Cell Cycle and Cancer


Research Area: Cell Cycle and Cancer
	Bambara Hilf Keng Land	Maines Miller Senior Young Zain


Robert A. Bambara, Ph.D. Steroid hormone receptor proteins regulate gene expression for growth and development. In tumors, these receptors respond to hormones to promote growth. Our research investigates how agonists and antagonists bind the nuclear hormone receptors and modulate the binding and activity of transcriptional regulatory machinery with gene promoters that are actived in breast cancer.


Russell Hilf, Ph.D. A number of hormones have been implicated in the etiology and growth of mammary cancers. Hormones bind to specific cell receptors, which are internalized to regulate gene expression and cell growth. Our studies are directed at understanding the molecular mechanisms of how the following compounds affect or regulate tumor growth and neoplasia: estrogens, anti-estrogens, insulin and insulin-like growth factors.

Peter Keng, Ph.D. Effects of radiation and chemotherapeutic agents on DNA repair and cell cycle regulation. Biochemical and biophysical studies of human leukemic leukocytes.

Hartmut Land, Ph.D. Carcinogenesis is caused by multiple cooperating genetic lesions, leading to a progressive deregulation of intra-cellular signaling and cell cycle control. Such mutations result in oncogene activation or loss of tumor-suppresser gene function. We are studying the mechanisms by which these mutant genes cooperate in malignant transformation. This transformation process involves the integration of multiple signals that regulate cell cycle-dependent kinase complexes, which can switch cells into a state of uncontrolled rapid cell proliferation--cancer.

Mahin D. Maines, Ph.D. Neurons are susceptible to oxygen free-radicals, and oxidative stress can induce neuronal cell death. Protection from neuronal oxidative damage is mediated by the heat shock family 32 protein, heme oxygenase-1. We are using a transgenic mouse model system to study the gene regulation and protective properties of heme oxygenase isozymes. Furthermore, our studies are also extending to the investigation of the reaction products of the heme oxygenases, which produce signaling molecules and regulate the expression of a cascade of genes.

Leon L. Miller, M.D., Ph.D. Hormones and metabolic inhibitors regulate the net biosynthesis of specific plasma proteins by the liver. Our research studies the rat liver, perfused for 12 or 24 hours, in a closed metabolic system for evaluating the regulatory effects of hormones and metabolic inhibitors. Current studies emphasize the acute phase proteins and seeking to define the production of Interlukin-6.

Alan E. Senior, Ph.D. Cancer chemotherapy often fails because tumors develop resistance to multiple drugs simultaneously. The culprit is multidrug-resistance protein (MDR), a transport protein that uses ATP to pump drugs out of the cell. The long-term goal or our research is to learn ways to disable MDR protein in cancer cells. We are also using molecular genetics in bacteria in a biophysical study of the mechanism of action of ATP-linked membrane transporters.

Donald A. Young, M.D. We study the ways that steroids control the production of protein molecules inside cells. Our team demonstrated that production of one such protein (cox-2 enzyme) is triggered by two kinds of molecular messengers called inflammatory cytokines and growth factors. In addition to the remarkable ability of cox-2 inhibitors to control pain and inflammation, drugs that inhibit cox-2 can also prove useful in reducing incidence of cancer and Alzheimer's disease. Our work, therefore, has established a critical link between cox-2 and cancer.

Sayeeda B. Zain, Ph.D. The amyloid precursor protein (APP) is a molecule centrally involved in neurodegenerative pathology of Alzheimer disease, but whose normal function is still poorly understood. Our research focuses on studying how the cellular machinery is perturbed in the diseased state in transgenic mice and PC12 cell lines over-expressing APP. In parallel, our lab also studies tumor progression and metastasis, using an in vivo breast carcinoma metastasis model.