Jeffrey W. Grover

Boston, MA E-mail: jeffrey.w.grover@gmail.com

Education

2020 – Ph.D. – Molecular and Cellular Biology
The University of Arizona
Advisor: Dr. Rebecca Mosher
Dissertation: Investigating the Role of RNA-directed DNA Methylation in Plant Reproduction and Development of Computational Resources Enbaling Epigenomic Research

2015 – Professional Science Masters (PSM) – Applied Biosciences
Specialization: Molecular and Cellular Biology
The University of Arizona
Advisor: Dr. Rebecca Mosher
Thesis: Investigation of Nuclear-Cytoplasmic Shuttling of AGO4 and its Effect on RNA-directed DNA Methylation in Arabidopsis thaliana

2011 – B.S. – Biochemistry and Molecular Biology
Additional Major: Chemistry
Michigan State University

Professional/Research Experience

Entrada Therapeutics - Boston, MA

2024-Present – Senior Scientist I - NGS & Bioinformatics
2022-2024 – Scientist II - NGS & Bioinformatics
Discovery Biology/Quantitative Biology Divisions

Entrada's first bioinformatics and NGS hire, tasked with building-out bioinformatics and NGS capabilities.
Led NGS laboratory and instrumentation set-up.
Led set-up and management of bioinformatics compute and data storage infrastructure.
Supervised and trained junior staff in bioinformatics, data science, and NGS lab work.
Managed the company’s Illumina sequencing instruments and all NGS data/metadata.
Acted as subject matter expert across therapeutic programs to assess feasibility and actionability of NGS, bioinformatics, and data science project proposals.
Collaboratively led the transcriptomic (bulk and single-cell) characterization of therapeutics providing data to de-risk programs.
Designed and executed RNAseq studies for off-target assessment of oligonucleotide therapeutics on tight timelines.
Led the development of a multiplex splicing assay by targeted RNAseq.
Led the development of an interactive dashboard for exploration of RNAseq data by wet lab personnel.
Developed a strategic plan for computational infrastructure and data storage in coordination with IT.
Analyzed NGS data for differential gene expression, whole-exome sequencing, alternative splicing, gene editing, scRNAseq, and spatial transcriptomics.
Developed bioinformatics workflows with NextFlow.
Instituted best practices for bioinformatics workflow development and deployment for HPC and cloud compute.
Authored SOPs to ensure reproducibility of computational analyses and data integrity.

Seven Bridges Genomics - Boston, MA

2020-2022 - Genomics Scientist
Public Programs Division

Built reproducible bioinformatics analysis workflows with cloud computing, Docker containers, the Seven Bridges Platform, and the Common Workflow Language (CWL).
Analyzed patient-derived xenograft cancer genomics data (transcriptomics and whole exome) for the NCI’s PDXNet Consortium (https://www.pdxnetwork.org/).
Managed access to PDXNet data through the Seven Bridges/NCI Cancer Genomics Cloud (https://www.cancergenomicscloud.org/).
Contributed to development of the PDXNet Portal (https://pdxnet.shinyapps.io/portal/) using R Shiny.
Prototyped new analysis workflows and Seven Bridges Platform functionality.
Contributed to Seven Bridges Platform development, proposing new features, bug fixes, and strategies to capture new bioinformatics use cases and users.
Oversaw the integration of workflows for the analysis of whole-genome bisulfite/methyl-seq, ATACseq, and ChIPseq on the Seven Bridges Bioinformatics Cloud Platform.
Gave public presentations to the National Cancer Institute and other CGC users on advanced Seven Bridges Platform functionality.

The University of Arizona - Tucson, AZ

2014-2020 – Graduate Student
Lab: Dr. Rebecca Mosher - Molecular and Cellular Biology & The School of Plant Sciences

Worked to determine the role of small RNAs and and RNA-directed DNA Methylation (RdDM) in plant reproduction, using Brassica rapa as a model system.
Assessed the role of small RNAs and RdDM in genomic imprinting in Brassica rapa.
Led the development of reproducible analysis pipelines for small RNA sequencing and whole-genome bisulfite sequencing using Snakemake and Docker containers.
Administered a Linux-based bioinformatics server for multiple users.
Developed workflow functionality for the CoGe (https://genomevolution.org/) bioinformatics and comparative genomics web platform (in collaboration with the Lyons lab at Arizona).
Investigated the mechanism of subcellular localization of Argonaute 4 (AGO4) and the role of its localization in the function of RNA-directed DNA Methylation (RdDM).

MPI Research, Inc. - Mattawan, MI

2011-2013 – Research Associate
Cellular, Molecular, and Biochemical Sciences Department

Performed qPCR-based biodistribution assays and expression profiling by qPCR arrays.
Performed high throughput DNA/RNA isolation with laboratory automation.
Conducted assays in compliance with the FDA regulations (GLPs).
Authored GLP-compliant experimental protocols and reviewed data for GLP compliance.

Michigan State University - East Lansing, MI

2007-2011 – Undergraduate Research Assistant
Lab: Dr. Robert Last - Department of Biochemistry and Molecular Biology

Assayed Arabidopsis thaliana mutants for lipid content by gas chromatography.
Mapped lipid phenotypic traits to candidate genomic loci using microarrays.

Highlighted Skills

Programming Languages
Python, R, BASH/shell, SQL

Computational Infrastructure
Linux system administration, Containers (Docker, Singularity), HPC, version control (git), cloud computing (AWS, Azure, GCP),

Workflow Management Frameworks
Snakemake, Nextflow, CWL

Bioinformatics Analysis
RNAseq, differential gene expression, alternative splicing, DNA methylation, variant calling, small RNAseq, scRNAseq, spatial transcriptomics

Data Science Libraries/Tools
R – Tidyverse (dplyr, ggplot2, et al.), R-markdown, Rstudio
Python – Jupyter, Pandas, numpy, matplotlib, seaborn, scikit-learn

Molecular Biology
RNA/DNA isolation, gel electrophoresis, PCR, RT-PCR, qPCR, sequencing library prep (Illumina)

Skills Continued

Collaboration and Communication
Scientific project management, mentorship of junior scientific staff, training junior staff on computational methods, training junior staff on molecular biology techniques, scientific presentations, presenting data to non-scientists, presenting computational analyses to wet-lab scientists, experimental report writing

Bioinformatics Analysis
RNAseq, targeted RNAseq, differential gene expression, alternative splicing, transcriptome assembly, transcriptome annotation, whole-genome bisulfite sequencing, enzymatic methyl-seq, differential DNA methylation, DNA sequencing, whole-exome sequencing, targeted exome sequencing, variant calling, small RNAseq (siRNA, miRNA, et al.), differential small RNA expression, small RNA locus annotation, single-cell RNAseq (scRNAseq), single-nucleus RNAseq (snRNAseq), spatial transcriptomics (Vizgen Merscope, 10X Xenium), cell type annotation, single cell and spatial transcriptomics data integration, dimensionality reduction (PCA, UMAP), statistical testing

Bioinformatics Tools
Bowtie, Bowtie 2, BWA, STAR, STARsolo, HISAT2, Minimap2, bismark, bwa-meth, shortstack, bedtools, Picard, GATK, fastqc, multiqc, samtools, vcftools, bcftools, deepvariant, VEP (Ensembl variant effect predictor), Salmon, alevin, kallisto, bustools, RSEM, rMATS, SUPPA, PASA, trinity, StringTie, trim galore, cutadapt, trimmomatic, UMI-tools

Bioinformatics Workflow Management
Bioinformatics workflow design, workflow development for HPC, workflow development for cloud computing (AWS), workflow development for public-use (Seven Bridges Cancer Genomics Cloud, PDXNet), Snakemake, Nextflow, CWL

Bioinformatics Software Packages/Libraries
R/Bioconductor – DESeq2, edgeR, limma, SummarizedExperiment, methylkit, tximport, GenomicRanges, Rsamtools, pcatools, biomaRt, clusterProfiler, Seurat, harmony, SingleCellExperiment, scuttle, scran, scater, batchelor, sva
Python – pyDESeq2, scverse, scanpy, squidpy, spatialdata, scvi-tools, pysam, htseq, biopython, scikit-bio, deepTools

Bioinformatics Databases/Web Tools
Sequence Read Archive (SRA), Gene Expression Omnibus (GEO), European Nucleotide Archive (ENA), Database of Genotypes and Phenotypes (dbGAP), Catalogue Of Somatic Mutations In Cancer (COSMIC), Ensembl, UCSC Genome Browser/Tools, Leiden Open Variation Database (LOVD), ClinVar, Human Protein Atlas, GTEx

Data Science and Other Software Packages/Libraries
R – Tidyverse, readr, tibble, dplyr, dbplyr, dtplyr, tidyr, stringr, purrr, forcats, readxl, jsonlite, rvest, httr, glue, data.table, ggplot2, ggpubr, R-shiny, tidymodels, caret, mlr3, pcatools, uwot, umap, R-markdown, Irkernel, Rstudio, plotly, pheatmap, ComplexHeatmap, viridis, reticulate, RSQLite, devtools, roxygen2
Python – Jupyter, Pandas, numpy, matplotlib, seaborn, altair, plotnine, plotly, dash, scikit-learn, statsmodels, rpy2, requests, BeautifulSoup, Selenium, sqlite3

Computational Infrastructure
Linux system administration, containers (Docker, Singularity, Apptainer), HPC, job schedulers (ex. SLURM, LSF, PBSPro), version control (git), cloud computing (AWS, Azure, GCP)

Molecular Biology
RNA/DNA isolation, gel electrophoresis, PCR, RT-PCR, qPCR, sequencing library prep (Illumina), RNAseq library preparation, whole-genome bisulfite sequencing library preparation, enzymatic methyl-seq library preparation, DNA sequencing library preparation, western blotting

Teaching Experience

2019 – Teaching Assistant, University of Arizona
MCB301: Molecular Basis of Life (3rd Year: Biochemistry and Molecular Biology)

2017 – Teaching Assistant, University of Arizona
MCB304: Molecular Genetics (3rd/4th Year: Genetics)

Broader Impacts

Tool Development

Epigenomics on the Cancer Genomics Cloud (CGC)
Oversaw the addition of ChIPseq and ATACseq workflows to the CGC in collaboration with Seven Bridges Bioinformatics team in Europe.

Provided technical and scientific consulting regarding their implementation.
Publicized these workflows in a talk at the CGC Summer Symposium 2021.

PDXNet Public Data Portal
Guided development of the PDXNet Public Data Portal (https://pdxnet.shinyapps.io/portal). The PDXNet Portal is an R Shiny-based web application where analyses performed on data generated by the PDXNet initiative can be visualized and the consortium data is made available to the public.

WGBS Snakemake Pipeleine
An automated whole-genome bisulfite sequencing pipeline. Available on Github and as a Docker container. Compatible with Singularity for deployment on HPC systems.

sRNAseq Snakemake Pipeleine
An automated small-RNA sequencing pipeline. Available on Github and as a Docker container. Compatible with Singularity for deployment on HPC systems.

Supervised its creation by undergraduate student, Maya Bose.
The pipeline is based on the methods from Grover et al. 2018

LoadExp+
Web-based analysis pipelines next-generation sequencing experiments CoGe. Integrated with the CyVerse datastore.

Publicly Available Data

PDXNet RNAseq and Whole-exome Sequencing
- Available through https://pdxnet.shinyapps.io/portal
- Processed over 80TB of raw sequencing data

Small RNA Sequencing from B. rapa ovules and leaves - R-o-18, nrpd1, nrpe1, and rdr2 mutants
NCBI SRA Accession: SRP114437

Small RNA Sequencing from B. rapa R-o-18xR500 reciprocal cross seeds
NCBI SRA Accession: SRP114469

RNA Sequencing from B. rapa R-o-18 and nrpd1 mutant ovules and seeds
NCBI SRA Accession: SRP132223

B. rapa Seed Epigenome Profiling
- Tissues: Whole seeds, dissected seed tissues, ovules, and leaves
- Genotypes: RdDM mutants, wild-types of two B. rapa varieties, and reciprocal crosses
- Data Types: Small RNAseq, whole-genome bisulfite sequencing, and mRNA-seq
- NCBI SRA Accession: SRP229027

Conference Presentations

Oral Presentations

2021 – NCI Containers and Workflows Interest Group Webinar Series
Developing Scalable Bioinformatics Workflows on the Cancer Genomics Cloud

2021 – The Cancer Genomics Cloud Summer Symposium
Epigenomics On the Cancer Genomics Cloud: Enabling Scalable Analysis Using Cloud Computing

Attended by over 100 CGC users

2018 – The University of Arizona Joint Biology Retreat
Dissection of the Spatiotemporal Dynamics of RNA-directed DNA Methylation During Seed Development

2017 – Plant and Animal Genome Conference, San Diego, CA
User-friendly Whole Genome DNA Methylation Analysis with FlowGe

Poster Presentations

2021 – Bioinformatics Open Source Conference, Online
Linking Standards through the BioCompute App to Support Workflow Interpretability and Execution

2019 – Plant and Animal Genome Conference, San Diego, CA
Spatiotemporal Dynamics of Small RNA Accumulation During Seed Development in Brassica rapa

2017 – The University of Arizona Joint Biology Retreat
PolIV-dependent siRNAs from Maternal Somatic Tissue Are Required for Seed Development in Brassica rapa

2016 – Arizona RNA Symposium
AGO4 Nuclear Import and Export Impact RNA-directed DNA Methylation

2016 – The University of Arizona Joint Biology Retreat
AGO4 Nuclear Import and Export Impact RNA-directed DNA Methylation

2015 – The University of Arizona School of Plant Sciences Departmental Retreat
Investigation of Nuclear-Cytoplasmic Shuttling of AGO4 and its Effect on RNA-directed DNA Methylation in Arabidopsis thaliana

Publications

Burgess D, Chow HT, Grover JW, Freeling M, Mosher RA. Ovule siRNAs methylate protein- coding genes in trans. The Plant Cell. 2022;34(10):3647-3664. https://doi.org/10.1093/plcell/koac197

Koc S, Lloyd MW, Grover JW, Xiao N, Seepo S, Subramanian SL, Ray M, Frech C, DiGiovanna J, Webster P, Neuhauser S, Srivastava A, Woo XY, Sanderson BJ, White B, Lott P, Dobrolecki LE, Dowst H, PDXNet Consortium, Evrard YA, Wallace TA, Moscow JA, Doroshow JH, Mitsiades N, Kaochar S, Pan CX, Chen MS, Carvajal-Carmona L, Welm AL, Welm BE, Lewis MT, Govindan R, Ding L, Li S, Herlyn M, Davies MA, Roth J, Meric-Bernstam F, Robinson PN, Bult CJ, Davis-Dusenbery B, Dean II DA, Chuang JH. PDXNet portal: patient-derived Xenograft model, data, workflow and tool discovery. NAR Cancer. 2022. https://doi.org/10.1093/narcan/zcac014

Becktel DA, Zbesko JC, B. Frye JB, Chung AG, Hayes M, Calderon K, Grover JW, Li A, Garcia FG, Tavera-Garcia MA, Schnellmann RG, Wu HJ, Nguyen TV, Doyle KP. Repeated administration of 2-hydroxypropyl-β-cyclodextrin (HPβCD) attenuates the chronic inflammatory response to experimental stroke. Journal of Neuroscience. 2021. https://doi.org/10.1523/JNEUROSCI.0933-21.2021

Chakraborty T, Kendall T, Grover JW, Mosher RA. Embryo CHH hypermethylation is mediated by RdDM and is autonomously directed in Brassica rapa. Genome Biology. 2021. https://doi.org/10.1186/s13059-021-02358-3

Grover JW, Burgess D, Kendall T, Baten A, Pokhrel S, King GJ, Meyers BC, Freeling M, Mosher RA. Abundant expression of maternal siRNAs is a conserved feature of seed development. PNAS. 2020. https://doi.org/10.1073/pnas.2001332117

Grover JW*, Kendall T*, Baten A, Burgess D, Freeling M, King GJ, and Mosher RA. Maternal components of RNA‐directed DNA methylation are required for seed development in Brassica rapa. The Plant Journal. 2018. https://doi.org/10.1111/tpj.13910

* These authors contributed equally to this work.
Chosen as the cover article by The Plant Journal.
Covered by a research highlight in the Plant Journal.
Mentioned in Plantae’s “What We’re Reading” blog.

Grover JW, Bomhoff M, Davey S, Gregory BD, Mosher RA, Lyons E. CoGe LoadExp+: A web‐based suite that integrates next‐generation sequencing data analysis workflows and visualization. Plant Direct. 2017. https://doi.org/10.1002/pld3.8