Antibody News

By Christina Towers, PhD.

In the last 20 years, epigenetic regulation has become front and center for almost all fields of biology and its role in diseases like cancer and neurodegeneration are being heavily studied. Epigenetics can be defined as a change in phenotype without a change in genotype that is caused by remodeling the chromatin landscape and is often mediated by changes in histone marks, like methylation, acetylation, phosphorylation, SUMOylation, ubiquitination, and glycosylation to name a few. The cellular recycling process of autophagy is among one of the many processes...

By Yoskaly Lazo-Fernandez, PhD

Introduction

Evidence has accumulated recently indicating that common cancer therapies might stimulate metastasis in a significant number of cancer patients¹. In fact, neoadjuvant chemotherapy (NAC) drugs, which are administered preoperatively as a first line of treatment, have been associated with increased infiltration of endothelial progenitor cells and macrophages in primary tumors, resulting in higher angiogenesis and tumor regrowth². Mechanisms by which these cellular injury responses induce metastasis, both in preclinical in vivo models, and in human...

By Christina Towers, PhD.

Parkinson's disease is a debilitating neurodegenerative condition defined by the accumulation of alpha-synuclein-containing (alpha-SYN) intra-cytoplasmic inclusions, called Lewy bodies. The protein degradative processes of autophagy, and most specifically chaperone mediated autophagy and mitophagy, play an important protective role against this disease by targeting neurotoxins for lysosomal mediated degradation¹. Alpha-SYN neurotoxins most commonly affect neurons, but they can also...

By Jamshed Arslan Pharm.D.

Motor neurons control our ability to speak, walk, swallow, and even, breath. People with a motor neuron disease called amyotrophic lateral sclerosis (ALS) cannot perform these primal functions optimally. A point mutation (P56S) in VAMP associated protein isoform B (VAPB), a protein associated with the membrane around the endoplasmic reticulum, causes late-onset familial ALS8 by prompting VAPB to aggregate and lose its job of preventing buildup of abnormal proteins. To study ALS8, C. elegans is one of the animals of choice due to its simple neurophysiology: a single worm has only 302 neurons and 113 of them are...

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...