Louis Pasteur said that chance favors the prepared mind. For Dennis Liotta, Samuel Candler Dobbs Professor of Chemistry, that's a fitting description of drug discovery in the basic sciences.

Emtriva is one of the most advanced HIV fighters on today's market. In Liotta's words, hard work and "a certain amount of serendipity" led him and colleagues Raymond Schinazi and Woo-Baeg Choi to discover the compound in the late 1980s. The FDA approved Emtriva for the treatment of HIV infection in 2003; it is available as Truvada or Atriple, once-a-day pills that deliver safe and effective fixed-dose combination medications.

A similar pairing of preparation and fortuity may be helping Liotta and his research team to make advances in cancer treatment. Most currently available cancer therapies ravage the body; they are extremely toxic and cannot be taken daily. Using chemical compounds based on the natural product curcumin, the main ingredient in the spice turmeric, the Liotta team has begun identifying "safe anti-cancer agents" that are low in toxicity, thereby potentially permitting for long-term use and enhanced quality of life during treatment. Curcumin, which provides the savory aroma and yellow coloring in curries and many mustards, has been shown to have modest anti-cancer properties in people whose diet contains it in large quantities. Liotta's lab has discovered structural analogs of curcumin that are 20 to 30 times as potent as curcumin, but equally safe.

Non-toxic compounds such as these could be used in a number of ways, including in combination with traditional therapies. "These compounds work on their own, but they also have very good synergy with radiation," Liotta says. "Many tumor cells are resistant to radiation, and these compounds could help address that problem." Radiation works by creating 'reactive oxygen species' in the body; these, in turn, cause DNA to fragment, and affected cells to undergo apoptosis (programmed cell death). In resistant cells, the reactive oxygen species are "scavenged" by agents like glutathione, making DNA fragmentation and apoptosis impossible. Liotta wants to turn this pattern around. In cellular studies, the compounds identified by the Liotta laboratory have been shown to deplete these 'scavenger agents' and make tumor cells more responsive to radiation. The research will move to the clinical trials stage within eighteen months. Says Liotta: "This is potentially a paradigm shift for how we treat cancer."

Liotta and his colleagues also tackle metastatic disease. "When a tumor migrates to a second site, it becomes an infinitely more challenging disease to control," he says. In partnership with scientists at Metastatix, a company Liotta founded, researchers are working to halt the progression of metastatic cancer. Their focus is a protein called CXCR4. Located on cell surfaces, CXCR4 is responsible for much of normal cell movement; but it also comprises 60% of the "metastatic phenotype," the various characteristics that describe metastatic cancer. "We're developing compounds that help antagonize the CXCR4 receptor, so that microclusters of tumor cells do not break off and lodge somewhere else," he says. Despite promising findings, Liotta cautions that more research is needed. In this regard Metastatix will file an Investigational New Drug (IND) application in Fall 2007 for clinical trials to assess the safety and efficacy of these compounds.

For Liotta, who has been a member of the Emory faculty since 1976, excellent research also involves identifying and mentoring the next generation of scientists. In addition to his work with graduate students, he teaches introductory Organic Chemistry to undergraduates. Over the course of a semester, his students progress from fear of the subject matter to curiosity about it, to logical and systematic ways of thinking with it. "I never fail to learn from them," he says of Emory's undergraduates and the questions they ask him.

Liotta also supports the next generation of scientists in the developing world. He has started a company in Johannesberg called iThemba (translated as 'hope') Pharmaceuticals, whose goal is to make compounds that address the healthcare needs of sub-Saharan Africa. He's been back and forth to South Africa more than a dozen times to get the project started. iThemba has received funding from the South African government and is preparing to tackle tuberculosis, HIV, and malaria - "the big three" in the sub-Saharan region. "Philanthropy alone won't solve the problems in Africa," Liotta says. "What they need is the expertise to address their own healthcare issues." iThemba will transfer expertise from top Western scientists to South African researchers, so that the latter can devise their own creative indigenous solutions to a range of healthcare problems.

It's an ambitious goal. For Liotta, that's nothing new. If chance favors the prepared mind, it also aids the determined one.