molecular biologist, bioinformatician, photographer
Hi, I’m Miguel. I’m a Postdoctoral Fellow in the Next-generation Sequencing (NGS) lab in the FDA Office of New Drugs. In the NGS lab, I use bioinformatic approaches to evaluate B-cell receptor sequencing (BCR-seq) assays, identify signatures of disease progression, and explore fundamental questions about mutational dynamics in cancer. I’m passionate about the power of bioinformatics to drive precision oncology, and I firmly believe in the potential of NGS technologies to facilitate universal early cancer detection.
Outside of the lab, I seek to capture the beauty of people, our planet, and the cosmos through photography.
Research Summary
Developing standards for capturing the Adaptive Immune Receptor Repertoire
Each of our bodies possesses a diverse set of molecules known as the Adaptive Immune Receptor Repertoire (AIRR). Each individual’s AIRR is shaped by their cumulative encounters with external pathogens and internal factors such as chronic disease, autoimmunity, and cancer. The wealth of information in an individual’s AIRR represents an invaluable asset to biomedical research, as access to complete repertoires could revolutionize cancer detection and provide insight into the role of the immune system in complex diseases such as schizophrenia and other neurological disorders.
As a Postdoctoral Fellow, I helped develop standards for benchmarking B-cell receptor sequencing (BCR-seq) assays. As part of the BCR-SEQC Consortium led by the FDA, I evaluated the performance of bulk and single-cell BCR-seq datasets, utilizing a workflow control comprised of B lymphoma cell lines and peripheral blood mononuclear cells (PBMCs) designed to model low-abundance clones in a diverse, clinically relevant background. This work laid the foundation for exhaustive benchmarking of several commercial BCR-seq assay kits, with the goal of providing the scientific community with resources that will aid in the design of AIRR experiments.
The ribosome: A sentinel for cellular stress
As a graduate student, I became captivated by RNA biology. During my Ph.D. in the Green Lab at JHMI, I focused my studies on the signaling roles carried out by the translational machinery of the cell, using yeast genetics and bioinformatic analyses to assemble a study at the intersection of translational control and cellular stress.
NGS expertise from bench to command line
My graduate work highlights nuances in mechanisms of Integrated Stress Response (ISR) activation. By employing a combination of RNA-seq, mass spectrometry, and polysome profiling, I identify novel connections between ribosome collisions and the Integrated Stress Response. I show that induction of ribosome collisions using the translation inhibitor cycloheximide (CHX) leads to a partial mobilization of ISR-target genes:
Gcn4-dependent gene lists defined by analysis of data from Natarajan et al. 2001; displayed RNA-seq data is my own.
Scientific Publications
Pacheco ME, Morrison C, Taylor S, Zhao Y, Xiao W. (2025). Evaluation of Chromium Next-GEM and GEM-X for single-cell B cell receptor sequencing. In preparation.
Pacheco ME, Xiao W. (2025). Dynamics of genetic drift in donor-matched tumor-normal cell lines. In preparation.
Pacheco ME, Xiao W, BCR-SEQC consortium. (2025). Resources for establishing reference materials for B cell receptor profiling analysis using NGS technologies. In preparation.