Variant characterization for clinical diagnosis
The Jacob Lab focuses on translating whole genome sequencing into a clinical tool for understanding human complex and rare diseases.
My research focus is on combining in silico tools with bench top research to understand proteins, how they evolve, what regulates their expression, and how modifications alter their function. I utilize computer tools such as evolutionary analysis, promoter analysis, codon selection, protein modeling, and molecular dynamic simulations to name a few in order to study what features of proteins are conserved and how those elements may function. This computer work is currently funded by a K01 from the NIH Big Data to Knowledge (BD2K) initiative to develop a deep Sequence-to-Structure-to-Function analysis for disease variants. Once we have computer generated hypotheses for function, we utilize biochemistry, molecular genetics, and physiological approaches to test our predictions. Recently, my work has focused in two areas, using evolution to determine novel peptide inhibitors/activators particularly in signaling biology and studying genetic variants that contribute to disease. For diseases we are currently focusing on utilization of whole genome sequencing for rare/undiagnosed diseases in addition to dissecting the mechanisms for Genome Wide Association Data (GWAS) in common diseases such as cardiovascular/kidney disease and cancer.
Nadiya Sosonkina, PhD, is a postdoctoral fellow in the Jacob Lab. Sosonkina investigates rare variants that cause rare diseases and works on cellular models that would enable functional studies of these variants. She is especially interested in autism spectrum disorders (ASD) that combine common and rare features because while ASD is a rather common diagnosis, it is genetically very heterogeneous and includes many unique subphenotypes. Before joining HudsonAlpha in 2015, Sosonkina worked on research in lung and thyroid cancer at the Medical College of Wisconsin in Milwaukee. She received her bachelors degree in ecology and a masters degree in environmental science from the National University of “Kyiv-Mohyla Academy” in Kiev, Ukraine. Her career interests shifted when she accepted a position as a research assistant in the Human Genetics Laboratory at Nagasaki University Graduate School of Biomedical Science in Nagasaki, Japan. She earned her PhD in pharmaceutical science at Health Sciences University of Hokkaido in Tohbetsu, Japan, where she was a research associate working in human genetics. At Health Sciences University, her interests included the genetics of common traits and, among other topics, she studied the polymorphism in the ABCC11 gene that determines the type of earwax – wet or dry – a person has and its role in susceptibility to breast cancer.
Emily J. Ross is a graduate student in Vanderbilt University’s Chemical and Physical Biology program and a research assistant in the Jacob Lab. She is interested in the genetics of rare, undiagnosed and complex diseases. To study this field, the lab has developed a strategy for genetic variant analysis using both computational applications and downstream biochemical and cellular pathway approaches. This work will be accomplished by utilizing our NIH-funded deep-Sequence-to-Structure-to-Function analysis tools that predict gene function. The data will be combined with wet lab work using CRISPR/Cas9-generated mutated variants in mammalian cellular lines that are seen in patients. These modified cells will be investigated using different cellular assays, affinity capture experiments and pathway analysis. This current approach provides the ability to assess both coding (changes in the sequence of a protein) and non-coding (near a gene but does not alter the protein sequence) variants for any disease. Our goal with this approach is to bring a diagnosis to the patient on a time scale of weeks to months needed for individual treatment and care instead of the months to years required by extensive animal research.
Ross earned her MS in chemistry from Vanderbilt University in Nashville. Working in Dr. Sandra Rosenthal’s laboratory in the chemistry department, she completed her master’s thesis on the development of quantum dot-based live-cell pharmacological assays aimed at membrane transporters and receptors. While in the lab of Dr. Gregg Stanwood at Vanderbilt, Ross examined how genetic and environmental alterations in neurotransmitter signaling, especially dopamine, alter the formation of brain architecture and contribute to the prodromal phases of mental illness. In 2008, she earned dual BS degrees in chemistry and biology from the University of Alabama in Huntsville. Ross joined the Jacob Lab in 2016, returning to the HudsonAlpha campus where she previously worked as a lab technician for Conversant Bio until 2009 and a lab associate for Thermo Fischer (Legacy Open Biosystems) until 2008.