The G1/S cell cycle checkpoints control whether eukaryotic cells enter the S phase (synthesis phase) of DNA synthesis after having properly completed the G1 phase to ensure the cell has enough energy and resources to begin DNA replication. Two cell cycle kinase complexes, CDK4/6-Cyclin D and CDK2- Cyclin E, work together to relieve the inhibition of dynamic transcriptional complexes containing retinoblastoma protein (Rb) and E2F. In cells undefined during the G1 phase, hypophosphorylated Rb binds to the E2F-DP1 transcription factor and forms an inhibitory complex with HDAC, thereby inhibiting downstream key transcriptional activities. Clear entry into the S phase is achieved by continuous phosphorylation of Rb by Cyclin D-CDK4/6 and Cyclin E-CDK2, which separates the transcription factor E2F from the inhibitory complex and allows transcription of the gene required for DNA replication. After the growth factor disappears, the expression level of cyclin D is down-regulated by down-regulation of protein expression and phosphorylation-dependent degradation. Without a proper G1/S checkpoint, the cell could arrest or potentially undergo aberrant processes that could lead to disease states such as cancer.

Proteins known as transcription factors play a crucial role in gene regulation by activating, enhancing, and even silencing a gene’s expression.  Many textbooks and resources compare transcription factors (TFs) to something like an on/off switch for gene transcription. However, it is a bit more complicated than just turning gene expression on or off. Various properties (e.g. binding affinity, specificity, and genetic variance of binding sites) impact the binding of TFs to DNA, thereby altering gene expression. To study transcription and how it is regulated, scientists study TF-DNA interactions on a genome-wide level. 

Embryonic stem cells (ES cells) are pluripotent stem cells isolated from an inner cell mass of early-stage embryo-blastocysts. ES cells have a high differentiation potential., which means that they have the capacity to develop into whatever cell type the body needs depending on the signals received by the ES cell. At the same time, while ES cells are undifferentiated, they retain the potential to infinitely replicate, making them highly attractive and renewable subjects for targeted cell therapy and regenerative medicine.

Cluster of differentiation, or CD molecules, are cell surface markers that are used for identification of cell types in pathology and other bioscience disciplines. The expression levels of CD markers may increase or decrease (or disappear altogether, at least to undetectable levels) when cells (for example, leukocytes, red blood cells, platelets, and vascular endothelial cells, etc.) differentiate into new and different lineages. Depending on the CD marker, the expression level may identify a phenotype for different segments of cells, such as when they become active or diseased. Most CD molecules are transmembrane proteins or glycoproteins, including extracellular regions that bind a ligand or opposing receptor, transmembrane regions to anchor the CD marker into the cell, and cytoplasmic regions that may confer some adaptor or catalytic function. Some CD molecules can also be "anchored" on the cell membrane by means of inositol phospholipids. A few CD molecules are carbohydrate haptens. The study of CD molecules can be used in many basic immunology research fields, such as the relationship between CD antigen structure and function, cell activation pathway, signal transduction and cell differentiation, etc. It can be used clinically for disease mechanism research, clinical diagnosis, disease prognosis, efficacy tracking and treatment, and more. CD molecules such as CD4, CD8, CD25, etc. can be used to identify populations of cells when studying samples by flow cytometry or immunofluorescence.

The Literature Review

Literature reviews are some of the most widely read and highly cited papers in academia, but writing one can be a daunting task, requiring an expert understanding of the topic at hand. To write a review article is so much more than simply summarizing recent studies published in the field. The most valuable literature reviews, which I find myself going back to again and again, are those that:

The Problem with Cancer Models

Very few cancer drugs succeed in clinical trials, despite showing promise in the lab. Treatments that may work on animal models, cell lines, or even patient-derived xenografts often do not have the same efficacy in patients. The underlying reason is tumor environments within the human body are far more complex than in research models. For example, the tissue structure (histological complexity) and genetic heterogeneity of an animal model is different than that of humans. Even cell lines and patient-derived xenografts, which are human-derived, have their own pitfalls such as genetic mutations and animal-specific tumor evolution, respectively. Due to the inability to reproduce human tumor environments, many drugs fail clinical trials after lengthy and costly development.