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 300 - Advanced Cell Biology I

Advanced course studying various topics in modern molecular cell biology emphasizing the design of experiments, the interpretation of their results and the extrapolation of their findings. Examines aspects of eukaryotic cell structure and function. Includes, but not restricted to, areas such as protein targeting, organelle biogenesis, intracellular signaling, pathogen-cell interactions and cell-cell interactions. Makes extensive use of scientific literature to illustrate important concepts. Prerequisites: BIOL 201 or CELL 201 and BIOCH 200.

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CELL 398 - Research Project

Directed research carried out in a laboratory of a member participating in the Cell Biology Program. Credit may be obtained for this course only once. Successful completion requires laboratory skills training and a written report on the research project. Normally for students in their third year of study. Pre- or co-requisite: any 300-level Science course, CELL 300 recommended, and the consent of the course coordinator.

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CELL 400 - Techniques in Cell Biology

A laboratory course that teaches the application of modern cell biology techniques, including cell growth, microscopy and genetic manipulation to understand cell structure and function. Prerequisite: any 300-level Science course. Enrollment is limited, and registration is by permission of the department.

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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 405 - Cell Biology of Disease

This course focuses on the nature and mechanisms of disease processes. Through integration of practical classes with lectures, abnormalities in the structure and function of cells, tissues and organs that underlie disease are explored. Emphasis is placed on current research aimed at understanding the mechanisms of disease and disease therapy. Topics covered may include genetic disorders, cancer, cellular pathology, immunology, microbiology, parasitology and virology. 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 498 - Research Project

Directed research carried out in a laboratory of an assigned member participating in the Cell Biology Program. Credit may be obtained for this course more than once. Successful completion requires application of laboratory skills and a written report on the research project. Prerequisites: A 300-level CELL, Biological Sciences, or Biochemistry course and the consent of the course coordinator.

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CELL 499A - Research Project

Directed research carried out in a laboratory of a member participating in the Cell Biology Program. The project normally continues through Fall and Winter Terms. Successful completion of this course requires application of laboratory skills, a written report and an oral presentation on the research project. Prerequisite: A 300-level CELL, Biological Sciences, or Biochemistry course and consent of the course coordinator.

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CELL 499B - Research Project

Directed research carried out in a laboratory of a member participating in the Cell Biology Program. The project normally continues through Fall and Winter Terms. Successful completion of this course requires application of laboratory skills, a written report and an oral presentation on the research project. Prerequisite: A 300-level CELL, Biological Sciences, or Biochemistry course and consent of the course coordinator.

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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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CELL 505 - Cell Biology of Disease

This course focuses on the nature and mechanisms of disease processes. Through integration of practical classes with lectures, abnormalities in the structure and function of cells, tissues and organs that underlie disease are explored. Emphasis is placed on current research aimed at understanding the mechanisms of disease and disease therapy. Topics covered may include genetic disorders, cancer, cellular pathology, immunology, microbiology, parasitology and virology. Enrolment is limited and registration is by permission 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;