Although the overall five-year survival of patients with pancreatic cancer is dismal, there are substantial differences in disease progression, therapeutic response, and overall survival between cases with clinically and pathologically indistinguishable characteristics. Our inability to distinguish between these cases presents a major challenge in patient clinical management and continues to prevent our ability to treat this disease. Therefore, there is an urgent clinical need to better understand the molecular mechanisms behind of this disease to enable the improvement of therapeutic strategies.
Keratin 17 (K17) is a novel, tumor-cell specific biomarker that identifies the patient subgroup with the most aggressive disease in several types of solid tumor malignancies including PDAC even among patients with advanced-stage disease and in cases with negative surgical margins in PDAC. More recently, analyses of a PDAC clinical trial shows that K17-expressing PDACs are the least responsive to adjuvant therapy, suggesting that K17 can predict response to therapy. PDAC tumors are composed of immunosuppressive cells and tumor-associated stroma that contribute to poor response to chemo and immunotherapy. We and others have shown that K17 expression is associated with immune-mediated functions in tissues, and we recently observed differences in spatial relationships between tumor cells and macrophage infiltration in PDAC.
Our research focuses on understanding how K17 impacts immune cell function while enhancing tumor growth and metastasis. Additionally, we aim to determine the biological contribution of K17 on tumor aggression and response to standard-of-care therapeutic agents. These studies may lead to the development of a novel prevision medicine tool and can provide pre-clinical evidence of a novel therapeutic target in PDAC.
Pancreatic Ductal Adenocarcinoma
Meet The Team
Kenneth Shroyer, MD, PhD
Chairman Department of Pathology
Dr. Shroyer is Board Certified in Anatomic and Clinical Pathology. Ongoing areas of investigation in Dr. Shroyer’s laboratory are focusing on the discovery of the mechanistic basis of nuclear keratin 17 as a prognostic biomarker in carcinomas of the female genital tract, pancreas, and other anatomic sites.
Natalia Marchenko, PhD
Luisa Escobar-Hoyos, PhD
Research Assistant Professor
Senior Research Support Specialist
Lyanne is currently working on a project that utilizes multiplex immunohistochemistry to characterize the tumor microenvironment in pancreatic cancer in tumors that do and do not express the Keratin 17 biomarker to determine if any differences correlate with patient outcomes and treatment responses. This work has the potential to identify signatures that can help guide patient clinical management.
Monisankar Ghosh, PhD
Dr. Ghosh is a Research Scientist and is currently working to uncover the molecular mechanisms associated through which Keratin-17 drives metastasis and induces microenvironmental modulations. He is also keenly interested in understanding how Keratin-17 associated nucleotide imbalance promotes an inflammatory microenvironment, ultimately leading to tumor progression.
Shayan is a doctoral candidate affiliated to the Molecular and Cellular Biology Graduate Program at Stony Brook University. The overall goal of his project is to demystify the mechanism by which Keratin-17 drives biological aggression in pancreatic ductal adenocarcinoma (PDAC), with emphasis on its correlation with different pathways that drive tumor progression. He is also interested in understanding the regulation of Keratin-17 expression in human PDAC.
Yinghuan (Lydia) Lyu
Lydia is a graduate student in the Molecular and Cell Biology Program at Stony brook University. Her current work is focus in studying the mechanism behind K17 reprogramming and how its expression its turn on and off in certain tumors.
Karen Bai, MD
Karen completed her Bachelor’s of Science from the University of Toronto in 2012. She then went on to complete her Master of Science in diabetic drug discovery at St Michael’s Hospital, a teaching hospital affiliated with the University of Toronto. Karen is interested in investigating diagnostic and/or prognostic biomarkers in uterine cancer.
Sruthi Babu, MBBS, MPH, PhD
Sruthi has an interest in working on the Cancer biomarker predicting patient outcome. Currently, her work is focused on identifying urine cytology based diagnostic biomarker for bladder cancer and prognostic biomarker in lung and other cancer.
Michael received his bachelor’s degree in Biochemistry at Stony Brook University in 2020 and his master’s degree in Chemistry at Stony Brook University in 2021. Michael is a current 1st year medical student at SUNY Buffalo. Michael research focuses on understanding the keratin 17 mechanisms that drive chemoresistance and tumor aggression in pancreatic cancer.
Chun-Hao Pan, PhD
Chun-Hao is interested in studying pancreatic cancer. Specifically, his research focus is to understand why cancer cells are resistant to chemotherapeutic agents. His goal is to uncover the molecular mechanisms that drive chemoresistance and find a way to overcome it. In his project, he identified that Keratin 17, a signature gene overexpressed in the most lethal subtype of pancreatic ductal adenocarcinoma (PDAC), is both prognostic and predictive, and it directly promotes chemoresistance.