Meet Our Exceptional Collaborators!
Our Collaborative Projects...
Investigating and Targeting Contextual Immunosuppression within the Dissemination Machinery
Premise: We have recently published a working model of contextual immunosuppression, associated with the prometastatic myeloid cell-supported niche in the primary tumor microenvironment. In this working model (Frontiers in Immunology), we suggest that the cancer cell dissemination machinery represents a prominent niche for lymphocyte exclusion and exhaustion. In this project, we are committed to explore the precise cellular and molecular mechanisms driving these phenomena in an effort to propose novel and rational therapies that will eliminate the immunosuppressive cues from the prometastatic machinery, thus increasing the efficiency of current immunotherapies, and rendering metastatic dissemination less efficient.
Team: To address this problem, we have put together a highly-competitive and multi-disciplinary team of basic scientists and clinicians, all currently operating in the New York area. The team has stemmed from the New York Pathology Oncology Group (NYPOG), as a subgroup specifically dedicated to the study of the immune components of the tumor microenvironment (iNYPOG ), led by Dr. Karagiannis, and additionally includes the following members: Dr. Sacha Gnjatic from the Icahn School of Medicine at Mount Sinai, who is the developer of the Multiplexed Immunohistochemical Consecutive Staining on Single Slide (MICSSS), a key method that we use to multiplex up to 10 immune (lineage) markers for high-dimensional tissue analyses; Dr. Maja H. Oktay, breast cancer pathologist at the Albert Einstein College of Medicine, who is paramount to the translational component of our work; Dr. Douglas K. Marks, a medical oncologist at NYU Langone Health with documented expertise and research experience in the involvement of machine learning and artificial intelligence in image analysis and quantification, and; Dr. David Entenberg, a recognized expert in microscopy and imaging, who brings in a broad skillset in optical, mechanical, electrical, software and instrument design to our research questions. Our team is frequently enriched by motivated and talented pathology and oncology residents, as well as other experts and associates with documented interest in computational pathology.
Quantifying Metastatic Potential of Solid Cancers using Magnetic Resonance Imaging (MRI)
Premise: TMEM-mediated vascular permeability represents a key rate-limiting step in the metastatic cascade: TMEM assembly and activity correlate with an increased risk of developing metastatic disease, at least in the context of preclinical and clinical models of breast cancer. In our prior work, we have also demonstrated that TMEM activity measurement is sensitive in detective prometastatic lesions elicited by neoadjuvant chemotherapy in a variety of preclinical animal models (Karagiannis et al., 2017). We reasoned that measuring TMEM activity in a non-invasive setting (e.g., Magnetic Resonance Imaging) could prove a useful companion diagnostic, to guide physician-based decision making during treatment of breast cancer patients.
Team: To address this question, we assembled a highly-effective and multi-disciplinary team of basic scientists and clinicians, the golden recipe for successful translational projects! Along with our Radiology team, led by Dr. Craig Branch and Dr. Anthony Bianchi, we proposed a novel MRI feature, "TMEM Activity-MRI", using a gadolinium-based contrast agent. We have been able to validate TMEM Activity-MRI in a number of preclinical animal models and longitudinal animal studies. Moving forward, we received an approval from our Institution to further investigate TMEM Activity-MRI in breast cancer patients, and our results are particularly promising. The breast cancer patient cohort has been assembled by our Oncology collaborators Dr. Joseph A. Sparano and Dr. Jesus Anampa. TMEM Activity-MRI has the potential to be embedded in the standard-of-care MRI examination of breast cancer patients in the course of their treatment, and provides additional prognostic information.
... and some International Collaborations!
Developmental Pathways Provide Early Signaling Cues for Colon Neoplasmatogenesis
Theofilos Poutahidis, DVM, PhD; Aristotle University of Thessaloniki, School of Veterinary Medicine
Katerina Angelopoulou, PhD; Aristotle University of Thessaloniki, School of Veterinary Medicine
Premise: A number of developmental pathways (BMP, Notch) have been previously linked with colorectal neoplasmatogenesis, although their exact contributions have been rather elusive. We are trying to understand how BMP and Notch pathway dysregulations, originating from the local colonic microenvironment, may lead to the development of preneoplastic lesions.
Midkine: Deciphering Mechanisms in Cancer Progression and Translational Opportunities
Panagiota Filippou, PhD; Teesside University
Premise: Midkine (MDK) is a pluripotent growth factor, participating in tissue development and homeostasis. Multiple lines of evidence, however, suggest that MDK is also actively involved in pathologic angiogenesis during cancer development, as well as in metastatic disease. We are trying to decipher the exact molecular prerequisites and underlying mechanisms for the involvement of MDK in cancer progression, as well as to propose novel MDK-based prognostic or therapeutic approaches to monitor and/or suppress metastatic disease, respectively.