When NIDCR's Hynda Kleinman turns out the lights of her lab for the last time in December, she will leave behind a host of fans — including scientists and students who have profited both from her mentoring and her pioneering policy making. She will also leave a legacy of royalties from her scientific discoveries during her 30-year sojourn at NIH. Chief of the Cell Biology Section in the dental institute, Kleinman's basic research has focused on extracellular matrix components and cellular receptors involved in tumor growth and metastasis, angiogenesis, and nerve regeneration. Along with the intellectual fruits of this research, it has also yielded Kleinman authorship on nine patents, including one for Matrigel — one of the 20 top royalty-generating patents at NIH. Her service to current and future generations of scientists at NIH is reflected in her work as chair of the Task Force on the Status of NIH Intramural Women Scientists and as a recipient in 1999 of the Association for Women in Science, Bethesda chapter, Mentoring Award. Says Joan Schwartz, assistant director, OIR, "She has set a real example for the women scientists on this campus in terms of fighting for our rights [and] keeping our consciousness raised at all times."

Hynda Kleinman did not expect to use bikini waxing as a lab technique or to invent the next great remedy for baldness when she came to NIH 30 years ago. http://www.nih.gov/catalyst/2001/01.03.01/page2.html

But her long and productive history of basic and translational research, which has landed nine patents — including one for Matrigel basement membrane matrix, among the top 20 NIH royalty generators has indeed featured some surprising developments.

"I started with angiogenesis," Kleinman said, tracing this particular journey in a parting interview with The NIH Catalyst, "and then I wound up in wound healing, and then . . . in hair. It really was a stretch."

Poised to exit NIH at year's end, the NIDCR cell biology chief credits the NIH environment with having enabled her to follow her research down the parallel angiogenic pathways related to cancer, heart disease, wound healing, and hair restoration.

Tracking Thymosin b-4

The protein that sent Kleinman on this hair-raising adventure is thymosin b-4 (Tb4), a small actin-binding peptide. At the NIH Research Festival in the fall of 2000, she elaborated on its potential role in metastasis (see "Aiming to Control a Double-Edged Sword," The NIH Catalyst, March-April 2001); at the Research Festival in the fall of 2005, she elaborated on its wound-healing and hair- growth properties.

Topically applied to the wounded skin of rodents, Kleinman said, Tb4 speeds wound closure by increasing collagen deposition and blood vessel formation, with help from its anti-inflammatory and antimicrobial activities. It is also showing promise in other types of healing, such as corneal re-epithelialization and cardiac repair. The surprising observation, she said, was hair growth accompanying wound closure and, beyond that, hair growth even on unwounded skin.  

There are currently two patents for Tb4; it is being tested in wound healing in Phase 2 clinical trials for the elderly, diabetes patients, and epidermolysis bullosa patients, and it has more recently been licensed for hair-growth studies.

Kleinman became interested in Tb4 in the early 1990s, when her group searched for genes involved in angiogenesis. They found that Tb4 was upregulated sixfold in tube-forming endothelial cells.

To understand the clinical relevance, they tested it on wounds and saw a dramatic enhancement in healing.  Kleinman applied for a patent through NIH, and NIH developed a CRADA with RegeneRx Biopharmaceuticals to develop Tb4 as a wound-healing drug. 

It was in their effort to develop a formulation for clinical use that the group discovered the new potential application of hair growth. Deborah Philp, a fellow in Kleinman's lab, noticed that around the edges of a Tb4-treated wound, the rats' skin resembled the bottom of an old broom."It looked like big, thick straw coming out of the edges of the wound, and it was a darker color and much thicker" than normal hair, Kleinman recalled.

As a result, she laughed, "we had many days when we were in the lab, bikini-waxing mice," to test whether this effect could be repeated on unwounded skin. Kleinman and colleagues obtained a separate patent covering Tb4's effect on hair growth, and it has now been licensed to two companies to be developed as a hair-loss treatment.

And there may be more to come from Tb4. "We are obviously interested in stem cells," Kleinman said, because Tb4 "focuses them to migrate and differentiate."  Also, the cellular receptor for Tb4 is unknown. It may function as a transcription factor, since it is found in the nucleus. She is eager to explore what other clinical applications may exist.

Tracking Gender Bias at NIH

The intensity of her research program not withstanding, Kleinman also found time to take the lead in bringing to light and brightening the status of women scientists at NIH. As chair of the Task Force on the Status of NIH Intramural Women Scientists, she guided the development of a 1992 report on gender inequities at NIH and recommendations to eliminate them; several of these recommendations have been implemented (for an overview, see "Ten Years and Counting: Have NIH Women Scientists Advanced Since the Task Force Report?" The NIH Catalyst, September-October 2001).

Kleinman is now part of the Second Task Force on the Status of Intramural Women Scientists, which is examining the progress women have made since the first report. A report is currently in preparation and should be available within the next few months. 

The biggest change, in Kleinman's view, is that women have more visibility and recognition as scientists. Pay equity and resources have also been tackled, she said, and there is more awareness in general of women's issues all important advances.  

However, she noted, the percentage of tenured women (approximately 20 percent) has remained lower than the percentage of women who are postdoctoral fellows (at least 40 percent).  "That's been the painful reality, that women haven't advanced up,"  Kleinman said. Moreover, there are "still subtle, back-door issues that remain to be resolved" and will be addressed in the second task force report.

The report will also address mentoring, particularly for tenure-track women at NIH. "I would say that many women at NIH feel very isolated," Kleinman said. Mentoring, she said, is something that NIH, as an institution, should work on. She suggested the need for a structured mentoring program.

 Mentoring has been one of Kleinman's favorite activities at NIH and one for which she has been honored. Listening is a major part of mentoring, she advised — "sometimes people just need to let off steam." There's also promoting productivity and creativity, getting a sense for what someone's best potential is and keeping her or him on track, and generally keeping up morale — these are the key elements of good mentoring, Kleinman said. And it pays off: "If you mentor people well, they'll be more productive, they'll work harder, and they'll want to contribute more to their lab."

Tracking a New Path

Kleinman is leaving NIH for a position at Washington, D.C.'s George Washington University — professor in the Department of Biochemistry and Molecular Biology; she also plans to work with industry on new model systems for Tb4. 

Despite the translational research component of the NIH Roadmap, Kleinman said, "I don't feel it's valued," in that achievement is still measured by the number of Cell, Science, and Nature papers produced; still, she predicts "that's going to change with time."

The bottom line about NIH in Kleinman's life, though, she said, is that it "has been good to me — there's no question that this has been a creative and fast-moving environment" for research. Not having to be "constrained by what my grant says I have to do," she noted, made her more productive.

Before she starts her new job, Kleinman will be riding off into the sunset — literally.  She's planning a bike trip across the United States with her husband.  n

Ed.Note: The NIH Catalyst would like to bid Hynda Kleinman, who has served us so well on our Board of Editorial Advisors, a very fond adieu and the very best of luck.

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