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June Lab Connect Bios & Glossary

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June Lab Connect Bios & Glossary Speck Lab Bios Nancy Speck, Ph.D. Dr. Speck is well-known in the field of developmental hematopoiesis, especially as it pertains to translating research into fighting leukemia. She is Chair of the Department of Cell and Developmental Biology in the Perelman School of Medicine at the University of Pennsylvania, as well as Chair of The RUNX1 Research Program’s Scientific Advisory Board. She has been working on RUNX1 for over 30 years. Alexandra Zezulin, Alexandra Zezulin is an MD-PhD student at the University of Pennsylvania in the Speck lab. She is studying the mechanism by which RUNX1 regulates inflammatory signaling in hematopoietic cells. Dana Bellissimo, M.D., Ph.D. Dana Bellissimo is a pediatrics resident at the Children’s Hospital of Philadelphia who recently completed her MD-PhD research in the Speck Lab. Her PhD research identified a new role for RUNX1 in regulating neutrophil inflammation. Suean Fontenard, Ph.D. Dr. Fontenard is a Postdoctoral Researcher in the Speck Lab, studying the somatic mutations that contribute to clonal hematopoiesis and subsequent leukemic transformation. Glossary Allele: An individual inherits two alleles for each gene, one from each parent. These control our physical traits and health and are either dominant (one brown eyes allele + one blue eyes allele = brown eyes) or recessive (one blue eyes allele + one blue eyes allele = blue eyes). Blood Stem Cell: An immature cell that can develop into all types of blood cells, including white blood cells, red blood cells and platelets. These are also called hematopoietic stem cells. Clonal Fitness: How an individual stem cell fares among other stem cells within the bone marrow. For example, whether it grows faster or slower. Cytokines: Small proteins that are crucial in controlling the growth and activity of other immune system cells and blood cells. When released, they signal the immune system to do its job. They also affect the growth of all blood cells and other cells that help the body's immune and inflammation responses. Disease Models: An animal or cells that display some or all of the disease features characterized in humans with the actual disease. Disease models help scientists study how a disease starts and progresses over time, and are critical for testing potential treatments. Erythroleukemia: A type of leukemia involving red blood cells. Gene: A unit of DNA that defines the characteristics of a specific trait determined by the protein generated from that gene. RUNX1 is a gene that creates a protein called RUNX1. The RUNX1 protein controls important characteristics of the blood, like platelet number or function. Genome: The complete set of genes in a cell or organism. Genotype: The set of genes in DNA responsible for a particular trait or phenotype. Germline Mutations: A change in the DNA that is passed down from parent to child, and thus exists in every cell in the body. Hematopoiesis: The production of blood cells and platelets, which occurs in the bone marrow. Hematopoietic Stem Cells (HSCs): The stem cells that give rise to other blood cells. Hemopoiesis: The formation of new cellular components of the blood in bone marrow or lymphatic tissue. Heterozygous: An individual inherits different forms (alleles) of a particular gene from each parent that can create variations in offspring. For example, inheriting one allele for red hair and one allele for brown hair. Brown hair is a dominant trait, so the child will have brown hair. In the case of RUNX1-FPD, patients have one mutated RUNX1 allele and one normal RUNX1 allele, therefore are heterozygous for the RUNX1 mutant allele. Homozygous: An individual inherits the same alleles for a particular gene from both parents. For example, inheriting one allele for blue eyes from the biological father and one allele for blue eyes from the biological mother. Blue eyes are a recessive trait, so the child will have blue eyes as there isn’t a dominant allele of another color present. No one with homozygous RUNX1 mutant alleles is alive since two mutant RUNX1 alleles are incompatible with survival. Knockout: Genetically engineering an organism to not have one or more specific genes. Scientists create knockouts so they can study the impact of the missing genes and learn something about the genes' function. LPS = Lipopolysaccharide: Found in the outer membrane of a certain type of bacteria, it causes inflammation in the body because it protects the bacteria from attack by immune system cells and some medications. Lymph: A clear to pale-white fluid that circulates throughout the lymphatic system. It has several purposes, including bringing white blood cells to fight infection. Lymphatic System: Part of the immune system, it has many functions including protecting the body from illness, maintaining body fluid levels, absorbing digestive tract fats and removing cellular waste. Malignant: Cells or tissue that tend to invade normal tissue because of uncontrolled growth and lack of normal function; cancerous. Monoallelic: Also known as genomic imprinting, it means one allele is off (can be either recessive or dominant) while the other is on. Imprinted genes are more vulnerable to the negative effects of mutations because the gene that is off does not act as back-up, making it possible for diseases to occur. mRNA (messenger RNA): A copy of the information in a gene that can be translated into a protein. Mutations: Changes in the DNA from the "normal" general population genetic sequence. Also called variants, one can think of them like a spelling error. Genes and chromosomes can mutate in either somatic (not hereditary) or germinal (hereditary) tissue. Neutrophils: A white blood cell that protects us from infections. They make up approximately 40% to 60% of the white blood cells in our bodies, and are the first cells to arrive on the scene when we experience a bacterial infection. Pathogenic: Causing disease. Phenotype: Observable characteristics or traits. For example, having blue eyes is a phenotype; lacking the gene for brown eyes is a genotype. Pre-malignant: Describes cells or tissue that is not yet malignant (cancerous), but is poised to become malignant. Protein: Large, complex molecules that do most of the work in cells and are required for the structure, function and regulation of the body's tissues and organs. Somatic Mutations: The opposite of germline (inherited) mutations, these occur in a single body cell and are not inherited. Stem Cell: A cell with the unique ability to develop into specialised cell types in the body. T cell leukemia: A type of leukemia involving the T cell lineage. T cells are a type of white blood cell. Thymus: A specialized organ of the immune system where T lymphocytes mature. TNF = Tumor Necrosis Factor: A (cytokine) protein made and released by white blood cells to alert other immune system cells to an antigen or infection through an inflammatory response. It may boost a person’s immune response and also may cause necrosis (cell death) of some types of tumor cells. TNF is being studied in the treatment of some types of cancer. Transcription factor: A protein that binds to DNA near a gene, and determines whether or not a mRNA will be produced from that gene. VAF = Variant Allele Frequency: Allele frequency represents the number of a particular gene variant in a population of cells in the body. VAF is the mathematical formula scientists apply to this number in order to determine whether this variant is somatic (mutated on its own) or germline (inherited from parents)..
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