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Why He Seeks to Discover

Posted on Dec 06, 2018

David Graham, Ph.D., leads the Molecular Determinants Core at Johns Hopkins All Children's Hospital
David Graham, Ph.D., leads the Molecular Determinants Core. He came to Johns Hopkins All Children's Hospital after an extensive career in HIV research.

David Graham’s inspiration as a scientist emerged from fear.

Growing up in the 1970s and ’80s in Greater Sudbury, a nickel-mining town of about 165,000 in northern Ontario, Graham worried about his older brother, Rob, his friends and other people he knew. Rob Graham is gay, and the emergence of HIV in that era had many people living in fear for themselves or loved ones.

“When HIV—or the ‘gay cancer’ as it was called back then—came onto the scene all of a sudden I just remember a palpable sense of terror in that community,” says David Graham, Ph.D. “He was fortunate never to contract HIV, but I just started to see people disappear and the circle of friends thin out and people dying.”

Graham asked questions. He wanted to understand. He fought forest fires to put himself through college. Graham became the first university graduate in his family with a degree in biomedical and health sciences from the University of Guelph. He earned a master’s biology at McMaster University in Hamilton, Ontario.

“I realized science is about asking questions, being really stubborn and having perseverance,” Graham says.

Graham went to work for the AIDS Vaccine Program for two years. For research purposes, they grew enough HIV to infect every man, woman and child on the planet. Graham worked with and learned from excellent scientists.

Still, he had questions.

Setting a Course for Discovery

Graham was 29 years old when he enrolled at The Johns Hopkins University in pursuit of his Ph.D. Most of the other students were younger, fresh from their degrees. Graham completed his doctorate in biochemistry, cellular and molecular biology in three years and three months, a record.

Graham’s research demonstrated how HIV cells mimic other cells as they establish themselves in the body.

“As soon as you’re infected with HIV, it’s essentially foreign like an organ transplant,” Graham says. “That’s how the virus hides. When you’re initially being infected, some of the immune responses are actually used by the virus to establish itself and hide. Once it has gone through one round of replication in your cells, it’s now you.

"I became fascinated to understand how even virus particles that were noninfectious could trick our immune system into causing cells to become non-responsive.”

Graham continued at Johns Hopkins for post-doctoral work and joined the faculty, developing expertise in mass spectrometry, an analytical technique that sorts ions based on their mass-to-charge ratio, and proteomics. He used the techniques to discover and catalogue hundreds of host proteins, creating a plethora of research opportunities for labs around the world. He wrote HIV-1 Proteomics, the first book tracing HIV protein analysis from the experimental days into the mass spectrometry era.

As Graham answered some of his questions, his postdoctoral research helped surface more questions and new areas for discovery.

“I started looking at the impacts of viral interactions in the immune system, and that’s what led me to metabolomics,” says Graham, also an associate professor in the Department of Molecular and Comparative Pathobiology in the Johns Hopkins University School of Medicine. “That’s another area where mass spectrometry is used.”

About four years ago, he discovered cross-talk among molecules in the peripheral nervous system and the central nervous system that was predictive of what would develop in the brain. He immediately realized the discovery could have applications to diseases such as Parkinson’s, Alzheimer’s and traumatic brain injury.

A new set of questions.

“That meant me re-evaluating my entire career,” Graham says.

A New Mission

As Graham was embarking on new areas of exploration, Allen Everett, director of the Pediatric Proteome Center at The Johns Hopkins University, connected him to Jonathan Ellen, M.D., president and vice dean at Johns Hopkins All Children’s Hospital in St. Petersburg, Florida.

Ellen was executing an ambitious plan for expanding the hospital’s mission beyond clinical care and into education and research.

“They had a vision of focusing some of these analytical tools as a platform for their research and education and hopefully to impact patient care,” Graham says. “It was a huge risk for me. I was comfortably funded based on my HIV scholarship. But it became clear I needed to go where the science led me.”

Graham became the hospital’s first director of the Molecular Determinants Core.

Since moving to Florida, Graham and his team have worked with the hospital’s research projects to develop a kit to stabilize dry blood sample cards that they believe can transform the way medical samples are collected and stored worldwide. They also have developed sophisticated applications of spectrometry to allow targeted discovery and unbiased discovery simultaneously in the same sample, which might come from a single heel stick. At a hospital such as Johns Hopkins All Children’s that routinely treats low birth weight babies, this is a critical advancement.

“It makes me proud and gives me shivers to say we have shown that we can work with those small volumes of blood from dry blood spot cards, from heel sticks, of babies,” Graham says.

Graham looks forward to a controlled expansion of the Molecular Determinants Core as it gains new lab space in the hospital’s Research and Education Building. He envisions a day when low-cost blood testing will be available to the masses through the internet, allowing self-monitoring and expanding access to the best health care around the globe.

“I do feel that there’s really not a limit, that we can give a massive bang for the buck as part of Johns Hopkins Medicine,” Graham says. “We have a far reach.”

On that, he has no questions.

The Molecular Determinants Core offers services to support research in integrative biology with comprehensive offerings in metabolomics, lipidomics, proteomics and targeted protein measures, with full bioinformatics integration capabilities. This story first appeared in Leading Care magazine, published by Johns Hopkins All Children’s Hospital.


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