Blogs for March 2018

Killing two birds with one stone: Treating inflammation and cancer by inhibiting prolyl-4-hydroxylase-1

Tuesday, March 27, 2018 - 10:41
Bi-directional Cross-talk Between HIF1-alpha and NF kappa B

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....

Getting Physical: Link between Lipid Metabolism and Hypoxia Target Genes

Tuesday, March 20, 2018 - 11:16
Autophagy Mechanisms

By Jamshed Arslan Pharm.D.

von Hippel-Lindau (VHL) disease is associated with tumors arising in multiple organs. Activation of hypoxia-inducible factor (HIF)-alpha underlies the VHL disease pathogenesis. In normoxia, VHL tumor-suppressor protein (pVHL) and E3 ubiquitin ligase lead to proteosomal degradation of HIF-alpha. In hypoxia, HIF-alpha escapes degradation, partly because pVHL binding to HIF-alpha depends on a posttranslational modification (hydroxylation of proline residues) on HIF-alpha that only occurs in normoxia. The exact role of pVHL in tumor hypoxia, when HIF-alpha is stabilized, is poorly...

Autophagy inhibition in pediatrics: One physician-scientist’s brave decision

Tuesday, March 13, 2018 - 13:05
Autophagy Pathway

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...

Cleaner gone bad: Autophagy regulates motor neuron loss in spinal muscular atrophy

Wednesday, March 7, 2018 - 11:10
Autophagy Mechanisms

By Jamshed Arslan Pharm.D.

Neuromuscular disorders affect the peripheral nervous system and muscles. Spinal muscular atrophy (SMA) is one such incurable disease in which muscles fail to receive signals from the spinal motor neurons (MNs), and consequently, weaken due to inactivity. MN degeneration and muscle atrophy lead to the premature death of the victims. Like most of the neuromuscular disorders, SMA is genetic, and its genetic causes are known: the inactivation of survival motor neuron 1 (SMN1) gene, which reduces the...

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