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Investigators

Investigators

Headshot of Nigel Key, M.B.,CH.B.,F.R.C.P.

Key

My group collaborates with other BRC faculty on several disease-oriented projects. Although my expertise is primarily in the development and implementation of coagulation assays in human blood, many of our projects include both human and mouse components. These include studies on the vascular biology of sickle cell disease (with Rafal Pawlinski), cancer-associated thrombosis (with Nigel Mackman) and acute liver failure (with Rafal Pawlinski and Jian Liu). We also collaborate with several extramural research teams in studies of coagulopathy of trauma, and thrombosis associated with cancer and other disorders.

Maria Aleman

Aleman

Research in the Aleman Lab is centered on basic mechanisms regulating erythropoiesis in health and disease. Differentiation of hematopoietic stem cells down the erythroid track requires coordinated gene expression, including RNA regulation, and accumulation of iron for hemoglobin production. Our current work focuses on a family of bifunctional proteins (poly C binding proteins) which both regulate RNA processing and chaperone iron within cells. Using biochemical, cellular, and in vivo models we explore the cross talk between iron trafficking and RNA regulation mediated by poly C binding proteins and how these activities are modulated by disease.

Antoniak

As a member of the UNC Blood Research Center, we are able to interact and collaborate with experts in blood coagulation and platelet biology. My lab is especially interested in investigating the contribution of the coagulation and platelets to anti-viral immune responses. Furthermore, in a collaborative effort with clinical experts of the UNC Blood Research Center, we are investigating potential pathways to improve cancer patients’ quality of life by reducing cardiotoxic side effects of highly efficient anti-cancer therapies.

Berkowitz

I am a clinician and clinical researcher focused on hemostasis. Many patients we evaluate for abnormal bleeding have a normal laboratory work-up despite clinically significant symptoms. The majority of these patients are women with histories of heavy menses, post-operative bleeding, and post-partum bleeding. I collaborate with BRC members to improve the diagnosis and management of patients with undiagnosed bleeding disorders, integrating clinical, laboratory, and epidemiologic data.

Boucher

My primary clinical and research interest focus is on sickle cell disease. Past efforts have focused on improving the care of patients with sickle cell disease through quality improvement initiatives such as improving time to antibiotics in children with SCD presenting with fevers as well as improving delivery of analgesia in the ED setting. As a Hispanic female physician, it is an honor and, indeed part of my mission as an academic physician, to serve as a mentor and sponsor to trainees, particularly those from backgrounds historically marginalized, underserved and underrepresented in medicine.

Dominguez

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.

Photo of Patrick Ellsworth

Ellsworth

Assistant Professor, Research interests: I am interested in the interaction between endothelium and coagulation proteins as well as blood cells. I have recently presented data showing an increase of factor Xa generation on endothelium in the presence of emicizumab and factor IXa. I am active in investigating the mechanism of thrombosis and thrombotic microangiopathy in the use of emicizumab and have an interest in improving the treatment of breakthrough bleeding in patients on emicizumab. I am more generally interested in the development of systems that can shed light on the mechanisms and complications of emerging, non-factor therapies for hemophilia.

Flick

Our role in the Blood Research Center (BRC) is to provide a unique perspective on the contribution of coagulation and fibrinolytic factors to a wide spectrum of disease pathologies, independent of the traditional roles of these factors in bleeding and thrombosis. We utilize mouse models to analyze specific mechanisms by which proteins such as prothrombin, fibrinogen, and plasminogen contribute to the progression of inflammatory, infectious, and malignant disease. Working with our collaborative basic science and clinical partners in the BRC provides an unparalleled opportunity for rapidly advancing our understanding of the multifaceted role of the hemostatic system in hemostasis, thrombosis, and beyond.

Hisada

Research Interests My research interest focuses on the mechanisms of cancer-associated thrombosis and bleeding. My primary interest is mechanisms of pancreatic cancer-associated venous thrombosis because pancreatic cancer has one of the highest rates of venous thrombosis. I have found that tumor-derived tissue factor positive extracellular vesicles, neutrophils and neutrophil extracellular traps, and plasminogen activator inhibitor-1 independently contribute to venous thrombosis in mouse models of pancreatic cancer.

Hur

My research program is focused on identifying the bidirectional relationship between hemostatic system components and cardiometabolic diseases. Obesity (defined as body mass index >30) currently affects >650 billion adults and >340 million children worldwide. Obesity is characterized by a state of chronic low-grade inflammation and induces qualitative and quantitative changes in hemostatic proteins, resulting in a prothrombotic state. I am interested in the following: 1) Determining the cellular and molecular mechanisms by which fibrin(ogen)-macrophage interactions promote the development of high-fat diet induced obesity and associated pathologies, 2) Determining the role of fibrinolytic system components in the development of obesity and associated pathologies and 3) Elucidating the molecular mechanisms by which obesity and metabolic pathologies exacerbate thrombosis.

Portrait of Raj Kasthuri, MD

Kasthuri

Bleeding and clotting disorders, and Hereditary Hemorrhagic Telangiectasia Dr. Raj Kasthuri is a clinician, researcher and clinical educator. Dr. Kasthuri’s clinical and research interests are in disorders of thrombosis and hemostasis, and Hereditary Hemorrhagic Telangiectasia. (HHT). Dr. Kasthuri is Associate Director for Clinical Research for the BRC. He is also Director of the UNC HHT Center of Excellence. He participates in and/or leads a number of clinical research studies evaluating the natural history of HHT and the evaluation of efficacy of novel therapies for the treatment of HHT. His laboratory interests include the mechanism(s) of coagulation activation in HHT, gene therapy for HHT, and he collaborates with other BRC investigators on research on mechanisms of thrombosis in cancer.

Kasztan

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.

Little

Dr. Little's clinical and research interests are in Sickle Cell Disease and erythropoiesis. We are interested in the physical properties of red cells, especially from people with sickle cell disease, under ambient and hypoxic conditions. We are using microfluidic devices in collaboration with colleagues at UNC and at CWRU to study red cells and to associate these findings with clinical phenotypes, before and after treatment. We are also part of a sickle cell disease registry, in order to capture data prospectively and pool resources with over 8 other institutions nationally.

Mooberry

To date, my research interests have focused primarily on the investigation of the coagulation system in inflammatory disorders with a thrombotic phenotype. There is known to be a close interplay between inflammation and coagulation, however, not all inflammation predisposes to thrombosis. My work aims to help better understand the role and mechanism(s) of coagulation activation in certain inflammatory disorders, and how this coagulation activation may lead to both increased thrombotic risk as well as heightened inflammation through positive feedback mechanisms.

Nichols

I am the Director of the Francis Owen Blood Research Laboratory (FOBRL), the mission of which is to reduce human and animal suffering from bleeding, thrombosis and atherosclerosis by the study of unique, genetically-determined animal models of these diseases. The FOBRL was established in 1960 by Dr. Kenneth M. Brinkhous and has provided work and study opportunities for many undergraduate, M.D., D.V.M. and Ph.D. students, post-doctoral students, and faculty at UNC and from several institutions worldwide.

Obadina

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.

Pawlinski

One area of interest is to investigate how the coagulation cascade contributes to the pathophysiology of neuroinflammation using mouse models of stroke and multiple sclerosis. We also study mechanisms of coagulation activation and clot formation in mouse models of sickle cell disease, and our goal is to identify the best mechanism of anti-coagulation to reduce the incidence of vaso-occlusive crisis, chronic inflammation, and end-organ damage associated with this blood disorder. The BRC enables us to interact with clinicians that are experts in sickle cell disease, which elevates the clinical relevance and impact of our research.

Polacheck

My lab develops microfluidic models of the blood and lymphatic vasculature for basic science and translational purposes. Specific projects relevant to the Blood Research Center are: 1) Understanding the role of Notch receptor signaling in vascular endothelial adherens junction assembly and stability; 2) A nascent collaboration with Dr. Prabir Roy-Chaudhury at the UNC Kidney center to screen patient plasma in microfluidic models of the vasculature to predict risk of cardiovascular complications in kidney disease.

Raffield

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.

Silvia Ramos

Ramos

I am an enthusiastic and solid medical scientist, passionate about RNA and hematopoietic stem cells (HSC), an extremely relevant research area of interest of the BRC. Eventually, I aim to improve our transfusion and bone marrow transplant practices based in novel discoveries. Our lab is committed to embrace individuals from all backgrounds and groups, including, but not restricted to those from historically excluded minorities. The diversity of our team creates an inclusive, collegial, supportive-equitable team, sustained by our different backgrounds united towards scientific understanding. We consider the education process as being dynamic and transformative. In ways that that the unforeseen novel knowledge leads a to an empowered society. These are also goals shared by the BRC mission at UNC.

Samuel Wilson

Wilson

As individuals with sickle cell disease (SCD) are living longer, there is a growing adolescent and young adult population with unique manifestations of SCD that are poorly understand. My research interests are broadly in understanding clinical outcomes in SCD management, characterizing individuals at greater risk for complications and in improving guideline-based care of those with SCD, especially in the diagnosis and management of iron overload. I am joining the non-malignant hematology faculty at UNC and am interested in pursing research in non-malignant hematology. As a member of the BRC, I will have the support and opportunity to continue my research pursuits.