We develop and apply genomic and computational methods to investigate the genetic architecture of complex traits, including disease risk and drug response. We are interested in what can be learned from DNA sequence and multi-omics data about disease mechanism, therapeutic intervention, molecular evolution, and genome function. An ongoing project involves understanding gene regulation to gain insights into disease mechanisms and therapeutic targets. We utilize large-scale DNA biobank data linked to electronic health records, along with data science and computation, to identify genes involved in human health and disease in diverse populations, to discover novel biomarkers, and to enable a comprehensive systems view of the disease phenome.
Current research interests in complex traits genetics include characterizing the genetic architecture of hematopoietic diseases, including Myelodysplastic Syndromes (MDS) and Acute Myeloid Leukemia (AML). We are developing functional genomics resources for probing molecular mechanisms underlying hematopoiesis and hematologic disorders. Studies of hematopoietic stem- and progenitor-cells (HSPCs), accumulating genetic modifications, and resulting clonal expansions are of interest. We are interested in the connection between Clonal Hematopoiesis of Indeterminate Potential (CHIP) — positive selection of certain somatic mutations in hematopoietic stem cells — and other complex diseases.
Ongoing research also includes modeling the transcriptional regulatory programs in the brain, in collaboration with human geneticists, neuroscientists, and evolutionary biologists. This work has obvious relevance to understanding the molecular basis of neuropsychiatric and neurodegenerative disorders.
Recent advances have enabled precise genome editing with high efficiency and minimal off-target effects. Meanwhile, EHR-linked DNA biobanks have been unprecedented in their efficiency for human genetic discovery. We are conducting studies and developing methods across systems. In recent collaboration with colleagues at Vanderbilt, we integrated human phenomic data and in vivo loss-of-function models generated using CRISPR-Cas9 genome editing strategies and morpholino (MO) oligonucleotide-based protein knockdown to characterize a mechanism that implicates vascular biology in the eye disease phenome.
In recent highly interdisciplinary work, Dr Gamazon is developing computational approaches to studying the structure, dynamics, and stability of biological molecules within Density Functional Theory (DFT), molecular dynamics, and coarse-grained modelling and using experimental techniques (e.g., X-ray crystallography, NMR spectroscopy, and cryo-electron microscopy). He is co-founder of the Chemistry and Disease Genomics Group (CDGG) with David Collison (Manchester) and Lalarukh Akhter (Cambridge).
Dr Gamazon is part of the GTEx Consortium, having served as co-chair of its GWAS Working Group, and the T2D-GENES Consortium. He was also a member of the International Warfarin Pharmacogenetics Consortium. As part of the Pharmacogenomics of Anticancer Agents Research (PAAR) Group at the University of Chicago, he developed and applied computational approaches to the study of the genetic basis of cancer susceptibility and of response to a wide array of functionally diverse chemotherapeutics.
He is a member of the faculty in the Division of Genetic Medicine in the Department of Medicine, the Vanderbilt Genetics Institute, and the Vanderbilt Data Science Institute.
He is a recipient of the inaugural Genomic Innovator Award from the National Institutes of Health (NIH).
He is now a Life Member (2019 -- present) of Clare Hall, University of Cambridge, able to return any time to participate in the intellectual life of the college. Clare Hall is the University's "Institute for Advanced Study," a unique college devoted to research and scholarship and a culturally rich and intellectually exciting academic community. In 2018, he was elected to a Clare Hall Visiting Fellowship to advance his research and scholarship and mentor graduate students. He was also a visiting scholar in the Department of Medicine, the MRC Epidemiology Unit, and the MRC Biostatistics Unit of the University of Cambridge.
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MeSH terms are retrieved from PubMed records. Learn more.Adult Antineoplastic Agents Biomarkers, Tumor Brain Breast Neoplasms, Male Carbohydrate Metabolism CD36 Antigens Chromosomes, Human, Pair 6 Deoxycholic Acid Deoxycytidine Epithelial Cells Fibrosis Frontal Lobe Gene Expression Profiling Genotype Glucose HapMap Project Heterozygote Hypothalamus Inheritance Patterns Insulin Secretion Intestine, Large Mixed Function Oxygenases Protein Interaction Mapping Proto-Oncogene Proteins c-akt Soybeans Species Specificity Symbiosis Thionucleosides Ubiquitin Thiolesterase