The Lymphoma Program at the Meyer Cancer Treatment Center at Weill Cornell Medicine and NewYork Presbyterian Hospital, emphasizes a bench to bedside approach to bring the latest advances in lymphoma research to our patients. The following is a description of the work done by our intra-institutional collaborators. These are the scientists from a variety of disciplines, whose work allows us to turn today’s research into the cures of tomorrow for lymphoma patients.
In the course of his research Leandro Cerchietti, MD has sought to develop more effective drug combinations for the treatment of cancer. Dr. Cerchietti’s research focuses on cancer pharmacology and is fully dedicated to translational research in cancer. His lab has performed in depth mechanistic studies on targets of interest and pharmacological studies with candidate molecules in vitro, in animal models, and in patients. He has designed strategies to modify targets that were previously seen as “un-targetable”, including transcription factors and protein on protein interactions. He has also developed new techniques and assays to study T- and B-cell lymphoma, solid tumor (breast cancer, lung cancer, and melanoma) cell metabolism, and responses to stress in real time under several conditions. Dr. Cerchietti and his lab members have demonstrated that that such rational design strategies could lead to combinatorial multi-target therapy with the potential to eradicate tumors with minimal to no chemotherapy.
A trained pathologist, Dr. Ethel Cesarman’s primary lymphoma related research interest concern the process of viral oncogenesis. This includes the molecular characterization of immunodeficiency-associated non-Hodgkin and classical Hodgkin lymphomas, those associated with AIDS, and those presenting in solid organ transplant recipients. These lymphomas are often associated with infection by Epstein-Barr virus (EBV) or Kaposi’s sarcoma herpes virus (KSHV/HHV-8). Ongoing research in the laboratory is aimed at characterizing the oncogenes encoded by KSHV and EBV, with the goal of dissecting the mechanism of transformation by these viruses to understand their role in the development of malignant lymphoma or Kaposi’s sarcoma. In characterizing the viral proteins that provide survival signals to the tumor cells, researchers hop to understand the role they play in carcinogenesis. Currently the lab is developing inhibitors as a novel approach for the treatment of EBV- and KSHV-related malignancies. Dr. Cesarman is also developing new diagnostic assays for detection of these viruses in poor-resource settings, such as in Africa where they are most common. Ultimately, Dr. Cesarman’s research seeks to understand the role of EBV and KSHV in the development of cancer, in order to better diagnose these and find novel targeted therapies.
Using a multi-disciplinary approach Olivier Elemento, PhD and his lab member’s work focuses on cancer systems biology. They combine Big Data analytics with experimentation to develop new ways to help prevent, diagnose, understand, treat, and ultimately cure cancer. This work can range from using computational modeling to investigate how genes are regulated in cancer cells and how gene regulation in cancer cells differs from normal cells to creating novel computational algorithms that identify new cancer mutations and the mechanics behind their occurrence. Dr. Elemento’s work also extends to the investigation of the epigenomics of cancer. His lab uses high-throughput experimental approaches and pattern detection techniques to investigate what the gene coding for proteins that modify, maintain, and read the epigenome do and the genome wide epigenomic patterns they mediate. The lab also utilizes high-throughput sequencing, in an effort to investigate how the tumor genome (and epigenome) evolves in time and the affect this takes upon drug treatment.
A majority of tumors are caused by mutations or inappropriate expression of master regulatory factors that can “reprogram” normal cells into cancerous tissue. Researchers under the direction of Ari Melnick, MD are developing ways to identify these master regulatory proteins and to dissect out their molecular mechanisms of action. The goal of his research group is to understand the mechanisms through which transcriptional and epigenetic regulation, occur during normal differentiation and how these processes become disrupted in human cancers. The hope is to use this information to develop specific and potent therapeutic strategies. By combining sophisticated gene mapping tools that can track the location of these factors throughout the genome, together with advanced structural biology and biochemistry methods, Dr. Melnick’s team has discovered how several of these cancer causing factors work at the most basic level, by hijacking and taking control of thousands of different genes using a variety of biochemical mechanisms. Building on these studies his group has developed new classes of lymphoma fighting drugs, which are non-toxic to normal tissues and are being translated for use in the clinic. These findings are leading directly to novel forms of treatments for patients with B-cell lymphoma, leukemia, and other tumors.