תוצאות

The Immunology and Advanced CAR-T therapy, has laid the fundamental groundwork for genetically engineering patients’ immune T cells against their own cancer, based on the recognition and execution of cancer cells by cytotoxic T cells. This is done by adding a Chimeric Antigen Receptor (CAR) to the T cells to recognize the cancerous cells. CAR-T are white blood T cells outfitted with receptors that specifically seek out and identify tumors, promoting their destruction. This novel treatment combines the advantages of two immune system components: antibodies, which are capable of recognizing tumors but cannot efficiently penetrate them, and T cells, which -in principle- can carve through cancerous tissue, but often lack the ability to recognize and home in on the tumor. Over the course of two decades, CAR-T cell technology transformed from a revolutionary idea that works in the lab to a feasible treatment that is effective and safe in patients. Today, the FDA has approved this technology to treat leukemia and lymphoma patients. However, solid tumors are still a challenge, as well as manufacturing the CAR-T in a more productive way and developing an off-the-shelf CAR-T product. Our lab ‎is focused on producing many new CAR-T cells, with ‎specific recognition, or dual recognition to cancer cells, ‎as well as developing solutions for the current ‎challenges in this era.‎

Cancer is a leading cause of morbidity and mortality worldwide. Accurate diagnosis of disease type and molecular profile are crucial for effective and targeted therapy to patients. Additionally, cancer is a dynamic process, both clinically and at the molecular level and therefore useful tools for disease monitoring could help tailor personalized treatment for each patient. Our research focuses of developing better diagnostic tools, both at the molecular level and the histomorphological level. Toward this aim we establish tissue specific, next generation sequencing (NGS) mutational panels – to identify the common cancer drivers in each tumor type. Additionally, we apply deep learning and artificial intelligence for the development of algorithms that improve microscopy based diagnosis. These algorithms come on top of our digital pathology platform, used for routine diagnosis. Another significant focus of our research is aimed at monitoring cancer progression and response to therapy. This is done via analysis of circulating tumor DNA.

Extracellular vesicles (EVs) include exosomes and microvesicles are shed from various cells. EVs express antigens and genetic molecules characteristic of their parent cells and play a central role in intercellular communication by transferring their "cargo" to target cells.
In recent years, our lab has contributed substantially to the field of research related to EVs. We exploring their various roles in the pathophysiology of pregnancy related complications, hematological malignancies (myeloma, AML), chronic graft vs. host disease (cGVHD), solid tumors such as breast, colon, and gastrointestinal stromal tumors, congenital disorders like thalassemia, and dementia. We have also explored the effects of EVs that are shed from cell culture upon stimulation on target cells functions.
Another area of our research focuses on the therapeutic potential of EVs, as we have made significant progress in our study investigating the use of EVs derived from CAR-T cells as a potential therapy for cancer.
In these studies, we demonstrated that EVs affect and reflect disease dynamics, and may be used not only for diagnosis and monitoring of therapy, but also as a mainstay of treatment.

The Genomic Research Laboratory for Lung Fibrosis (Unterman lab)

Our goal: to uncover the basic mechanisms underlying lung fibrosis and develop new treatments.

Interstitital lung diseases (ILDs) consist of over 200 different diseases. Many patients, in particular those who are diagnosed with idiopathic pulmonary fibrosis (IPF), develop severe lung scarring (called lung fibrosis) that necessitates lung transplantation for survival. Despite multidisciplinary approaches to diagnose ILD patients, in many cases the exact diagnosis is unclear. Furthermore, current treatment options may delay disease progression but cannot provide cure. In our laboratory, we employ cutting-edge genomic technologies, including single cell RNA sequencing (scRNA-seq) and spatial transcriptomics, to study ILD patient-derived samples. We believe that by using these tools, we may come one step closer towards elucidating the biology of these intricate diseases, identify new biomarkers and develop novel treatments for ILD patients.

Dr. Unterman (lab PI) is a physician-scientist that serves as the head of the Pulmonary Fibrosis Center of Excellence at Ichilov, the largest center that treats ILD patients in Israel. He received his post-doc training in pulmonary fibrosis and advanced genomic techniques at Yale University. Dr. Yan Stein (lab manager) received his PhD from the Weizmann Institute, and is experienced in molecular and cell biology, and in computational analysis of genomic data.