Pathology unit uses molecular tools to refine treatments

By Amanda Siegfried
Office of News and Publications

A new initiative at UT Southwestern encourages basic scientists and clinicians to work in concert to quickly and efficiently translate the knowledge gleaned in the laboratory to the development of new medical treatments.

The Division of Translational Pathology, within the Department of Pathology, has been established in an effort to improve diagnosis and treatment of various diseases by taking advantage of new technologies.

"Pathologists are moving towards new technologies to supplement information gleaned from the microscope, which has been their primary tool for 150 years," said Dr. Errol Friedberg, chairman of pathology and holder of the Senator Betty and Dr. Andy Andujar Distinguished Chairmanship of Pathology.

"In addition to looking at tissue samples under the microscope, we are now also looking at them with cutting-edge molecular tools, many of which were developed as a result of the Human Genome Project."

Pathology has been completely transformed by technologies such as gene expression arrays and protein arrays, which allow researchers to pin point specific "molecular signatures" that individual types of tumors or disease states exhibit. For example, microarrays, or gene chips, can be used to determine which genes are being expressed and at what levels in a tumor sample. This information may soon be a routine way of determining which targeted therapy to use.

"There's now a very close interface between the pathologists and the oncologists, who are not just asking for diagnosis. We are also helping them address whether there is a new way of classifying tumors and the way tumors behave based on these technologies," Dr. Friedberg said.

Two faculty members have been recruited to work within the new division, and Dr. Friedberg anticipates bringing two or three more on board to work with cancer clinicians on campus as well as develop their own research programs.

Dr. Kevin Rosenblatt, assistant professor of pathology, has incorporated proteomics into UT Southwestern's translational pathology repertoire, an approach Dr. Friedberg said few other academic pathology departments in the nation have taken. Dr. Rosenblatt, a graduate of UT Southwestern's Medical Scientist Training Program (MSTP), uses a powerful analytical tool called mass spectrometry to examine thou sands of proteins in tissue samples and blood. The technology allows investigators to study how protein profiles differ in normal tissue and cancerous tissue.

"We are developing methods to detect cancer earlier and to determine other important clinical parameters, such as cancer stage, as well as to predict the patient's response to therapy, all based on a minute sample of blood," Dr. Rosenblatt said. "It's exciting to take emerging high-tech tools and apply them directly to diagnostic problems."

Researchers are just beginning to learn what various types of molecular signatures are and to correlate them with particular diagnoses, prognoses, and treatment options, said Dr. Diego Castrillon, assistant professor of pathology. He also is a graduate of UT Southwestern's MSTP.

"We are in an investigative stage, but the nature of translational research is that it feeds back into the treatment area very quickly," he said. "More and more we are realizing that a response or lack of response to a particular drug is linked to specific molecular signatures that can be reliably identified using these new technologies."

One of the keys to translational research efforts on campus is the new UT Southwestern Tissue Resource (UTSTR), a tissue bank facility being formed in a joint effort between the translational pathology division and the Harold C. Simmons Comprehensive Cancer Center.

"The tissue bank plays a fundamental role in a comprehensive cancer center," said Dr. Richard Scheuermann, associate professor of pathology and co-director of the translational pathology division. "Facilities like this end up serving as cross-disciplinary hubs that bring together investigators with different back grounds and research interests."

Tissue samples gathered from consenting UT Southwestern patients are processed and stored at the new facility in the Simmons Building. DNA, RNA and proteins are extracted from the tissues and cryogenically preserved.

"The samples are stored so that we can do studies now or many years from now, when technologies are even better," said Dr. Castrillon, whose translational research focuses on endometrial, or uterine, cancer. "Initially, our efforts are dedicated to specific types of cancer that are especially important clinically and affect large numbers of patients. Over time, we hope that the capabilities of the tissue bank will grow and include more types of cancer and other diseases to further encourage translational research at UT Southwestern."