The work of Dr. Berkowitz is probably as close to rocket science as an anesthesiologist is going to get. He is trying to understand the mechanisms that underlie vascular disorders, but one of his main concentrations is the effect of deep space radiation on the cardiovascular system. In space, astronauts are exposed to dangerous levels of high-energy radiation. Therefore, NASA and the National Space Biomedical Research Institute are funding Dr. Berkowitz to determine not only the damage that such energy causes, but what interventions or therapeutics could be used to reverse the damage.
The cells that line our blood vessels (endothelial cells) are highly vulnerable to oxidant damage. To learn more about this, Dr. Berkowitz and his graduate student Kevin Soucy are conducting experiments at the Brookhaven National Laboratory near Stony Brook, New York, where they have access to a particle accelerator, which creates radiation similar to what astronauts could encounter. In pre-clinical studies, Dr. Berkowitz and his team use the radiation produced to examine its effects on vascular stiffness and endothelial cell function.
Dr. Berkowitz believes that the high-energy radiation activates an enzyme called xanthine oxidase (XO), and that XO is responsible for maintaining a chronic cycle of oxidant production. He thinks that the use of an XO inhibitor can interrupt this cycle of stress to the cells and thereby limit the damage. This ability to target the XO enzyme could have additional applications, such as for patients who need radiotherapy or in the event of a terrorist attack. In the long term, he hopes to uncover the molecular mechanisms responsible for cardiovascular injury as well as natural pathways of repair.
- Benjo A, Thompson RE, Fine D, Hogue CW, Alejo D, Kaw A, Gerstenblith G, Shah A, Berkowitz DE, Nyhan D. “Pulse pressure is an age-independent predictor of stroke development after cardiac surgery.” Hypertension. 2007 Oct;50(4):630-5. Epub 2007 Sep 4.
- Santhanam L, Lim HK, Lim HK, Miriel V, Brown T, Patel M, Balanson S, Ryoo S, Anderson M, Irani K, Khanday F, Di Costanzo L, Nyhan D, Hare JM, Christianson DW, Rivers R, Shoukas A, Berkowitz DE. “Inducible NO synthase dependent S-nitrosylation and activation of arginase1 contribute to age-related endothelial dysfunction.” Circ Res. 2007 Sep 28;101(7):692-702. Epub 2007 Aug 17.
- Soucy KG, Lim HK, Benjo A, Santhanam L, Ryoo S, Shoukas AA, Vazquez ME, Berkowitz DE. “Single exposure gamma-irradiation amplifies xanthine oxidase activity and induces endothelial dysfunction in rat aorta.” Radiat Environ Biophys. 2007 Jun;46(2):179-86. Epub 2007 Jan 26.
- Tuday EC, Meck JV, Nyhan D, Shoukas AA, Berkowitz DE. “Microgravity-induced changes in aortic stiffness and their role in orthostatic intolerance.” J Appl Physiol (1985). 2007 Mar;102(3):853-8. Epub 2006 Nov 2.
- Soucy KG, Ryoo S, Benjo A, Lim HK, Gupta G, Sohi JS, Elser J, Aon MA, Nyhan D, Shoukas AA, Berkowitz DE. “Impaired shear stress-induced nitric oxide production through decreased NOS phosphorylation contributes to age-related vascular stiffness.” J Appl Physiol (1985). 2006 Dec;101(6):1751-9.
Dr. Berkowitz directs an integrated cardiovascular biology lab that has ongoing funding from the National Institute of Health, NASA and the National Space Biomedical Research Institute (NSBRI).
The primary focus of his laboratory work is geared toward understanding the role of nitroso-redox regulation and dyregulation in vascular biology and pathobiology, particularly as it relates to aging, atherosclerosis, and radiation-induced vascular endothelial function. Other focuses of the lab include understanding how basic cellular processes are altered in disease states, developing therapies for vascular diseases and helping lead space research team.