Gary Eitzen

Area of Study / Keywords

Rho GTPase exocytosis drug discovery mast cells inflammation

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About

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Research

Research in the Eitzen lab is focused on two topics:

1. Pro-inflammatory mechanisms regulated by Rho GTPase signaling

The Eitzen lab studies the regulation of secretory granule exocytosis by Rho GTPases. Rho proteins, such as Rho, Rac and Cdc42, belong to the ras GTPase superfamily. They function as molecular switches, cycling between inactive (GDP bound) and active (GTP bound) states, to control numerous cellular processes. The lab focused on how Rho GTPases control the production and release of pro-inflammatory mediators, via exocytosis, from immune cells.  These molecular switches act to transduce external signals (e.g. pathogen detection) into downstream responses that include cell morphological transitions through dynamic regulation of cytoskeleton remodeling, vesicle mobilization and release of pro-inflammatory mediators. 

 

2. Drug discovery methods for selective interference of protein signaling

The Eitzen lab has developed a drug discovery system that is optimized for the identification of small molecule protein-protein interaction inhibitors through screening of compound libraries.  The lab is currently using this system in high-throughput screens (HTS) for new inhibitors of Rho signaling complexes.  

Rho signaling complexes have been intractable target in drug discovery for several reasons: Rho proteins are lipid modified; they require a membrane environment for function; GEF activators are large multi-domain proteins that are hard to purify; active complexes require post-translation modification. To circumvent these problems, the Eitzen lab uses a model system based on yeast two-hybrid and protein complementation assays (PCA).  This method is an adaptation of membrane yeast two-hybrid technology used to interrogate binary protein interactions.  In the PCA strategy, two proteins of interest are fused to complementary fragments of a reporter protein; if the reporter fragments are brought together via a two-hybrid interaction, the PCA activity is reconstituted.  The advantage of our approach is that we use yeast to make the Rho and GEF targets within cells which facilitates their folding, solubility and activity, while PCA provides a sensitive readout that is well-suited to HTS. Thus, this project uses an innovative approach to discover drugs for human targets by expressing them in a yeast model system. The system is highly adaptable and can be used to identify inhibitors for virtually any binary protein interaction. Therefore, this project also creates opportunities for clinical drug development and commercial ventures.

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Teaching

Cell 402/502 Birth and Death of a Cell

Cell 445/545 Current Topics in Cell Biology

Cell 398/498/499 Undergraduate Research Projects

CELL 402 - The Birth and Death of a Cell

An advanced course dealing with cell differentiation, intracellular and extracellular signaling processes, the cell cycle, apoptosis and necrosis. Consists of lecture material and small group learning sessions. Topics include stem cell research, cancer therapy and human disorders involving cell death (e.g., Alzheimer's and cardiovascular disease). Requires reading and discussion of current research articles. Prerequisite: CELL 201 or BIOL 201 and any 300-level Science course (CELL 3xx or BIOCH 3xx recommended) or consent of Department.

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CELL 502 - The Birth and Death of a Cell

An advanced course dealing with cell differentiation, intracellular and extracellular signaling processes, the cell cycle, apoptosis and necrosis. Consists of lecture material and small group learning sessions. Topics include stem cell research, cancer therapy and human disorders involving cell death (e.g. Alzheimer's and cardiovascular disease). Will require reading and discussion of current research articles. Lectures are the same as for CELL 402 but with additional assignments and evaluation appropriate to graduate studies. May not be taken if credit has already been obtained in CELL 402. Prerequisites: Consent of the Department.

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Browse more courses taught by Gary Eitzen

American Chemical Society. 2022 March;

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Ibanga J., Zhang E.L., Eitzen G., Guo Y.

PLoS One. 2022 March; 17 (3 March) 10.1371/journal.pone.0265122

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Azad A.K., Farhan M.A., Murray C.R., Suzuki K., Eitzen G., Touret N., Moore R.B., Murray A.G.

FASEB JOURNAL. 2022 January; 36 (1) 10.1096/fj.202100554R

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Lu L., Raj S., Arizmendi N., Ding J., Eitzen G., Kwan P., Kulka M., Unsworth L.D.

Acta Biomaterialia. 2021 September; 136 10.1016/j.actbio.2021.09.011

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Liu Y., Weaver C.M., Sen Y., Eitzen G., Simmonds A.J., Linchieh L., Lurette O., Hebert-Chatelain E., Rachubinski R.A., Di Cara F.

Frontiers in Cell and Developmental Biology. 2021 August; 9 10.3389/fcell.2021.714710

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Banerjee H., LaPointe P., Eitzen G., Rachubinski R.A.

Frontiers in Cell and Developmental Biology. 2021 July; 9 10.3389/fcell.2021.703603

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Experimental Biology. 2021 April;