Dr Zheng Cui’s lab studies 2 major areas of research.

1)     Innate immunity against cancer in mice and humans.  Why don’t most humans get cancer despite of big body mass, long lifespan and even some intentional exposures to known carcinogens (such as cigarette smoking)?  The answer may come from a single male BALB/c mouse that unexpectedly survived challenges of highly lethal cancer cells in 1999.  The survival of this mouse was very surprising since that no other mouse of any strain had ever survived this type of cancer.  Even more surprising was that about 40% of offspring of this male mouse also survived many different cancer challenges, meaning that this cancer resistance is a genetic trait.  This trait has now been passed on to more than 2000 offspring in more than 15 generations and in several different mouse strains.  In the last several years, intense study has revealed additional surprises.  1) Although the inheritance pattern of this trait is simple, the genetics is not conventional.  There was no conventional linkage found so far between the trait and a fixed location on any chromosome, suggesting a possibility for a jumping gene (transposon) or a “paramutation”-like element.  2) The cancer resistance is entirely mediated by the leukocytes of innate immunity that are able to sort out cancer cells for specific killing without harming normal cells.  The cancer resistant mice are healthy and long-lived.  3) The mice can resist a wide array of cancer cells and endogenous malignancies.  4) The resistance can be transferred to normal mice via isolated macrophages or neutrophils for highly effective treatment of established cancers and for long-term protection against future cancer challenges.  5) Some humans may have similar cancer resistance in their leukocytes.  This project will continue in the directions of cancer resistance gene-mapping, immune mechanism, cancer-associated molecular targets and the search for natural cancer resistance in humans and new cancer treatment strategies.

Representative publications in this topic:

Hicks AM, Riedlinger G, Willingham MC, Alexander-Miller MA, Von Kap-Herr C, Pettenati MJ, Sanders AM, Weir HM, Du W, Kim J, Simpson AJ, Old LJ, Cui Z.  “Transferable anticancer innate immunity in spontaneous regression/complete resistance mice”  Proc Natl Acad Sci U S A. 2006 May 16;103(20):7753-8. Epub 2006 May 8.

Cui Z, Willingham MC, Hicks AM, Alexander-Miller MA, Howard TD, Hawkins GA, Miller MS, Weir HM, Du W, DeLong CJ. Spontaneous regression of advanced cancer: identification of a unique genetically determined, age-dependent trait in mice. Proc Natl Acad Sci U S A. 2003 May 27;100(11):6682-7. Epub 2003 Apr 30. 

2)    Lipidomics and Metabolipidomics.  Lipids and lipid metabolism are perhaps the most important aspects associated with human health and human nutrition. Fat content varies greatly from individual to individual and may have an intimate association with many human diseases, such as diabetes, heart and coronary diseases and cancer. Yet, lipid analyses had traditionally been a less developed area of research in comparison to other fields due to a lack of powerful analytical technologies at the molecular level.  The advent of tandem mass spectrometry technology (MS/MS) has brought a new dawn to the world of lipid analysis with unprecedented sensitivity, resolution and ease of use.  One of our research interests is to continue our efforts in using MS/MS to find new ways for lipid analysis and lipid profiling.  We also developed several new ways of analyzing lipid metabolism using stable isotope labeling of lipid metabolites in combination with MS/MS. We also have particular interests in phospholipids and gangliosides and their associated human diseases.

Representative publications in this topic:

Bleijerveld OB, Houweling M, Thomas MJ, Cui Z.  Metabolipidomics: profiling metabolism of glycerophospholipid species by stable isotopic precursors and tandem mass spectrometry. Anal Biochem. 2006 May 1; 352(1): 1-14. Epub 2006 Mar 10.

DeLong CJ, Hicks AM, Cui Z. Disruption of choline methyl group donation for phosphatidylethanolamine methylation in hepatocarcinoma cells. J Biol Chem. 2002 May 10; 277(19): 17217-25. Epub 2002 Feb 25.

DeLong CJ, Shen YJ, Thomas MJ, Cui Z. Molecular distinction of phosphatidylcholine synthesis between the CDP-choline pathway and phosphatidylethanolamine methylation pathway. J Biol Chem. 1999 Oct 15; 274(42): 29683-8.