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VMI
 


Vascular Medicine Institute
University of Pittsburgh
BST E1240
200 Lothrop Street
Pittsburgh, PA 15261
Phone: 412-383-5853
Fax: 412-648-5980

Enrico M. Novelli, MD, MS

 

Enrico M Novelli MD MS

 

Enrico Novelli, MD, MS

Assistant Professor of Medicine,
Division of Hematology/Oncology

Medical Director,
UPMC Adult Sickle Cell Anemia Program

Associate Director,
Hemophilia Center of Western PA

E1257 BST
200 Lothrop Street
Pittsburgh, PA 15261

Phone: 412-624-2591
Lab Phone: 412-648-3187
Email: noveex@upmc.edu


Novelli Lab

   

Bio

Dr. Novelli obtained his MD degree from the University of Milan, Italy in 1996. He was a postdoctoral fellow at Johns Hopkins University from 1996 to 1999 where he developed expertise in cellular biology and gene therapy. His research project under the mentorship of Dr. Civin elucidated the repopulating potential of cultured CD34+ hematopoietic stem cells and explored the phenotype of their progeny in the immunodeficient mouse model NOD/SCID. In 1999 he moved to the University of Pittsburgh where he applied his expertise in gene therapy of hematopoeitc stem cells to develop a gene therapy approach to Gaucher disease. He enrolled in the UPMC Internal Medicine residency program with a plan to obtain subspecialty training in Hematology Oncology. At the end of his residency, he volunteered as Internal Medicine Specialist at Lilongwe Central Hospital in Malawi, Africa in 2005. This experience cemented his resolve to develop clinical expertise and research projects to alleviate the disease burden of populations that have limited access to healthcare. Upon returning to the United States, he enrolled in the UPMC Hematology/Oncology fellowship program, where his research project focused on characterizing malarial anemia in Kenya. He became faculty at the University of Pittsburgh upon completion of his fellowship in June 2008.

Clinical Interests

Dr. Novelli's main areas of interest are sickle cell disease and disorders of hemostasis. Dr. Novelli holds a sickle cell disease and hemoglobinopathy clinic at the Hillman Cancer Center and a hemophilia and thrombosis clinic at the Hemophilia Center of Western Pennsylvania. In addition, he works as a member of the inpatient hematology consult service for several weeks of the year.  Another longstanding interest of Dr. Novelli’s is in developing global health research and training initiatives in Tropical Hematology.

Research Interests

One recent interest of Dr. Novelli's is elucidating the fundamental mechanisms underlying hemolysis-associated thrombosis and vascular dysfunction in SCD.  Patients with SCD suffer from severe chronic hemolytic anemia and acute episodes of RBC trapping and destruction in the microvasculature (vaso-occlusive crises). Hemolysis has been associated with a clinical hypercoagulable state that leads to a high prevalence of thrombotic complications, which manifest as both venous and arterial thromboembolic phenomena and are responsible for high morbidity and mortality. It is therefore critical to elucidate the link between hemolysis and thrombosis in SCD, so that effective preventive and therapeutic strategies can be developed. Dr. Novelli's current research project explores the role of Thrombospondin-1 (TSP1), a glycoprotein abundantly present in platelet α-granules is emerging as a key regulator of hemostasis and thrombosis (Figure 1).

Figure 1

  Novelli Fig 2
     

Another research project aims at exploring the role of the interaction between TSP1 and CD47 in SCD. In SCD, vaso-occlusion and hemolysis lead to platelet and hemostatic activation, pulmonary hypertension and vascular disease. Transgenic-knockout sickle (BERK) mice that express exclusively human α- and βS-globins mimic SCD in humans by displaying reduced NO bioavailability, impaired NO-mediated vascular reactivity and pulmonary hypertension. Our hypothesis is that during platelet activation in patients with SCD and BERK mice, increases in circulating plasma levels of TSP1, via binding to the CD47 receptor, disrupt pulmonary vascular endothelial NO production and stimulate smooth muscle ROS production and endothelin 1 signaling, which lead to pulmonary hypertension. This project also explores the hypothesis that therapeutic disruption of the TSP1-CD47 ligand-receptor interaction will both prevent and reverse pulmonary hypertension in SCD (Figure 2).


Key Publications

EM Novelli, C Huynh, MT Gladwin, CG Moore, MV Ragni. 2012. Pulmonary Embolism in Sickle Cell Disease: A Case-Control Study. Journal of Thrombosis and Hemostasis (In press).

EM Novelli, GJ Kato, MV Ragni, Y Zhang, ME Hildesheim, M Nouraie, S Barge, MP Meyer, AC Hassett, VR Gordeuk, MT Gladwin, JS Isenberg. 2012. Plasma thrombospondin-1 is increased during acute sickle cell vaso-occlusive events and associated with acute chest syndrome, hydroxyurea therapy and lower hemolytic rates. American Journal of Hematology. 87(3):326-30

EM Novelli, JB Hittner, GC Davenport, C Ouma, T Were, S Obaro, S Kaplan, JM Ong'echa and DJ Perkins. 2010. Clinical predictors of severe malarial anaemia in a holoendemic Plasmodium falciparum transmission area. British Journal of Haematology. 149 (5):711-721.

Pubmed link