Hasan Korkaya, DVM, PhD
Associate Professor, Biochemistry and Molecular Biology
Associate Professor, School of Graduate Studies
Member, Molecular Oncology & Biomarkers Program
Research in the Korkaya lab focuses on the understanding of the early molecular events during the metastatic cascade. Unfortunately, women with metastatic disease have limited treatment options and shorter lifespans compared to those with indolent tumors. Current understanding of the metastatic process suggests that successful metastatic colonization in distant organs requires disseminated mesenchymal stem cells (EMT/CSC) to revert back to the epithelial phenotype (MET/CSC) via mesenchymal-epithelial-transition (MET). Ongoing research in the Korkaya lab provided some evidence that these processes might be regulated by the cross-communication between the tumor cells and immunosuppressive myeloid cells within the tumor microenvironment (TME) and premetastatic niches. The major focus going forward will be to identify key molecular players in each stage of the metastatic cascade and testing their therapeutic utility in preclinical settings.
The Hasan Korkaya Lab
Health Sciences Campus
Georgia Cancer Center - M. Bert Storey Research Building
1410 Laney Walker Blvd., CN-2136, Augusta, GA 30912
It is now widely believed that cancers are driven by a subset of cells called cancer stem cells (CSCs) or tumor-initiating cells (TICs) that mediate metastasis, recurrence and treatment resistance. However, the emerging evidence suggested that the plasticity of CSCs between the EMT and MET phenotype has been associated with aggressive/metastatic property of solid tumors. One of the projects in the Korkaya lab aims to understand the spatiotemporal regulation of the CSC plasticity and identify critical players in these processes.
Although, the role of immunosuppressive TME/pre-metastatic niche in disease progression and treatment response has been well recognized, the molecular mechanisms that regulate these processes remain elusive. Preclinical and clinical data provide some evidence that immune cells of myeloid origin (macrophages, neutrophils, MDSCs) are major components of the TME and may play role in resistance to ICIs. A recently funded project in the Korkaya lab aims to dissect the molecular mechanism by which stress-induced HSP70 regulates both protection of tumor cells from cytotoxic agents (including CTLs) by regulating the CSC plasticity and generates an immunosuppressive TME/pre-metastatic niche via the modulation of immunosuppressive myeloid cells. The team aims to investigate whether targeting HSP70 using the new generation allosteric inhibitors will sensitize tumor cells to standard of care including the ICIs and induce immune-stimulatory cells within the TME/pre-metastatic niche to activate effector T cells.
Fulya Koksalar Alkan and Hasan Korkaya. Therapeutic utility of immunosuppressive TREM2+ macrophages: an important step forward in potentiating the immune checkpoint inhibitors. Signal transduction and Targeted Therapy in press November 2020
Eunmi Lee, Raziye Piranlioglu, Max S. Wicha and Hasan Korkaya*. Plasticity and potency of mammary stem cell subsets during mammary gland development. International Journal of Molecular Sciences (Accepted May 13, 2019).
Raziye Piranlioglu, Eunmi Lee, Maria Ouzounova, Ali Arbab, John Cowell, Muthusamy Thangaraju, Ahmed Chadli, Khaled Hassan, Max S. Wicha, Esteban Celis and Hasan Korkaya*. Primary tumor-induced immunity eradicates disseminated tumor cells in syngeneic mouse model. Nature Communications 2019, March 29;10(1):1430.
Eunmi Lee, Maria Ouzounova, Raziye Piranlioglu, Minh Thu Ma, Mustafa guzel, Daniela Marasco, Ahmed Chadli, John K. Cowell, Max S. Wicha, Khaled Hassan and Hasan Korkaya*. The pleiotropic effects of TNFa in breast cancer subtypes is regulated by TNFAIP3/A20. Oncogene 2019 Jan;38(4):469-482.
Maria Ouzounova‡, Eunmi Lee‡, Raziye Piranlioglu, Abduljabar El Andaloussi, Ravindra Kolhe, Mehmet F. Demirci, Daniela Marasco, Iskander Asm, Ahmed Chadli, Khaled A. Hassan, Muthusamy Thangaraju, Ganga Zhou, Ali S. Arbab, John K. Cowell, Hasan Korkaya*. Monocytic and granulocytic myeloid derived suppressor cells differentially regulate spatiotemporal tumor plasticity during metastatic cascade. Nature Communication 2017 Apr 6;8:14979.
Haihong Zhong, April Davis, Maria Ouzounova, Rosa A. Carrasco, Cui Chen, Shannon Breen, Yong S. Chang, Jiagi Huang, Zheng Liu, Yihong Yao, Elaine Hurt, Jacques Moison, Michael Fung, David A. Tice, Zhan Xiao, Shawn G. Clouthier, Max S. Wicha, Hasan Korkaya* and Robert E. Hollingsworth*. A novel IL-6 antibody sensitizes multiple tumor types to chemotherapy including trastuzumab-resistant tumors. Cancer Research 2016 Jan 15;76(2):480-90.Rosemarie C. D’Angelo, Maria Ouzounova, April Davis, Daejin Choi, Stevie M. Tchuenkam, Gwangil Kim, Tahra Luther, Ahmed A. Quraishi, Yasin Senbabaoglu, Sarah Conley, Shawn Clouthier, Khaled Hassan, Max S. Wicha, Hasan Korkaya*. Notch reporter activity in breast cancer cell lines identifies a subset of cells with stem cell activity. Cancer Therapeutics 2015 March;14(3):779787).
Gwangil Kim, Maria Ouzounova, Ahmed A. Quraishi, April Davis, Nader Tawakkol, Shawn G. Clouthier, Fayaz Malik, Amanda K. Paulson, Rosemarie C. D’Angelo, Sumeyye Korkaya, Trenton L. Baker, Elif S. Esen, Aleix Prat, Suling Liu, Celina G. Kleer, Dafydd G. Thomas, Max S. Wicha and Hasan Korkaya*. SOCS3-mediated regulation of inflammatory cytokines in PTEN and p53 inactivated triple negative breast cancer model. Oncogene 2015 Feb;34(6):671-80.
Suthinee Ithimakin, Kathleen C. Day, Fayaz Malik, Qin Zen, Scott J. Dawsey, Tom F. Bersano-Begey, Ahmed A. Quraishi, Kathleen Woods Ignatoski, Stephanie Daignault, April Davis, Christopher L. Hall, Nallasivam Palanisamy, Amber N. Heath, Nader Tawakkol, Tahra K. Luther, Shawn G. Clouthier, Whitney A. Chadwick, Mark L. Day, Celina Kleer, Dafydd G. Thomas, Daniel F. Hayes, Hasan Korkaya* and Max S. Wicha*. HER2 drives luminal breast cancer stem cells in the absence of HER2 amplification: Implications for efficacy of adjuvant trastuzumab. Cancer Research 2013 1;73(5):1635-46 * Co-corresponding author
Hasan Korkaya*, Gwang-il Kim, April Davis, Fayaz Malik, N. Lynn Henry, Suthinee Ithimakin, Ahmed A. Quraishi, Nader Tawakkol, Rosemarie D’Angelo, Amanda Paulson, Susan Chung, Tahra Luther, Hayley S. Paholak, Suling Liu, Khaled Hassan, Qin Zen, Shawn G. Clouthier and Max S. Wicha. Activation of an IL-6 Inflammatory Loop Mediates Trastuzumab Resistance in HER2 Overexpressing Breast Cancers by Expanding the Cancer Stem Cell Population. Molecular Cell 2012 August 24. 47, 570-584.