Senior Investigator, Lady Davis Institute
Dr. Koromilas graduated from the Aristotelian University of Thessaloniki, Greece, with a B.Sc. in Chemistry in 1984 and a Ph.D in Biochemistry in 1988. His undergraduate studies were supported by a studentship from the Hellenic State Scholarship Foundation (IKY). In 1987, he was awarded a short-term fellowship from the European Molecular Biology Organization (EMBO) for training in Cellular Immunology at Stockholm University, Sweden. After his graduation in 1988, he joined Tasuku Honjo’s group in Kyoto University, Japan, for post-doctoral studies in Molecular Biology and Immunology. During his stay in Japan, Dr. Koromilas was supported by fellowships from the Toyobo Biotechnology Foundation and Ciba-Geigy Foundation for Promotion of Science.
He moved to Montreal in 1990 for his second post-doctoral training with Nahum Sonenberg in Biochemistry, McGill University. His training in the Sonenberg lab was supported by an international fellowship from the Human Frontier Science Program Organization. In July 1993, he was appointed Assistant Professor in the Department of Oncology, Faculty of Medicine, McGill University and Project Director at Lady Davis Institute, Jewish General Hospital. He became a full Professor in June 2006.
In 2003, Dr. Koromilas joined the laboratory of Dr. Akihiko Yoshimura at the Institute of Bioregulation, Kyushu University, Japan, for his sabbatical training. As an independent investigator, Dr. Koromilas has won several awards including an international Scholarship from the American Foundation for AIDS Research (AmFAR) in 1993, a Chercheur Boursier Fonds de la Recherché en Sante du Quebec (FRSQ) in 1997, a Scientist award from the Canadian Institute of Health Research (CIHR) in 1998 and a Visiting Scientist award from the Japan Society for the Promotion of Science (JSPS) in 2003. Since his initial appointments with McGill University and Lady Davis Institute, Dr. Koromilas’s research has been supported by national (i.e. National Cancer Institute of Canada, Health and Welfare of Canada, Canadian Institutes of Health Research, Cancer Research Society of Canada, Canadian Foundation for AIDS Research, Canadian Breast Cancer Research Alliance, Quebec Foundation of Breast Cancer) and international research grants (American Foundation for AIDS Research, Human Frontier Science Program Organization). Dr. Koromilas is a member of the Editorial Board of the Journal of Biological Chemistry published by the American Society for Biochemistry and Molecular Biology.
Major Research ActivitiesDr. Koromilas investigates (i) the functions of eIF2α kinases in regulation of protein synthesis, cell proliferation and apoptosis in response to various forms of environmental stress including virus infection, genotoxic stress and oncogenic stress, and (ii) the tumor suppressor properties of transcription factor Stat1 in response to oncogenic insults that contribute to development of cancer with emphasis on breast cancer.
His studies demonstrated the ability of eIF2α kinases to exhibit a cytoprotective function in response to distinct forms of stress that converge on the tumor suppressor p53. Current work on this project investigates the biological significance of eIF2α kinase activation under conditions that mimic tumor microenvironment, such as hypoxia and nutrient deprivation, and their role in the treatment of hypoxic tumors with chemotherapeutic drugs. Moreover, he investigates the role of eIF2α phosphorylation pathway in induction of senescence and regulation of tumourigenesis in response to oncogenic stress.
He investigate the mechanisms of PI3K activation by examining the ability of eIF2α kinases to regulate the function of PI3K or tumor suppressor PTEN (Mounir et al., 2009). In addition, he examines the possible role of eIF2α kinases in mediating the anti-proliferative effects caused by the disruption of PI3K signaling as a result of PTEN activation or treatment with chemotherapeutic drugs targeting PI3K, Akt or mTOR.
He uses mouse models of ErbB2/Her2 tumorigenesis deficient in eIF2α kinase activity or phosphorylation of eIF2α at serine 51 to examine the oncogenic properties of ErbB2/Her2. and also examines the response of eIF2α kinases to chemotherapeutic drugs targeting Erb2/Her2 and the biochemical properties that underlie the functional interplay between ErbB2/Her2 and eIF2α phosphorylation in breast tumors.
Stat1 exhibits strong anti-viral, anti-proliferative and tumor suppressor functions. He has been investigating the role of Stat1 phosphorylation in oncogenic signaling induced in breast tumors and has found that Stat1 phosphorylation is an important determinant in suppression of oncogenic Ras. Current work focuses on the role of Stat1 in ErbB2/Her2-mediated oncognesis using tissue culture and transgenic mice approaches.