Dr. Ezekiel is a basic science researcher studying the effects of phytochemicals on cancer cells, small molecule-induced differentiation of cells and development of gene targeting methods.
Current Research Project
Main Research Focus:
- Anti-proliferative effects of phytochemicals on colon cancer cells.
- Methods to increase gene targeting efficiency.
Study Design: basic science, quantitative research
- to understand phytochemical effect on colon cancer cells
- to develop methods to increase gene targeting efficiency
Anti-proliferative effects of phytochemicals on colon cancer cells
Phytochemicals in certain combinations are present in the diet and may be effective in preventing colon cancer. The focus of my research is to study the interaction of phytochemicals singly and/or in combination and to make assessments of anti-proliferative effect and mechanism of action on colon cancer cells. Phytochemical compounds can exert their preventative action on cancer cell proliferation at multiple steps. Examples of preventative actions are: (i) protecti on against DNA damage by inhibition of uptake or inactivation of carcinogen (initiation phase of carcinogenesis); (ii) inhibition of cell proliferation; (iii) modulation of signal transduction (promotion phase of carcinogenesis); and (iv) suppression of invasion of cancer cells by inhibition of angiogenesis or effect on cell adhesion molecules (progression phase of carcinogenesis). These effects can be mediated by targeting several different mechanisms, such as signal transduction pathways, transcription factor expression or activation, methylation at the DNA level or miRNA regulation.
Methods to increase gene targeting efficiency
Gene targeting is a genetic technique that uses homologous recombination to direct changes in cellular genes according to predetermined DNA templates. Applications of gene targeting technologies include gene knockout or replacement in animals and in model cell systems as well as gene therapy to modify defective genes. Current gene therapy using viruses has advantages, such as efficient gene delivery, but also has limitations with major ones being safety concerns related to random integration events causing inactivation or activation of endogenous genes. Current drawbacks to the use of homologous recombination in mammalian cells for gene targeting purposes are its inherent inefficiency and relative low frequency of targeted integration. My research goal is to increase homologous recombination efficiency for direct applications of use in the area of gene therapy applications.
Student Research Projects
1. Identification and characterization of bacteriophages
Bacteriophages are viruses that exhibit a high degree of specificity in that they only infect specific strains of bacteria. Bacteriophage exhibit lytic or lysogenic cycles as mechanisms of causing bacterial infection. Upon adsorption, lytic phages inject their nucleic acid into the host cell and use the bacterial cell machinery to replicate and produce phage offspring which then leads to the demise of the host and dispersion of progeny phages which then find new hosts to infect. Before the advent of antibiotics, bacteriophages were commonly used for treatment of infections. Recently, there is a reemergence of interest in phage therapy due to the fact that there is an ever-increasing amount of bacterial resistance to antimicrobic drugs and a slowed emergence of new antimicrobics with which to effectively treat bacterial infections. The focus of this research project is to identify and characterize lytic bacteriophages specific for certain pathogenic bacteria.
2. Development of assay platforms
This research project focuses on developing immunoassays that are standardized and validated yet also cost-effective.
Sponsor: National Science Foundation
Project Title: A technology that improves gene targeting
Role: Principal Investigator
Funding Period: 2008
Sponsor: National Institute of General Medical Sciences
Project Title: mtDNA mutations at zeptomole sensitivity without PCR
Funding Period: 2010-2012
Sponsor: Saint Louis University (SLU) Beaumont Faculty Development Fund
Project Title: Antiproliferative effect of phytochemicals mediated by epigenetic regulation
Role: Principal Investigator
Funding Period: 2012-2013
UR Ezekiel, M Muthuchamy, JS Ryerse, RM Heuertz (2007). Single embryoid body formation in a multi-well plate. Electronic Journal of Biotechnology 2(10). ISSN 0717-3458.
S Duessel, UR Ezekiel, RM Heuertz (2008). Growth inhibition of human colon cancer cells by plant compounds. Clin Lab Sci. 21(3): 151-7.
Heuertz RM, UR Ezekiel (2010). A review of biofilms produced by pathogenic bacteria. ADVANCE for Medical Laboratory Professionals Sep 20, 2010 online.
AM Foskett, UR Ezekiel, JP Trzeciakowski1, DC Zawieja, M Muthuchamy (2011). Hypoxia and ECM proteins influence angiogenesis and lymphangiogenesis in mouse embryoid bodies. Frontiers in Physiology, 103:1-11, 2011.
Embryoid body-based screen. USPTO Number; 7,803,619.
Methods and systems for high homologous recombination targeting efficiency. USPTO Number; 7,892,823.
(pictured above) Plaque formation by bacteriophages specific for Pseudomonas aeruginosa.
(pictured below) Gene Targeting at the HPRT locus.