Research

We are entering into a new era of genomics where truly complete, high-quality “telomere-to-telomere” chromosome assemblies are finally within reach. This technological advance is revealing unexplored sequence and epigenetic variants to study in the context of basic cellular biology and human disease. Importantly, these emerging high-resolution reference maps will offer an unprecedented opportunity to explore a new ‘functional landscape’ in the human genome, where DNA-binding proteins, transcriptional regulation and spatial organization can be examined with base-level resolution across different stages of development and disease. The Miga lab is uniquely positioned to lead innovative functional studies in these regions previously thought to be intractable, and in doing so, we aim to establish a new niche in the field of genomics for the study of satellite DNA biology.

T2T Genomics

What sequences are missing from our reference genome? How do we advance new technologies to study these regions across a large number of individuals? And what new ‘functional’ elements (genes, transcription factor motifs, small RNAs, new transposable element families) can we detect in these previously unexplored corners of the genome? A primary objective of my research is to study the genomic organization, evolution, and functionality of hundreds of millions of bases previously omitted from the human reference genome assembly. Notably, this research focus is very much aligned with UCSC’s legacy as part of the original Human Genome Project. Many projects are supported by the development of long read data using nanopore sequencing. Therefore, research in my lab will include nanopore data production to support T2T reference production initiatives, and research and development to improve T2T long-read sequencing, assembly and validation methods. I welcome any student that wants to fully engage with T2T genomics and technology (offering both wet or dry lab training).

Human Satellite DNA Variation

T2T genomes will present a large, unexplored source of sequence variation in the human population. Cytogenetic literature has revealed that many of the largest gaps in our reference genome, known to span centromeric regions, have visible expansions in repeat copy number associate with predisposition of cancer, infertility, and aneuploidy. The full extent of this variation remains unknown, and the role these genetic differences play in cellular function and biomedical disease remains almost entirely unexplored. Therefore, our research will aim to study how these sequences change over time (that is, between cells, different individuals, as well as ancient hominin populations and diverse species). This work will address a fundamental unknown in medical genetics, where these regions of the genome are known to present a large amount of sequence variation yet no methods currently exist to detect and incorporate into disease studies.

Human Satellite DNAs: Basic Cellular Function and Role in Human Disease

The Miga lab aims to understand the role of satellite DNAs in basic cellular function and how the these sequences contribute to our understanding of human disease. These regions were omitted from all previous epigenetic initiatives, and as a result, our understanding of genome biology, evolution, and regulation became disproportionately informed by data collected from the accessible parts of the reference genome. Ultimately, the structure and function of these highly repetitive regions of our genome present a large, unexplored epigenomic landscape. The Miga Lab aims to complete our epigenetic maps, and expand studies of epigenetic regulation over early development, aging and disease. To reach these goals, we will drive new innovation to expand functional long-read methods and datasets to reach a better understanding of how these regions are regulated.