GENETIC MECHANISMS OF CANCER RESEARCH
IMMUNOLOGY RESEARCH
TUMOR BIOLOGY AND PROGRESSION RESEARCH
WOMEN'S CANCER RESEARCH
TRANSPLANT BIOLOGY AND THERAPY RESEARCH

Masonic Cancer Center

Despite recent advances in the diagnosis and treatment of cancer, tumor cell progression and metastasis constitute a major cause of morbidity and mortality in cancer patients. Understanding the molecular and cellular mechanisms that contribute to tumor formation, progression and metastasis is a major challenge in cancer research.

Members of the Cancer Biology Track of MICaB graduate program utilize a multidisciplinary approach to study cancer. Research opportunities in many of the faculty laboratories address the genetics and biology of tumor formation, progression, invasion and metastasis. Faculty laboratories also focus on the development of new cancer therapies including developing new inhibitors of angiogenesis, improving immune-based therapies, and studying novel compounds that can inhibit the growth and/or survival of malignant tumors.

A major area of research emphasis in the Cancer Biology Track is the relationship between genetic changes and biochemical signaling pathways in the development of cancer. Recent years have witnessed an explosion of information regarding how external signals (e.g., growth factors) bind to cell surface receptors and subsequently transduce biochemical signals that ultimately lead to changes in cell survival, proliferation, differentiation, resistance/sensitivity to apoptosis, migration and invasion.

Genetic changes in cancer alter the balance and flow of information through these signaling pathways; understanding them reveals how cancer cells survive and proliferate. A thorough knowledge of the differences between altered signaling pathways in cancer cells and the homeostatic signaling pathways in normal cells will lead to the design of new therapeutic strategies for suppressing the tumorigenic and invasive potential of malignant tumors. What follows are examples of research opportunities in these broad areas.

GENETIC MECHANISMS OF CANCER RESEARCH

Members work to understand how mutant genes cause cancer and to test gene therapies. They investigate what occurs inside the cells to trigger cancer and what can be done to stop these processes before cancer begins.

Research questions asked include:

• What specific genes and pathways drive tumor development using genetic screens in mice?
• Can canine models of cancer be used to understand and treat similar human disease?
• How do transcription factors control cancer and development?
• How is the protein synthesis machinery commandeered during carcinogenesis to preferentially select potentially pro-oncogenic mRNA from among the available pool of mRNA for translation into protein?
• How are proliferation and apoptosis regulated in normal and cancer cells?
• Can the potential of apoptotic cell death be harnessed therapeutically for the treatment of cancer?
• How can gene therapy be used to treat genetic diseases and cancer?
• How do chromosome instability and copy number variation affect tumor susceptibility in mice?
• How do deregulations in microRNA mediated gene regulatory networks contribute to cancer development and progression?
• What genetic events contribute to lymphoid malignancies like multiple myeloma?

Faculty Researchers
Bagchi, Bardwell, Bitterman, Hallstrom, Largaespada, Mansky, McIvor, Modiano, Shima, Starr, Subramanian, Van Ness

IMMUNOLOGY RESEARCH

Members of the Immunology Research Program work to enlist the body's own immune system to fight cancer by focusing on tumor immunology, immunotherapy, and on white blood cell development and behavior. Their goal is to uncover answers about these areas that can lead to effective new anticancer immunotherapies.

Research questions asked include:

• Can inducing tumor cell death via immunotherapy stimulate systemic anti-tumor responses?
• What mechanisms control survival and death in developing B-lineage cells and ALL and how do these promote clonal expansion?
• How can cancer vaccines and stem cells be used for the treatment of brain and other tumors?
• How can the efficacy of DNA-based cancer vaccines be improved?

Faculty Researchers
Griffith, LeBien, Low, Pennell

TUMOR BIOLOGY AND PROGRESSION RESEARCH

Members of this program focus on three areas: The biology of tumor growth and survival, prostate cancer development and treatment, and development of novel therapies to improve the treatment of various cancers of the blood and bone, and solid tissue tumors.

Research questions asked include:

• By what mechanism does the protein kinase CK2 direct pathogenesis of various cancers (prostate, head and neck, breast), and can cancer cell specific targeting of CK2 eradicate certain tumors?
• What mechanisms drive bone cancer development and what therapies can treat it?
• What molecular changes in prostate cancer cells drive resistance to androgen receptor targeted therapies?
• How are pro-survival and pro-apoptotic pathways regulated in cancer cells?
• How does the tumor microenvironment affect tumor progression?
• How does the inflammatory microenvironment contribute to the promotion and progression of breast cancer?
• How do brain tumors evade the immune response and what immunotherapy based strategies can be developed to effectively exploit that knowledge?
• What role do heat shock proteins play in apoptotic resistance of pancreatic cancer cells?
• What is the function of O-glycosylated proteins in the invasion and metastasis of carcinomas in an inflammatory environment?
• Can genetic engineering be used to modify and devise new anti-cancer biological drugs that can serve as an alternative to chemotherapy in cancer patients that become refractory to conventional therapy?

Faculty Researchers
Ahmed, Clohisy, Dehm, Kelekar, McCarthy, Ohlfest, Saluja, Schwertfeger, St. Hill, Vallera

WOMEN'S CANCER RESEARCH

Members of this program work to improve detection, treatment, and prevention of women's cancers to improve outcomes. Toward that end, they seek to discover improved methods for early detection, understand the biology of breast and gynecologic cancers, and enhance treatment through more precisely targeted therapies.

Research questions asked include:

• What is the role of the ubiquitin-dependent protein degradation in initiating and sustaining of solid cancers?
• What mechanisms cause pain in sickle cell disease, and which targets can be focused on to develop novel opioid based analgesics?
• How do progesterone receptors interact with protein kinase signaling pathways and estrogen receptors in order to drive breast cancer progression towards endocrine resistance?
• How does the activation status of the protein synthesis machinery regulate normal and neoplastic cell growth?
• How do cytochrome 450 epoxygenases promote breast cancer progression and can these mechanisms be targeted for therapy?
• How do hypoxia and modulation of angiogenesis affect tumor biology?
• What specific genetic changes drive tumor development?
• What biomarkers can be identified from ovarian cancer biospecimens that will be specific and sensitive enough to use to screen the general population for ovarian cancer?
• How does activation of growth factor receptors affect cancer cell biology?

Faculty Researchers
Bazzaro, Gupta, Lange, Polunovsky, Potter, Ramakrishnan, Skubitz, Yee

TRANSPLANT BIOLOGY AND THERAPY RESEARCH

Through basic research in stem cell biology and immunology, members of the Transplant Biology and Therapy Program work together to discover new stem cell transplantation therapies and treatments for cancers relating to the blood and bone marrow. This program represents the research arm of the University of Minnesota's world-famous Blood and Marrow Transplant (BMT) Program.

Research questions asked include:

• What are the similarities and differences between stem cells and cancer cells in terms of cell proliferative capacity and cell metabolism?
• How does inflammation affect the pathophysiology of sickle cell anemia?

Faculty Researchers
Kikyo, Vercellotti