Staff Profile:Dr Philip Dash

Name::
Position / Job Title:
Lecturer in Biomedical Science
Responsibilities:
Areas of Interest:

Our main research interest is the role of the gaseous signalling molecule nitric oxide (NO) in the regulation of a variety of cellular processes, including cell migration and apoptosis, that are important for human health and disease.

Cell migration or movement is important in a number of normal physiological processes such as embryo development, blood vessel development and the functioning of the immune system. It is also important in diseases such as cancer where increased migration of cancer cells plays a role in the spread of the diseases - a process known as metastasis. Nitric oxide is known to be an important regulator of cell migration and we are investigating the mechanisms through which NO controls the migration of a variety of cancer cells and also investigating its role in the regulation of migration in other cell types such as trophoblasts and endothelial cells. These last two cells types play an important role in cardiovascular disease. Trophoblasts are cells that make up the placenta in pregnancy and a sub-type of these cells known as extravillous trophoblasts migrate into the uterine wall as far as the maternal blood vessels and remodel those blood vessels to adapt them for the increased blood flow that is required by the developing fetus. Failure of these cells to fully invade and remodel the uterine environment has been linked with pre-eclampsia, a disease of hypertension in pregnancy that causes around 76,000 maternal deaths and over 500,000 infant deaths per year worldwide.

Endothelial cells are the cells that line blood vessels and their migration is important for wound healing and the formation of new blood vessels - a process known as angiogenesis. Nitric oxide is known to play an important role in the biology of endothelial cells and we are investigating the mechanisms through which NO is invloved in their migration.

We are also interested in how NO regulates apoptosis or programmed cell death. Nitric oxide inhbits apoptosis in trophoblast cells and may be linked with the increases resistance to apoptosis that is often found in cancer cells.

Research groups / Centres:

Cardiac physiology, stem cells and repair

Vascular function and pathophysiology

Publications:
  • Harris LK, McCormick J, Cartwright JE, Whitley GS & Dash PR (2008) "S-nitrosylation of proteins at the leading edge of migrating trophoblasts by inducible nitric oxide synthase promotes trophoblast invasion" Exp.Cell.Res 314: 1765-1776
  • LaMarca HL, Dash PR, Vishnuthevan K, Harvey E, Sullivan DE, Morris CA & Whitley GStJ (2008) “EGF -stimulated extravillous cytotrophoblast motility is mediated by the activation of PI3-K, Akt and both p38 and p42/44 MAPKase.” Hum. Rep. 23(8):1733-41
  • Dash PR, McCormick J, Thomson MJ, Johnstone AP, Cartwright JE & Whitley GS (2007) "Fas ligand-induced apoptosis is regulated by nitric oxide through the inhibition of fas receptor clustering and the nitrosylation of protein kinase C epsilon" Exp.Cell Res. 313(16):3421-31
  • Ganapathy R, Whitley GS, Cartwright JE, Dash PR, Thilaganathan B (2007) "Effect of heparin and fractionated heparin on trophoblast invasion" Hum.Rep. 22(9):2523-7
  • Whitley GStJ, Dash PR, Ayling LJ, Prefumo F, Thilaganathan B & Cartwright JE (2007) “First Trimester Extravillous Trophoblasts from Pregnancies at Risk of Developing Preeclampsia are More Sensitive to Apoptotic Stimuli” Am.J.Path. 170(6):1903-9

Contact Details

Email:
p.r.dash@reading.ac.uk
Telephone:
+44 (0) 118 378 7400

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