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The Wolfgang Laboratory is interested in understanding the metabolic properties of neurons and glia at a mechanistic level in situ. Some of the most interesting, enigmatic and understudied cells in metabolic biochemistry are those of the nervous system. Defects in these pathways can lead to devastating neurological disease. Conversely, altering the metabolic properties of the nervous system can have surprisingly beneficial effects on the progression of some diseases. However, the mechanisms of these interactions are largely unknown.
We use biochemical and molecular genetic techniques to study the molecular mechanisms that the nervous system uses to sense and respond to metabolic cues. We seek to understand the neurometabolic regulation of behavior and physiology in obesity, diabetes and neurological disease.
Current areas of study include deconstructing neurometabolic pathways to understand the biochemistry of the nervous system and how these metabolic pathways impact animal beh...avior and physiology, metabolic heterogeneity and the evolution of metabolic adaptation. view more
The Mihaela Pertea Lab develops computational tools for RNA sequence analysis, gene finding, splice-site prediction and sequence-motif finding. Previous research projects led to the development of open-source software systems related to finding genes.
The Miho Iijima Laboratory works to make a further connection between cells' signaling events and directional movement. Our researchers have identified 17 new PH domain-containing proteins in addition to 10 previously known genes in the Dictyostelium cDNA and genome database. Five of these genes contain both the Dbl and the PH domains, suggesting these proteins are involved in actin polymerization. A PTEN homologue has also been identified in Dictyostelium that is highly conserved with the human gene. We are disrupting all of these genes and studying their roles in chemotaxis.
The Mohamed Farah Lab studies axonal regeneration in the peripheral nervous system. We've found that genetic deletion and pharmacological inhibition of beta-amyloid cleaving enzyme (BACE1) markedly accelerate axonal regeneration in the injured peripheral nerves of mice. We postulate that accelerated nerve regeneration is due to blockade of BACE1 cleavage of two different BACE1 substrates. The two candidate substrates are the amyloid precursor protein (APP) in axons and tumor necrosis factor receptor 1 (TNFR1) on macrophages, which infiltrate injured nerves and clear the inhibitory myelin debris. In the coming years, we will systematically explore genetic manipulations of these two substrates in regard to accelerated axonal regeneration and rapid myelin debris removal seen in BACE1 KO mice. We also study axonal sprouting and regeneration in motor neuron disease models.
Our Molecular Oncology lab seeks to understand the genomic wiring of response and resistance to immunotherapy through integrative genomic, transcriptomic, single-cell and liquid biopsy analyses of tumor and immune evolution. Through comprehensive exome-wide sequence and genome-wide structural genomic analyses we have discovered that tumor cells evade immune surveillance by elimination of immunogenic mutations and associated neoantigens through chromosomal deletions. Additionally, we have developed non-invasive molecular platforms that incorporate ultra-sensitive measurements of circulating cell-free tumor DNA (ctDNA) to assess clonal dynamics during immunotherapy. These approaches have revealed distinct dynamic ctDNA and T cell repertoire patterns of clinical response and resistance that are superior to radiographic response assessments. Our work has provided the foundation for a molecular response-adaptive clinical trial, where therapeutic decisions are made not based on imaging but b...ased on molecular responses derived from liquid biopsies. Overall, our group focuses on studying the temporal and spatial order of the metastatic and immune cascade under the selective pressure of immune checkpoint blockade with the ultimate goal to translate this knowledge into “next-generation” clinical trials and change the way oncologists select patients for immunotherapy. view more
The Mollie Meffert Lab studies mechanisms underlying enduring changes in brain function. We are interested in understanding how programs of gene expression are coordinated and maintained to produce changes in synaptic, neuronal and cognitive function. Rather than concentrating on single genes, our research is particularly focused on understanding the upstream processes that allow neuronal stimuli to synchronously orchestrate both up and down-regulation of the many genes required to mediate changes in growth and excitation. This process of gene target specificity is implicit to the appropriate production of gene expression programs that control lasting alterations in brain function.
Research in the Nathaniel Comfort Lab looks at the history of biology. Areas of particular interest include heredity and health in 20th century America, genetics, molecular biology, biomedicine, the history of recent science, oral history and interviewing.
The Nauder Faraday Lab investigates topics within perioperative genetic and molecular medicine. We explore thrombotic, bleeding and infectious surgical complications. Our goal is to uncover the molecular determinants of outcome in surgical patients, which will enable surgeons to better personalize a patient’s care in the perioperative period. Our team is funded by the National Institutes of Health to research platelet phenotypes, the pharmacogenomics of antiplatelet agents for preventing cardiovascular disease, and the genotypic determinants of aspirin response in high-risk families.
The Peisong Gao Lab’s major focus is to understand the immunological and genetic regulation of allergic diseases. We have been involved in the identification of the genetic basis for atopic dermatitis and eczema herpeticum (ADEH) as part of the NIH Atopic Dermatitis and Vaccinia Network-Clinical Studies Consortium. Major projects in the Gao Lab include immunogenetic analysis of human response to allergen, identification of candidate genes for specific immune responsiveness to cockroach allergen, and epigenetics of food allergy (FA).
The Phenotyping Core promotes functional genomics and other preclinical translational science at Johns Hopkins. We assist and collaborate in the characterization and use of genetically and phenotypically relevant animal models of disease and gene function.
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