Department of Chemical Engineering
Room 66-465
Massachusetts Institute of Technology
77 Massachusetts Avenue
Cambridge, MA 02139-4307 USA

Telephone 617 253-6440
Email: khemboy@mit.edu

Brian Skinn

Graduate Research Assistant

Research Interests

Methods for Peroxynitrite Delivery in Toxicity Studies

Clinically, a correlation has been observed between prolonged infection and/or inflammation and incidence of cancer, and it is thought that nitric oxide (NO) and species derived from it represent the causal link in this system. NO is released at low levels by many cells in the body, serving various regulatory functions. However, when an immune response is mounted, cells involved in the non-specific immune response, primarily macrophages, release NO at a significantly elevated rate. In addition, these cells also release high levels of superoxide anion, O₂^-, which reacts with NO near the bimolecular diffusion-controlled limit to form peroxynitrite. Peroxynitrite (ONOO^-) is a strong oxidant, capable of damaging a wide variety of biomolecules, including proteins, DNA, lipids, and polysaccharides. In addition, ONOO^- can react with a number of small molecules found in vivo. This broad reactivity implicates ONOO^- as a major player in the cellular damage pathways leading to cancer.

In addition to its oxidative capabilities, peroxynitrite has very interesting chemical properties, one of the most significant being a short ( < 1 second) half-life at physiological conditions (pH 7.4, 37°C), while being long-term stable at high pH (half-life > 1 year at pH 13 and -80°C). This short lifetime under biologically relevant conditions makes bench-top study of ONOO^- reactions very challenging, as the well-mixed assumption cannot be made. This limitation can be overcome by reducing the physical dimensions of the reactor. Thus, I plan to design and construct one or more microfluidics devices for use in studying ONOO^- and its reactions. In conjunction with COMSOL models, these devices should permit quantitative investigation of the reactions of ONOO^- with a variety of targets, including proteins, DNA, cells, etc. The improved understanding of ONOO^- kinetics, transport properties, and damage mechanisms provided by the microdevice should allow for more detailed study of the action of ONOO^- within the body, and thus a better understanding of the biochemical pathways leading to carcinogenic tumor formation.

Personal Interests

My interest in this research topic ultimately stems from my early interest in chemistry and mathematics. Transport phenomena in reacting systems intrinsically combine these two subjects, and thus represent a logical choice of field for my research. The complexity of the chemistry of nitric oxide and peroxynitrite should prove an enjoyable challenge throughout my thesis work. In addition, this project involves inter-related modeling and experimental work, a combination I wanted in my PhD work from the beginning. Also, in terms of broader societal impact, even though my work does not contribute directly to a cure for cancer, the tools I am developing will hopefully be valuable to other researchers (at MIT and perhaps elsewhere) in applications that will make significant inroads in the fight against cancer. Apart from my research interests, I am pursuing Japanese language study; enjoy music, science fiction, and video games; and volunteer weekly with Kids Church at the Cambridge site of the Boston Vineyard. I have also been known to play Settlers of Catan from time to time.