The UScholar lunches are your opportunity to learn about the work of other UScholars while enjoying FREE FOOD. UScholar students and faculty meet for lunch every Friday to hear a student or UScholar alum present his or her research and answer any questions.
TIME: Fridays at noon
PLACE: Fireside Room, 2nd Floor of the ARCH building
SPEAKERS: If you are interested in presenting, contact . For presentation guidelines, click here
Hear Penn’s Undergraduate Research Award recipients and Penn’s University Scholars discuss their work while enjoying a catered lunch! Fridays at noon in the Fireside Room (unless otherwise noted).
This semester’s speaking schedule:
Hypoxia Inducible Factors (HIFs) are transcription factors that respond to changes in oxygen in the cellular environment. A central element of the oxygen-sensing pathway is the family of enzymes known as the Prolyl Hydroxylase Domain proteins (PHD)¬, which hydroxylates the oxygen sensitive α
subunit of HIF on two prolyl residues– Pro402 and Pro564. This site-specific modification to HIFα allows recognition by the von Hippel Lindau tumor suppressor protein (VHL), a component of the E3 ubiquitin ligase complex that targets HIF-α for constitutive degradation by the ubiquitin-proteasome pathway.
Both PHD2 and VHL are negative regulators of HIF-α, where a loss of function of either PHD2 or VHL leads to the stabilization of HIF-α, thereby causing the irregular up-regulation of HIF target genes, such as EPO. Both mutations in VHL and PHD2 have been reported to result in either a partial loss of function, leading to erythrocyotosis, or a complete loss of function, predisposing to cancer.
More recently, studies have identified mutations in the HIF-2α gene as a third cause of erythrocytosis attributed to defects in the oxygen-sensing pathway. Evidence that implicates HIF-2α as the central HIF-α isoform regulating EPO in human adults comes from observations that mutations in the HIF-2α gene are associated with cases of erythrocytosis. All reported mutations to date are heterozygous missense mutations that affect residues that are C-terminal to the primary hydroxylation site in HIF-2α which have been found to hinder the interaction with PHD2 and/or VHL. A new heterozygous mutant, F540L, has recently been identified by Dr. Melanie Percy and colleagues of Belfast City Hospital and Queen’s University Belfast (personal communication to Dr. Frank S. Lee), in a patient with erythrocytosis. Similar to all reported cases, the affected residue in question, Phe540→Leu, is C-terminal to the primary hydroxylation site in HIF-2α. The objective was to determine if the mutation produces a functional defect in the interaction with PHD2 and/or VHL.