Scientist Recognized for Contributions to Women's Health

Lisa Henske, MD, works to find answers to a rare disease called lymphangioleiomyomatosis, which mostly affects women who are represented by patches on a quilt outside of her office.

Just outside Lisa Henske's office, a framed quilt spanning about five feet drapes the wall. Each square represents a woman with lymphangioleiomyomatosis or LAM, a rare lung disease that develops almost solely in women. Lisa Henske, MD, knows well the stories behind each patch. The quilt is a tangible manifestation of her scientific and emotional connection to women suffering from the disease.

A medical oncologist and scientist, Henske heard about LAM after coming to Fox Chase Cancer Center more than 11 years ago. Until then, she had been focusing on the genetic disorder tuberous sclerosis complex (TSC), which causes seizures, mental retardation, autism and benign tumors. The tumors commonly form in the brain, kidney, heart and skin as a result of mutations in TSC genes. In some cases, LAM is associated with TSC, but often a spontaneous mutation develops in the TSC1 or TSC2 genes that causes LAM.

LAM is categorized by abnormal benign tumor cells that spread to the lungs. Behaving as though they are malignant, these tumors destroy the normal lung, causing the lungs to collapse because of emphysema-like cysts.

Henske's work, including the discovery that mutations in TSC genes also cause LAM and that benign tumors can spread, qualified her to win the Society for Women's Health Research Medtronic Prize for Scientific Contributions to Women's Health—a $75,000 cash prize.

Henske's most recent work involves studying the role of female hormones in the growth and metastasis of LAM cells.

"It is so heart-wrenching," says Henske. "The only treatment is a lung transplant and many women do not survive this procedure."

According to Henske, women who develop LAM are normally in their late 20s or early 30s—in excellent health before they experience chronic shortness of breath. X-rays appear normal until late stages in the disease, so LAM may go undiagnosed until a lung collapses. Additionally, LAM seems to worsen during pregnancy. Without lung transplantation, LAM often causes incapacity and premature death.

Henske studies diseases like LAM and TSC because she believes that understanding the genetic causes of tumor formation and metastasis as well as how tumor cells choose different forms provides an optimal starting point in understanding cancer formation in the general population.

"This research tells us about the earliest events that occur in rare diseases," Henske explains. "If you can understand the basics of rare diseases, then you can extrapolate what you've learned and apply it to more common diseases. For example, there might be a connection between LAM and breast cancer metastasis, since both can be driven by estrogen."

Henske's lab also is investigating a link between LAM and the protein mTOR (mammalian target of rapamycin), which is a key protein within cells that regulates cell proliferation, growth and survival. Activated in diseases such as diabetes and kidney cancer, mTOR also is activated in LAM, Henske has found.

An mTOR inhibitor, temsirolimus, studied by Fox Chase medical oncologist Gary Hudes, MD, has recently been approved by the FDA for treatment of advanced renal cell carcinoma. Henske believes that this will lead to treatment for LAM and other illnesses.

"This is a great example of how we can focus on a genetic disease but also find ways to treat common diseases," says Henske.