Understanding the Role of miR-29a in the Regulation of RAG1, a Gene Associated with the Development of the Immune System.

The process of Ag receptor diversity is initiated by RAGs consisting of RAG1 and RAG2 in developing lymphocytes. Besides its role as a sequence-specific nuclease during V(D)J recombination, RAGs can also act as a structure-specific nuclease leading to genome instability. Thus, regulation of RAG expression is essential to maintaining genome stability.

Deficiency of ligase IV leads to reduced NHEJ, accumulation of DNA damage, and can sensitize cells to cancer therapeutics.

Ligase IV is a key enzyme involved during DNA double-strand breaks (DSBs) repair through nonhomologous end joining (NHEJ). However, in contrast to Ligase IV deficient mouse cells, which are embryonic lethal, Ligase IV deficient human cells, including pre-B cells, are viable. Using CRISPR-Cas9 mediated genome editing, we have generated six different LIG4 mutants in cervical cancer and normal kidney epithelial cell lines.

Fibroblast-derived PI16 sustains inflammatory pain via regulation of CD206 myeloid cells.

Originally identified in fibroblasts, Protease Inhibitor (PI)16 was recently shown to be crucial for the development of neuropathic pain via effects on blood-nerve barrier permeability and leukocyte infiltration, though its impact on inflammatory pain has not been established. Using the complete Freund's Adjuvant inflammatory pain model, we show that Pi16 mice are protected against sustained inflammatory pain. Accordingly, intrathecal delivery of a PI16 neutralizing antibody in wild-type mice prevented sustained CFA pain.

Exposure to endosulfan can cause long term effects on general biology, including the reproductive system of mice.

Increased infertility in humans is attributed to the increased use of environmental chemicals in the last several decades. Various studies have identified pesticides as one of the causes of reproductive toxicity. In a previous study, infertility was observed in male mice due to testicular atrophy and decreased sperm count when a sublethal dose of endosulfan (3 mg/kg) with a serum concentration of 23 μg/L was used.

Depletion of RNASEH2 Activity Leads to Accumulation of DNA Double-strand Breaks and Reduced Cellular Survivability in T Cell Leukemia.

Ribonuclease H2 (RNase H2) is a member of the ribonuclease H family of enzymes involved in removal of RNA from RNA-DNA hybrids as well as ribonucleotides which get misincorporated into the genomic DNA. Recent studies have shown that RNase H2 function is also needed for successful DNA repair through NHEJ events where DNA pol µ uses ribonucleotides during the gap filling stage. Mammalian RNase H2 is composed of three subunits, RNASEH2A, RNASEH2B and RNASEH2C.

G4 DNA present at human telomeric DNA contributes toward reduced sensitivity to γ-radiation induced oxidative damage, but not bulky adduct formation.

Purpose: DNA, the hereditary material of a human cell generally exists as Watson-Crick base paired double-stranded B-DNA. Studies suggest that DNA can also exist in non-B forms, such as four stranded G-quadruplexes (G4 DNA). Recently, our studies revealed that the regions of DNA that can fold into G-quadruplex structures are less sensitive to ionizing radiation (IR) compared to B-DNA.

Acute toxicity analysis of Disarib, an inhibitor of BCL2.

Small molecule inhibitors targeting BCL2 are explored as anticancer therapeutics. Previously, we have reported identification and characterization of a novel BCL2 inhibitor, Disarib. Disarib induced cancer cell death in a BCL2 dependent manner in different cancer cell lines and mouse tumor models when it was administered intraperitoneally.

G-quadruplex Structures Contribute to Differential Radiosensitivity of the Human Genome.

DNA, the fundamental unit of human cell, generally exists in Watson-Crick base-paired B-DNA form. Often, DNA folds into non-B forms, such as four-stranded G-quadruplexes. It is generally believed that ionizing radiation (IR) induces DNA strand-breaks in a random manner.

T Cells as an Emerging Target for Chronic Pain Therapy.

The immune system is critically involved in the development and maintenance of chronic pain. However, T cells, one of the main regulators of the immune response, have only recently become a focus of investigations on chronic pain pathophysiology. Emerging clinical data suggest that patients with chronic pain have a different phenotypic profile of circulating T cells compared to controls.