Marilyn Telen

Overview:

Dr. Telen is recognized as an expert in the biochemistry and molecular genetics of blood group antigens and the pathophysiological mechanisms of vaso-occlusion in sickle cell disease. She is the Director of the Duke Comprehensive Sickle Cell Center.

Dr. Telen's laboratory focuses on structure/function analysis of membrane proteins expressed by erythroid cells, as well as the role of these proteins in non-erythroid cells. Proteins are also studied in transfectant systems, and research focuses especially on adhesion receptors. The goals of this work are (1) to understand the mechanism and role of red cell adhesion to leukocytes and endothelium in sickle cell disease; (2) to understand the signaling mechanisms leading to activation (and inactivation) of red cell adhesion molecules; (3) to understand the molecular basis of blood group antigen expression, and (4) to understand the interactions of erythroid membrane proteins with other cells and with extracellular matrix..

Recent investigations have focused on the role of signaling pathways in the upregulation of sickle red cell adhesion. Present studies include (1) investigation of beta-adrenergic signaling pathway responsible for activation of B-CAM/LU and LW adhesion receptors; (2) understanding how nitric oxide and ATP downregulate sickle red cell adhesion; (3) studying the effect of these processes in animal models.

Dr. Telen is also involved in a large multicenter study looking for genetic polymorphisms that affect clinical outcomes in sickle cell disease, as well as a multi-center study investigating the mechanisms and treatment of pulmonary hypertension in sickle cell disease.


Key Words:

Adhesion molecules
Erythrocyte membrane
Sickle cell disease
Transfusion medicine
Immunohematology
CD44
B-CAM/LU
Genetic polymorphisms

Positions:

Wellcome Clinical Professor of Medicine in Honor of R. Wayne Rundles, M.D.

Medicine, Hematology
School of Medicine

Professor of Medicine

Medicine, Hematology
School of Medicine

Associate Professor of Pathology

Pathology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Affiliate, Duke Global Health Institute

Duke Global Health Institute
Institutes and Provost's Academic Units

Education:

M.D. 1977

New York University

Intern, Medicine

State University of New York at Buffalo

Resident, Medicine

State University of New York at Buffalo

Fellowship, Hematology/ Oncology

Duke University School of Medicine

Grants:

Duke-UNC Clinical Hematology and Transfusion Research Career Development Program

Administered By
Medicine, Hematology
Awarded By
National Institutes of Health
Role
Associate Program Director
Start Date
End Date

Instrumentation for Quantitative Phosphoproteomics and Acetylomics

Administered By
Duke Center for Genomic and Computational Biology
Awarded By
National Institutes of Health
Role
Major User
Start Date
End Date

The Genomic Analysis of Erythrocyte microRNA in Sickle Cell Diseases

Administered By
Molecular Genetics and Microbiology
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

Improving Pain in Sickle Cell Patients With Targeted Antithrombotic Therapy

Administered By
Medicine, Hematology
Awarded By
National Institutes of Health
Role
Co-Mentor
Start Date
End Date

Patient Preference Information: Bridging Regulatory Decisions and Clinical Practice

Administered By
Duke Clinical Research Institute
Awarded By
Food and Drug Administration
Role
Co Investigator
Start Date
End Date

Publications:

Communications: To contributors to the 2017 issues

Authors
Alther, RA; Arndt, P; Bailey, D; Barron, C; Benitez, N; Boyd, JS; Bryant, BJ; Castilho, LM; Cooling, L; Crews, WS; Daniels, G; Davenport, R; Delaney, M; Fadeyi, EA; Figueroa, D; George, MR; Halverson, GR; Horn, T; Hustinx, H; Hyland, C; Johnson, ST; Kaufman, R; Keller, J; Mansfield, PM; Lima, J; Mathur, A; Meny, GM; Poisson, J; Ramsey, G; Gerald Sandler, S; Sheppard, C; Shulman, IA; Telen, MJ; Trimble, J; Villa, CH; Bernadette West, F; Nance, S; Flickinger, C
MLA Citation
Alther, R. A., et al. “Communications: To contributors to the 2017 issues.” Immunohematology, vol. 33, no. 4, Jan. 2017, pp. 173–172.
URI
https://scholars.duke.edu/individual/pub1404618
Source
scopus
Published In
Immunohematology
Volume
33
Published Date
Start Page
173
End Page
172

Therapeutic strategies for sickle cell disease: towards a multi-agent approach.

For over 100 years, clinicians and scientists have been unravelling the consequences of the A to T substitution in the β-globin gene that produces haemoglobin S, which leads to the systemic manifestations of sickle cell disease (SCD), including vaso-occlusion, anaemia, haemolysis, organ injury and pain. However, despite growing understanding of the mechanisms of haemoglobin S polymerization and its effects on red blood cells, only two therapies for SCD - hydroxyurea and L-glutamine - are approved by the US Food and Drug Administration. Moreover, these treatment options do not fully address the manifestations of SCD, which arise from a complex network of interdependent pathophysiological processes. In this article, we review efforts to develop new drugs targeting these processes, including agents that reactivate fetal haemoglobin, anti-sickling agents, anti-adhesion agents, modulators of ischaemia-reperfusion and oxidative stress, agents that counteract free haemoglobin and haem, anti-inflammatory agents, anti-thrombotic agents and anti-platelet agents. We also discuss gene therapy, which holds promise of a cure, although its widespread application is currently limited by technical challenges and the expense of treatment. We thus propose that developing systems-oriented multi-agent strategies on the basis of SCD pathophysiology is needed to improve the quality of life and survival of people with SCD.
Authors
Telen, MJ; Malik, P; Vercellotti, GM
MLA Citation
Telen, Marilyn J., et al. “Therapeutic strategies for sickle cell disease: towards a multi-agent approach..” Nat Rev Drug Discov, vol. 18, no. 2, Feb. 2019, pp. 139–58. Pubmed, doi:10.1038/s41573-018-0003-2.
URI
https://scholars.duke.edu/individual/pub1361078
PMID
30514970
Source
pubmed
Published In
Nat Rev Drug Discov
Volume
18
Published Date
Start Page
139
End Page
158
DOI
10.1038/s41573-018-0003-2

Sevuparin binds to multiple adhesive ligands and reduces sickle red blood cell-induced vaso-occlusion.

Sevuparin is a novel drug candidate in phase II development as a treatment for vaso-occlusive crises (VOC) in patients with sickle cell disease (SCD). As a heparin-derived polysaccharide, sevuparin has been designed to retain anti-adhesive properties, while the antithrombin-binding domains have been eliminated, substantially diminishing its anticoagulant activity. Here, we demonstrate that sevuparin inhibits the adhesion of human sickle red blood cells (SS-RBCs) to stimulated cultured endothelial cells in vitro. Importantly, sevuparin prevents vaso-occlusion and normalizes blood flow in an in vivo mouse model of SCD vaso-occlusion. Analyses by surface plasmon resonance (SPR) and fluorescence correlation spectroscopy (FCS) demonstrate that sevuparin binds to P- and L-selectins, thrombospondin, fibronectin and von Willebrand factor, all of which are thought to contribute to vaso-occlusion in SCD. Despite low anticoagulation activity, sevuparin has anti-adhesive efficacy similar to the low molecular weight heparin tinzaparin both in vitro and in vivo. These results suggest that the anti-adhesive properties rather than the anticoagulant effects of heparinoids are critical for the treatment of vaso-occlusion in SCD. Therefore, sevuparin is now being evaluated in SCD patients hospitalized for treatment of VOC.
Authors
Telen, MJ; Batchvarova, M; Shan, S; Bovee-Geurts, PH; Zennadi, R; Leitgeb, A; Brock, R; Lindgren, M
MLA Citation
Telen, Marilyn J., et al. “Sevuparin binds to multiple adhesive ligands and reduces sickle red blood cell-induced vaso-occlusion..” Br J Haematol, vol. 175, no. 5, Dec. 2016, pp. 935–48. Pubmed, doi:10.1111/bjh.14303.
URI
https://scholars.duke.edu/individual/pub1140105
PMID
27549988
Source
pubmed
Published In
Br J Haematol
Volume
175
Published Date
Start Page
935
End Page
948
DOI
10.1111/bjh.14303

Pan-Selectin Antagonist Rivipansel (GMI-1070) Reduces Soluble E-Selectin Levels While Improving Clinical Outcomes in SCD Vaso-Occlusive Crisis

Authors
Wun, T; Telen, MJ; Krishnamurti, L; McCavit, TL; DeCastro, LM; Flanner, H; Kuypers, FA; Larkin, SK; Rhee, S; Magnani, JL; Thackray, HM
URI
https://scholars.duke.edu/individual/pub1071489
Source
wos
Published In
Blood
Volume
124
Published Date

Novel optical signature for sickle cell trait red blood cells

We identified unique optical signatures for sickle cell trait, a condition where heterozygous individuals are carriers for the hemoglobin allele that causes sickle cell anemia, by using wide-field interferometric microscopy. © OSA 2012.
Authors
Satterwhite, LL; Shaked, NT; Cyr, DD; Telen, MJ; Truskey, GA; Wax, A
MLA Citation
Satterwhite, L. L., et al. “Novel optical signature for sickle cell trait red blood cells.” Frontiers in Optics, Fio 2012, Dec. 2012.
URI
https://scholars.duke.edu/individual/pub1020562
Source
scopus
Published In
Frontiers in Optics, Fio 2012
Published Date