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The main focus of the Becker lab has been on the mechanisms and consequences of post-ischemic myocardial inflammation.
Genomic control of platelet function:
Aggregation of blood platelets initiates clotting in coronary arteries, the main cause of heart attacks. Our laboratory conducts experiments to understand how genes control platelet function. Through funding by the National Heart Lung and Blood Institute, we have performed candidate gene analysis, linkage studies, whole genome association studies, and now whole genome sequencing in about 2000 healthy subjects from families with early onset coronary artery disease. The subjects are siblings or offspring of an individual identified with coronary artery disease before age 60 in the GeneSTAR Research Program (Genetic Studies of Atherosclerosis Risk). We have identified a large number of common and rare genetic variants associated with platelet aggregation, and although some variants are located in genes known to be important in... the biology of platelet function, most are in non-protein coding regions of genes (introns) or in intergenic regions of the genome. To understand better how these variants influence platelet function, we created pluripotent stem cells from blood mononuclear cells in 257 genotyped GeneSTAR subjects and then transformed the stem cells to megakaryocytes, the source of platelets in the bone marrow. We have determined the entire transcriptome of these megakaryocytes to measure gene expression levels in an effort to functionally link genetic variation with platelet function. We are also interested in epigenetic effects which regulate the amount of gene transcription and resulting protein formation. We have done similar transcriptomic and proteomic studies in blood platelets as we have in stem cell-derived megakaryocytes.
Our goal is to identify new therapeutic targets for drug development to control excessive platelet aggregation and reduce the risk of heart attack in susceptible individuals. We also hope to use the genetic information to predict who is at greatest risk for platelet aggregation or bleeding, and tailor treatment to effectively apply individualized precision medicine.
The Becker laboratory also extends its cardiovascular work well beyond platelet function, as noted on the GeneSTAR Research Program website. view less
Dr. Colantuoni and his colleagues explore human brain development and molecular mechanisms that give rise to risk for complex brain disease. His team uses genomic technologies to examine human brain tissue as well as stem models and vast public data resources.
The C. Kwon Lab studies the cellular and molecular mechanisms governing heart generation and regeneration.
The limited regenerative capacity of the heart is a major factor in morbidity and mortality rates: Heart malformation is the most frequent form of human birth defects, and cardiovascular disease is the leading cause of death worldwide. Cardiovascular progenitor cells hold tremendous therapeutic potential due to their unique ability to expand and differentiate into various heart cell types.
Our laboratory seeks to understand the fundamental biology and regenerative potential of multi-potent cardiac progenitor cells – building blocks used to form the heart during fetal development — by deciphering the molecular and cellular mechanisms that control their induction, maintenance, and differentiation. We are also interested in elucidating the maturation event of heart muscle cells, an essential process to generate adult cardiomyocytes, which occurs after terminal differentiation ...of the progenitor cells. We believe this knowledge will contribute to our understanding of congenital and adult heart disease and be instrumental for stem cell-based heart regeneration.
We have developed several novel approaches to deconstruct the mechanisms, including the use of animal models and pluripotent stem cell systems. We expect this knowledge will help us better understand heart disease and will be instrumental for stem-cell-based disease modeling and interventions for of heart repair.
Dr. Chulan Kwon is an assistant professor of medicine at the Johns Hopkins University Heart and Vascular Institute. view more
The Dara Kraitchman Laboratory focuses on non-invasive imaging and minimally invasive treatment of cardiovascular disease. Our laboratory is actively involved in developing new methods to image myocardial function and perfusion using MRI. Current research interests are aimed at determining the optimal timing and method of the administration of mesenchymal stem cells to regenerate infarcted myocardium using non-invasive MR fluoroscopic delivery and imaging. MRI and radiolabeling techniques include novel MR and radiotracer stem cell labeling methods to determine the location, quantity and biodistribution of stem cells after delivery as well as to noninvasively determine the efficacy of these therapies in acute myocardial infarction and peripheral arterial disease.
Our other research focuses on the development of new animal models of human disease for noninvasive imaging studies and the development of promising new therapies in clinical trials for companion animals.
The Artemov lab is within the Division of Cancer Imaging Research in the Department of Radiology and Radiological Science. The lab focuses on 1) Use of advanced dynamic contrast enhanced-MRI and activated dual-contrast MRI to perform image-guided combination therapy of triple negative breast cancer and to assess therapeutic response. 2) Development of noninvasive MR markers of cell viability based on a dual-contrast technique that enables simultaneous tracking and monitoring of viability of transplanted stems cells in vivo. 3) Development of Tc-99m and Ga-68 angiogenic SPECT/PET tracers to image expression of VEGF receptors that are involved in tumor angiogenesis and can be important therapeutic targets. 4) Development of the concept of “click therapy” that combines advantages of multi-component targeting, bio-orthogonal conjugation and image guidance and preclinical validation in breast and prostate cancer models.
Utilizing a combination of tissue-based, cell-based, and molecular approaches, our research goals focus on abnormal telomere biology as it relates to cancer initiation and tumor progression, with a particular interest in the Alternative Lengthening of Telomeres (ALT) phenotype. In addition, our laboratories focus on cancer biomarker discovery and validation with the ultimate aim to utilize these novel tissue-based biomarkers to improve individualized prevention, detection, and treatment strategies.
The mission of the Elisseeff Lab is to engineer technologies to repair lost tissues. We aim to bridge academic research and technology discovery to treat patients and address clinically relevant challenges related to tissue engineering. To accomplish this goal we are developing and enabling materials, studying biomaterial structure-function relationships and investigating mechanisms of tissue development to practically rebuild tissues. The general approach of tissue engineering is to place cells on a biomaterial scaffold that is designed to provide the appropriate signals to promote tissue development and ultimately restore normal tissue function in vivo. Understanding mechanisms of cellular interactions (both cell-cell and cell-material) and tissue development on scaffolds is critical to advancement of the field, particularly in applications employing stem cells. Translation of technologies to tissue-specific sites and diseased environments is key to better design, understanding, and... ultimately efficacy of tissue repair strategies. We desire to translate clinically practical strategies, in the form of biomaterials/medical devices, to guide and enhance the body's natural capacity for repair. To accomplish the interdisciplinary challenge of regenerative medicine research, we maintain a synergistic balance of basic and applied/translational research. view more
The Erika Matunis Laboratory studies the stem cells that sustain spermatogenesis in the fruit fly Drosophila melanogaster to understand how signals from neighboring cells control stem cell renewal or differentiation. In the fruit fly testes, germ line stem cells attach to a cluster of non-dividing somatic cells called the hub. When a germ line stem cell divides, its daughter is pushed away from the hub and differentiates into a gonialblast. The germ line stem cells receive a signal from the hub that allows it to remain a stem cell, while the daughter displaced away from the hub loses the signal and differentiates. We have found key regulatory signals involved in this process. We use genetic and genomic approaches to identify more genes that define the germ line stem cells' fate. We are also investigating how spermatogonia reverse differentiation to become germ line stem cells again.
Schizophrenia, autism and other neurological disorders are caused by a complex interaction between inherited genetic risk and environmental experiences. The overarching goal of the group are to reveal molecular mechanisms of gene by environment interactions related to altered neural development and liability for brain disorders. Our research uses a hybrid of human stem cell models, post-mortem tissue and computational approaches to interrogate the contribution of epigenetic regulation and somatic mosaicism to brain diseases. Our previous work has demonstrated that the human brain exhibits extensive genetic variability between neurons within the same brain, termed "somatic mosaicism" due to mobile DNA elements which mediate large somatic DNA copy number variants. We study environment-responsive mechanisms and consequences for somatic mosaicism and are discovering the landscape of somatic mosaicism in the brain. We also study the epigenetic regulation of cell specification and activity-d...ependent states within the human dorsal lateral prefrontal cortex and striatum. view more
The Frederick Anokye-Danso Lab investigates the biological pathways at work in the separation of human pluripotent stem cells into adipocytes and pancreatic beta cells. We focus in particular on determinant factors of obesity and metabolic dysfunction, such as the P72R polymorphism of p53. We also conduct research on the reprogramming of somatic cells into pluripotent stem cells using miRNAs.
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.
The Reeves Lab complements genetic analyses in human beings with the creation and characterization of mouse models to understand why and how gene dosage imbalance disrupts development in Down syndrome (DS). These models then provide a basis to explore therapeutic approaches to amelioration of DS features. We use chromosome engineering in embryonic stem cells (ES) to create defined dosage imbalance in order to localize the genes contributing to these anomalies and to directly test hypotheses concerning Down syndrome "critical regions" on human chromosome 21.
The Richard J. Jones Lab studies normal and cancerous stem cells in order to make clinical improvements in areas such as blood and marrow transplantation (BMT). We discovered one of the most common stem-cell markers, Aldefluor, which identifies cells based on their expression of aldehyde dehydrogenase 1 (ALDH1), and have used this marker to detect and characterize normal stem cells and cancer stem cells from many hematologic malignancies. We also developed post-transplant cyclophosphamide and effective related haploidentical BMT.
Founded in the late 1980s, our Lab has been exploring the fundamental mechanisms of neural responses to traumatic and degenerative signals as well as mechanisms of neural repair. Our current interests include: traumatic brain injury and models; mechanisms and treatments of traumatic axonopathies; molecular neuropathology of traumatic brain injury; induced pluripotent stem cells as models of disease.
The Yarema Lab uses chemical biology, molecular and cell biology, and materials science methods to study and manipulate glycosylation. The goal of our research is to better understand human disease while furthering carbohydrate-based therapies. Our laboratory's research goals are to (1) Develop sugar analogs into viable and versatile drug candidates, (2) Apply metabolic glycoengineering to tissue engineering and stem cell research, (3) Use non-invasive magnetic stimuli to probe the effects of glycoengineering (and also to treat neurological disorders), and (4) Extend our sugar-based drug candidates into animal models and the clinic
The Wang lab focuses on the signals that direct the differentiation of pluripotent stem cells, such as induced-pluripotent stem (iPS) cells, into hematopoietic and cardiovascular cells. Pluripotent stem cells hold great potential for regenerative medicine. Defining the molecular links between differentiation outcomes will provide important information for designing rational methods of stem cell manipulation.
The Zambidis Labratory studies the formation of pluripotent stem cells and the subsequent hematopoietic, endothelial and cardiac differentiation, as well as the potential therapeutic uses of pluripotent stem cell-derived cells.
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