Katia Petroni
e-mail: katia.petroni AT unimi.it
affiliation: Università di Milano
research area(s): Genetics And Genomics
Course:
Biomolecular Sciences
University/Istitution: Università di Milano
University/Istitution: Università di Milano
Katia Petroni obtained her degree in Biological Sciences in the University of Milan in 1994 discussing a thesis on the epigenetic phenomenon of paramutation of anthocyanin regulatory genes in maize. In 1999 she obtained her specialisation in Applied Genetics in the same university discussing a thesis MYB and bHLH transcription factors of maize and Arabidopsis. In the same year she started to work in the Department of Biomolecular Sciences and Biotechnology as technical assistant and since 2002 as researcher.
In the last 15 years she has studied the control of flavonoid and anthocyanin biosynthesis in maize and more recently in tomato. She has isolated different members of the R1/B1 and C1/Pl1 families, coding bHLH and MYB transcription factors regulating anthocyanin biosynthesis in maize. This research is recently focused on the determination of the protective role of flavonoids in health in the European projects FLORA (EU FP6) and ATHENA (EU FP7).
She has worked in different European projects on transcriptional control of metabolism (EU FP4 MYB function search) and aimed to determine the function of Arabidopsis MYB and bHLH transcription factors (EU FP5 REGIA). She has been responsible for projects funded by national agencies (MIUR PRIN 2003 and PRIN 2006).
Results of this research have been published in 22 papers on international scientific and peer-reviewed journals, presented as poster and oral communications in several national and international scientific meetings and included in two patents and chapters of books. She is referee for the international scientific journals BMC Biology and Plant Science.
In the last 15 years she has studied the control of flavonoid and anthocyanin biosynthesis in maize and more recently in tomato. She has isolated different members of the R1/B1 and C1/Pl1 families, coding bHLH and MYB transcription factors regulating anthocyanin biosynthesis in maize. This research is recently focused on the determination of the protective role of flavonoids in health in the European projects FLORA (EU FP6) and ATHENA (EU FP7).
She has worked in different European projects on transcriptional control of metabolism (EU FP4 MYB function search) and aimed to determine the function of Arabidopsis MYB and bHLH transcription factors (EU FP5 REGIA). She has been responsible for projects funded by national agencies (MIUR PRIN 2003 and PRIN 2006).
Results of this research have been published in 22 papers on international scientific and peer-reviewed journals, presented as poster and oral communications in several national and international scientific meetings and included in two patents and chapters of books. She is referee for the international scientific journals BMC Biology and Plant Science.
Her scientific interests are focused on two main subjects.
One major focus of her studies is to deciphere the logic of transcriptional control and gene regulation in plant model systems (Arabidopsis, maize, tomato) during seed development and in secondary metabolism, such as flavonoid biosynthesis.
A second major focus is to understand the role of bioactives (such as anthocyanins) in preventing chronic diseases, such as obesity and cancer. To this purpose, main interest of her studies is to develop model foods enriched in specific nutrients/bioactives and use them in feeding trials in animal models or human subjects to assess the impact of such compounds on health using "omic technologies.
One major focus of her studies is to deciphere the logic of transcriptional control and gene regulation in plant model systems (Arabidopsis, maize, tomato) during seed development and in secondary metabolism, such as flavonoid biosynthesis.
A second major focus is to understand the role of bioactives (such as anthocyanins) in preventing chronic diseases, such as obesity and cancer. To this purpose, main interest of her studies is to develop model foods enriched in specific nutrients/bioactives and use them in feeding trials in animal models or human subjects to assess the impact of such compounds on health using "omic technologies.
1) Martin C., Butelli E., Petroni K., C. Tonelli How can research on plants contribute positively to human diets and health? Plant Cell, 2011 doi: 10.1105/tpc.111.083279
2) Calvenzani V., Martinelli M., Lazzeri V., Giuntini D., Dall"Asta C., Galaverna G., Tonelli C., Ranieri A., Petroni K. Response of wild-type and high pigment-1 tomato fruit to UV-B depletion: flavonoid profiling and gene expression. Planta 231: 755-765, 2010
3) Titta L, Trinei M, Stendardo M, Berniakovich I, Petroni K, Tonelli C, Riso ,P Porrini M, Minucci S, Pelicci PG, Rapisarda P, Reforgiato Recupero G, Giorgio M, 2010, Blood orange juice inhibits fat accumulation in mice Int J Obesity, 34:578-88.
4) Toufektsian MC, de Lorgeril M, Nagy N, Salen P, Donati MB, Giordano L, Mock HP, Peterek S, Matros A, Petroni K, Pilu R, Rotilio D, Tonelli C, de Leiris J, Boucher F, Martin C, 2008, Chronic dietary intake of plant-derived anthocyanins protects the rat heart against ischemia-reprefusion injury. J. Nutr. 138, 747-752.
5) Pilu R, Piazza P, Petroni K, Ronchi A, Martin C, Tonelli C, 2003, pl-bol3, a complex allele of the anthocyanin regulatory pl1 locus that arose in a naturally occurring maize population. Plant Journal 36:510-521.
2) Calvenzani V., Martinelli M., Lazzeri V., Giuntini D., Dall"Asta C., Galaverna G., Tonelli C., Ranieri A., Petroni K. Response of wild-type and high pigment-1 tomato fruit to UV-B depletion: flavonoid profiling and gene expression. Planta 231: 755-765, 2010
3) Titta L, Trinei M, Stendardo M, Berniakovich I, Petroni K, Tonelli C, Riso ,P Porrini M, Minucci S, Pelicci PG, Rapisarda P, Reforgiato Recupero G, Giorgio M, 2010, Blood orange juice inhibits fat accumulation in mice Int J Obesity, 34:578-88.
4) Toufektsian MC, de Lorgeril M, Nagy N, Salen P, Donati MB, Giordano L, Mock HP, Peterek S, Matros A, Petroni K, Pilu R, Rotilio D, Tonelli C, de Leiris J, Boucher F, Martin C, 2008, Chronic dietary intake of plant-derived anthocyanins protects the rat heart against ischemia-reprefusion injury. J. Nutr. 138, 747-752.
5) Pilu R, Piazza P, Petroni K, Ronchi A, Martin C, Tonelli C, 2003, pl-bol3, a complex allele of the anthocyanin regulatory pl1 locus that arose in a naturally occurring maize population. Plant Journal 36:510-521.
Project Title:
Role of dietary anthocyanins in reducing the induction and progression of cancer
BACKGROUND One of the most pressing challenges for the next fifty years is to reduce the impact of chronic diseases, including cardiovascular disease, cancers and age-related degenerative diseases. Polyphenols are examples of bioactives from plants that have beneficial influences on a number of important risk factors associated with such diseases. Traditionally they have been thought to act through their unifying property of being relatively potent antioxidants. However, it is now generally agreed that the protective effects of dietary polyphenols can not only result from their direct activity as antioxidants, but it is likely that many dietary polyphenols activate endogenous antioxidant defence systems and signaling pathways and act indirectly to promote health.
Tumorigenesis in mammals is intimately linked to oxidative stress, since both the initiation and progression stages of oncogenesis are promoted by oxidative stress. Among polyphenols, anthocyanins are the red, purple and blue plant pigments available in a range of fruits and have been shown to prevent obesity, to offer a significant cardioprotection and delay the progression of cancer in animal studies. In cellular assays, anthocyanins have been shown to inhibit the activity transcription factors promoting carcinogenesis and cell transformation and have also been reported to promote apoptosis. However, how anthocyanins reduce the induction and progression of cancer is still far from being fully understood.
AIM OF THE PhD PROJECT will be to determine whether inclusion of anthocyanins in the diet at relatively high levels and over relatively long periods of time can promote health and protect against cancer. Furthermore, our aim will be to establish the fate of anthocyanins assumed through diet and the molecular mechanism underpinning their beneficial action. With these activities, we expect to contribute to the understanding of how and why anthocyanins contribute to promote health and to reduce cancer progression.
EXPERIMENTAL APPROACH AND WORKPLAN
The project will be divided in four different tasks, including:
1) Maize production and chemical analyses. To test the beneficial effect of anthocyanins, feeding trials with model mice to study cancer will be perfomed. To obtain corn lines with different dosages of anthocyanins in kernel, we will create by classical breeding isogenic maize lines that produce kernels with no anthocyanins and maize lines with increasing content of anthocyanins in kernels. Each maize line will be analysed to determine the quality and quantity of anthocyanins produced in the kernel. These lines will be also used as source of anthocyanins extracts for cell-based experiments.
2) Production of labeled cyanidin 3-glucoside. To test the bioavailability of anthocyanins and to follow their fate after they are assumed with food, we will feed mice by gavage with labeled anthocyanins and monitor their absorption. To produce labelled anthocyanins, a protocol using a maize genotype characterized by a strong light-dependent anthocyanin pigmentation in seedling tissues will be set up. Anthocyanins will be then extracted and labelled anthocyanins purified.
3) Effects of anthocyanins supplied or endogenously produced in cells. Besides studying effects of anthocyanins rich diet, we also want to understand the molecular mechanism underpinning their beneficial action. To achieve this, total anthocyanin extracts from corn and pure anthocyanins will be supplied to different murine and mammalian cell lines. We also want to test the effect of anthocyanins endogenously produced in mammalian cells engineered with the complete biosyntethic pathway of anthocyanins. Engineering antioxidants by de novo biosynthesis can conceivably improve cell replacement therapy by prolonging the life span of donor cells.
4) Effects of dietary anthocyanins on DNA methylation patterns. To determine the influence of diet on the epigenome, the effects of dietary supplementation with anthocyanins on DNA methylation patterns induced by high fat diets in the fetus or by chronic dietary obesity will be investigated by real-time PCR. Furthermore, histone modifications at defined genomic regions will be investigated by ChIP-chip and any differences associated with anthocyanin-enriched dietary supplementation will be examined.
Tumorigenesis in mammals is intimately linked to oxidative stress, since both the initiation and progression stages of oncogenesis are promoted by oxidative stress. Among polyphenols, anthocyanins are the red, purple and blue plant pigments available in a range of fruits and have been shown to prevent obesity, to offer a significant cardioprotection and delay the progression of cancer in animal studies. In cellular assays, anthocyanins have been shown to inhibit the activity transcription factors promoting carcinogenesis and cell transformation and have also been reported to promote apoptosis. However, how anthocyanins reduce the induction and progression of cancer is still far from being fully understood.
AIM OF THE PhD PROJECT will be to determine whether inclusion of anthocyanins in the diet at relatively high levels and over relatively long periods of time can promote health and protect against cancer. Furthermore, our aim will be to establish the fate of anthocyanins assumed through diet and the molecular mechanism underpinning their beneficial action. With these activities, we expect to contribute to the understanding of how and why anthocyanins contribute to promote health and to reduce cancer progression.
EXPERIMENTAL APPROACH AND WORKPLAN
The project will be divided in four different tasks, including:
1) Maize production and chemical analyses. To test the beneficial effect of anthocyanins, feeding trials with model mice to study cancer will be perfomed. To obtain corn lines with different dosages of anthocyanins in kernel, we will create by classical breeding isogenic maize lines that produce kernels with no anthocyanins and maize lines with increasing content of anthocyanins in kernels. Each maize line will be analysed to determine the quality and quantity of anthocyanins produced in the kernel. These lines will be also used as source of anthocyanins extracts for cell-based experiments.
2) Production of labeled cyanidin 3-glucoside. To test the bioavailability of anthocyanins and to follow their fate after they are assumed with food, we will feed mice by gavage with labeled anthocyanins and monitor their absorption. To produce labelled anthocyanins, a protocol using a maize genotype characterized by a strong light-dependent anthocyanin pigmentation in seedling tissues will be set up. Anthocyanins will be then extracted and labelled anthocyanins purified.
3) Effects of anthocyanins supplied or endogenously produced in cells. Besides studying effects of anthocyanins rich diet, we also want to understand the molecular mechanism underpinning their beneficial action. To achieve this, total anthocyanin extracts from corn and pure anthocyanins will be supplied to different murine and mammalian cell lines. We also want to test the effect of anthocyanins endogenously produced in mammalian cells engineered with the complete biosyntethic pathway of anthocyanins. Engineering antioxidants by de novo biosynthesis can conceivably improve cell replacement therapy by prolonging the life span of donor cells.
4) Effects of dietary anthocyanins on DNA methylation patterns. To determine the influence of diet on the epigenome, the effects of dietary supplementation with anthocyanins on DNA methylation patterns induced by high fat diets in the fetus or by chronic dietary obesity will be investigated by real-time PCR. Furthermore, histone modifications at defined genomic regions will be investigated by ChIP-chip and any differences associated with anthocyanin-enriched dietary supplementation will be examined.