• ENCODE: A free, publicly-funded source for reagent validation
    The ENCODE project is an NIH-funded initiative designed to generate and provide publicly-available data related to the human genome. ENCODE, or The Encyclopedia of DNA Elements, is an ongoing project that will characterize all of the functional elements in the human and mouse genomes. Currently in its fourth round of funding, the NIH has provided grants to a consortium of institutions from across the United States to conduct research under this project. Not only will results from ENCODE consortium experiments be made available, but the methods, reagents, and data processing pipelines used in ENCODE experiments will be validated and published as well. This ensures consistency between ENCODE experiments conducted at different sites and develops open resources for all researchers to also improve the validation of their experiments.
  • Epithelial–mesenchymal Transition
    Body surfaces, cavities, and the lining of hollow organs are comprised of epithelial cells. These cells are characterized by apical-basal polarity and tight cell-cell junctions, and are tightly packed together with little extracellular matrix.1 Due to these cells’ function as coverings and linings, they have one free surface not in contact with other cells, and are attached to underlying connective tissue via noncellular basement membrane.
  • FOXP3: Critical for the Immunosuppressive Function of Regulatory T cells
    Regulatory T cells (Treg) are essential for preventing autoimmunity and maintaining peripheral tolerance by downregulating the activation and expansion of effector T cells. Treg are phenotypically diverse and express a number of biomarkers. These biomarkers include cluster of differentiation 4 (CD4) and CD25, while a subset of Treg also express the transcription factor forkhead box P3 (FOXP3). Located on the X chromosome, FOXP3 is crucial for maintaining the functions of Treg.1 FOXP3 plays a critical role in Treg differentiation, and its expression is directly linked to the immunosuppressive activity of these cells.2
  • GITR Research in Tumor Immunotherapy
    Investigation into new potential targets for tumor immunotherapy has been ongoing now for over a decade. One protein that has long been studied in this framework is GITR (TNFRSF18), a member of the TNF superfamily of proteins that is expressed on T cells. Its ligand, GITRL, is expressed on antigen presenting cells such as dendritic cells. This pathway modulates the T cell immune response through a dual mechanism1 that primarily enhances the proliferation of regulatory T cells (Tregs)2 and also enhances the metabolism of effector T cells3. Because of these dual effects, understanding how best to target GITR in the setting of immunotherapy has remained challenging. Luckily, advances have recently been seen, and the stimulatory effect on regulatory T cells does not appear to be a factor in the cancer setting.
  • Genetic Conservation Across Species
    The pandemic caused by the coronavirus disease known now as Covid-19 has brought up questions regarding the ability of viruses to “jump” to new species. How can humans contract a bat disease? Coronaviruses are common in bats, and this is the third coronavirus disease originating from bats that has been able to cause a pandemic in the last 100 years1. The other two diseases, severe acute respiratory syndrome (SARS)- CoV and Middle East respiratory syndrome (MERS)-CoV, killed 7742 and 7123 people respectively. Bats, like humans, are mammals. They produce milk, and they have hair, but there the similarities seem to end.
  • Genome stability and Chromosome Segregation: a Unique SET of Functions
    hSET1, encoded by gene SETD1A, and also known as MLL, is a human lysine methyltransferase. hSET1 functions as a subunit of the histone H3K4 methyltransferase complex and is most functional within the COMPASS complex1. hSET1 interacts with numerous other nuclear proteins to regulate transcription and cellular differentiation through H3K4 methylation, and this function is conserved in SET1 orthologs across eukaryotes including yeast, drosophila, mice, and humans1-4.
  • Granzyme B and tumor cells: An enzymatic death
    The ability for cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells to target and eliminate harmful cells in our body is paramount for preventing various diseases1. Central to this is the serine proteinase Granzyme B (GrB), which when released in cytotoxic secretary vesicles alongside the pore-forming protein perforin (PEN) initiate cell death in targeted cells including virally infected and tumor cells. Expanding on this role, GrB has also been shown to be expressed in a plethora of non-cytotoxic cell types including basophils2, mast cells3 and neutrophils4 suggesting a more complex role than once thought. Furthermore, efforts to develop targeted therapies utilizing GrB, while facing roadblocks, has increased interested in the therapeutic harnessing of enzymatic death.
  • IDO1 - An intracellular target for cancer therapy
    Indoleamine 2,3-dioxigenase 1 (IDO1) is an enzyme that catalyzes the rate limiting step in the conversion of the essential amino acid tryptophan to kynurenine. IDO1 was first identified in the 1950s, but it wasn’t until the 1990s that the immunosuppressive nature of the enzyme was described. IDO1 is expressed in both primary and metastatic tumor tissue, and its expression is correlated with advanced disease stage and decreased survival.3,4 Both substrate (tryptophan) and product (kynurenine) of the IDO1-catalyzed reaction can be measured in blood, and an increased ratio of product to substrate has been associated with poor prognosis in breast, cervical, and non-small cell lung cancer, as well as in acute myeloid leukemia and melanoma.4
  • In-Depth with CD137
    CD137, also known as 4-1BB, ILA, and TNFRSF9, is a member of the TNF family that was originally identified through genetic screens as being expressed on activated T cells1. CD137 is expressed on transitional CD45RA+ CD45RO+ T cells2 and activated CD8+ and CD4+ T cells3,4. It can be used as a marker for CD8+ T cells that are antigen-experienced. CD137 can also be expressed on dendritic cells, where ligation promotes cell survival and activation, and increases the duration of contact between dendritic cells and T cells5,6.
  • It's Getting Hot In Here: CD163 and Inflammation
    It finally happened! The moment you've been waiting for: your manuscript was accepted for publication! You decide to take a vacation to celebrate. You deserve the break, and you haven’t taken a vacation in years. You think somewhere tropical might be nice. You pack quickly but forget one crucial item: mosquito repellant. What happens if you get malaria? Malaria is a blood disease caused by microorganisms and transmitted by mosquitos in certain parts of the world. In advanced malaria, blood cells are lysed in the human host, releasing hemoglobin from the cells1.
  • January is Cervical Health Awareness Month
    The United States (US) Congress has designated January to be Cervical Health Awareness Month, and for good reason; at one time, cervical cancer was the leading cause of cancer death for women in the US. The incidence of cervical cancer is not restricted to the US or to developed nations, however. Cervical cancer is the fourth most common cancer in women worldwide, and represents approximately 8% of all female cancers.1
  • Just Tell It Like It Is
    Okay it’s been a month since daylight savings time took effect, and I think that just now my body is starting to get on schedule. My son is also finally getting used to the change, but at the beginning he was so confused with the concept, we had multiple conversations concerning the topic.
  • KAP-1: Many Names, Even More Functions
    Krüppel-associated box (KRAB) domain-associated protein 1 (KAP-1), also known as tripartite motif-containing 28 (TRIM28), transcriptional intermediary factor 1 beta (TIF1β), and KRAB-A-interacting protein 1 (KRIP1) was first identified over 20 years ago.1 Since then, the function of KAP-1 in numerous cellular processes has been described, including in neurology, stress behavior, immunology, developmental biology, cellular proliferation and maturation, virology, genome integrity, cancer biology, and DNA damage response.1,2
  • Ki-67: A Nuclear Antigen Uniquely Qualified as a Marker of Cellular Proliferation
    Cellular proliferation is a fundamental biological process controlled by complex regulatory networks. Careful control of these networks is necessary for normal growth and development as well as for the body’s systemic response to infection or injury. Disruption or dysregulation of the mechanisms controlling cellular proliferation may result in inappropriate proliferation, such as in the formation and growth of tumors.
  • LAG3 and T cell exhaustion
    Normally, T cell activation leads to clonal expansion and acquisition of effector function, allowing cytotoxic T cells to lyse target cells and mount an effective immune response. However, in situations where T cells are exposed to a specific antigen for an extended period of time, such as in chronic viral infection or cancer, T cells can become dysfunctional as a result of antigen desensitization. Dysfunctional T cells multiply inefficiently, progressively fail to produce cytokines, and ultimately become ineffective at killing target cells.1 This process of antigen desensitization and subsequent dysfunction is known as T cell exhaustion, and illustrates a particular challenge in the immune response to chronic viral infection and cancer.