. Ectopic either FLOWER YABBY3...

10.1242/dev.126.18.4117 article EN Development 1999-09-15

Background Despite the popularity of zebrafish as a research model, its sex determination (SD) mechanism is still unknown. Most cytogenetic studies failed to find dimorphic chromosomes and no primary determining switch has been identified even though assembly genome sequence near completion high resolution genetic map available. Recent publications suggest that environmental factors within natural range have minimal impact on ratios populations. The aim this study out more about how...

10.1371/journal.pone.0034397 article EN cc-by PLoS ONE 2012-04-10

One critical mechanism through which prostate cancer (PCa) adapts to treatments targeting androgen receptor (AR) signaling is the emergence of ligand-binding domain-truncated and constitutively active AR splice variants, particularly AR-V7. While AR-V7 has been intensively studied, its ability activate distinct biological functions compared with full-length (AR-FL), role in regulating metastatic progression castration-resistant PCa (CRPC), remain unclear. Our study found that, under...

10.1172/jci168649 article EN cc-by Journal of Clinical Investigation 2024-04-30

The shape and polarity of the C. elegans gonad is defined during early gonadogenesis by two somatic gonadal precursor cells, Z1 Z4, their descendants. Z4 divide asymmetrically to establish proximal-distal axes generate regulatory leader cells that control organ shape. In this paper, we report pop-1, TCF/LEF-1 transcription factor, controls first Z1/Z4 asymmetric division hence axis formation. We have identified pop-1(Sys) alleles (for symmetrical sisters) render divisions symmetrical....

10.1242/dev.129.2.443 article EN Development 2002-01-15

The diversity of inputs that guide sexual fate during development is both intriguing and daunting. In the field fish biology, study sex determination great importance. For example, in aquaculture, sexually dimorphic growth rates overall size leads to one being more marketable than other. Moreover, for breeding purposes it important maintain balanced ratios. Furthermore, sensitive environmental factors, such as temperature contaminants, which can lead skewed ratios, intersexes sterility wild...

10.1111/j.1095-8649.2010.02594.x article EN Journal of Fish Biology 2010-05-01

Abstract The generation and analysis of mutants in zebrafish has been instrumental defining the genetic regulation vertebrate development, physiology, disease. However, identifying changes that underlie mutant phenotypes remains a significant bottleneck mutants. Whole-genome sequencing recently emerged as fast efficient approach for mutations nonvertebrate model organisms. this not applied to due complicating factors having large genome lack fully inbred lines. Here we provide method...

10.1534/genetics.111.136069 article EN Genetics 2011-12-16

Abstract FOXA family proteins act as pioneer factors by remodeling compact chromatin structures. FOXA1 is crucial for the binding of androgen receptor (AR) in both normal prostate epithelial cells and luminal subtype cancer (PCa). Recent studies have highlighted emergence FOXA2 an adaptive response to AR signaling inhibition treatments. However, role transition regulating lineage plasticity remains unclear. Our study demonstrates that binds distinct classes developmental enhancers multiple...

10.1038/s41467-024-49234-9 article EN cc-by Nature Communications 2024-06-08

Abstract To form the proximal-distal axis of C. elegans gonad, two somatic gonadal precursor cells, Z1 and Z4, divide asymmetrically to generate one daughter with a proximal fate distal fate. Genes governing this process include lin-17 frizzled receptor, wrm-1/β-catenin, pop-1/TCF transcription factor, lit-1/nemo-like kinase, sys-1 gene. Normally, all these regulators promote Here we show that nuclear levels pop-1 GFP fusion protein are less abundant in than Z1/Z4 daughters. This POP-1...

10.1534/genetics.166.1.171 article EN Genetics 2004-01-01

Germ cells give rise to eggs or sperm. However, recent analyses in medaka (Oryzias latipes) showed that germ are also important for feminization of gonads, although this novel role has not been characterized detail. Here, we show the feminizing effect is inherent and affected by gametogenic stages sexual fate cells. Three mutants were generated demonstrate effect: figlα mutants, which follicle formation disrupted; meioC unable commit gametogenesis meiosis; dazl do develop into gonocytes. All...

10.1371/journal.pgen.1007259 article EN cc-by PLoS Genetics 2018-03-29

Calcium in the flagellum controls sperm navigation. In of marine invertebrates and mammals, Ca2+ signalling has been intensely studied, whereas for fish little is known. sea urchin sperm, a cyclic nucleotide-gated K+ channel (CNGK) mediates cGMP-induced hyperpolarization that evokes influx. Here, we identify freshwater Danio rerio novel CNGK family member featuring non-canonical properties. It located head rather than controlled by intracellular pH, but not nucleotides. Alkalization...

10.7554/elife.07624 article EN cc-by eLife 2015-12-09

Ribosome biogenesis is vital for sustaining stem cell properties, yet its regulatory mechanisms are obscure. Herein, we show unique properties of zebrafish meioc mutants in which spermatogonial cells (SSCs) do not differentiate or upregulate rRNAs. Meioc colocalized with Piwil1 perinuclear germ granules, but depletion resulted accumulation nucleoli. Nucleolar interacted 45S pre-rRNA. piwil1 +/− spermatogonia reduced upregulated rRNAs, and ;meioc −/− recovered differentiation later than those...

10.7554/elife.104295 preprint EN 2025-01-22

Ribosome biogenesis is vital for sustaining stem cell properties, yet its regulatory mechanisms are obscure. Herein, we show unique properties of zebrafish meioc mutants in which spermatogonial cells (SSCs) do not differentiate or upregulate rRNAs. Meioc colocalized with Piwil1 perinuclear germ granules, but depletion resulted accumulation nucleoli. Nucleolar interacted 45S pre-rRNA. piwil1 +/− spermatogonia reduced upregulated rRNAs, and ;meioc −/− recovered differentiation later than those...

10.7554/elife.104295.1 preprint EN 2025-01-22

Ribosome biogenesis is vital for sustaining stem cell properties, yet its regulatory mechanisms are obscure. Herein, we show unique properties of zebrafish meioc mutants in which spermatogonial cells (SSCs) do not differentiate or upregulate rRNAs. Meioc colocalized with Piwil1 perinuclear germ granules, but depletion resulted accumulation nucleoli. Nucleolar interacted 45S pre-rRNA. piwil1 +/- spermatogonia reduced upregulated rRNAs, and ;meioc -/- recovered differentiation later than those...

10.7554/elife.104295.2 preprint EN 2025-04-16

Abstract We describe here the isolation and cytogenetic characterization of three meiotic prophase I mutants, denoted ietsugu ( its ), iesada isa iemochi imo isolated by a novel N‐ethyl‐N‐nitrosourea mutagenesis screen for adult zebrafish gonadogenesis. Histological examination flow cytometry analysis testes from these mutants showed that each contained neither spermatids nor sperm. Staining Sycp3 cleaved Caspase‐3 TUNEL (terminal deoxynucleotidyl transferase–mediated...

10.1002/dvdy.22661 article EN Developmental Dynamics 2011-05-18

Molecular dissection and chemical screening on a complex process such as spermatogenesis could be facilitated by cell culture approaches that allow easy access for experimental manipulation live imaging of specific molecules; however, technical limitations have thus far prevented the complete reconstruction spermatogenic events in culture. Here, we describe production functional sperm from self-renewing spermatogonial stem cells (SSCs) conditions, using zebrafish testicular hyperplasia...

10.1242/dev.129643 article EN cc-by Development 2015-01-01

Significance The transcriptional repressor protein Capicua (Cic) is a conserved regulator of organ growth and tissue patterning, mutations in the CIC gene humans result brain cancer oligodendroglioma. Cic activity controlled by receptor tyrosine kinase (RTK) signaling pathway. Here, we identify Minibrain (Mnb) its adaptor Wings apart (Wap) as regulators. Mnb Wap bind to phosphorylate protein, inhibit ability repress expression. Mnb-dependent down-regulation necessary for proper multiple...

10.1073/pnas.1609417113 article EN Proceedings of the National Academy of Sciences 2016-09-06

Dysregulation of histone lysine methyltransferases and demethylases is one the major mechanisms driving epigenetic reprogramming transcriptional networks in castration-resistant prostate cancer (CRPC). In addition to their canonical targets, some these factors can modify critical transcription factors, further impacting oncogenic programs. Our recent report demonstrated that LSD1 demethylate 270 FOXA1 (PCa) cells, leading stabilization chromatin binding. This process enhances activities...

10.1073/pnas.2220472120 article EN cc-by-nc-nd Proceedings of the National Academy of Sciences 2023-08-07

The double stranded RNA binding protein Adad1 (adenosine deaminase domain containing 1) is a member of the adenosine acting on RNAs (Adar) family with germ cell-specific expression. In mice, necessary for sperm differentiation, however its function outside mammals has not been investigated. Here, through an N-ethyl-N-nitrosourea (ENU) based forward genetic screen, we identified adad1 mutant zebrafish line that develops as sterile males. Further histological examination revealed complete lack...

10.1371/journal.pgen.1010589 article EN cc-by PLoS Genetics 2023-08-08

Germ cell differentiation and maintenance relies on complex regulation of mitotic meiotic progression. Cyclin-dependent kinases (CDKs) their activating cyclin partners are known to have specialized roles in regulating cycle progression across tissues, including germ cells. Very little is about CDK/cyclin function zebrafish or the differentiation. In a forward genetic screen for gonadogenesis defects zebrafish, mutation disrupting cdk21 ( cyclin-dependent kinase 21 ) was identified, which...

10.1530/rep-18-0386 article EN Reproduction 2019-02-14
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