Pulmonary Hypertension in MPNs
We have identified a remarkably high incidence of pulmonary hypertension in patients with MPNs. Pulmonary hypertension is associated with clinically significant symptoms of fatigue and breathlessness. Survival of patients with pulmonary hypertension is shortened. We are now working to identify the mechanisms of pulmonary hypertension in MPNs and to determine how best to treat this complication to alleviate symptoms and prolong survival. We are also collaborating with the European LeukemiaNet (ELN) to prospectively study pulmonary hypertension in MPNs.
Research Team: Drs. Joseph Scandura, Jonathan Weinsaft (Cardiology), Jiwon Kim (Cardiology), Augustine Choi (Pulmonary), Alexandra Racanelli (Pulmonary), Richard Devereux (Cardiology), Evelyn Horn (Cardiology), Attilio Orazi (Pathology), Spencer Krichevsky (Silver MPN Center) and Mia Yabut-Weise (Scandura Lab)
Ruxolitinib Hyperphagy in the MPNs
Patients taking ruxolitinib commonly gain significant weight and often report increased appetite. Leptin signaling in the brain is a major regulator of appetite. Leptin signaling is mediated by JAK2. We are evaluating whether ruxolitinib-associated hyperphagy and weight gain is a direct, on target consequence of its blocking leptin receptor signaling in the ventral medial thalamus of the brain.
Research Team: Drs. Pouneh Kermani, Joseph Scandura, Ellen Ritchie, Richard T. Silver, and Nicole Mollé (Scandura Lab) and Spencer Krichevsky (Silver MPN Center)
Long-Term Follow Up of Silver MPN Center Patients with Polycythemia Vera
The goal of this research is to draw from our experience and knowledge in treating patients with myeloproliferative diseases over many years in order to evaluate the long-term treatment outcomes of interferon and other standard therapies. We have studied over 450 patients with polycythemia vera who have been treated by Weill Cornell Medicine Silver MPN Center physicians over a period of more than 25 years. This work has been preliminarily presented at the 2019 American Society of Hematology (ASH) Annual Meeting.
Research Team: Drs. Ghaith Abu-Zeinah, Joseph Scandura, Richard T. Silver, and Spencer Krichevsky (Silver MPN Center), and Niamh Savage (Silver MPN Center).
Inflammatory Bowel Disease and MPNs
It is widely recognized that patients with inflammatory bowel disease (Crohn’s Disease and Ulcerative Colitis) often have abnormally high blood cell numbers. Conversely, patients with MPNs frequently report gastrointestinal symptoms. Emeritus director of the MPN Center, Richard T. Silver, M.D., working with Ellen Scherl M.D., and Randy Longman, M.D., Ph.D. from the Jill Roberts Center for Inflammatory Bowel Disease, identified several patients with IBD and elevated blood cell numbers who also carried MPN mutations in their blood (Kuriakose, et al).
Research Team: Drs. Richard T. Silver, Randy Longman (Gastroenterology), Joseph Scandura, Ellen Scherl (Gastroenterology), Attilio Orazi (Pathology) and Spencer Krichevsky (Silver MPN Center).
Myelofibrosis in Hypereosinophilic Syndrome
Retrospective review of the incidence and determinants of myelofibrosis in patients with hypereosinophilic syndrome.
Research Team: Drs. Andrew Schafer, Attilio Orazi (Pathology), and Hana Lim (Weill Cornell Hematology & Medical Oncology Fellow).
Complications of Ruxolitinib Therapy in MPNs
Ruxolitinib is a tyrosine kinase inhibitor approved by FDA for treatment of symptomatic myelofibrosis and patients with polycythemia vera who have not adequately responded to hydroxyurea. Despite the clinical benefits of ruxolitinib in these settings, like all anti-cancer agents, there are also some apparent toxicities. Trials have shown an increased risk of infections and secondary cancers in patients taking ruxolitinib. We are performing a retrospective review of the prevalence and types of infections and secondary malignancies in patients treated with ruxolitinib at the Silver MPN Center and presented this research at the American Society for Hematology (ASH) 2017 Annual Meeting.
Research Team: Dr. Ellen Ritchie, Spencer Krichevsky (Silver MPN Center)
View our open clinical trials for myeloproliferative neoplasms (MPNs).
Targeting the MPN stem cell
The pattern of clonal enrichment of an MPN stem cell during hematopoiesis is unique to individual patients and varies significantly among Polycythemia Vera (PV), Essential Thrombocythemia (ET), and Primary Myelofibrosis (MF). Our research has shown that changes in the MPN stem cell population can predict changes in the disease trajectory and course of treatment.
Collaborative project using novel methods to perform a forward genetic screen to identify genes necessary for JAK2V617F MPN propagation but dispensable for normal hematopoietic stem cells.
The Silver MPN Center has collaborated with Dr. Dan Landau to develop a technique to for the first-time ever identify the abnormal gene expression in MPN stem and progenitor cells. This points to several therapeutic approaches for MPNs that are currently being studied in the laboratory.
Research Team: Drs. Joseph Scandura, Omar Abdel-Wahab (MSKCC), Shahin Rafii (Regenerative Medicine), Nassima Messali (Scandura Lab), Anna Lam (Pathology), and Dan Landau (Hematology & Oncology).
MPN Research Foundation (MPN-RF) Interferon Initiative
Interferon is the only therapy for myeloproliferative neoplasms (MPNs) that is known to induce clinical, histologic and molecular responses. The problem is that we don’t understand how interferon works so we don’t know how to build upon this clinical observation. Most cells can respond to interferon so its clinical efficacy may result from effects on MPN cells, on normal hematopoietic cells or on the microenvironmental cells that support them in the body. MPN-RF has a assembled an international team of investigators to tackle this complexity and identify how best to use this knowledge to advance treatment of MPNs.
Silver MPN Center Research Team: Drs. Joseph Scandura, Silvana Di Giandomenico (Scandura Lab), Ghaith Abu-Zeinah (Scandura Lab).
TGFβ-driven phenotypes of MPNs
TGFβ signaling is abnormal in the MPNs. This project is defining how abnormal TGFβ signaling promotes MPN phenotypes.
Research Team: Dr. Joseph Scandura, Silvana Di Giandomenico (Scandura Lab), Pouneh Kermani (Hematology-Oncology), Nicole Mollé (Scandura Lab).
Collaborative project to develop in vitro methods to test agents targeting MPN stem and progenitor cells and to produce patient-derived MPN xenografts to test new MPN therapies.
Research Team: Drs. Joseph Scandura, Giorgio Inghirami (Pathology), Silvana Di Giandomenico (Scandura Lab), and Ghaith Abu-Zeinah (Scandura Lab, Division of Hematology & Medical Oncology).
Autologous Cure of MPNs
Collaborative project with the goal of using novel methods to generate genetically normal hematopoietic stem cells from blood lining endothelial cells of patients with MPNs and MPN models.
Research Team: Drs. Joseph Scandura, Shahin Rafii (Regenerative Medicine), Hans-Peter Kiem (Fred Hutchinson Cancer Center, Seattle), Nassima Messali (Scandura Lab).
Deciphering Mechanisms for Different Disease Phenotypes of JAK2V617F MPNs
Collaborative project using single-cell transcriptomics to identify mechanisms underlying the phenotypic divergence of JAK2V617F PV and ET.
Research Team: Drs. Joseph Scandura, Dan Landau (Medicine, Physiology and Biophysics), Seung Nam (Pathology), Silvana Di Giandomenico (Scandura Lab), Ghaith Abu-Zeinah (Scandura Lab).
Two-photon excited fluorescence microscopy in real time was used to examine the hemodynamic mechanisms and cellular pathophysiology underlying observed impairment of capillary flow in JAK2V617F transgenic mice (Santisakultarm et al).
Research Team: Drs. Andrew Schafer, Richard Silver, Chris Schaffer (Cornell University Biomedical Engineering)