The Barbara Ann Karmanos Cancer Institute has established eleven cores to support research studies.
The Bioactive Lipids Research Program laboratory focuses on bioactive lipids and integrin receptors and the role they play in various aspects of tumor progression, namely, cell growth and apoptosis, angiogenesis and tumor cell matrix interactions. There are a plethora of bioactive lipids formed as a result the metabolism of arachidonic acid, by numerous oxygenases. Dr. Honn's laboratory focuses on lipoxygenases, and in particular 12-lipoxygenases and its metabolic product 12-(S) HETE. The overexpression of 12-lipoxygenase has been demonstrated to protect tumor cells from the induction of apoptosis by environmental insult such as radiation due to an up-regulation of integrins, in particular αvβ3 and αvβ5. In addition, 12-HETE stimulates endothelial cell migration and enhances angiogenic responses by tumor cells through the release of vascular endothelial growth factor. Activation of 12-lipoxygenase occurs in response to a variety of cytokines and is modulated by the enzymes physical interaction with the cytoplasmic tail of the β4 integrin, an integrin known to play a major role in the invasive process of numerous cancers.
Additional work in Bioactive LIpids research group laboratory focuses on their discovery of naturally occurring truncated integrins which they believe play a role in cell detachment at the trailing edge during the locomotion process.
From the lab to the clinic
The Bioactive Lipids Research Program group is actively engaged in translating their research results into the clinic. Collaborations with organic chemists and biochemists at Wayne State University has led the Honn group to synthesize two major classes of 12-lipoxygenase inhibitors which were subsequently patented by the University and licensed to an independent biotech firm. Moreover, Dr. Honn is actively engaged in the testing of a nutraceutical which is a natural 12-lipoxygenase inhibitor. Finally, Dr. Rao Maddipati, a member of Dr. Honn's cancer biology group, has recently been awarded a grant to make glucuronide derivatives of 12-lipoxygenase inhibitors as a mechanism for increased bioavailability at the tumor site.
The research laboratory space (approx. 4,400 sq. ft.) is contained within two laboratories that comprise the Bioactive Lipids Research Program group located in the Chemistry Building at Wayne State University, Main Campus. Regarding the two laboratories: one of which has an adjacent 55 sq. ft. cold room; and one which contains a 200 sq. ft. dedicated cold room. Each lab contains four double-sided biochemistry benches and three work benches. Each bench is equipped with water, gas, vacuum, distilled water, etc. Three radioisotope hoods, five additional multi-purpose hoods, and three laminer flow hoods are available.
Laboratory equipment includes two Waters 500 HPLC systems, rotary evaporator, Beckman Vi-Cell cell counter and viability detector, two Baker SterilFARD III cell culture hoods, two biosafety tissue culture hoods, five tissue culture CO2 incubators, two bacteria incubators (Baxter), rotary floor model bacteria incubator, four cryomed liquid nitrogen storage chambers, Alpha Innotech FluorChem imaging system, Nikon digital camera, Nikon immunofluorescence microscope with digital SPOT RT-SE6 Digital Imaging System, two Nikon microscopes, three Nikon inverted phase contrast microscopes, Beta and gamma scintillation counters, Beckman XL-90 ultracentrifuge with SW50.1 and NVT rotors, Beckman JE-6 floor centrifuges, two table top Sorval refrigerated centrifuges, Beckman J2-21 refrigerated centrifuge, three –800 ultralow freezers, five –20 freezers, 4 refrigerators, IBI gel reader, LKB ultrascan-XL laser densitometer, gel dryer (BioRad), electroelution tank (ISCO), TECAN florescent/visible microplate reader, Biorad microplate reader, complete electrophoresis equipment including agarose gel (horizontal and vertical) and acrylamide gel, electrotransblot, autoclave, dishwasher, two analytical balances, two UV light boxes, and a SpeedVac (Savant). Available in core facilities in the School of Medicine are confocal microscopy, flow cytometery, and photographic and imaging services.