Hartwell fellowship aids childhood asthma research

Postdoctoral fellow Lisa Lenertz spends her days at the University of Wisconsin–Madison studying how one protein, critical for proper immune function, moves from the inside to the surface of white blood cells.

"It’s hard to think of how this tiny contribution affects human disease," she says. But understanding the movement of this protein, with its "Star Wars" sounding name of P2X7, could help unlock the secret of why some children are more likely to develop asthma, as well as providing new insight into mechanisms and treatment of tuberculosis, colon cancer, bipolar affective disorder and arthritic pain.

"You just don’t think about how little your part is," Lenertz says. "You remember that you’re part of a group that works on similar projects as researchers in other laboratories, and, collectively, we can make significant progress as a scientific community."

A two-year fellowship from The Hartwell Foundation gives Lenertz funding to pursue P2X7 and its link to childhood asthma and other airway disorders through December 2009.

"The primary mission of The Hartwell Foundation is to grant awards to individuals for innovative and cutting-edge biomedical applied research that potentially benefits children," says President Fred Dombrose. "The Hartwell Fellowships support scientists early in their careers by enabling them to pursue specialized training as part of their career development. The postdoctoral fellowship provides support for two years at $50,000 a year for direct costs."

"Institutions that fully participated in the 2007 process for Hartwell Individual Biomedical Research Awards received the right to designate a Hartwell Fellowship award," Dombrose adds. UW–Madison was asked to participate as one of Hartwell’s top 10 biomedical research centers for 2007.

Lenertz, a native of Red Wing, Minnesota, who earned her doctorate in cellular regulation from the University of Texas Southwestern Medical Center, joined UW–Madison Professor Paul Bertics‘ biomolecular chemistry lab in 2007. Lenertz is a strong postdoctoral researcher and the fellowship makes results that much more rapidly achievable, Bertics says.

To step into the basic science world where Lenertz and Bertics work is to begin to see how understanding small pieces of cells can lead to life-changing breakthroughs.

Bertics’ research focuses on how environmental and hormonal factors affect cell function. Lenertz is looking at how tissue damage can activate immune cells to help

destroy pathogens causing the damage and to help repair the damage, Bertics says.

Allergies and asthma damage the lungs, and white blood cells called macrophages (it means "big eater") try to consume whatever’s causing the problem. The cells also can call in reinforcements to get the job done, Bertics says.

The macrophage cells can sense damage and when substances that should be inside of cells have gotten out, Bertics says. It’s as if someone comes home to find the sofa on the curb: "You know something is wrong."

That’s where Lenertz’ work with P2X7, an ATP receptor, comes in.

The energy from ATP is essential to survival, allowing animals to do everything from breathing to metabolizing sugar, Bertics says. ATP fuels the engine of a cell, but it needs to be inside the cell, not outside.

ATP is released at inflammation sites, Lenertz says. P2X7 moves from the inside of the macrophage to the cell surface, where it can be activated by ATP and promote a variety of immune responses. It can, for example, dilate and form a pore in the cell that can enhance the immune function of the cell. It sometimes causes cell death, which prevents excessive or needlessly prolonged immune responses.

How P2X7 moves to the cell surface in the first place is only poorly understood, Lenertz says, but it seems to have a role in inflammation and even cell death. This tiny protein does affect human disease. Variations in the protein have been connected with asthma, tuberculosis, colon cancer and bipolar affective disorder.

Animal studies have shown that inhibiting P2X7 can reduce arthritis pain.

"P2X7 is a difficult protein to manipulate, but I thought someone should do it," Lenertz says. She also just thinks the protein is cool, structurally and biochemically.

The Hartwell Fellowship means Lenertz will have more time to pursue her research instead of looking for funding. It will also give her a track record to apply for more funding. "It’s hard to manipulate biology, so it takes a lot of time to get answers and a lot of money," she says.

UW-Madison was selected as one of Hartwell’s top ten centers for biomedical research in 2006 and 2007, making researchers eligible for grants, Dombrose says. Last year, Sean B. Fain, a professor in the Department of Medical Physics in the School of Medicine and Public Health, won $100,000 for each of three years for his work with magnetic resonance imaging of the lungs in early childhood asthma. Bruce Klein, a professor in the Department of Pediatrics, also was awarded a three-year, $100,000 a year grant, for his work to stem the growing tide of systemic fungal infections in children. Postdoctoral fellow Jim Holmes also received a two-year, $50,000 a year fellowship for his work in Fain’s lab.

"Philanthropic organizations such as The Hartwell Foundation help us turn a great university into an extraordinary one by providing funding for research that will benefit the state, the nation and the world," says Sandy Wilcox, president of the University of Wisconsin Foundation. The Foundation is an independent nonprofit, tax-exempt corporation that raises, invests and distributes fund for the benefit of the UW–Madison.