Nathan Hoverter Email & Phone Number

• Responsible for all aspects of technical development from Concept to Launch• Design and execute benchmark, verification, and validation studies• Phase exit approval from PAC committee• Data wrangling, statistical analysis, and visualization in Python• Managed direct reports

Pleasanton

• Managed direct reports• Chemistry development and integration• NGS experimental design, execution, primary, and secondary analysis

Pleasonton, Ca

• Individual contributor that made foundational chemistry and systems integration contributions to Purigen's Ionic Platform

Uc Irvine

I worked in Peter Donovan's lab on human embryonic stem cell fate. One long term goal of the Donovan lab is to understand the molecular mechanisms of primitive streak development during early development. In my short but satisfying time in the Donovan lab, I focused on how the transcription factor TCF7L1 antagonizes the differentiation of embryonic stem cells. This research has ramifications for the use of stem cells in therapies for degenerative diseases. I performed bioinformatics analysis of TCF7l1 ChIP-seq in human embryonic stem cells utilizing a ChIP-seq pipeline that I setup from scratch(Bowtie -> Samtools -> MACS2 -> IDR). I have performed an analysis of the reproducibility of the biological replicates with the Irreducibility Discovery Rate pipeline. In order to determine the direct transcriptional targets of TCF7l1, I integrated TCF7l1 ChIP-seq and expression profiling with a program called BETA.

Uc Irvine

Colon cancer is the second leading cause of cancer-related mortality in the United States, with about 50,000 deaths caused per year. Although there are many signaling pathways and molecular players involved in the disease, early development of the majority of colon cancer cases are driven by aberrant activation of the Wnt signaling pathway. In the Waterman laboratory, we study the LEF/TCF family of transcription factors, which relay Wnt signals to the control of gene expression. My thesis work was on the mechanisms by which LEF/TCF transcription factors select their DNA binding sites for the regulation of genes critical to the development of colon cancer. For my short postdoc at the Waterman lab, I worked on publishing new aspects of my thesis work. I also assisted a former member of the Waterman lab publish her thesis work by collaborating with her on experiments and assisting with the writing and editing process.

My thesis work was on the DNA binding activities of TCF transcription factors (T-cell Factors), downstream effectors of the Wnt signaling pathway. I investigated an auxiliary DNA binding domain called the C-clamp that is present in the ancestral TCF, but has been relegated to alternatively spliced isoforms of TCF1 and TCF4 in vertebrates (the “E” tail isoforms). I have found that the C-clamp harbors sequence specificity for GC-rich “Helper” elements and that this interaction enables TCF1E and TCF4E to regulate a subset of Wnt target genes. I have also determined that the C-clamp-Helper interaction is vital to Wnt-mediated repression of p21 in the intestinal epithelium. This has important implications for cancer because hyperactivation of the Wnt pathway and aberrant repression of p21 is a requirement for the early development of the majority of colon cancers. Additionally, I have performed genome-wide ChIP-seq experiments that demonstrate the C-clamp-Helper site interaction plays an important role in the genome-wide binding profile of TCF1E in colon cancer cells. These experiments have also implicated the C-clamp as a potential mediator of DNA sliding to allow TCFs to rapidly locate their high affinity binding sites. I also performed 4’Thiouridine-seq (a new RNA-seq based technique) experiments to determine the effect of C-clamp DNA binding on immediate changes in gene expression. 4'Thiouridine-seq experiments coupled with ChIP-seq experiments revealed dozens of potential new direct transcriptional target genes of the Wnt pathway. Determining the role of these novel target genes in colon cancer will be an exciting project for future researchers in the Waterman lab.

Doctor Of Philosophy (Phd), Biomedical Sciences, General

Biological Sciences