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Dr. Singh, senior scientist in the Cancer Cell Biology Program, director of the Cancer Genetics Program and Joy and Bill Harbert Endowed Chair in Cancer Genetics, found his focus on mitochon- dria shortly after completing his postdoctoral work at Harvard University and taking up a faculty position at Johns Hopkins University. Convincing his colleagues of the significance of mitochondria in cancer proved chal- lenging. That s where my journey began, Dr. Singh says. I didn t realize that either I was ahead of my time or I was stupid. He wrote a paper and a grant on the subject, neither of which was published, and began run- ning up on the end of his three-year funding deadline for his teaching contract. It was do or die, he says.

Most people s careers, particularly as a young assistant professor, begin by publishing a paper, he continues. My career went the opposite way usu- ally, you write or edit a book at the end of your career. That first of three books and more than 75 research publications, Mitochondrial DNA Mutations in Aging, Disease and Cancer, laid the foundation for the field of mitochondrial research in cancer and revealed that, indeed, Dr. Singh was ahead of his time. As I edu- cated myself to edit that book, I realized that there s an emerging set of hundreds of diseases that haven t been described in literature, he says. The scientific field hasn t realized what many physicians already knew. I realized that there s a lack of knowledge and a disconnect between the physicians, the scientists and the patients.

Crosstalk To address that disconnect, Dr. Singh single-hand-

edly founded the Mitochondria Research Society. He took a class at Johns Hopkins to learn how to design a Web site, which he launched at his own expense. He surveyed scientists at a Keystone Symposium in Santa Fe, New Mexico, to judge their interest in joining such an organization, and the positive response led him to

create a newsletter and rope his wife and children into distribution. One of my friends and I developed the newsletter, and my family put on the stamps, he says. You send it to Israel, you send it to England, you send it here. We were working for a while, but I realized that just doing a society wasn t enough. We had to bring the scientists and physicians together. So I started a journal titled Mitochondrion.

For all the light he was shining on mitochondrial disease, Dr. Singh felt he was failing in one important area: gaining funding for his own research at Johns Hopkins. You can do all this, but it s all cosmetic if you don t get a grant and you re out, he says. Between con- ferences and newsletters, he scoured Netscape for fund- ing opportunities. His first funds came in the form of a handwritten check for $204,088.00 from the Elsa U. Pardee Foundation, which he keeps framed on his wall.

That was a breakthrough, because it was an oppor- tunity to talk about mitochondria-to-nucleus crosstalk, which can improve our understanding of the disease, Dr. Singh says. His next grant came from the American Heart Association to study the long-term effects of anthracycline on children s hearts. That was followed by a grant to study the DNA repair mechanism in mito- chondria. So that saved my career, Dr. Singh says. And made it: He has organized scientific meetings and work- shops around the world, advised government and profes- sional organizations in numerous countries, reviewed journal articles and grant proposals, and given interviews in print and broadcast to demystify this tiny yet signifi- cant organelle. And lived to tell the story, he says.

Coming Together Much of Dr. Singh s work has been inspired by

that of scientist and Nobel laureate Otto Warburg, M.D., who in the early- to mid-20th century postu- lated that damaged mitochondria were a major factor behind cancer. Over time, it was forgotten, Dr. Singh says. When I came to Johns Hopkins, it was laughed at It s a small genome, a small organism, what does

scientist profile

Dr. Singh s

first book,

Mitochondrial

DNA Mutations

in Aging, Disease

and Cancer, laid

the foundation

for the field of

mitochondrial

research in

cancer.

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