A5048863754- DNA Repair Mechanisms
- Cancer-related Molecular Pathways
- Microtubule and mitosis dynamics
- Genomics and Chromatin Dynamics
- Epigenetics and DNA Methylation
- Ubiquitin and proteasome pathways
- CRISPR and Genetic Engineering
- Genetics and Neurodevelopmental Disorders
- RNA modifications and cancer
- Single-cell and spatial transcriptomics
- Cell Image Analysis Techniques
- Fungal and yeast genetics research
- Gene Regulatory Network Analysis
- Pluripotent Stem Cells Research
- Chromosomal and Genetic Variations
- RNA Research and Splicing
- Mitochondrial Function and Pathology
- Doctoral Education Challenges and Solutions
- Cancer Genomics and Diagnostics
- Angiogenesis and VEGF in Cancer
- Plant-Microbe Interactions and Immunity
- Advanced Breast Cancer Therapies
- Biomedical Ethics and Regulation
- Health and Medical Research Impacts
- MicroRNA in disease regulation
University of North Carolina at Chapel Hill
2016-2025
University of North Carolina Health Care
2019-2025
Cornell University
2023
Weill Cornell Medicine
2023
University of North Carolina System
2022
Communities In Schools of Orange County
2011-2021
University of Edinburgh
2021
UNC Lineberger Comprehensive Cancer Center
2007-2020
ORCID
2019
Segeberger Kliniken
2008-2018
Haploid cells of budding yeast Saccharomyces cerevisiae respond to mating pheromones by inducing genes required for conjugation, arresting cell cycle progression, and undergoing morphological changes. The same nutrient deprivation altering pattern invasive growth. Both developmental alternatives vegetative proliferation require the MAP kinase Kss1 transcriptional transactivator Ste12. Using a two-hybrid screen gene products that interact with Kss1, two homologous previously uncharacterized...
The minichromosome maintenance (MCM) proteins, together with the origin recognition complex (ORC) proteins and Cdc6, play an essential role in eukaryotic DNA replication through formation of a pre-replication at origins replication. We used yeast two-hybrid screen to identify MCM2-interacting proteins. One we identified is identical ORC1-interacting protein termed HBO1. HBO1 belongs MYST family, characterized by highly conserved C2HC zinc finger putative histone acetyltransferase domain....
The mitogen-activated protein kinase (MAPK) Kss1 has a dual role in regulating filamentous (invasive) growth of the yeast Saccharomyces cerevisiae . stimulatory function requires both its catalytic activity and activation by MAPK/ERK (MEK) Ste7; contrast, inhibitory neither. This study examines mechanism which inhibits invasive growth, how Ste7 action overcomes this inhibition. We found that unphosphorylated binds directly to transcription factor Ste12, binding is necessary for Kss1-mediated...
PhD recipients acquire discipline-specific knowledge and a range of relevant skills during their training in the life sciences, physical computational social engineering. Empirically testing applicability these to various careers held by graduates will help assess value current models. This report details results an Internet survey science PhDs (n = 8099) who provided ratings for fifteen transferrable skills. Indeed, analyses indicated that doctoral develops skills, crucial success wide...
Cell cycle phase transitions are tightly orchestrated to ensure efficient cell progression and genome stability. Interrogating these is important for understanding both normal pathological proliferation. By quantifying the dynamics of popular FUCCI reporters relative into out S phase, we found that their substantially variably offset from true boundaries. To enhance detection transitions, generated a new reporter whose oscillations directly coupled DNA replication combined it with APC/C...
The cell cycle is canonically described as a series of four consecutive phases: G1, S, G2, and M. In single cells, the duration each phase varies, but quantitative laws that govern durations are not well understood. Using time-lapse microscopy, we found follows an Erlang distribution statistically independent from other phases. We challenged this observation by perturbing through oncogene activation, inhibition DNA synthesis, reduced temperature, damage. Despite large changes in populations,...
Complete and robust human genome duplication requires loading minichromosome maintenance (MCM) helicase complexes at many DNA replication origins, an essential process termed origin licensing. Licensing is restricted to G1 phase of the cell cycle, but length varies widely among types. Using quantitative single-cell analyses, we found that pluripotent stem cells with naturally short phases load MCM much faster than their isogenic differentiated counterparts long phases. During earliest stages...
Nuclear proteins bind chromatin to execute and regulate genome-templated processes. While studies of individual nucleosome interactions have suggested that an acidic patch on the disk may be a common site for recruitment chromatin, pervasiveness binding whether other hot-spots exist remain unclear. Here, we use affinity proteomics with library nucleosomes disrupts all exposed histone surfaces comprehensively assess how recognize nucleosomes. We find two adjacent are primary interactions,...
Kss1 and Fus3 are mitogen-activated protein kinases (MAPKs or ERKs), Ste7 is their activating MAPK/ERK kinase (MEK), in the pheromone response pathway of Saccharomyces cerevisiae. To investigate potential role specific interactions between these enzymes during signaling, ability to associate with each other was examined both solution vivo. When synthesized by vitro translation, could form a tight complex (Kd approximately 5 nM) absence any additional yeast proteins. These complexes were...
Kss1, a yeast mitogen-activated protein kinase (MAPK), in its unphosphorylated (unactivated) state binds directly to and represses Ste12, transcription factor necessary for expression of genes whose promoters contain filamentous response elements (FREs) pheromone (PREs). Herein we show that two nuclear proteins, Dig1 Dig2, are required cofactors Kss1-imposed repression. Dig2 cooperate with Kss1 repress Ste12 action at FREs regulate invasive growth naturally strain. Dig-dependent repression...
The Cdc6 protein is an essential component of pre-replication complexes (preRCs), which assemble at origins DNA replication during the G1 phase cell cycle. Previous studies have demonstrated that, in response to ionizing radiation, ubiquitinated by anaphase promoting complex (APC(Cdh1)) a p53-dependent manner. We find, however, that damage caused UV irradiation or alkylation methyl methane sulfonate (MMS) induces degradation independently p53. further demonstrate after these forms also...
KEAP1 is a substrate adaptor protein for CUL3-based E3 ubiquitin ligase. Ubiquitylation and degradation of the antioxidant transcription factor NRF2 considered primary function KEAP1; however, few other substrates have been identified. Because altered in number human pathologies has proposed as potential therapeutic target therein, we sought to better understand through systematic identification its substrates. Toward this goal, combined parallel affinity capture proteomics candidate-based...
Many US biomedical PhD programs receive more applications for admissions than they can accept each year, necessitating a selective process. Typical selection criteria include standardized test scores, undergraduate grade point average, letters of recommendation, resume and/or personal statement highlighting relevant research or professional experience, and feedback from interviews with training faculty. Admissions decisions are often founded on assumptions that these application components...
Abstract STING is an innate immune sensor for surveillance of viral/bacterial infection and maintenance immune‐friendly microenvironment to prevent tumorigenesis. However, if how exerts immunity‐independent function remains elusive. Here, the authors report that expression increased in renal cell carcinoma (RCC) patients governs tumor growth through non‐canonical signaling involving mitochondrial ROS calcium homeostasis. Mitochondrial voltage‐dependent anion channel VDAC2 identified as a new...