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
Cancer-related research interests of Dr. Lake focus on tumor immunology, specifically, how the immune system can recognize and destroy tumors. Since cancer can be simply defined as an uncontrolled proliferation of self tissue, it is difficult for the immune system to attack cancer because it is tolerant to self. However, there is evidence that cancer patients’ immune systems do respond to their own tumors. Reasons the immune system cannot eliminate cancer include secretion of immune-suppressive factors by the tumor such as transforming growth factor-β (TGF-β) and interleukin-10 (IL-10), loss of histocompatibility molecules on the tumor cell surface and regulatory T cells that suppress anti-tumor cytotoxic T lymphocytes (CTL). Each of these mechanisms can make a tumor immuno-silent so it can stealth against the immune system while it grows.
Current cancer vaccines are therapeutic. This means we wait until someone has cancer, treat them with chemotherapy and/or radiation, with or without surgery, and then if none of these treatments work, give the patient an experimental cancer vaccine. Unfortunately, this is contrary to the way vaccines work. Vaccines are almost always given prophylactically to prevent disease. The same can be done with cancer—prevent cancer with a vaccine before it causes disease. Dr. Lake, in collaboration with Dr. Stephen Johnston, director of the Center for Innovations in Medicine at The Biodesign Institute is developing a prophylactic cancer vaccine for multiple types of cancers. They are identifying a set of tumor-derived proteins and peptides unique to tumor cells. The goal is to identify and develop enough tumor-derived peptides for each type of cancer to include in a cancer vaccine that would “pre-arm” the immune system to protect individuals against cancer before it has a chance to grow out of control.
Dr. Lake is 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 Dr. Lake’s 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 | CV (PDF)
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.