A5029207742- Prostate Cancer Treatment and Research
- Cancer Genomics and Diagnostics
- RNA Research and Splicing
- Cancer-related molecular mechanisms research
- Ovarian cancer diagnosis and treatment
- Hormonal and reproductive studies
- Cancer, Lipids, and Metabolism
- Genetic Neurodegenerative Diseases
- Mitochondrial Function and Pathology
- Immune Cell Function and Interaction
- Scientific Computing and Data Management
- Aquatic Invertebrate Ecology and Behavior
- Genomics and Rare Diseases
- Genetic diversity and population structure
- T-cell and B-cell Immunology
- Acute Lymphoblastic Leukemia research
- Prostate Cancer Diagnosis and Treatment
- Genetic factors in colorectal cancer
- Immunotherapy and Immune Responses
- CRISPR and Genetic Engineering
- Estrogen and related hormone effects
- Epigenetics and DNA Methylation
- MicroRNA in disease regulation
- RNA Interference and Gene Delivery
- Radiopharmaceutical Chemistry and Applications
University of Minnesota
2015-2024
Max Planck Institute for Biology
2023-2024
Pittsburgh Supercomputing Center
2019-2022
Minnesota Supercomputing Institute
2007-2020
Computational Physics (United States)
2015-2020
Max Planck Institute for Developmental Biology
2018
University of California, Santa Barbara
2008-2013
Friedrich Miescher Laboratory
2013
Max Planck Society
2013
Duke University
2004-2009
Brassinosteroids, which control plant growth and development, are sensed by the leucine-rich repeat (LRR) domain of membrane receptor kinase BRASSINOSTEROID INSENSITIVE 1 (BRI1), but it is unknown how steroid binding at cell surface activates cytoplasmic receptor. A family somatic embryogenesis kinases (SERKs) has been genetically implicated in mediating early brassinosteroid signaling events. We found a direct steroid-dependent interaction between BRI1 SERK1 LRR domains analysis their...
Abstract Molecular tools perform at their best when integrated with other data and approaches. The value of integrating approaches is especially high the underlying genetic signal relatively weak, as occurs in many marine species. Recently, studies combining genetic, oceanographic, behavioural modelling have provided new insights into spatial ecology populations, particular regarding larval migration, barriers to dispersal source‐sink population dynamics. In this perspectives piece, we...
Abstract Molecularly targeted therapies for advanced prostate cancer include castration modalities that suppress ligand-dependent transcriptional activity of the androgen receptor (AR). However, persistent AR signalling undermines therapeutic efficacy and promotes progression to lethal castration-resistant (CRPC), even when patients are treated with potent second-generation AR-targeted abiraterone enzalutamide. Here we define diverse genomic structural rearrangements ( -GSRs) as a class...
Abstract Purpose: Androgen receptor (AR) variant AR-V7 is a ligand-independent transcription factor that promotes prostate cancer resistance to AR-targeted therapies. Accordingly, efforts are under way develop strategies for monitoring and inhibiting in castration-resistant (CRPC). The purpose of this study was understand whether other AR variants may be coexpressed with promote Experimental Design: We utilized complementary short- long-read sequencing intact mRNA isoforms characterize...
Spinocerebellar ataxia type 1 (SCA1) is a dominantly inherited caused by expansion of translated CAG repeat encoding glutamine tract in the ataxin-1 (ATXN1) protein. Despite advances understanding pathogenesis SCA1, there are still no therapies to alter its progressive fatal course. RNA-targeting approaches have improved disease symptoms preclinical rodent models several neurological diseases. Here, we investigated therapeutic capability an antisense oligonucleotide (ASO) targeting mouse...
Abstract Invariant NKT cells differentiate into three predominant effector lineages in the steady state. To understand these lineages, we sorted undifferentiated invariant NK T progenitor and each population analyzed their transcriptional profiles by RNAseq. Bioinformatic comparisons were made to subsets among other lymphocytes, specifically Th cells, innate lymphoid (ILC), γδ cells. Myc-associated signature genes enriched progenitors, like hematopoietic progenitors. Only NKT1 but not NKT2...
Abstract Multiple studies have identified transcriptome subtypes of high-grade serous ovarian carcinoma (HGSOC), but their interpretation and translation are complicated by tumor evolution polyclonality accompanied extensive accumulation somatic aberrations, varying cell type admixtures, different tissues origin. In this study, we examined the chronology HGSOC subtype in context these factors using a novel integrative analysis absolute copy-number gene expression The Cancer Genome Atlas...
Prostate cancer is the second leading cause of male deaths. Castration-resistant prostate (CRPC) a lethal stage disease that emerges when endocrine therapies are no longer effective at suppressing activity androgen receptor (AR) transcription factor. The purpose this study was to identify genomic mechanisms contribute development and progression CRPC.
With a dataset of more than 600 million small RNAs deeply sequenced from mouse hippocampal and staged sets cells that underwent reprogramming to induced pluripotent stem cells, we annotated the stem-loop precursors known miRNAs identify isomoRs (miRNA-offset RNAs), loops, non-preferred strands, guide strands. Products both strands were readily detectable for most miRNAs. Changes in dominant isomiR occurred among cell types, as did switches preferred strand. The terminal nucleotide aligned...
Tumor-associated macrophages contribute to tumor progression and therapeutic resistance in breast cancer. Within the microenvironment, tumor-derived factors activate pathways that modulate macrophage function. Using vitro vivo models, we find induce activation of Janus kinase (JAK)/signal transducer activator transcription 3 (STAT3) pathway macrophages. We also demonstrate loss STAT3 myeloid cells leads enhanced mammary tumorigenesis. Further studies show tumors JAK/STAT inhibitor...
CD8 effector T cells with a CD127
Targeted therapies for aggressive breast cancers like triple negative cancer (TNBC) are needed. The use of small interfering RNAs (siRNAs) to disable expression survival genes provides a tool killing these cells. Cyclin dependent kinase 11 (CDK11) is protein that regulates RNA transcription, splicing and mitosis. Casein 2 (CK2) suppresses cell death. Eliminating the has potential therapeutic utility cancer.Expression levels CDK11 CK2 mRNAs associated proteins were examined in lines tissue...
Abstract Prostate cancer is the second leading cause of male deaths due to disease progression castration-resistant prostate (CRPC). Androgen receptor (AR) splice variants including AR-V7 function as constitutively active transcription factors in CRPC cells, thereby promoting resistance AR-targeted therapies. To date, there are no AR variant–specific treatments for CRPC. Here we report that splicing well AR-V1 and AR-V9 regulated coordinately by a single polyadenylation signal intron 3....
Clinical laboratories have adopted next generation sequencing (NGS) as a gold standard for the diagnosis of hereditary disorders because its analytic accuracy, high throughput, and potential cost-effectiveness. We describe implementation single broad-based NGS assay to meet genetic testing needs at University Minnesota. A hybrid capture library preparation was used each test ordered, data informatically blinded clinically-ordered genes, identified variants were reviewed classified by...
Timing the acquisition of a beneficial microbe relative to evolutionary history its host can shed light on adaptive impact partnership. Here, we investigated onset and molecular evolution an obligate symbiosis between Cassidinae leaf beetles Candidatus Stammera capleta, γ-proteobacterium. Residing extracellularly within foregut symbiotic organs, upgrades digestive physiology by supplementing plant cell wall-degrading enzymes. We observe that is shared symbiont across tortoise hispine...
Comparisons among loci with differing modes of inheritance can reveal unexpected aspects population history. We employ a multilocus approach to ask whether two types independently assorting mitochondrial DNAs (maternally and paternally inherited: F‐ M‐mtDNA) nuclear locus (ITS) yield concordant estimates gene flow divergence. The blue mussel, Mytilus edulis, is distributed on both North American European coastlines these populations are separated by the waters Atlantic Ocean. Gene across...