As part of an innovative lab, I am involved in many projects, but my primary research interests include identifying genetic factors that underlie complex diseases and adverse drug reactions particularly in underrepresented populations.
Prediction and treatment of heparin-induced thrombocytopenia (HIT)
Despite the widespread use of heparin and the high mortality associated with HIT, clinicians are not able to predict those patients who will develop this severe adverse drug reaction. I have experience in association analysis identifying genomic associations with HIT as well as creating imputation pipelines to utilize the Trans-Omics for Precision Medicine (TOPMed) program to better inform these studies. TOPMed, sponsored by the National Institutes of Health (NIH) National Heart, Lung and Blood Institute (NHLBI), is part of a broader Precision Medicine Initiative, which aims to provide disease treatments tailored to an individual’s unique genes and environment. I have experience using this large and diverse reference population provided for imputation purposes for our array data in relation to HIT studies. By providing genomic predictors of HIT, I have worked towards establishing new knowledge of HIT and providing potential genomics predictors that might be translated into clinical care.
- Giles JB, Steiner HE, Rollin J, Shaffer CM, Momozawa Y, Mushiroda T, Inai C, Selling K, Thiele T, Pouplard C, Heddle NM, Kubo M, Miller EC, Martinez KL, Phillips EJ, Warkentin TE, Gruel Y, Greinacher A, Roden DM, Karnes JH. Genome-wide association study of platelet factor 4/heparin antibodies in heparin-induced thrombocytopenia. Blood Advances. 2022, 6(14): 4137-4146.
- Karnes JH, Rollin J, Giles JB, Martinez KL, Steiner HE, Shaffer CM, Momozawa Y, Inai C, Bombin A, Shi M, Mosely JD, Stanaway I, Selleng K, Thiele T, Mushiroda T, Pouplard C, Heddle NM, Kubo M, Phillips EJ, Warkentin TE, Gruel Y, Greinacher A, Roden DM. ABO O blood group as a risk factor for platelet reactivity in heparin-induced thrombocytopenia. Blood. 2022, 140(3): 274-284.
Defining the hypermobile subtype of Ehlers-Danlos syndrome (hEDS) and identifying its underlying genetics
As a graduate student I help establish the first hEDS cohort study which continues its efforts to the present day. The hEDS GENE study is a multicenter, cohort study with the goal of identifying genes associated with hEDS. Ehlers-Danlos syndrom (EDS) describes a collection of rare hereditary connective tissue disorders with heterogeneous phenotypes. Despite hEDS being the most prevalent EDS subtype, hEDS is the least understood and the only EDS subtype without any consensus on associate causal genes or variants The study sought to enroll 150 people who meet the 2017 hEDS criteria but has since expanded upon that initial recruitment goal. During my time as part of the hEDS GENE study, I helped to clinically define the hEDS phenotype and conducted preliminary genetic studies using linkage analysis as well as investigating structural variants using whole-genome sequencing data. Though my research efforts have since focused elsewhere, I have successfully written grants that are currently funding projects under the hEDS GENE study to continue its efforts to elucidate the genetics underlying hEDS.