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Human induced pluripotent stem cells (hiPSCs) provide unprecedented opportunities for cell replacement approaches, disease modeling and drug discovery in a patient-specific manner. The Gabsang Lee Lab focuses on the neural crest lineage and skeletal muscle tissue, in terms of their fate-determination processes as well as relevant genetic disorders.
Previously, we studied a human genetic disorder (familial dysautonomia, or FD) with hiPSCs and found that FD-specific neural crest cells have low levels of genes needed to make autonomous neurons--the ones needed for the "fight-or-flight" response. In an effort to discover novel drugs, we performed high-throughput screening with a compound library using FD patient-derived neural crest cells.
We recently established a direct conversion methodology, turning patient fibroblasts into "induced neural crest (iNC)" that also exhibit disease-related phenotypes, just as the FD-hiPSC-derived neural crest. We're extending our research to the ne...ural crest's neighboring cells, somite. Using multiple genetic reporter systems, we identified sufficient cues for directing hiPSCs into somite stage, followed by skeletal muscle lineages. This novel approach can straightforwardly apply to muscular dystrophies, resulting in expandable myoblasts in a patient-specific manner.
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The Grayson Lab focuses on craniofacial and orthopaedic tissue engineering. Our research addresses the challenges associated with spatio-temporal control of stem cell fate in order to engineer complex tissue constructs. We are developing innovative methods to guide stem cell differentiation patterns and create patient-specific grafts with functional biological and mechanical characteristics. We employ engineering techniques to accurately control growth factor delivery to cells in biomaterial scaffolds as well as to design advanced bioreactors capable of maintaining cell viability in large tissue constructs. These technologies are used to enable precise control of the cellular microenvironment and uniquely address fundamental questions regarding the application of biophysical cues to regulate stem cell differentiation.
The Green Group is the biomaterials and drug delivery laboratory in the Biomedical Engineering Department at the Johns Hopkins University School of Medicine. Our broad research interests are in cellular engineering and in nanobiotechnology. We are particularly interested in biomaterials, controlled drug delivery, stem cells, gene therapy, and immunobioengineering. We are working on the chemistry/biology/engineering interface to answer fundamental scientific questions and create innovative technologies and therapeutics that can directly benefit human health.
The Greider lab uses biochemistry to study telomerase and cellular and organismal consequences of telomere dysfunction. Telomeres protect chromosome ends from being recognized as DNA damage and chromosomal rearrangements. Conventional replication leads to telomere shortening, but telomere length is maintained by the enzyme telomerase. Telomerase is required for cells that undergo many rounds of divisions, especially tumor cells and some stem cells. The lab has generated telomerase null mice that are viable and show progressive telomere shortening for up to six generations. In the later generations, when telomeres are short, cells die via apoptosis or senescence. Crosses of these telomerase null mice to other tumor prone mice show that tumor formation can be greatly reduced by short telomeres. The lab also is using the telomerase null mice to explore the essential role of telomerase stem cell viability. Telomerase mutations cause autosomal dominant dyskeratosis congenita. People with ...this disease die of bone marrow failure, likely due to stem cell loss. The lab has developed a mouse model to study this disease. Future work in the lab will focus on identifying genes that induce DNA damage in response to short telomeres, identifying how telomeres are processed and how telomere elongation is regulated. view more
The clinical development of novel immune and stem cell therapies calls for suitable methods that can follow the fate of cells non-invasively in humans at high resolution. The Bulte Lab has pioneered methods to label cells magnetically (using tiny superparamagnetic iron oxide nanoparticles) in order to make them visible by MR imaging.
While the lab is doing basic bench-type research, there is a strong interaction with the clinical interventional radiology and oncology groups in order to bring the methodologies into the clinic.
Research in the Jeremy Sugarman Lab focuses on biomedical ethics—particularly, the application of empirical methods and evidence-based standards to the evaluation and analysis of bioethical issues. Our contributions to medical ethics and health policy include work on the ethics of informed consent, umbilical cord blood banking, stem cell research, international HIV prevention research, global health and research oversight.
Research in the Jerry Spivak Lab focuses on chronic myeloproliferative disorders, particularly their molecular mechanisms and methods for distinguishing them diagnostically and interventionally. By analyzing gene expression in polycythemia vera stem cells, we have learned that patients with polycythemia vera can be differentiated from those with erythrocytosis and can be diagnosed as having either aggressive or slow-growing disease. We are also studying the roles played by specific molecular markers in the pathogenesis and diagnosis of polycythemia vera.
While there has been an explosion of knowledge about human carcinogenesis over the last 2 decades, unfortunately, this has not translated into the development of effective therapies for either preventing or treating the common human cancers. The goal of the Isaacs’ lab is to change this situation by translating theory into therapy for solid malignancies, particularly Prostate cancer. Presently, a series of drugs discovered in the Isaacs’ lab are undergoing clinical trials in patients with metastatic cancer.
The ongoing drug discovery in the lab continues to focus upon developing agents to eliminate the cancer initiating stem cells within metastatic sites of cancer. To do this, a variety of bacterial and natural product toxins are being chemically modified to produce “prodrugs” whose cytotoxicity is selectively activated by proteases produced in high levels only by cancer cells or tumor associated blood vessel cells. In this way, these prodrugs can be given systemically to metastati...c patients without un-acceptable toxicity to the host while being selectively activated to potent killing molecules within metastatic sites of cancer.
Such a “Trojan Horse” approach is also being developed using allogeneic bone marrow derived Mesenchymal Stem cells which are genetically engineered to secrete “prodrugs” so that when they are infused into the patient, they selectively “home” to sites of cancers where the appropriate enzymatic activity is present to liberate the killing toxin sterilizing the cancer “neighborhood”. view less
Research in the Kendall Moseley Lab is focused on the interplay between type 2 diabetes, aging and osteoporosis. We also study the function of bone stem cells in the regulation of bone remodeling.
Researchers in the Pankaj Jay Pasricha Lab are interested in the molecular mechanisms of visceral pain and restoration of enteric neural function with novel strategies, including neural stem cell transplants. Recent research has focused on the enteric nervous system and gut-brain axis, and the complexity of pain in chronic pancreatitis. Another recent study indicates that patients with underlying small intestinal bacterial overgrowth have significant delays in small bowel transit time as compared to those without, while another explored the safety and efficacy of carbon dioxide cryotherapy for treatment of neoplastic Barrett's esophagus.
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