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 Distinguished 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
Principal Investigator
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
Co Investigator
Start Date
End Date

Transcriptomic, therapeutic and genetic investigations of sickle cell nephropathy

Administered By
Duke Molecular Physiology Institute
Awarded By
National Institutes of Health
Role
Co 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

Publications:

Nitric oxide loading reduces sickle red cell adhesion and vaso-occlusion in vivo.

Sickle red blood cells (SSRBCs) are adherent to the endothelium, activate leukocyte adhesion, and are deficient in bioactive nitric oxide (NO) adducts such as S-nitrosothiols (SNOs), with reduced ability to induce vasodilation in response to hypoxia. All these pathophysiologic characteristics promote vascular occlusion, the hallmark of sickle cell disease (SCD). Loading hypoxic SSRBCs in vitro with NO followed by reoxygenation significantly decreased epinephrine-activated SSRBC adhesion to the endothelium, the ability of activated SSRBCs to mediate leukocyte adhesion in vitro, and vessel obstruction in vivo. Because transfusion is frequently used in SCD, we also determined the effects of banked (SNO-depleted) red blood cells (RBCs) on vaso-occlusion in vivo. Fresh or 14-day-old normal RBCs (AARBCs) reduced epinephrine-activated SSRBC adhesion to the vascular endothelium and prevented vaso-occlusion. In contrast, AARBCs stored for 30 days failed to decrease activated SSRBC adhesivity or vaso-occlusion, unless these RBCs were loaded with NO. Furthermore, NO loading of SSRBCs increased S-nitrosohemoglobin and modulated epinephrine's effect by upregulating phosphorylation of membrane proteins, including pyruvate kinase, E3 ubiquitin ligase, and the cytoskeletal protein 4.1. Thus, abnormal SSRBC NO/SNO content both contributes to the vaso-occlusive pathophysiology of SCD, potentially by affecting at least protein phosphorylation, and is potentially amenable to correction by (S)NO repletion or by RBC transfusion.
Authors
McMahon, TJ; Shan, S; Riccio, DA; Batchvarova, M; Zhu, H; Telen, MJ; Zennadi, R
MLA Citation
McMahon, Timothy J., et al. “Nitric oxide loading reduces sickle red cell adhesion and vaso-occlusion in vivo..” Blood Adv, vol. 3, no. 17, Sept. 2019, pp. 2586–97. Pubmed, doi:10.1182/bloodadvances.2019031633.
URI
https://scholars.duke.edu/individual/pub1409877
PMID
31484636
Source
pubmed
Published In
Blood Adv
Volume
3
Published Date
Start Page
2586
End Page
2597
DOI
10.1182/bloodadvances.2019031633

Knowledge, Cultural, and Structural Barriers to Thalassemia Screening in Migrant Populations in Thailand

<jats:title>Abstract</jats:title> <jats:p>BACKGROUND: Thalassemia syndromes are inherited hemoglobin (Hb) disorders that most severely affect Southeast Asia (SEA). As a result of population migration, thalassemia has grown into a global health issue, posing challenges to health services in many host countries. However, little attention has been paid to mass migration within SEA and its implications for regional prevention and control of Hb disorders. Thailand, with one of the highest burdens of thalassemia in the world, has a successful national prevention and control program, but ~4 million migrants living in Thailand, largely from neighboring countries, are excluded. Lack of thalassemia screening and diagnosis for migrants may undermine national efforts to prevent new births with severe thalassemia. Strategies for thalassemia screening in migrants are needed. Therefore, we sought to characterize the burden of disease, as well as the knowledge, attitudes, and practices (KAP) of migrants surrounding thalassemia in Thailand.</jats:p> <jats:p>METHODS: We surveyed Myanmar and Cambodian migrant workers (age 18-49 years) presenting for health registration and Thai subjects presenting for outpatient care at Laem Chabang Hospital (Chonburi, Thailand). Demographic and KAP surveys were developed and assessed for face and ethnographic validity. Demographic surveys were completed by all subjects. Only subjects with awareness of thalassemia completed the 31-question KAP survey. We offered thalassemia testing to all migrants and compared frequency of Hb variants in our migrant cohort to a Thai cohort. Statistical analysis was performed using SAS 9.4 (SAS Systems, Cary, NC). The study was approved by ethical review boards at Mahidol and Duke Universities.</jats:p> <jats:p>RESULTS: Median age was similar in the three nationalities (Table 1). Migrants were more likely to be married (p=0.003). Only 33.9% of migrants had entered secondary education, compared to 87.6% of Thai. ~30% of migrants did not speak any Thai. Fewer migrants attended doctor visits and used health insurance compared to Thai (both p&lt;0.0001), but migrants showed a stronger preference for health education from doctors (p=0.01). Interestingly, migrants reported residing in Thailand for a median of 5 years, and the majority had never moved within Thailand. Nonetheless, 24.5% of migrants were still unregistered, and unregistered status was associated with a shorter residence in Thailand (p=0.01) and fewer doctor visits (p=0.0003).</jats:p> <jats:p>Only 4.1% of migrants had awareness of thalassemia, compared to 79.6% of Thai; a large knowledge gap also existed for awareness of anemia (Table 1). Female gender (OR 2.12 [95% CI 1.05-4.29]; p=0.03), secondary education (OR 2.69 [95% CI 1.08-6.71]; p=0.03), and awareness of anemia (OR 11.07 [95% CI 4.82-25.44]; p&lt;0.0001) predicted thalassemia awareness in Thai, whereas only anemia awareness (OR 4.89 [95% CI 4.89-72.84]; p&lt;0.0001) and length of residence in Thailand (p=0.0002) predicted awareness in migrants.</jats:p> <jats:p>Among subjects aware of thalassemia, the KAP survey identified important misconceptions in both migrant and Thai populations that may lead to stigmatization of thalassemia carriers and decreased screening uptake. For example, 45.4% and 62.7% of migrants believe that thalassemia is an infectious disease and is rare in Asia, respectively. Though migrants had a lower median knowledge score than Thai (p=0.002), their median attitude score was similar (p=0.21). Both groups generally held positive attitudes towards thalassemia testing, but migrants held particularly negative attitudes towards abortion.</jats:p> <jats:p>Of those migrants offered thalassemia testing who had available blood samples (n=286), 96.9% consented; 3.1% declined. Interestingly, α- and β-globin variants and Hb E were more common in our migrant cohort than in a Thai cohort characterized separately (Table 2).</jats:p> <jats:p>DISCUSSION: We conclude that the burden of thalassemia in migrant populations is at least as high as in the Thai population and that thalassemia screening is highly acceptable to migrants. However, a tremendous gap in awareness of thalassemia exists between Thai and migrants, suggesting that public education targeted to migrant populations is desperately needed. Other issues identified, including language barriers, lack of insurance, low healthcare utilization, and negative attitudes toward abortion, merit further consideration when designing future health programs for migrants in Thailand and globally.</jats:p> <jats:p /> <jats:sec> <jats:title>Disclosures</jats:title> <jats:p>Telen: Pfizer, Inc.: Consultancy, Research Funding. Viprakasit:F. Hoffmann-La Roche Ltd: Consultancy, Research Funding; Protagonist Therapeutics: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Agios: Consultancy, Research Funding.</jats:p> </jats:sec>
Authors
Xu, JZ; Tanongsaksakul, W; Suksangpleng, T; Ekwattanakit, S; Riolueang, S; Kaiser, BN; Thielman, NM; Telen, MJ; Viprakasit, V
MLA Citation
Xu, Julia Z., et al. “Knowledge, Cultural, and Structural Barriers to Thalassemia Screening in Migrant Populations in Thailand.” Blood, vol. 132, no. Supplement 1, American Society of Hematology, 2018, pp. 2228–2228. Crossref, doi:10.1182/blood-2018-99-114117.
URI
https://scholars.duke.edu/individual/pub1374042
Source
crossref
Published In
Blood
Volume
132
Published Date
Start Page
2228
End Page
2228
DOI
10.1182/blood-2018-99-114117

RNA-sequencing of isolated cell populations expressing human APOL1 G2 risk variant reveals molecular correlates of sickle cell nephropathy in zebrafish podocytes.

Authors
Telen, M; Bundy, J
URI
https://scholars.duke.edu/individual/pub1414853
Source
manual

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

Depression, quality of life, and medical resource utilization in sickle cell disease.

Sickle cell disease (SCD) is a chronic, debilitating disorder. Chronically ill patients are at risk for depression, which can affect health-related quality of life (HRQoL), health care utilization, and cost. We performed an analytic epidemiologic prospective study to determine the prevalence of depression in adult patients with SCD and its association with HRQoL and medical resource utilization. Depression was measured by the Beck Depression Inventory and clinical history in adult SCD outpatients at a comprehensive SCD center. HRQoL was assessed using the SF36 form, and data were collected on medical resource utilization and corresponding cost. Neurocognitive functions were assessed using the CNS Vital Signs tool. Pain diaries were used to record daily pain. Out of 142 enrolled patients, 42 (35.2%) had depression. Depression was associated with worse physical and mental HRQoL scores (P < .0001 and P < .0001, respectively). Mean total inpatient costs ($25 000 vs $7487, P = .02) and total health care costs ($30 665 vs $13 016, P = .01) were significantly higher in patients with depression during the 12 months preceding diagnosis. Similarly, during the 6 months following diagnosis, mean total health care costs were significantly higher in depressed patients than in nondepressed patients ($13 766 vs $8670, P = .04). Depression is prevalent in adult patients with SCD and is associated with worse HRQoL and higher total health care costs. Efforts should focus on prevention, early diagnosis, and therapy for depression in SCD.
Authors
Adam, SS; Flahiff, CM; Kamble, S; Telen, MJ; Reed, SD; De Castro, LM
MLA Citation
Adam, Soheir S., et al. “Depression, quality of life, and medical resource utilization in sickle cell disease..” Blood Adv, vol. 1, no. 23, Oct. 2017, pp. 1983–92. Pubmed, doi:10.1182/bloodadvances.2017006940.
URI
https://scholars.duke.edu/individual/pub1294917
PMID
29296845
Source
pubmed
Published In
Blood Advances
Volume
1
Published Date
Start Page
1983
End Page
1992
DOI
10.1182/bloodadvances.2017006940