Douglas Lake
Background
Dr. Lake is a cellular and molecular immunologist who came to ASU in 2006 after 12 years at the University of Arizona Cancer Center in Tucson where he performed research on Cancer, Valley Fever and AIDS. He directed the Flow Cytometry Core Laboratory and co-directed the Immunotherapy and Gene Therapy program at the Arizona Cancer Center. While teaching medical students at the UA College of Medicine, Dr. Lake received a Deans Teaching Scholar award and was involved in medical curriculum development and teaching methods.
Research
My research utilizes molecular, proteomic and cellular methods to discover and characterize tumor-derived proteins and peptides. Cancer research in my laboratory has 2 foci. The first is to find biomarkers for the early detection of cancer. Early detection of cancer facilitates treatment with a more favorable outcome than if tumor growth advances and spreads to other organs such that surgery is not an option. Plasma, the liquid portion of blood, is a well-accepted source to look for proteins that a tumor might shed into circulation. One problem with plasma is that it is a complex mixture of thousands of different proteins. Furthermore, most of the mass of plasma is composed of just 10 proteins. These highly abundant proteins obscure the detection of small amounts of protein produced by a tumor. We developed methods to enrich for tumor-derived protein in plasma from cancer patients. Our goal is i) to trace proteins found at high frequencies in cancer patients back to tumors using immunohistochemical techniques and ii) to develop sensitive and specific tests to detect tumor-derived proteins in plasma for the early detection of cancer.
The second focus of my laboratory is to identify, characterize and optimize tumor-derived peptides to be used as components of a cancer vaccine. We can take advantage of the fact that tumor cells are genetically unstable to find aberrant peptides that tumor cells produce but normal cells do not. I am studying the molecular interactions between tumor-derived peptides and major histocompatibility complex molecules (MHC). Very often, the sequences of naturally occurring peptides bind poorly to the binding cleft of MHC molecules. Therefore, one can optimize peptides for binding to MHC such that they retain their abilities to activate anti-tumor T cells. Recent data demonstrates that combining multiple optimized peptides along with the natural tumor-derived peptide elicits broader T cell responses among different individuals. This concept is important in designing cancer vaccines that would benefit the largest number of people. Another area of research in my laboratory is studying the immunology of Coccidioides infection (Valley Fever). Coccidioides sp. (Cocci) is a fungus that lives in the soil in the desert southwest and in the central valley in California. When soil is disrupted (digging, dust/wind storms, construction, even earthquakes), spores from the fungus float into the air and can be inhaled by humans and animals. When the spores enter the lung, they germinate and multiply. Most of the time, the infection manifests as an upper respiratory infection that is controlled by the immune system and resolves within a few weeks. In some individuals, however, the infection is not controlled properly and results in prolonged illness (over 6 months) or dissemination of the fungus beyond the chest wall into skin, bone, central nervous system and other organs. One mystery concerning Cocci infection is in people who have disseminated coccidioidomycosis. Individuals with disseminated coccidioidomycosis respond normally to other pathogens, but not to cocci. Dr. Lake is studying the immune response to Coccidioides to understand how and why some people control an infection while others do not. His laboratory generates dendritic cells, immune cells that are among the very first cells to activate the immune response against infectious pathogens. By studying the initiating events that occur upon interaction of dendritic cells with Coccidioidal proteins (antigens), we may be able to identify protective versus non-protective antigens. Antigens that elicit a “protective” immune cytokine profile would be candidates for a vaccine against cocci.Selected Publications
Cancer:
Dionne SO, Lake DF, Grimes WJ, Smith MH. Identification of HLA-Cw6.02 and –Cw7.01 allele-specific binding motifs by screening synthetic peptide libraries. Immunogenetics 56:391-398 (2004).
Dionne SO, Myers CE, Smith MH, Lake DF. Reactivity of anti-Her-2/neu CTL to Her-2/neu modified peptides. Cancer Immunol. Immunother 53:307-314 (2004).
Dionne SO, Smith MH, Error! Contact not defined., FM, Lake DF. Functional Characterization of CTL Against gp100 Altered Peptide Ligands. Cancer Immunol and Immunother. 52:199-206 (2003).
Dionne SO, Smith MH, Lake DF. CTL stimulation elicited by bead-bound antigenic peptides. Cellular Immunology 214:139-144 (2001).
Cocci:
Dionne SO, Podany AB, Ruiz YW, Ampel NM, Galgiani JN, Lake DF. Spherules derived from Coccidioides posadasii promote dendritic cell maturation and activation. Infect. Immun. 74:2415-22 (2006).
Ampel NM, Nelson DK, Li L, Dionne SO, Lake DF, Simmons KA, Pappagianis D. The mannose receptor mediates the cellular immune response in human coccidioidomycosis. Infect Immun. 73:2554-5 (2005).
Richards JO, Ampel NM, Lake DF. Reversal of coccidioidal anergy by dendritic cells from patients with disseminated coccidioidomycosis. J. Immunol 169:2020-2025 (2002).
Richards JO, Ampel NM, Galgiani JN Lake DF. Coccidioides immitis lysate induces dendritic cell maturation and activates naïve T cells. Journal of Infectious Diseases 184:1220-1224 (2001)
Dr Lake is looking for graduate students.