Research Interests

     Our research is focused on defining the role of carotenoids in human health, with current emphasis on understanding the metabolic and physiological roles of beta-cryptoxanthin, lycopene, and beta-carotene.  These carotenoids are antioxidants, and they may enhance immunological functions and cell-to-cell communications.  In addition, beta-carotene might help prevent cancer in non-smokers; lycopene might help prevent prostate cancer, while beta-cryptoxanthin might help prevent osteoporosis.  We use human, animal, and cell culture models coupled with biochemical and immunological tools to explore the functional roles of these carotenoids, and advanced isotope techniques to study carotenoid absorption and metabolism.  Our laboratory also investigates how beta-carotene and beta-cryptoxanthin are converted to vitamin A.  Most of the world's people derive their vitamin A from carotenoids, which are found in inexpensive fruits and vegetables.  Absorption is often poor from these sources.  Beta-cryptoxanthin may be better absorbed, and thus be an underappreciated source of vitamin A.  Carotenoid-rich plant varieties are tested in our research, with the goal of finding what factors in foods are most important in determining how carotenoids are absorbed and metabolized.

Research Accomplishments

·         Proved that people with multiple carboxylase deficiency (a genetic disease) had mutant holocarboxylase synthetases with low affinities for the nutrient biotin.  This was the first evidence of a genetic defect involving biotin in humans and one of the first demonstrations that people required biotin in their diet.  It led to the third successful prenatal nutritional treatment of a disease. 

·         Demonstrated that there were at least two forms of multiple carboxylase deficiency, which had different genetic defects and which differed in disease progression.

·         Discovered that carotenoids influenced hormone status in humans, an early demonstration that carotenoids had physiological roles independent of their role as antioxidants or as precursors of vitamin A.   Subjects in carotenoid depletion studies developed menstrual cycle changes and thyroid hormone abnormalities. 

·         Established that carotenoid depletion decreases antioxidant activity in humans, and that low concentrations of beta-carotene normalize this activity.  Higher pharmacological concentrations of carotenoids did not further improve this antioxidant activity, possibly explaining why most epidemiological studies show strong correlations between beta-carotene intakes and reduced mortality, but most clinical trials showed the potential for harm when high dose supplements were used.

·         Measured the conversion of beta-carotene to vitamin A and the normal variability of this conversion in healthy adult humans.  Showed that the conversion of beta-carotene to vitamin A is both poorer and more variable than historically assumed.   These results help explain the generally poor results from public health programs that attempt to improve vitamin A status through the incorporation of beta-carotene rich foods in the diet. 

·         Showed that retinyl esters-the storage form of vitamin A-could be formed by DGAT1 (diacylglycerol acyltransferase 1).  DGAT1 was the first enzyme identified as an ARAT (acyl retinol acyltransferase).  This means that we can begin to characterize the ARAT pathway for forming retinyl esters, and gain insight into why some people absorb and store vitamin A much better than others.