Gregg Johannes

Assistant Professor
245 N. 15th Street NCB 5606
Philadelphia PA 19102
Tel: (215) 762-8173
Email: Gregg.Johannes@drexelmed.edu

The research in my lab is focused on understanding the role of translation in modulating gene expression during cellular stress, disease and cancer progression. We are currently analyzing the effect of hypoxia (low oxygen) on gene expression in a model cancer cell line.

Tumors become hypoxic as they reach a size of approximately 1-2 mm in diameter and cannot grow further unless they induce the formation of new blood vessels (angiogenesis) and adapt to the hypoxic condition. Hypoxia is a potent pro-angiogenic stimulus and mediates this effect, in part, through transcriptional and post-transcriptional regulation of gene expression. One of the major post-transcriptional effects of hypoxia is the suppression of global protein synthesis.

However, during this translational inhibition, the mRNAs encoding VEGFA and HIF-1a continue to be efficiently translated. This indicates that certain cellular mRNAs have the ability to overcome the hypoxia-induced inhibition of translation. We hypothesize that: 1) these mRNAs have an alternative mechanism to recruit ribosomes that is unaffected by hypoxia and 2) the proteins encoded by these mRNAs play important roles in the cellular adaptation to hypoxia and induction of angiogenesis.

The long-term goal of this work is to identify the molecular mechanism that allows certain mRNAs to bypass the translational repression that occurs during hypoxia. This mechanism, once identified, may serve as a novel target for the development of therapeutics to treat cancer.

Current Research Projects

• Identify the mRNAs that have the ability to be translated during hypoxia. This goal will be accomplished by exposing the cells to hypoxic conditions and isolating the actively translating mRNA, followed by microarray analysis to identify the mRNAs that continue to be translated during hypoxia.
• Determine if internal initiation of translation is a common mechanism that allows mRNAs to be translated efficiently during hypoxia and identify the cis- and trans-acting factors required for this activity. Internal initiation of translation is an alternative mechanism by which mRNAs can recruit ribosomes. Once new mRNAs are identified that can be translated during hypoxia (above aim) they will also be analyzed to determine if they use this method to recruit ribosomes. These mRNAs will then be used to identify common cis- and trans-acting factors that are functionally important in internal initiation of translation during hypoxia.

Collaborations

Dr. Alessandro Fatatis, Assistant Professor, Department of Pharmacology and Physiology, DUCOM, Project: Understanding the role of the fractalkine receptor (CX3CR1) in the preferential bone metastasis of prostate cancer cells.