Antibody News

By Colin O'Neill, 2018 Novus Intern

The specificity and affinity of an antibody for its target protein—and only its target is valued as an indicator of its experimental reliability. The frustrating ability of an antibody to bind to multiple proteins has prompted a reproducibility crisis in the life science community. Specifically, if an antibody varies in specificity between batches, attempts to reproduce significant findings with that antibody may fail. With samples, time, and funding at stake, scientists have developed novel validation techniques to ensure antibodies solely bind to their intended targets to avoid false positives and ambiguous results. Nature's 2015 article...

By Jamshed Arslan Pharm.D.

Natural killer (NK) cells are lymphocytes of the innate immune system that were first discovered for their “natural” ability to kill cancer cells. To use NK cells as anti-cancer therapy, they are co-cultured with feeder cells that are sensitive to attack by NK cells. The killing of feeder cells in turn generates highly efficient tumor-killing NK cells. However, a major challenge in using these ex vivo expanded NK cells as anti-cancer therapy is the highly immunosuppressive tumor microenvironment, partly because the cancer cells, myeloid derived suppressor cells and other stromal cells produce excessive amounts of...

By Christina Towers, PhD.

Autophagy is a critical cellular process used by most cells in the body to recycle nutrients and prevent harmful buildup of damaged proteins. It is particularly important in the brain, where a handful of pathologies have been linked to autophagy dysregulation. Conditional neuronal knock out of the core autophagy gene, ATG7, results in viable mice that eventually succumb to neurodegeneration accompanied by an accumulation of ubiquitin protein aggregates^{1, 2}. Likewise, decreased levels of functional autophagy have been linked to the three most common neurodegenerative diseases including...

By Jamshed Arslan Pharm.D.

Glioblastoma is an aggressive type of cancer that forms from the star-shaped glial cells of the central nervous system, called astrocytes. Intriguingly, several genes linked to glioblastomas, including the gene for the tumor suppressor Von Hippel-Landau protein (VHL), do not exhibit mutations. VHL prevents tumorigenesis by binding and modulating the function of hypoxia-inducible factor HIF-1 alpha and hydroxylated serine-threonine kinase Akt. Developmental processes that maintain cells in a...

By Christina Towers, PhD.

Autophagy mediates the recycling of damaged cellular material into building blocks like amino acids and other necessary nutrients that can fuel metabolism and cell growth, especially under nutrient depleted conditions. There are currently over 60 clinical trials reported on ClinicalTrials.gov that are either completed or on-going using autophagy inhibition, mostly in combination with other targeted therapies. Autophagy has a pro-tumorigenic role in established tumors and consequently the vast majority of clinical trials focus on autophagy inhibition in cancer. Over the last decade, a dozen Phase I and I/II clinical trials...

By Christina Towers, PhD.

Role of Reactive Species in Cellular Function

Oxidative stress is a byproduct of an imbalance between oxidants and antioxidants present in the cell resulting in dysfunctional redox signaling. This disproportion is caused by naturally occurring reactive oxygen species (ROS) and reactive nitrogen species (RNS) that can be derived from either extracellular sources or intracellularly as byproducts of essential cellular processes like metabolism. These species oxidize and remove electrons from the molecules they interact with including many kinds of biomolecules which can be detrimental to overall cellular function¹. For example, ROS can induce...

By Christina Towers, PhD.

Lysosomal Dysfunction and Disease

Lysosomes are highly acidic organelles that are critical for cellular function and indispensable for degradative pathways like autophagy and endocytosis.  There are a number of different diseases that have been associated with lysosomal dysfunction, the most detrimental being neurological disorders including Huntington's Disease, Alzheimer's disease, and Parkinson's disease.  Other rare neurological diseases like Niemen-Pick disease Type C (NPC) have been directly linked to familial-mutations in endolysosomal genes.  All of these disorders are attributed to a buildup of the detrimental...

By Jamshed Arslan Pharm.D.

Adenosine triphosphate (ATP) is the major life’s energy-carrying molecule. It is mainly produced by mitochondrial ATP synthase (Complex V) through oxidative phosphorylation (Oxphos). For example, Oxphos-dependent oxidation of a glucose molecule generates about 30 molecules of ATP. In Oxphos, respiratory chain (r.c.) complexes catalyze the transfer of electrons from energy-rich molecules (NADH or FADH₂) to oxygen (O₂) and...

By Christina Towers, PhD.

Autophagy and ATG Proteins

Autophagy is a nutrient recycling process that cells use to fuel metabolism, particularly in response to nutrient deprivation.  It is critical for removal of damaged proteins as well as clearing certain infections.  It is a complex process that involves over 20 core autophagy genes (ATGs), most of which were originally identified in yeast but the mammalian homologs have now been well characterized.

The formation of a double membrane vesicle termed the phagophore is initiated by the ULK complex where the protein kinases ULK1 and...

By Christina Towers, PhD.

Cells use the complex process of autophagy to degrade and recycle cytoplasmic material.  There are over 20 proteins that have been implicated in this process and appropriately named core autophagy genes (ATGs).  Most of these were originally discovered in yeast, arguably the most famous being ATG8.  In higher eukaryotes ATG8 evolved into a family of proteins known as the GABA type A receptor-associated protein (GABARAP), which includes the Microtubule Associated Protein 1 light chain 3 (MAP1LC3), better known...

By Jamshed Arslan Pharm.D.

The cell’s oxygen-sensing machinery comprises prolyl-4-hydroxylases (P4Hs 1-3, PHDs 1-3, or EGLN 1-3) and their canonical target hypoxia-inducible factors (HIFs). When oxygen levels are low, PHDs become functionally inactive, leading to HIFs’ stability. PHD1 is thought to provide a link between hypoxia and inflammation, partly because it influences the prototypical proinflammatory transcription factor NF-kB in such a way that suppressing PHD1 reduces inflammation....

By Christina Towers, PhD.

The current time from when a discovery is first made on the bench to when that discovery might translate into an approved therapy in cancer patients is an astounding 10-15 years. Scientists and clinicians alike face a daunting uphill battle to find novel targeted therapies that can improve a patient’s outcome yet still maintain minimal adverse side effects.  However, recently Dr. Jean Mulcahy Levy, a pediatric neuro-oncologist and physician-scientist, found a way to bypass some of these hurdles.  In 2012 she was working as a research-fellow at the University of Colorado in the laboratory of Dr. Andrew Thorburn, an expert in the field of...