Page 5 - SFRBM dot - April 2015

involved in the design of redox-active luorescent probes, and in seeking guidelines suggest you include a section on “Expected results, data

to understand the mechanisms by which they react with reactive interpretations, and alternate strategies”. A researcher should also

oxygen species (superoxide, hydrogen peroxide, singlet oxygen, think along these lines when he or she does an experiment. You should

and lipid hydroperoxide, to list a few) and reactive nitrogen species be asking the question “what if?” all the time. Even if you ind exactly

(nitric oxide, peroxynitrite, nitroxyl anion, and nitrogen-di-oxide). We what you expected, you should make sure this is not something that

use a variety of analytical techniques (EPR, HPLC/MS luorescence, happened by chance. You should continue to verify the conclusion by

chemiluminescence) to elucidate the chemical mechanism through varying the experimental conditions, different cell lines, etc., and make

identiication and characterization of products.
sure you can properly interpret the results. You should have an open

mind and not be wedded to your preconceived ideas. You also need
The most notable research in recent years has been the rigorous
to know when to fold a particular experiment (not forever) but for a
identiication and elucidation of superoxide, hydrogen peroxide, and

peroxynitrite using speciic luorescent probes, and their diagnostic short time in order to give your brain a break and think about different

projects. Of course, you should be constantly reading related literature
marker products in biological and cellular systems. We are almost
to stimulate your brain to take a different approach. So this should be
there, and I am conident that, with the availability of additional custom-
a continuous process. Well, wisdom comes with age, and vice versa.
designed probes, we will be able to pinpoint the identity and measure
The life of a PI is a winding road with highs, lows, excitement, but never
speciic ROS in different cellular organelles.
boredom.

In collaboration with Navdeep Chandel, we pioneered the development
DOT: Clarify a common misconception about research.
of mitochondria-targeted compounds (Mito-Q, Mito-CP) as

antiproliferative agents in cancer, and with Anumantha Kanthasamy as It took me a long time to understand that the pursuit of knowledge

neuroprotective agents in a Parkinson’s disease model.
from cells to mice to man is not always linear. In order to obtain a

thorough understanding of the basic biology, one has to experiment in
DOT: What do you think is the direction the oxidative stress is
many different cellular systems and conditions. Drugs, concentrations,
heading? Well, it looks like most of the experiments have been carried
and endpoint measurements do not always seamlessly translate
out using the wrong probes or wrong assays. Future investigators may
to preclinical (mice/rat) systems. Although I have not yet had an
have to re-examine them using the new probes and more rigorous
opportunity to translate from the preclinical systems to humans, it
methodology. Simply trusting the “ROS assay kits” and not completely

appears that jumping from mice (with limited data) to man is a huge
understanding and interpreting the results have muddied our thinking
leap of faith and very rarely does one ind things working the same
and impeded progress in ROS research. For the most part, I don’t think
way. In this regard, I like the idea of repurposing FDA-approved drugs
we have done most of the measurements properly and came to the
from the existing libraries in several diseases. When we publicize our
right conclusions in this ield. The younger generation should dig deep
success in mice, we need to alert the public to the fact that this is a
and ind more deinitive answers. We should dismiss skepticism that
long way from becoming a reality for humans, but it is an essential short
surrounds the role of oxidants/oxidative stress in disease mechanisms

step in the right direction.
by being rigorous and thoughtful in the use of ROS and ROS-derived

assays, design of cell culture, preclinical, and clinical experiments. DOT: Under situations whereby funding is hard to get because of

There has to be more input from both basic and clinical researchers governmental budget cut, what is the best advice?

during the experimental design, data interpretations, statistics, etc.
First of all, you have to make sure you really believe in what you are doing

DOT: When an experiment stalls, what drives you to continue on?
and you have to be smart about it. You have to assess how crowded

is your area of research. You have to be certain that your research is
When writing the research strategy in R01/R21 NIH grants, the

SFRBM Newsletter // April 2015 // Radical View • Dr. Balaraman Kalyanaraman

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