Professor Paul Sharp

Profile

I am a nutrition scientist with an academic background in physiology and biochemistry. Following a postdoctoral fellowship in intestinal nutrient transport at the Royal Free Hospital medical school, I moved to the University of East Anglia and Institute of Food Research in 1995 to take up a Lectureship in Cell Biology & Physiology. In 2000 I moved to the University of Surrey as a Senior Lecture in Nutrition and from Surrey to King’s College London in 2000. At King’s I was promoted to Reader and then Professor of Nutritional Sciences and in 2016 I was appointed as Head of Department of Nutrition & Dietetics and I remained in this role until January 2024. I joined the University of Leeds in August 2024 as Head of School of Food Science & Nutrition and Professor of Nutritional Sciences.

I have published more than 90 peer-reviewed papers (H-index: 36 on Scopus; 45 on Google Scholar), many reporting advances in the understanding of the regulation of mineral bioavailability and metabolism. I have been a member of several external research panels and advisory committees and I currently chair the BBSRC Diet and Health Open Innovation Research Club Steering Group. I am also Deputy Editor for the British Journal of Nutrition.

Responsibilities

• Head of School of Food Science & Nutrition

Research interests

My research focuses on the digestion of foods and absorption of nutrients in the gastrointestinal tract. These processes are controlled by several factors including, the rate of release of nutrients from food during digestion, interaction with other food components in the gastrointestinal lumen, and a range of systemic factors that together regulate intestinal transporter expression and the rate of absorption. My group uses in vitro digestion models and feeding studies in human volunteers to understand the mechanisms involved in nutrient bioaccessibility and bioavailability. My work involves national and global collaborations with academic partners, the food industry, and non-governmental research institutions and is funded by UKRI, charities and industry.

Recent studies on iron bioavailability include:

• Assessing the impact of food processing on mineral bioavailability from cereals (a collaboration with the milling and baking industry). We have shown that physical disruption of plant cell walls by a modified milling process to produce smaller flour particles increases in vitro iron bioavailability from breads made using micronized wheat flour.

• Measuring the tissue distribution and bioavailability of minerals from novel engineered wheat lines (a collaboration with the John Innes Centre, University of Manchester and Rothamsted Research Institute). Iron bioavailability from a wheat variant over-expressing a vacuolar iron transporter and a naturally occurring mineral chelator (nicotianamine) is increased compared with a comparable non-transformed wheat variety.
• Determining zinc bioavailability from traditional Pakistani foods made using biofortified wheat (a collaboration with six national and international partners led by University of Central Lancashire). Studies show that zinc bioavailability from naan breads (which are leavened) is greater than from chapatti (unleavened bread), and within the naan group, zinc absorption was greater from the biofortified flour bread than the standard bread flour.

• A recently funded study to assess iron bioavailability from nutrient dense, environmentally sustainable, UK-grown pulses (Transforming UK Food Systems award led by University of Reading). In this collaboration we will work with partners in academia and industry to optimise the ratio of faba bean flour to white flour for use in bread making. We will then measure iron bioavailability from these breads in vitro with the best performing product being taken forward into human bioavailability studies.

In addition to work on mineral bioavailability, I also lead research projects investigating the mechanisms regulating the absorption and metabolism of nutrients at a cellular and molecular level.

• Iron-zinc interactions: We were the first group to characterise  iron transport via the divalent metal transporter DMT1 in intestinal epithelial cells. We established that the DMT1 protein is expressed at the apical surface of polarized intestinal Caco-2 cells and mediates pH-dependent uptake of Fe2+ . In collaboration with National Institute for Nutrition, Hyderabad, India we have shown that zinc is an important regulator of intestinal iron absorption. Zinc is a modulator of cell signalling and we have shown that zinc can increase intestinal iron transporter expression through a PI3K-activated mechanism. Zinc status is an important determinant of iron metabolism and we have put forward a working hypothesis that endogenous zinc secreted into the intestine, which is proportional to body zinc status, has a direct regulatory action on intestinal iron absorption.

• Hepcidin: My group, in collaboration with Professor Kaila Srai, University College London, was the first to show that hepcidin, the main systemic regulator of iron metabolism, acts directly on intestinal epithelial cells to decrease iron absorption. Furthermore, we demonstrated that the effects of hepcidin are cell-type specific and that macrophages respond rapidly to hepcidin to regulate serum iron levels. We have shown several factors regulate hepcidin levels in liver cells, including iron itself, pro-inflammatory cytokines, adipokines (e.g. leptin), and members of the TGF-β superfamily. We have recently reviewed the evidence that the iron-TGF-β axis is involved in the development of fibrosis in several liver pathologies. The possibility that inappropriately high levels of hepcidin contribute to pathology is also being investigated.

• Epigenetic regulation of iron metabolism: We are investigating epigenetic influences on iron homeostasis. Iron-dependent regulation of hepcidin mRNA is controlled by several iron sensing proteins including TfR2, Hfe, BMP6 and HJV. In collaboration with Professor Ian Morison (Otago) we demonstrated that hepcidin is differentially expressed in several liver cell lines and that this is related to DNA methylation of genes encoding these hepatic iron sensors. We established a link between activation of micro-RNAs of the miR-17 family in response to dietary polyphenols and decreases in ferroportin mRNA expression in intestinal Caco-2 cells. These data provide evidence for novel nutrient-gene interactions controlling iron bioavailability.

Qualifications

• BSc Physiological Sciences (Newcastle)
• PhD Biochemistry (London)

Professional memberships

• The Nutrition Society
• American Society for Nutrition
• The Physiological Society
• The International Society for the Study of Iron in Biology and Medicine