GABA activates liver regeneration pathways through regulation of CDK9 activity after one hour

Liver regeneration after partial hepatectomy requires a rapid production of growth factors in order to induce the hepatocyte cell cycle. During this process RNA Polymerase II plays a big role in transcription of mRNA for proteins needed for hepatocytes to go through the cell cycle appropriately. Cyclic-dependent kinase 9 (CDK9) aids in this process by phosphorylating and regulating RNA Polymerase II. Previously we have found that Gamma-Aminobutyric acid (GABA) can help with liver regeneration and has been found to arrest hepatocytes at the G2 phase of the cell cycle. The purpose of this study is to examine if GABA exerts its effect on cell cycle through CDK9 upregulation or activation. HepaRG cells were treated with GABA in vitro and CDK9 expression was examined by immunofluorescence at 0, 1, and 8 hours post GABA treatment. Results showed that peak CDK9 activity occurred during the first hour after GABA treatment and helps support the hypothesis that GABA induce liver regeneration partially through regulation of CDK9. These findings can help elucidate the pathway responsible for GABA related liver regeneration

In pursuit of an HIV cure: from stem cell transplants to gene therapies

Since 2009, seven people living with human immunodeficiency virus (PLHIV) have been declared cured of HIV after receiving allogeneic hematopoietic stem cell transplants (alloHSCTs) to treat hematologic malignancies. In this sense, cure signifies the absence of viral DNA/RNA and undetectable viral loads without the use of antiretroviral therapy (ART). Five of these transplants utilized mutated C-C motif chemokine receptor type 5 (CCR5Δ32/Δ32) stem cells. Much has been learned from these and past cases, and although effective, bone marrow transplants cannot be easily or safely translated to cure the millions of PLHIV across the globe. A successful eradicating cure includes both the prevention of HIV from entering new cells and the elimination of tissue reservoirs. Protecting hematopoietic stem and progenitor cells (HSPCs) from infection is a key consideration since there is evidence that HSPCs themselves, not only their descendants, are susceptible to infection. Gene therapy approaches have the potential to bring about an eradicating HIV cure that could be highly effective, broadly applicable, less expensive, and practical to implement. Current strategies are tackling this problem by removing the integrated proviral DNA from infected cells and/or eliminating the co-receptor(s) necessary for HIV viral entry into target cells. Both approaches hold promise, but they require overcoming key challenges (i.e., vector toxicity, transduction efficacy, elimination of reservoir cells, etc.). This review summarizes and examines the lessons learned about curing HIV through bone marrow transplants, the current gene therapy methodologies, pitfalls of eradication strategies as well as future directions of the field