Spotlight on Melinda Hollingshead, DVM, PhD
"A Pathway Opens Up and I Walk Down It"

Spotlight Archive

By Maritta Perry Grau

Melinda Hollingshead, DVM, Ph.D., has often taken the road less traveled and that has made all the difference for her—and for many others. Speaking of the events that led her to becoming chief of the Biological Testing Branch, she commented, "My whole life, a pathway opens up and I walk down it."

A Winding Path into Research
Her childhood dream was to become a veterinarian. Along the way, she veered onto a path to train and work as a medical technologist, then returned to the main path as a veterinarian for large and small animals, and later followed a path into research as the manager of a Biosafety level 3-star lab at Southern Research Institute in Birmingham, AL. She spent five-and-a-half years in Birmingham doing contract work for USAMRIID, NCI, and NIH. Finally, her path brought her to NCI-Frederick.

"I was always drawn to animals, and being a veterinarian seemed like a good way to be around the animals. I was the first graduate of the North Carolina State University College of Veterinary Medicine Graduate Program. That's where I learned to do research, and that's what I've done ever since."

But, she admitted in an understated way, while dealing with animals was fine, dealing with some of their owners was not so fine. "People do terrible things to their pets. I think people can become oblivious to their failings, and it was very bothersome to me. And so it was just better that I not do that anymore." That was when she decided to go into research-which led her first to Southern Research Institute and ultimately to NCI-Frederick.

"I think of myself as a jack-of-all-trades and a master of none," she said, explaining that she sees her role here as "predominately doing preclinical drug development to find new treatments for cancer." Dr. Hollingshead is chairperson of the Animal Care and Use Committee and is on the Institutional Biosafety Committee. She noted that the Biological Testing Branch does a variety of things: "We do a little in vitro work, some mechanism work. We run the DCTD Tumor Repository, and oversee the Charles River Animal Production contracts."

While she has met a number of people who "are almost obsessed with answering a particular research question," Dr. Hollingshead said, her own reason for working at NCI-Frederick is different. "I work here because I believe that research makes a difference in the well-being of human beings and ultimately our companion species; and cancer is diagnosed in an American every 22 seconds. So we need to do something to forestall that. I do very applied science."

For example, Dr. Hollingshead has worked closely with Dr. Ralph Parchment and his group in the Laboratory of Human Toxicology and Pharmacology and other collaborators on drug development projects for the Phase 0 clinical trials. Together, they have developed a set of protocols for using surgical techniques and needle biopsies in mice that mimic as closely as possible what would be done in humans.

In Dr. Parchment's laboratory, Dr. Robert Kinders, head of the PD Assay Development Section, NCI's NExT (NCI Experimental Therapeutics) program, developed the assays, and Dr. Hollingshead developed the methodology for getting the samples from the mice in a manner that is consistent with what can be done in a human being. "It's been a lot of fun. That's the kind of thing I like to do. There's a problem and you try to figure out the solution. And we continue to do preclinical modeling for the phase 0 trials. I personally think that the real key in the phase 0 trials is the development of a high-quality assay."

She noted that Dr. Kinders "has done a great job of establishing very highly validated assays that can be applied to a human being. He has developed these assays and validated them as though they were going to be clinically applied assays that you would have FDA approval for, that you would do in a standard human, clin-path lab. So we've taken that path with these animal studies; that is, to do the animal studies that direct the assay development so that you can develop a highly validated assay, and then generate enough samples so that you can confirm the assay.

"Now, we're working on a new target that, if all goes well, should go to human beings before the end of this calendar year," she continued. "We're generating quality control samples for the assay that Dr. Kinders developed. So the animals play a role at many levels in drug development, and my role in this is earlier in the development, not later, when you get to toxicology studies."

A Path to Working with Others
Dr. Hollingshead sees a lot of value in collaborations and team efforts. "It truly takes a team of people to make any significant steps along the way," she said. "There's no limit on the amount of success or progress that can be achieved if you don't care who gets the credit. And I think that's what a true team is. I would like to think that as being part of a team, I had some hand in assisting with some of the compounds currently in the clinic, or going to the clinic, or already in people and already benefitting them, because it truly is a team that moves these things forward. And I think we are a very good team of people. I've been incredibly fortunate to work with the quality of people that I work with."

Speaking of Dr. Parchment's laboratory, she said, "It's been fun. Bob and Ralph and the group of people they've brought together and the group of people that I work with regularly, Diane Newton, and everybody that I work with-they're all great people, they take what they do seriously, they care about it, and they want to do it well. That's really all you can ask for, that you work with a group of people who you respect, and you have faith in."

Her love of animals and her sense of humor are reflected in her office. Shelves are filled with Shrek creatures and moose. "I really like moose a lot," she said, although she cautioned that a face-to-face confrontation might not end well for the human. "They're really majestic animals, but they're territorial and not the friendliest of creatures," she noted.

Besides the creatures adorning the shelves of her office, Dr. Hollingshead has, of course, real ones—a dog, two cats, and two rabbits.

A Path to Helping the Community
Dr. Hollingshead also reaches out to the community, teaching weekend motorcycle safety classes about once every six weeks at Frederick Community College. "Many people are getting interested in motorcycles again because of the cost of gas," she said. "Cycles get about 40 to 50 miles per gallon. But people need to know how to operate them safely." She likes the contact with the public, and has many young people, often soldiers from Fort Detrick, who are required to complete the course before they can drive the cycles on base. With a motorcycle, she said, "you can't talk on the phone or a Blackberry, you have to 'be present in the moment.' And it's a good escape." Another of those paths she's so fond of taking.

A Path to Applying Research
When asked to identify the single aspect she would consider a significant achievement in her career, Dr. Hollingshead paused to think before settling on her development of the hollow fiber assay. The Developmental Therapeutics Program adapted the assay in 1995 "to provide quantitative indices of drug efficacy in heterogeneous tumors with minimal expenditures of time and materials. It is currently being used as the initial in vivo experience for agents found to have reproducible activity in the in vitro anticancer drug screen," according to the NCI web site, http://dtp.nci.nih.gov/timeline/noflash/milestones/M13_hollow_fiber.htm.

"I believe that what we do is important," she said firmly. "This program has touched a lot of compounds that are actually used: Taxol, which has really been phenomenal for people; the Developmental Therapeutics Program was involved in the early isolation of that compound and getting it to the clinic. We were the first people to test Velcade in animals. We did the very first assays on that molecule, and it has been benefitting people with not only multiple myeloma, but a variety of other things that are being assessed in clinical trials."

She concluded, "And I hope that I have played some role in helping people with cancer. Somebody's mother is alive today because of chemotherapy, somebody's father, somebody's husband, somebody's wife. And that's the important part: the people you love. All the rest of it can come and it can go, your house can burn down, your car can be stolen, every thing—that's all they are, just things. You can always get more things, but you can never get another loved one. They are irreplaceable. Anything that we do to allow people to hold on to that which is irreplaceable has been the right thing to do...I believe that ultimately, if we would all do just one good thing, if every single person on the face of the earth would do one truly good thing, that the world would have to be better. I really believe that."

Maritta Perry Grau,
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Scientific Publications, Graphics & Media
Advanced Technology Program
SAIC-Frederick, Inc.
National Cancer Institute at Frederick

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