Our lab focuses on the study of childhood neurodegenerative disorders. We combine animal models and human stem cell derived cultures, and apply sequencing, proteomic and imaging methods to gain insights into functional and molecular differences between resistant and vulnerable neuronal populations. Our ultimate goal is to better understand human brain complexity in health and disease and uncover therapeutic targets for neurological disorders.
Our laboratory is interested in the development of gene-based strategies for the treatment of bleeding and thrombotic diseases. In a collaborative effort, we and others have carried out early-phase clinical studies on adeno-associated viral (AAV) vectors for the treatment of severe hemophilia B (factor IX deficiency). Current projects are focused on translational research studies on the efficacy and safety of intravascular delivery of AAV vectors to skeletal muscle or liver of life models with severe hemophilia. We are also identifying biological factors that modulate AAV vectors transduction and the risk of inadvertent germline transmission in animal models.
The studies in Camire laboratory focus on the molecular mechanisms which are responsible for maintaining normal hemostasis. The generation of thrombin at the correct time and place is central to this process as inappropriate production can lead to hemorrhage or thrombosis. Our studies are directed toward understanding how discrete proteolysis of zymogen and procofactor proteins involved in blood coagulation relates to the expression of structural determinants (e.g. exosites, metal binding sites, active site, etc.) important to their function. Procofactors and zymogens cannot participate to any significant degree in their respective macromolecular enzymatic complexes. This indicates that proteolytic activation must result in appropriate structural changes that lead to the expression of sites which impart enzyme, substrate and cofactor binding capabilities.
Research in the Davidson Laboratory is focused on inherited genetic diseases that cause central nervous system dysfunction, with a focus on (1) recessive, childhood onset neurodegenerative disease, such as the lysosomal storage diseases mucopolysaccharidoses and Battens disease; and (2) dominant genetic diseases, specifically the CAG repeat disorders, Huntington’s disease and spinal cerebellar ataxia, and (3), understanding how noncoding RNAs participate in neural development and neurodegenerative disease processes.
The Gadue laboratory studies cell fate decisions, focusing on endoderm and mesoderm specification using human ES cells and iPS cells. ES/iPS cells can differentiate into all cell types in the body and can be propagated in culture almost indefinitely, generating a virtually unlimited number of cells. These unique characteristics lead to the exciting prospect of using these cells to study disease processes and developmental pathways in vitro and eventually to treat a wide variety of diseases using cell replacement therapies.
The long-range goal of research in the Gonzalez-Alegre Laboratory is to develop treatments for human diseases caused by basal ganglia dysfunction based on biological information gained from studies performed in cellular and animal systems and in patients seen in the clinic. We focus on the study of inherited diseases, mostly dystonia, Huntington’s Disease and inherited ataxias.
The Lin laboratory studies RNA modifications (a.k.a “epitranscriptomics”) in human diseases including cancer. Post-transcriptional RNA processing and modifications are important mechanisms for gene regulation and functional diversity in eukaryotic cells. We develop and apply high-throughput sequencing strategies and transcriptome engineering technologies to study the regulation and function of RNA modifications including A-to-I RNA editing and m6A RNA methylation.
Research in my laboratory uses basic biochemical, molecular as well as complex in vivo methodology within the field of coagulation with two goals: (1) to advance our understanding of molecular mechanisms involved in pro- and anti-coagulant reactions; (2) translational research for the treatment of coagulation defects. Despite their different endpoints, these goals exhibit remarkable cross talk since answering mechanistic questions on coagulation impacts the design of therapeutic approaches for coagulation defects.
The research in the Sabatino Laboratory is focused on the inherited bleeding disorder, hemophilia. The interests of the laboratory include (1) the study of variants of coagulation factor VIII to understand the biochemical properties of these proteins and to identify novel variants with enhanced function and (2) the development of gene-based therapeutic approaches for treating hemophilia.
The lab focuses on translational target discovery for a range of neurodegenerative diseases. We combine technology development of large-scale CRISPR based perturbation screens with application of such technology together with additional genomic approaches in two main routes:
The long-term goal of the lab is to elucidate the cellular and molecular basis governing the formation, maintenance and function of neural circuits under physiological and pathological conditions, using both Drosophila and mammalian models. With a background in neural development, neural circuits and behavior, fly and mouse genetics, injury and neurodegeneration models, our lab offers a unique skillset and perspective for addressing physiological questions in developmental/functional neurobiology and neurological diseases.
The research in our laboratory focuses on the development of bioinformatics methods to improve our understanding of the genetic basis of human diseases, and the integration of electronic health records and genomic information to facilitate genomic medicine on scale. Current projects include the development of computational tools to call structural variants and DNA modifications from long-read sequencing data, the identification/prioritization of disease-relevant genetic mutations, the use of deep neural network to predict prognosis and optimize therapy for patients with cancer, the application of systems biology approaches on single-cell gene expression data, and the data mining on electronic health records to predict genetic syndromes and causal genes.