Graduate student Darren Carpizo is among the many researchers around the world who are working with substances that inhibit angiogenesis, the formation of blood vessels from a pre-existing network of vessels. These substances represent a new class of cancer therapeutics that serve to strangle malignant tumors as they try to grow. Most are content to show that the substance shrinks tumors and does no obvious harm elsewhere. Darren and his adviser, Professor Luisa Iruela-Arispe, are trying to discover how the naturally occurring gene, METH-1, suppresses growth of blood vessels and what it does as its regular job in the body.

Because of their life-saving potential, approximately 19 anti-angiogenic therapies are already in the clinical pipeline, being tested with human subjects. However, for several of them it is not quite clear what their molecular mechanisms of action are to explain their anti-angiogenic properties, "and that worries some scientists," Darren says. "You have to wonder what else the substance is doing. That's a strong question that many people have on their minds."

For decades, drugs have moved to clinical trials before researchers understood at the molecular level exactly what they do and how they do it. However, a new paradigm is presently being employed, Darren says, "with molecular and cellular biology moving quickly to improve our ability to understand these substances much more fully, to understand the molecular mechanisms that give them their therapeutic characteristics."

There is a long-standing struggle between PhDs in basic science, who want to understand how drugs work before they're put to use, and MDs, who have patients in desperate need of treatment. Darren is unusual, Professor Iruela-Arispe says, in that "he feels very comfortable in both arenas. It's difficult to walk in these two very different worlds."

But doing just that is the premise of UCLA's Specialized Training in Advanced Research (STAR) program: Medical school graduates pursue a clinical specialty-in Darren's case, General Surgery-and at the same time obtain rigorous experience in basic science.

Darren always knew he would be a doctor: "Ever since I can remember, it's the only thing I have wanted to do," he says. At Cornell University, he took a special program, Biology and Society, which combined a core of courses in the biological sciences with courses in the social sciences and the humanities.

His interest in research grew at the University of Illinois Medical School, where he took a job to help pay for tuition and serendipitously, it changed his life. Working in the laboratory of the Chief of Gastroenterology was "strangely lucky for me," Darren says. In addition to the more routine tasks of a lab assistant, Darren had the opportunity to create an animal model for Gastro-Esophageal Reflux Disease (GERD).

Doctors have long correlated an overexposure of the esophagus to acid, as in GERD, with an increased risk of esophageal cancer, but the manner in which hydrogen ions induce the cells that line the esophagus to become cancerous had never been demonstrated scientifically. Using rabbits, Darren showed that exposing the esophagus to acid, which happens in GERD, caused a precancerous proliferation of cells. His findings led to a publication and presentations at major meetings of gastroenterologists, which gave him a crash course in the art of presenting research. More importantly, he discovered that he was "intrigued by the notion of how biological science can be used as a tool to understand human disease and solve medical problems."

So when he completed medical school, he looked for a residency program that would allow him to continue doing research while pursuing his specialized training in surgery. He was accepted into UCLA's General Surgery residency program which is a seven year program composed of five clinical years and two research years. When it came time for Darren to begin his research track of this program he originally was to begin to work in the laboratory of Dr. Helena Chang, Professor of Surgical Oncology and Director of the UCLA Revlon Breast Cancer Center.

When he switched to the STAR program, which provides more extensive research experience and a dual degree, he needed to find a basic science mentor with no clinical responsibilities. "The reasoning is that an MD/PhD like Dr. Chang usually has a lot of responsibilities that take them away from the laboratory," Darren explains. "They figure that to get the best scientific training, you're going to need a lot of mentoring with someone who focusses strictly on basic science." Professor Iruela-Arispe was a natural choice for Darren, as she has a dual appointment in Molecular, Cellular and Developmental Biology and in the Division of Surgical Oncology.

STAR's goal is to prepare doctors for a career in academic medicine. At UCLA, Darren has "learned that I really enjoy being in an academic environment where you're constantly being exposed to new ideas and various people with different ways of thinking." At UCLA, he also found that "I really enjoy teaching. I volunteer to teach medical students various aspects of surgery whenever I can."

As a result of his education, Darren will be able to pursue treatments for cancer on two fronts. In the laboratory, he can assist in the effort to find medicines that will inhibit or destroy cancer cells more effectively than the present chemotherapy drugs. The angiogenesis inhibitors, for example, might be used to shrink existing tumors and to prevent metastasizing cancers from "setting up shop" elsewhere in the body.

And in the meantime, as a practitioner of surgical oncology, he's on the frontline of present-day cancer treatment for solid organ cancers that are diagnosed at a fairly early stage" and thus offer a good prognosis, he says. To Darren, "the beauty of surgery is the experience of actually manipulating someone's body, with the opportunity potentially to cure them of some disease."

He also finds surgery the most challenging medical specialty as it requires the blending of both high level intellectual and technical skills but he admits, "it's the intellectual stimulation that drives me." His mentor values that quality. "He's very devoted and committed to his work," Professor Iruela-Arispe says. "When he believes in something, he goes at it with his full heart and soul."

Published in Winter 2002, Graduate Quarterly