Degrees and Certifications:
PhD

Rank and Title:
Professor of Medicine
Professor of Immunology/Microbiology

Department:
Hematology/Oncology

Endowed Professorship:

Office Location:
1753 West Harrison Street
JS953
Chicago, IL 60612

Laboratory Location:
1753 West Harrison Street
JS960, JS958
Chicago, IL 60612

Phone:
(312) 942-3450

Fax:
(312) 942-3452

E-mail:
jplate@rush.edu

Education:
Ph.D., Duke University Medical Center
Post-doctoral, Massachusetts General Hospital, Harvard University

Research Areas:

Laboratory Techniques:

Hyperlinks:
http://www3.interscience.wiley.com/cgi-bin/fulltext/109929672/PDFSTART
http://www.springerlink.com/content/k32k60584316817r/fulltext.pdf
http://www.begellhouse.com/authors/7ef0614347ccb5a1.html
http://www.edata-center.com/journals/2ff21abf44b19838,17f890ef49d056ce,1d200e807574eb98.html
http://www.nature.com/nature/journal/v260/n5549/abs/260329a0.html

Documents:

Faculty/Staff Description:
Dr. Janet Plate's research interests are in the regulation of immune cell differentiation including the role that cell surface molecules play in transmitting signals that initiate molecular steps in the differentiation pathway. The manner in which alterations in normal signaling pathways contribute to disease states are being investigated . Dr. Plate's laboratory investigates two main diseases: Chronic Lymphocytic Leukemia (CLL), the most common adult leukemic disease of B-lymphocytes, and, pancreatic cancer - the fourth leading cause of cancer deaths. A variety of molecular and cellular biological approaches are being used in these studies.

Dr. Plate's laboratory has been studying the regulation of gene expression and apoptosis in CLL leukemic B-cells. We have demonstrated that CLL leukemia cells express mRNA and protein for the cytokine, Interleukin-7 (IL-7) while normal human B-cells generally do not. The IL-7 gene, however, is down-regulated shortly after CLL leukemia cells are removed from the body and maintained at 37°C. Using microarray cDNA analyses, Dr. Plate's laboratory demonstrated expression of additional genes important to cell cycle progression in CLL leukemic cells and their down- regulation in culture. IL-7 and cell cycle gene down-regulation precedes the onset of apoptosis (programmed cell death) of these leukemic B-cells. Dr. Plate further demonstrated that signals transmitted through adhesion molecules expressed on leukemic B- cells can prevent IL-7 gene expression from being down-regulated and subsequently hold apoptosis in abeyance. iC3b, complement activation products serve as ligands for these adhesion molecules and contributed to the maintaince of leukemic cell viability. Dr. Plate's laboratory most recently demonstrated that the Akt kinase survival pathway is constitutively active in the leukemic B-cells. Inhibition of Akt kinase activation which is dependent upon PI3 kinase activity with inhibitors of PI3 kinase enhanced apoptosis of the leukemic cells. The substrates affected by Akt kinase in the leukemic cells are being identified. The goals of these studies are to determine the signals responsible for maintaining leukemic cell viability in vivo so that these pathways may be blocked with specific drugs thereby resulting in death of the leukemic cells.

Dr. Plate's laboratory is also studying the immunological status of patients with metastatic pancreatic cancer which is one of the most aggressive cancer known in man. Specific anti-tumor immunity has been demonstrated in peripheral blood mononuclear cells isolated from these patients. Dr. Plate's laboratory has sought to characterize helper T cell subsets, serum cytokines, cellular cytotoxicity, and tumor-derived, immunosuppressive products present in peripheral blood of patients with metastatic pancreatic cancer. Significantly heightened levels of Interleukin 2 (IL-2), a Th1 cytokine, were found in patients before treatment with chemotherapy while IL-10 levels were significantly lower than observed in normal donors tested between their fifth and seventh decades of life. In normal, healthy donors tested between the ages of 24 through 61, IL-10 levels increased progressively with age as a serum-bound protein. An age associated progression in IL-10 levels was not observed in pancreatic cancer patients. These data suggest that pancreatic cancer patients have activated type 1 helper T cells that could support development of cell-mediated immunity, and that their sera contain lowered levels of "anti-inflammatory" cytokine. Inflammation is an important component in the development of pancreatic cancer. Few patients had detectable serum levels of circulating soluble fas ligand but approximately half had elevated levels of a tumor marker CA-15.3, also known as soluble MUCIN 1 (sMUC1). Dr. Plate's laboratory demonstrated that the soluble form of this tumor marker antigen, sMUC1 can inhibit cytolytic effector cell functions. Preliminary studies indicated that treatment of activated T-cells with sMUC1 results in the down-regulation of expression of genes involved in immune reactivity and that protein phosphorylations were altered when the T cells were activated in the presence of the inhibitory tumor products. These data suggest that tumor derived inhibitory products including sMUC1 can also alter signal transduction pathways and gene expression in T cells. The goals of these studies are to define those pathways affected by sMUC1 with the aim of using that information to define drugs that will block its inhibitory effect on T cells such that immune cells within pancreatic cancer patients can eradicate their tumors.

Dr. Plate's laboratory is also characterizing the cytotoxic responses found in these patients with particular focus on defining antigens of pancreatic tumor cells.

Selected Publications:
Plate JMD, Petersen KS, Buckingham L, Shahidi H, and Schofield CM: Gene expression in chronic lymphocytic leukemia B-cells and changes during induction of apoptosis. Experimental Hematology 28:1214-1224, 2000.

Plate JMD, Long BW, and Kelkar SB: Role of beta2 integrins in the prevention of apoptosis induction in chronic lymphocytic leukemia B-cells. Leukemia 14:34-39, 2000.

Shahidi H, Vottero A, Stratakis CA, Taymans S, Karl M, Longui CA, Chrousos GP, Daughaday WH, Gregory SA, and Plate JMD: Altered expression of glucocorticoid receptor isoforms in B- cell chronic lymphocytic leukemia complicating systemic glucocorticoid resistance. Biochem and Biophys Research Commun 254:559-565, 1999.

Long BW, Witte PL, Abraham GN, Gregory SA and Plate JMD: Interleukin-7 gene expression and apoptosis induction in B-Chronic Lymphocytic Leukemia cells. Proc Natl Acad Sci USA 92:1416-1420, 1995.

Frishman JI, Long B, Knospe WH, Gregory SA, and Plate JMD: Genes for interleukin-7 are transcribed in leukemic cell subsets of individuals with Chronic Lymphocytic Leukemia. J Exp Med 177:955-964, 1993.

Plate JMD, Knospe WH, Harris JE and Gregory SA: Normal and aberrant regulation of cytokine expression in neoplastic cells from Chronic Lymphocytic Leukemia. Human Immunol 37:249-258, 1993.

Plate JMD, Shott, and Harris JE: Immunoregulation in pancreatic cancer patients. Cancer Immunology and Immunotherapy 48:270-279, 1999.

Plate JMD and Harris JE: Immune cell functions in pancreatic cancer. Critical Reviews in Immunology 20:375-392, 2000.