When the initial draft of the human genome was sequenced and released (2003) to researchers, many scientists thought it would immediately reveal the genetic basis for human disease. We soon realized that the human genome is much more complex than was ever imagined. Since then, technological advances have allowed us to evaluate thousands of genetic variants in large populations and conduct genome-wide association studies to identify which genes predispose a person to a particular disease or trait. More recently, we have entered a new era of affordable, rapid sequencing, which has provided scientists with unparalleled access to the high-quality, informative data needed to unravel the genetic relationships to human disease.
Not all diseases are created equal. Some diseases result from disruptions in a single gene, while others, including autoimmune diseases like lupus and Sjögren’s syndrome, are influenced by multiple genes. In autoimmunity, the immune system mistakenly recognizes self-molecules as foreign, leading to inflammatory processes and tissue damage to organs and worse prognosis if not treated. While the precise causes of autoimmune diseases are not fully known, it is well accepted that most arise from a complex interplay of multiple genetic risk factors and environmental triggers. Genetic studies in these diseases require international collaborations to assemble the large patient and healthy control populations needed to conduct large-scale genome-wide associations studies. To date researchers have identified more than 100 genes in lupus. In contrast, only 15 genes have been identified in Sjögren’s syndrome. The disparity between Sjögren’s and lupus is largely due to the lack of large, well-characterized patient collections and the later age of disease onset.
My lab studies the genetics of autoimmune-related traits. Our goal is to understand the complex interactions between the elements of the human genome to identify new biomarkers and to develop therapeutics that will ultimately improve the lives of patients affected by these serious autoimmune disorders.
In the post genome-wide association (GWA) era, my lab has been focused on determining the mechanisms by which these associations contribute to disease risk. Since more than 80% of the variants associated with complex traits are not coding and many of the molecular methods used to determine the functional/causal variant(s) have been low throughput, most risk loci have not been characterized mechanistically. Many large consortiums have worked to catalog features of the human genome outside of the coding sequence, which has helped us prioritize variants for functional characterization; however, many regulatory elements are cell type and/or context specific. Thus, these data only provide a selected view of the possible ways a variant may alter genomic regulation. One major observation made by ENCODE and other groups was that more than 60% of the human genome yields RNA molecules of more than 200bp in length; the functions of which are largely unknown. However, many of those that have been functionally determined work to regulate transcription both in cis and trans. Recent work, driven by advances in technology to evaluate single cells, have also opened new avenues into our understanding of cell populations, differentiation, and cell type specific differences between patients and healthy subjects.
The goal of my research is to better understand how regulation of protein coding gene expression is controlled by the non-coding genome, and how genetic variation and long non-coding RNAs can lead to dysregulation. We use bioinformatics, high throughput genotyping, short and long read sequencing, basic cell biology, biochemistry, and various in vitro cellular models. To date, my research has primarily focused on understanding the genetics of systemic lupus erythematosus and Sjögren’s syndrome. However, more recently, my work has expanded to include neuromyelitis optica (NMO), multiple sclerosis (MS), and rheumatoid arthritis. While all of these diseases have autoimmune phenotypes and established genetic influences, our research is aimed at uncovering how similarities and differences between these traits could synergistically improve our understanding of genomic regulation of the human immune system.
B.Sc., University of Minnesota, Minneapolis, MN, 2000
Ph.D., Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 2010
Postdoctoral Studies, Oklahoma Medical Research Foundation, 2012
Honors and Awards
|1999-present||Member, Golden Key National Honor Society|
|2008-2009||Barrett Predoctoral Scholarship Fund Award|
|2008||Notable Poster Award, American College of Rheumatology Annual Scientific Meeting, San Francisco, CA|
|2009||Paul Kimmelstiel Graduate Student Award for Excellence in Research and Presentation Skills, Department of Pathology, University of Oklahoma Health Sciences Center|
|2009||American College of Rheumatology Research and Education Foundation/Abbott Health Professional Graduate Student Research Preceptorship Award|
|2010||Paul Kimmelstiel Graduate Student Award for Excellence in Research and Presentation Skills, Department of Pathology, OUHSC|
|2010||Graduate Student Association Award for Outstanding Academic Achievement, OUHSC|
|2010||Outstanding Graduate Award (for a 4.0 GPA), OUHSC|
|2010||Notable Poster Award, American College of Rheumatology Annual Scientific Meeting, Atlanta GA|
|2011-present||Visiting Professor, Center for Autoimmune Disease Research (CREA), Universidad Del Rosario, Bogotá, Colombia|
|2011||OMRF Outstanding Paper Award for FY 2010-2011|
|2015||Notable Translational Abstract, EULAR 2015 (Rome, Italy)|
|2016||J. Donald and Patricia Capra Award for Scientific Achievement|
|2020||European League Against Rheumatism (EULAR) E-Congress Basic Science Abstract Award|
|2022||European League Against Rheumatism (EULAR) Congress Basic Science Abstract Award|
American Society of Human Genetics, 2007-present
American College of Rheumatology, 2016-present
American Academy of Neurology, 2015-2016
Joined OMRF Scientific Staff in 2007
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Michelle Joachims, Ph.D.
Mandi Wiley, Ph.D.
Associate Staff Scientist
Bhuwan Khatri, Ph.D.
Senior Computational Post-Doctoral Fellow
Cherilyn Pritchett Frazee
Research Technician IV
Anna "Ania" Stolarczyk
Research Technician III
Administrative Assistant III