Dr. Schwartz’s research studies seek to understand the molecular mechanisms and pathogenesis underlying pediatric myelodysplastic syndromes (MDS), specifically those syndromes caused by germline mutations in SAMD9 and SAMD9L.

His current focus is to better understand the biological consequences of SAMD9 and SAMD9L mutations in MDS through genomic and functional investigations in an induced pluripotent stem cell (iPSC) model system of pediatric MDS. This iPSC model system was developed through CRISPR/Cas9 knock-in of known pathogenic SAMD9 or SAMD9L mutations at the respective endogenous locus. Using additional CRISPR tools, Dr. Schwartz is working to selectively activate or repress transcription of these loci and interrogate differential expression patterns that result using RNA sequencing. These studies will help to uncover the important cellular functions of these two interesting genes.

Additionally, Dr. Schwartz hopes to describe the mechanisms and clonal evolution that underlie the SAMD9/9L-mediated development of monosomy 7 and, in some patients, subsequent spontaneous hematopoietic recovery through single-cell multi-omics. The knowledge gained from a deeper understanding of how SAMD9/9L mutations and chromosome 7 loss effects hematopoiesis and how these lesions clonally evolve over time will lead to the ability to deeply surveil patients with predispositions to develop MDS/AML. Thus, resulting in the ability to predict which patients may not need bone marrow transplant (particularly some of those patients with germline SAMD9/9L mutations), but also identify which patients are at highest risk of AML development such that transplant can occur prior to the development of malignancy.

Dr. Schwartz’s research and early physician-scientist career are supported through grant funding through the National Heart, Lung, and Blood Institute, V Foundation, and Hyundai Hope on Wheels. He has also been previously funded by Alex’s Lemonade Stand Foundation. Additionally, he has been appointed as a Carolyn Perot Rathjen Faculty Fellow. Dr. Schwartz’s clinical interests are also focused on pediatric inherited and acquired bone marrow failure and utilizing clinical genomic sequencings to guide therapy decisions.

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Dr. Stone is interested in diagnostic evaluations for children, adolescents, and adults with concerns related to autism spectrum disorder, learning disorders, and developmental delays.

Dr. Leonard Bacharier's research is focused on clinical research to help understand and improve the care of children with allergic and respiratory diseases, with a focus on asthma and food allergy. His clinical/translational research efforts are directed at the pathogenesis of allergies and asthma in early life and approaches to asthma management throughout childhood, including multi-center, federally funded clinical trials in asthma. He is actively studying novel treatment strategies for adolescents with severe asthma. Dr. Bacharier also collaborates with multiple investigators and research groups around the nation studying factors related to the development, prevention, and management of childhood asthma and food allergies. He also co-leads the Vanderbilt University Medical Center CoFAR Clinical Research Center, part of the NIAID CoFAR program studying novel approaches to the diagnosis and management of food allergies.

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Abnormalities of cardiac rhythm are a common and serious public health problem. However, the therapies used to treat arrhythmias are often ineffective, and can sometimes even exacerbate arrhythmias. Research in this laboratory is directed at elucidating mechanisms underlying abnormalities of cardiac rhythm and mechanisms underlying variable responses to antiarrhythmic drug treatments. Since antiarrhythmic drugs affect the function of cardiac ion channels, it is one working hypothesis in the laboratory that variable responses to drug therapy may reflect variable function or expression of genes encoding ion channels or proteins involved in drug disposition. Thus, a major focus of work in the laboratory is elucidation of factor(s) that determine ion channel gene expression in cardiac tissue. Approaches include identification of new genes, identification of DNA polymorphisms and characterization of their functional effects on disease and drug responses, and modulation of expression in cultured heart cells (e.g. by antisense) and gene knockout in mice.

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