Dr.
Takis S. Papas, fifth from left and seated, pauses for a photo with his
research team.
With a recent boost from a number of large federal research grants, including a five-year $6.6 million Program Project Grant, the university's Center for Molecular and Structural Biology is poised to accelerate its ongoing cancer genome research program.
The objective: To determine the molecular basis of cancer and thereby to target a select group of the most significant cancer-related genes so identified for the development of innovative cancer therapy.
The goal: To define and develop drugs for the treatment of specific cancer cells without harming their normal counterparts.
Genes already discovered in the center's cancer genome project have been tested in animal models and in some cases have proved effective in animals in reversing tumors. Center investigators are now developing the animal data and procedures required for clinical trials.
To identify the normal function of the genes and how this normal function is changed in cancer, investigators have turned to a tool developed in the center, a genetically engineered "knock-out" mouse model that allows the specific elimination of a gene's function. Thus the absence of the gene may result in developmental abnormalities that provide strong clues as to the gene's biochemical and biological function. The “knock out” experiments are delicate studies that require the latest technology and expertise.
The “knock-out” mouse facility, directed by Demetri Spyropoulos, Ph.D., offers an investigator a mouse in which all or part of a gene or genetic elements within a gene can be deleted, altered or replaced by parts of another gene whether the investigator is dealing with an entire collection of genes on a chromosome or one of the three billion single DNA nucleotide base-pairs that make up the cell's chromosomes.
When a knock-out gene leads to the death of the mouse, the system can be applied to make animal embryos formed entirely from the knock-out stem cell. This allows observation of how the embryonic development fails.
Clinical facilities at the university make it possible to carry ideas created in the center laboratory and transfer them to the clinical setting where patients have access to the latest therapies available, and often these are therapies unavailable anywhere else. This translational research, conducted by clinicians and medical students, is housed and supported by the center, creating a fertile environment for close, active research collaborations between basic and clinical scientists.
With a mission to perform basic and applied research directed at studying the molecular basis of cancer and the development of therapies based on understanding from those studies, the center has organized its research into the molecular oncology group and the developmental biology group.
Cancer, generally, is a developmental problem, but normal development is uncontrolled. Genes are turned on and off in normal development much the same as they are turned on and off in the various stages of cancer. But center investigators also want to clarify those genetic and biochemical mechanisms that lead to biological damage that initiates and enhances the progression of malignancies.
Takis S. Papas, Ph.D., Center for Molecular and Structural Biology director, is internationally considered among the founders of the molecular oncology research discipline. He is widely recognized for his unique contributions in molecular biology which have advanced the understanding of oncogenes.
Papas and his co-workers were the first to clone the myc oncogene, demonstrating that its expression is often elevated in malignant cells. He is best known for his pioneering work on the ETS family of oncogenes and its role in disease, which is the focus of the newly awarded Program Project Grant. Papas joined the laboratory of Biochemical Genetics at the National Institutes of Health in 1970. He remained at the NIH/NCI for the next two decades, holding many positions including head of the Laboratory of Molecular Oncology.
Papas has authored more than 350 publications, as well as several issued patents for practical applications of his discoveries. He has chaired and organized numerous scientific meetings, and he currently serves on the editorial boards of more than 10 journals.
The Center for Molecular and Structural Biology was established in 1993 as an independent university center located within the Hollings Cancer Center. University president James B. Edwards, DMD, with Sen. Ernest F. Hollings (D-S.C.) attracted center director Takis S. Papas, Ph.D., formerly the chief of the National Cancer Institute's Laboratory of Molecular Oncology. From a small nucleus of scientists who relocated to the university from the National Cancer Institute in Bethesda, Md., the center has grown to include support totaling more than $3.8 million annually in direct costs. Since 1993, center scientists have published more than 120 authored, many of which have attracted widespread interest.