The biology of cancer development and work with genetically linked illnesses are key focus areas for Delaware researchers. In the area of cancer biology, Dr. Daniel Carson, Chair of the Department of Biological Sciences, and a 2002 recipient of an NIH Merit Award, is studying processes that occur both in healthy embryo development and in the growth of a cancerous tumor. Following fertilization, embryos develop to a stage at which they acquire the ability to bind to and invade uterine tissue, reflecting an increase in the expression of embryonic adhesion-promoting molecules. One class of these molecules is heparan sulfate proteoglycans. Studies in both mouse and human model systems indicate that proteoglycans and novel cell surface proteoglycan-binding proteins support embryo-uterine interactions at early stages of embryo attachment. Expression of both the proteoglycans and their binding proteins persists through placental development and plays an important role in cartilage development. Similar proteoglycan-dependent interactions occur in a variety of tumor cell lines, including those of breast, melanoma and prostate.
Research in Dr. Cindy Farach-Carson’s laboratory centers on the biology and biochemistry of bone cells and bone matrix. An area of emphasis is the role of bone matrix in the progression of cancer following metastasis from primary sites, such as the breast or prostate, to bone. In many cases, primary tumors are fairly slow growing and do not become life threatening until they form tumors in bone, where bone matrix growth factors provide a rich environment to promote the growth of cancer cells that invade. Dr. Farach-Carson is trying to identify and isolate the growth factors responsible for cancer growth and progression, with the long-term goal of developing “molecular drugs” to combat cancer metastasis.
Two new prostate cancer researchers joined the cancer biology group in 2002, Dr. Carlton Cooper and Dr. Robert Sikes. Dr. Cooper is studying how cancer spreads from its point of origin in the prostate to its secondary site in bone. He is focused on what proteins, typically called cell adhesion molecules (CAMs) are being used by the cancer cell and the bone marrow endothelial cells to facilitate their interaction. These CAMs could be targeted in early-stage prostate cancer to prevent it from spreading to bone, where it can cause intense pain, spinal cord compression, and which can lead to paralysis and bone fracture.
Dr. Robert Sikes’ prostate cancer research is focused in two related areas, in distinguishing the cell types that develop into aggressive versus slow-growing cancers, and in identifying novel compounds that will inhibit cancer growth or its progression to a more aggressive form. He and collaborators are now researching the effects of targeted small molecule drugs in cancer cells to shrink tumors or to stop the progression of cancer.
In a successful industry-university partnership, another area of research applied to human health focuses on gene editing and repair that may lead to a cure for a number of devastating hereditary diseases. Dr. Eric Kmiec pioneered a gene editing technique in 1993 that is now being employed broadly on a variety of living organisms. The group is making rapid strides in their work with genes responsible for inherited diseases, including Huntington’s Disease and Sickle Cell Anemia.
Head of the Laboratory of Applied Genomics at the University of Delaware, Dr. Kmiec collaborates with his neighbors in the Delaware Biotechnology Institute — NaPro BioTherapeutics, Inc. — on repairing the gene that causes Huntington’s Disease, a fatal degenerative neurological disease that afflicts one in seventy Americans and their families. Dr. Kmiec and his team employ a variety of synthetic DNA vectors to cause nucleotide changes in specific DNA sequences identified with the disease. Through work with the Hereditary Disease Foundation, Dr. Kmiec and his team are studying samples from a Venezuelan native tribe devastated by endemic Huntington’s Disease.
Dr. Kmiec credits the rapid pace of developments to his ability to work daily with talented scientists from both industry and academia who work in the Institute’s state-of-the-art laboratories. “The Institute has allowed NaPro to come here and has given us the chance to work together. The presence of NaPro allows us to see our work move into the commercial field using the skills of their outstanding scientists, while my university lab can remain fully committed to basic research.”
In yet another area of human health research, new collaborations are developing with Christiana Care Health Services, Delaware’s largest health care provider. Christiana now leads an Academic Medicine Core through the NIH NCRR IDeA Network of Biomedical Research Excellence (INBRE) grant to Delaware. The core is focused on innovative research in biomedical imaging and in infrastructure to support expanded cancer research in Delaware.