Summer 2001 Newsletter: Young Investigator Awards

Each year, the Cancer Research Foundation accepts grant requests from young men and women engaged in first-project laboratory and/or clinical cancer research. These proposals come to the Foundation already reviewed and ranked by a faculty awards committee, using the National Institutes of Health peer review process. Only the innovative and bold proposals with practicable research plans are considered for funding.

After receipt by the Foundation, our medical consultants, Dr. Joseph B. Kirsner and Dr. Richard L. Schilsky, interpret the complex science to the trustees. Cancer Research Foundation trustees make all funding decisions.
Last October, five young scientists from the University of Chicago Medical Center were awarded young investigator grants:

• Maria Alegre, M.D., Ph.D.
• John Crispino, Ph.D.
• Karen Frank, M.D., Ph.D.
• Tong Chuan He, M.D., Ph.D.
• S. Diane Yamada, M.D.

These awards are for one year. At the end of the year, if the hypotheses have proven worthy of further study this early research will be used as a basis for application for major outside funding.

ROLE OF NF-kB ACTIVATION IN CTLA4 SIGNALING - $50,000

The immune system with its white blood cells is in charge of destroying cancerous cells as they arise, and prevents the development of full-blown tumors in the majority of people. This process is called "immune surveillance." The most important type of white blood cell for this purpose is called T lymphocyte.

The duration of activation of any given T cell is finite, whether the cancerous cell has been destroyed or not, and in some cases T cells rest before complete elimination of the transformed cells.

Dr. Alegre's research project focuses on trying to prolong the activation state of T lymphocytes, preventing them from going back to a resting state, and maximizing their capacity to fight even grown tumors.

The Role of LMO2 In T-Cell Leukemia - $50,000

Blood is composed of many different types of cells that perform special functions in the human body. Red blood cells carry oxygen to tissues, white cells provide immunity to infections and disease, and platelets control bleeding. The human body constantly replenishes its supply of blood cells in a process call hematopoiesis.

Every type of cell is distinguished by its specific pattern of gene expression: Red blood cells "turn on" genes that make proteins important in oxygen transport, such as hemoglobin. White blood cells "turn off" expression of these genes but "turn on" others important in the immune response, such as antibodies. Transcription factors comprise the molecular machinery that regulates the turning on and off of specific genes.

Leukemias typically arise when certain transcription factors, which are not normally expressed within white blood cells, are turned on. Dr. Crispino's research will be to study the mechanism by which these aberrantly expressed factors cause uncontrolled proliferation and cancer.

Identification of Potential Therapeutic Peptides for Human Osteosarcoma - $50,000

Osteosarcoma is the most common primary malignant tumor of bone. The peak of age incidence is usually during the second decade of life. conventional treatment for osteosarcoma involves preoperative chemotherapy followed by surgical removal of tumors. Nevertheless, osteosarcoma has a high frequency of recurrence and metastasis.

Dr. He's goal is to develop therapeutic agents for human osteosarcoma. His research plan is to create and direct a new molecular oncology laboratory, which will focus on: 1) the molecular genetic studies of soft tissue sarcomas in search for potential tumor suppressor genes, 2) identification of potential osteosarcoma tumor markers for novel diagnostic and/or therapeutic strategies, and 3) the development of genetic and/or novel therapy for other bone-related diseases.

Regulation of DNA Ligase IV in V(D)J Recombination and DNA repair - $50,000

In honor and fond memory of Dr. John E. Ultmann, Dr. Karen Frank is named the Dr. John E. Ultmann Young Investigator.

Dr. Frank's research involves the study of 1) maintaining a normal immune system and 2) the repair of DNA damage.

The first process involves the generation of antibodies that all individuals require to fight infections. During the process of making antibodies, the DNA is broken and rearranged in a controlled manner in white blood cells. If there is an error during this rearrangement of DNA, the incorrectly joined genes can lead to the development of leukemia or lymphoma.

The second process involves the study of DNA repair. DNA in any cell, not just blood cells, can be damaged from exposure to radiation or environmental chemicals, or from the products of metabolism. These DNA breaks are potentially harmful to the cell and must be repaired for the cell to survive. When errors occur in repairing these DNA breaks, abnormal genes that are formed can lead to the development of cancer in any organ.

EVALUATION OF MKK4 AS A METASTASIS SUPPRESSOR GENE IN OVARIAN CARCINOMA- $49,999

Ovarian cancer remains the most lethal gynecologic malignancy. The majority of ovarian cancer patients will develop and die of chemoresistant disease.

Dr. Yamada's research focuses on the regulation of tumor spread in ovarian cancer. Her preliminary data reveals that the expression of a particular protein (MKK4) is absent in perpetually growing ovarian cancer cell lines. She postulates that the restoration of this protein will suppress metastatic growth.