June 7, 2024
Jamie Madrigal, Mac Monroe, Suzanne Sindi, Karin Leiderman, from The University of North Carolina at Chapel Hill School of Medicine, had a new paper published in Mathematical Biosciences. “Modeling the Distribution of Enzymes on Lipid Vesicles: A Novel Framework for Surface-Mediated Reactions in Coagulation”. Abstract Blood coagulation is a network of biochemical reactions wherein dozens …
June 5, 2024
Abigail Ballard-Kordeliski, Robert H. Lee, Ellen Clelia O’Shaughnessy, Paul Y. Kim, Summer R Jones, Rafal Pawlinski, Matthew J. Flick, David S. Paul, Nigel Mackman, David Adalsteinsson, Wolfgang Bergmeier all of University of North Carolina at Chapel Hill had their research published in the journal Blood. Title: “4D intravital imaging identifies platelets as the predominant …
December 13, 2019
I am a clinical hematologist with an academic focus and national leadership role in the field of vascular anomalies. I built and co-directed the Vascular Anomalies Program at Vanderbilt University Medical Center and served as Associate Clinical Director of the Comprehensive Vascular Anomalies Program and Co-Director of the Pediatric Hereditary Hemorrhagic Telangiectasia Program at the …
December 12, 2019
Research Interests Gene regulation, RNA processing and RNA binding proteins in cell signaling and disease Research Synopsis The Dominguez lab studies how gene expression is controlled by proteins that bind RNA. RNA binding proteins control the way RNAs are transcribed, spliced, polyadenylated, exported, degraded, and translated. Areas of research include: Altered RNA-protein interactions in cancer RNA processing is massively altered in cancer. These observations can be explained by 1) mutations in RNA binding proteins that alter how they bind their target transcripts, 2) mutations in RNA sequences that are normally bound by specific RNA binding proteins. We use computational approaches and biochemical assays to characterize mechanisms underlying cancer-specific RNA processing defects. RNA binding by noncanonical domains Recent evidence indicates that non-canonical domains or even disordered regions also bind RNA. We employ large-scale biochemical approaches to study these interactions in vitro and and in vivo. Given the prevalence of low-complexity domains in the proteome and their association with disease, understanding how these domains interact with RNA will shed new light on normal and aberrant RNA biology. Cell signaling and RNA processing Cell signaling pathways are known to modulate gene expression. However, crosstalk/cross-regulation between RNA processing and cell signaling is not well understood. We use systematic screening approaches to dissect the impact of cell signaling pathways on RNA binding protein activity. This project involves the study of post-translational modifications of RNA binding proteins, the use of targeted drug screens and integrative analysis with RNA sequencing datasets.
December 10, 2019
I have been committed to building a strong translational research program to address novel challenges and questions related to blood and renal pathophysiology in rodents and humans. My work provided strong pre-clinical evidence that endothelin system significantly contributes to sickle cell renal pathophysiology. My collaborative efforts with Dr. Lebensburger identified predictors of the onset of long-term kidney insufficiency and uncovered clear sex differences in the rate of sickle cell nephropathy progression in patients and murine model of sickle cell disease. My current research focuses on functional significance of iron homeostasis in chronic kidney disease (CKD), in particular, the mechanisms of renal iron handling in progressive sickle cell nephropathy. Currently, my lab has three on-going research projects: 1) elucidating molecular mechanisms of endothelin system-mediated renal iron handling in murine models of iron overload; 2) mechanisms of renal dysfunction in sickle cell trait, 3) identifying risk factors for early progression to CKD in sickle cell pediatric patients.
December 5, 2019
I am a clinical researcher focused on identifying modifiable risk factors to improve survival and quality of life of adults with sickle cell disease. My ongoing research interests are to characterize the phenomenon of occult hypoxia in high-risk subset of adults with sickle cell disease, and to explore the experience of pregnancy and its complications in the sickle cell population. As a member of the BRC, I collaborate with colleagues to understanding the impact of red blood cell and placental health on pregnancy outcomes.
December 5, 2019
In my research program, I use human genomics and multi-omics to understand inherited and environmental risk factors for cardiometabolic diseases, Alzheimer’s disease and related dementias, and related quantitative traits, including hematology and hemostasis phenotypes. I work to link genetic variants to function through integration with multi-omics data, including transcriptomic, methylation, proteomic, and metabolomic measures. This work has important implications for disease risk prediction and improved understanding of disease biology. A focus on understudied populations is a central theme of my research; human genetics and molecular epidemiology research is dramatically unrepresentative of global populations, with for example >90% of genome-wide association study participants of European descent. As complex trait genetics moves into the clinic, increasing representativeness is essential to ensure that all populations benefit from the promise of precision medicine. Characterization of population-differentiated variants with impacts on hematological parameters, for example sickle cell trait and Duffy-null status, is an ongoing area of research for our lab, as are hematological trait polygenic risk scores and rare variant genetic discovery efforts. I play a leadership role in collaborative efforts in human genetics, for example serving as a Genetics Working Group co-chair for the Jackson Heart Study (JHS), one of the largest population-based studies of African American adults, and as a co-convener of the Multi-Omics working group for the NHLBI Trans-Omics for Precision Medicine (TOPMed) program.