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Richard T. Silver MD Myeloproliferative Neoplasms Center

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Our Research

Clinical Research Initiatives

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 (link to ASH abstract, twitter/facebook pages). 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.  

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) and Spencer Krichevsky (Silver MPN Center), Claudia Sosner (Silver MPN Center), 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, and Nicole Mollé (Scandura Lab) with Jeanne Hogg RDA (WCM CTSC) and consultation from Dr. Jeffrey Friedman (Rockefeller University).

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).

We are now working to determine the true .  

Research Team: Drs. Richard T. Silver, Randy Longman(Gastroenterology), Joseph Scandura, Ellen Scherl (Gastroenterology), Attilio Orazi (Pathology) and Spencer Krichevsky (Silver MPN Center), Claudia Sosner (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), Hana Lim (Medicine Resident)

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).

Laboratory Research Programs

Targeting the MPN stem cell
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.

Research Team: Drs. Joseph Scandura, Omar Abdel-Wahab (MSKCC), Shahin Rafii (Regenerative Medicine), Nassima Messali (Scandura Lab)

 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).

MPN Avatars
Collaborative project to produce patient-derived MPN xenografts to test new MPN therapies.

Research Team: Drs. Joseph Scandura, Giorgio Inghirami (Pathology), Silvana Di Giandomenico (Scandura Lab)

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).

Mechanisms of Impaired Cerebral Blood Flow in Mouse Models of Essential Thrombocythemia and Polycythemia Vera

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)

Scandura Lab Programs

Joseph Scandura, M.D., Ph.D. serves as Scientific Director for the Silver MPN Center. The Scandura Lab Team is working on many initiatives to better understand why myeloproliferative neoplasms (MPN) form in order to develop better treatments for MPN patients.

Dr. Scandura at Weill Cornell Medicine.

Inside the Scandura Lab.

Richard T. Silver MD Myeloproliferative Neoplasms Center 525 East 70th St., Starr Pavillion, 3rd Floor New York, NY 10021 SilverMPNCenter@med.cornell.edu