U.S. flag

An official website of the United States government

Here’s how you know
Here’s how you know

**Official websites use .gov**
A **.gov** website belongs to an official government organization in the United States.

**Secure .gov websites use HTTPS**
A **lock** ( A locked padlock) or **https://** means you’ve safely connected to the .gov website. Share sensitive information only on official, secure websites.
Search Query:
			MAIN MENU

																				
              Health Topics
								All Health Topics A-Z
					
													
		

		Asthma


				

															Heart-Healthy Living


				

															High Blood Pressure


				

															Sickle Cell Disease


				

															Sleep Apnea


				

															Information & Resources on COVID-19
																				
              Health Education
								Education Programs and Initiatives
					
													
		

		The Heart Truth®


				

															Learn More Breathe Better®


				

															Blood Diseases and Disorders Education Program


				

															Publications and Resources
																				
              The Science
								Research Focus Areas
					
													
		

		Blood Disorders and Blood Safety


				

															Sleep Science and Sleep Disorders


				

															Lung Diseases


				

															Health Disparities and Inequities


				

															Heart and Vascular Diseases


				

															Precision Medicine Activities


				

															Obesity, Nutrition, and Physical Activity


				

															Population and Epidemiology Studies


				

															Women’s Health


				

															Research Topics


				

															Clinical Trials


				

															All Science A-Z
																				
              Grants and Training
								Grants and Training Home


				

															Policies and Guidelines


				

															Funding Opportunities and Contacts


				

															Training and Career Development
																				
              News and Events
								News and Events Home
					
													
		

		Email Alerts


				

															All News
					
													
		

		NHLBI News


				

															NHLBI in the Press


				

															Research Features


				

															All Events
					
													
		

		Past Events


				

															Upcoming Events
																				
              About NHLBI
								About NHLBI Home
					
													
		

		Mission and Strategic Vision


				

															Leadership


				

															Divisions, Offices and Centers


				

															Advisory Committees


				

															Budget and Legislative Information


				

															Jobs and Working at the NHLBI


				

															Contact and FAQs


				

															NIH Sleep Research Plan
						
						HOME
		Search Text: Home/< Back ToThe Science/Sickle Cell Genetics and Pathophysiology
  Sickle Cell Genetics and Pathophysiology
    Research in the Laboratory of Sickle Cell Genetics and Pathophysiology, led by Dr. Swee Lay Thein, examines the genetic and biological factors underlying the phenotypic variability of sickle cell disease to accelerate translation of basic discovery to therapeutics.
    On This Page
    
          Swee Lay Thein
  Swee Lay Thein, B.S., F.R.C.P., F.R.C.Path., D.Sc., FMedSci
          Senior Investigator
          Email
      Meet the Team
            Contact us
  Senior Investigator Research Interests
            
  Research Interests
              The Thein group conducts research on the pathophysiology of sickle cell disease (SCD) applying insights from genotype-phenotype observations to accelerate translation of basic discovery to therapeutic applications. By combining clinical, laboratory, imaging and new diagnostic techniques, we hope to improve phenotypic definition of SCD at all levels and to introduce more targeted pharmaceutical therapies for SCD. The Thein laboratory is also involved in pre-clinical and clinical testing of drugs and innovative compounds that reduce sickle hemoglobin (HbS) polymerization, improve red cell rheology, or induce fetal hemoglobin.SCD is an inherited hemoglobin disorder prevalent in regions where malaria was historically endemic, including sub-Saharan Africa, India, the Middle East, and the Mediterranean. Currently, an estimated 300,000 affected babies are born each year, more than 80% of whom are in Africa. In the United States, SCD is considered “rare”, but nonetheless affects an estimated 100,000 Americans (the majority being of African descent) and 1 in 365 African-American births.The single nucleotide change underpinning SCD belies the extreme variability and severity of SCD complications, that becomes more apparent with aging, and presents major challenges in clinical management. Both acquired and inherited factors contribute to this clinical complexity of SCD. Numerous genetic association studies (candidate gene, genome-wide association (GWA), whole exome and whole genome sequencing) have attempted to identify genetic variants with particular disease complications. In a GWA study in 2007, the Thein group identified the *BCL11A* gene as a key repressor of gamma-globin gene, a finding that resuscitated the field in fetal hemoglobin regulation and therapeutic re-activation of gamma-globin genes for the beta-hemoglobinopathies. The finding has led to genetic strategies targeting *BCL11A* regulation for therapeutic reactivation in SCD and beta thalassemia under clinical development with promising results.Prediction of disease severity and clinical course of SCD has been the topic of many reviews and, to date there is no clear algorithm using genetic and/or imaging, and/or laboratory markers that can reliably predict mortality risk in SCD. The clinical implications of delineating the genetic modifiers of SCD are significant; it will provide us the ability to predict disease severity based on a genetic SCD “panel”, and dissecting the role of new genetic modifiers might suggest new therapeutic targets for investigation. A primary approach for disease risk prediction has been polygenic risk scoring but the results remain moderately successful; they may not be so applicable in a complex disorder such as SCD that has numerous potential predictor variables. Towards the advancement of personalized medicine, the Thein group is exploring new machine learning methods incorporating predictive biomarkers (laboratory, imaging, and physiological) with genetic (germline and somatic) risk variants into risk assessment algorithms to improve risk stratification before end organ damage sets in.While we apply insights from the basic research to identify new therapeutic targets, the Thein lab is also involved in a project with Dr Bill Eaton (Laboratory of Chemical Physics, NIDDK/NIH) to discover newer anti-sickling agents using high throughput screening of drug libraries. Not only will the compounds provide further insight on the sickling mechanisms, but those that show therapeutically significant effects at concentrations known to be non-toxic can be very rapidly approved for clinical trials as these agents are either already FDA-approved or under clinical development for other diseases. It could well be that this small molecule game changer for SCD already exists among the drugs that are being used for other disorders. Furthermore, unravelling the mechanisms of the anti-sickling effects of these agents could well reveal fresh insights on the HbS fiber formation.
  VideoOptimism for new drugs for treating sickle cell disease
Images






          Sickle cell red blood cells retain mitochondria.
      
        Click the image to expand
    Sickle cell red blood cells retain mitochondria.


        
            Confocal imaging of blood cells from a sickle cell disease patient stained with mitochondrial (MTG; green), and nuclear (Hoechst; blue) markers.


                      Electron microscopy analysis of sickle cell disease red blood cells (RBCs).
      
        Click the image to expand
    Electron microscopy analysis of sickle cell disease red blood cells (RBCs).


        
            Ultrastructural analysis of RBCs using electron microscopy. RBCs from sickle cell disease patient were processed using focused ion beam-scanning electron microscopy (FIB-SEM).
      Sickle cell red blood cells retain mitochondria.


                      
Electron microscopy analysis of sickle cell disease red blood cells (RBCs).
Clinical Trials and Studies
Natural History of Sickle Cell Disease
				Recruiting
											
											All Ages
					
											All Genders
					
																		Not Accepting Healthy Volunteers

				Do you or your child have sickle cell disease or sickle cell trait? This study is interested in understanding pain crises and lung complications that occur in sickle cell disease patients and patients who have other red blood cell disorders. To participate in this study, you must be at least 2 years old with known or suspected sickle cell disease, sickle cell trait, or other red blood cell disorders. Participants will have a physical exam and receive standard medical care for sickle cell disease, including routine follow-up tests and procedures. This study is located in Washington, D.C., and Bethesda, Maryland.Genotype -Phenotype Correlation of PKLR Variants With Pyruvate Kinase, 2,3-Diphosphglycerate and Adenosine Triphosphate Activities in Red Blood Cells of People With Sickle Cell Disease
				Recruiting
											
											Adult, Older Adult
					
											All Genders
					
																		Accepting Healthy Volunteers

				Are you an adult of African descent who hasn’t had a recent transfusion and doesn’t have a known pyruvate kinase deficiency? This study investigates how the PKLR gene affects the function of red blood cells and contributes to sickle cell disease. The PKLR gene helps make a protein called pyruvate kinase that is necessary for red blood cells to function properly. To participate in this study, you must be between 18 and 80 years old, with or without sickle cell disease. This study takes place in Bethesda, Maryland.Exploring Near Infrared Spectroscopy (NIRS) Technologies for Assessment of Muscle Physiology, Tissue Oxygenation, and Blood Flow in Patients With Sickle Cell Disease (SCD)
				Recruiting
											
											Adult, Older Adult
					
											All Genders
					
																		Not Accepting Healthy Volunteers

				Are you at least 18 years old and have sickle cell disease and taking the medication Hydroxyurea?
												For this study, researchers testing are tool for measuring oxygen levels, blood flow, and the makeup of skin and muscle in patients with sickle cell disease.  To participate in this study, you must be at least 18 years old and have sickle cell disease and also be taking the medication Hydroxyurea.  This study is taking place at the National Institutes of Health Clinical Center in Bethesda, Maryland.
Featured Publications
                Phenotypic screening of the ReFRAME drug repurposing library to discover new drugs for treating sickle cell disease.
            Authors:Belhu Metaferia, Troy Cellmer, Emily B. Dunkelberger, Quan Li, Eric R. Henry, James Hofrichter, Dwayne Staton, Matthew M. Hsieh, Anna K. Conrey, John F. Tisdale, Arnab K. Chatterjee, Swee Lay Thein, and William A. Eaton.
                                                                                                                        
            Proc Natl Acad Sci U S A
      
                2022 Sep 26;119(40):
        Read Publication
                      A Phase 1 Dose Escalation Study of the Pyruvate Kinase Activator Mitapivat (AG-348) in Sickle Cell Disease.
            Authors:Xu JZ, Conrey A, Frey I, Gwaabe E, Menapace LA, Tumburu L, Lundt M, Lequang T, Li Q, Glass K, Dunkelberger E, Iyer V, Mangus H, Kung C, Dang L, Kosinski PA, Hawkins P, Jefferies N, Eaton WA, Thein SL
                                                                
            Blood
      
                2022 May 16:
        Read Publication
                      Treatment of sickle cell disease by increasing oxygen affinity of hemoglobin.
            Authors:Henry ER, Metaferia B, Li Q, Harper J, Best RB, Glass KE, Cellmer T, Dunkelberger EB, Conrey A, Thein SL, Bunn HF, Eaton WA.
                                                                                                                        
            Blood.
      
                2021 Sep 30;138(13):1172-1181
        Read Publication
                      Circulating mitochondrial DNA is a proinflammatory DAMP in sickle cell disease.
            Authors:Tumburu L, Ghosh-Choudhary S, Seifuddin FT, Barbu EA, Yang S, Ahmad MM, Wilkins LHW, Tunc I, Sivakumar I, Nichols JS, Dagur PK, Yang S, Almeida LEF, Quezado ZMN, Combs CA, Lindberg E, Bleck CKE, Zhu J, Shet AS, Chung JH, Pirooznia M, Thein SL.
                                                                                                                        
            Blood.
      
                2021 Jun 03;137(22):3116-3126
        Read Publication
                      Genetic variants of PKLR are associated with acute pain in sickle cell disease
            Authors:Wang X, Gardner K, Tegegn MB, Dalgard CL, Alba C, Menzel S, Patel H, Pirooznia M, Fu YP, Seifuddin FT, Thein SL.
                                                                                                                        
            Blood Adv
      
                2022 Jun 14;6(11):3535-3540
        Read Publication
                                View More Publications
  Meet the Team

    Swee Lay Thein

            Swee Lay Thein, B.S., F.R.C.P., F.R.C.Path., D.Sc., FMedSci
                Senior Investigator
                Swee Lay Thein was educated in both Malaysia and the United Kingdom. She completed her specialist training in hematology at the U.K. Royal Postgraduate Medical School, Hammersmith, and the Royal Free Hospital, London. In 1982, she joined the U.K. Medical Research Council Molecular Hematology Unit in Oxford where she held various positions, including clinical training fellow, Wellcome Senior Fellow in Clinical Science, senior clinical scientist, and honorary consultant hematologist.

Dr. Thein was appointed in 2000 to the position of professor of molecular hematology and consultant hematologist at King’s College London, and served as clinical director of the Red Cell Centre in King’s College Hospital. At the hospital, she treated adult patients with sickle cell disease and also provided consultation to clinicians and researchers throughout the world on patients with unusual forms of thalassemias, inherited blood disorders that disrupt the normal production of hemoglobin, resulting in anemia.

Dr. Thein joined the NHLBI in spring 2015 as Senior Investigator and Chief of the institute’s newly formed Sickle Cell Branch.

Dr. Thein is author or co-author of more than 400 peer-reviewed research publications, invited review articles, and book chapters. She has been honored for her research with a fellowship from the U.K. Academy of Medical Sciences in the U.K. Dr. Thein also was awarded a visiting professorship from Kuwait University and an honorary professorship in pathology from the University of Hong Kong. She has served/serves on the editorial boards of the research journals Blood, Pathology, Annals of Haematology, Hemoglobin, and the American Journal of Hematology and was feature editor of the journal Blood’s Sickle Cell Disease hub, a micro-website that complements research published in the journal with links to articles, images and slideshows, and other multimedia.

Dr. Thein was chair of the European Hematology Association’s scientific working group for red blood cells and iron disorders from 2011–2014 and has organized annual international conferences on sickle cell disease (Sickle Cell in Focus, SCiF) since 2006. She also has been instrumental in organizing scientific and educational conferences on red blood cell disorders for the European Hematology Association and European School of Hematology.
    
          Contact the lab
    10 Center DrBethesda, MD 20814United States
        Phone:
                    301-402-6699
                Fax:
  Ingrid
    
            Ingrid Frey, RN, BSN, MS
        

    Research Nurse Specialist

        ingrid.frey@nih.gov
            photo of Anna Conrey
    
            Anna  Conrey, MSN, RN, CRNP-AC
        

    Senior Technical Laboratory Manager

        anna.conrey@nih.gov
            Kalpo
    
            Kolapo  Oyebola, PhD
        

    Postdoctoral Fellow (APTI)

        kolapo.oyebola@nih.gov
            Nancy Asomaning, MS, CCRC
        

    Clinical Research Coordinator

        Nancy.asomaning@nih.gov
            Laxminath
    
            Laxminath Tumburu, PhD
        

    Staff Scientist & Manager

        lax.tumburu@nih.gov
            avatar
    
            Xunde Wang, PhD
        

    Staff Scientist

        xwang@nhlbi.nih.gov
            avatar
    
            Eveline Gwaabe, MSN, APRN, NP-C, APCWCN
        

    Nurse Practitioner

        Eveline.gwaabe@nih.gov
        
                    View
                    Eveline's Profile
            Okusolubo
    
            Temiloluwa Okusolubo
        

    Postbaccalaureate IRTA Fellow

        temiloluwa.okusolubo@nih.gov
        
                    View
                    Temiloluwa's Profile
            Ray
    
            Rudra Ray, PhD
        

    Postdoctoral Fellow

        rudra.ray@nih.gov
        
                    View
                    Rudra's Profile
            Charles
    
            Ruth Pierre Charles, M.Ed., MHSc, DMSc, PA-C
        

    Physician Assistant/Advanced Practitioner

        Ruth.pierrecharles@nih.gov
        
                    View
                    Ruth's Profile
            Kang Le, Ph.D.
    
            Kang Le, Ph.D.
        

    Staff Scientist

        kang.le@nih.gov
            Mahaseny
    
            Behzad Mahaseny
        

    Laboratory Technician

        behzad.mahaseny@nih.gov
            Britney Kruah, MS
    
            Britney Kruah, M.S.
        

    Laboratory Manager

        britney.kruah@nih.gov
            Megan Lormore
    
            Megan Lormore, BS, CCRC
        

    Clinical Research Coordinator

        megan.lormore@nih.gov
            Quinlan Batcheller
    
            Quinlan Batcheller, MPH
        

    Post-bacc IRTA Fellow

        quinlan.batcheller@nih.gov
            Tiffany Chen
    
            Tiffany Chen
        

    Staff Assistant

        tiffany.chen4@nih.gov
            Yechan Cho, B.A.
        

    Post-bacc IRTA Fellow

        yechan.cho@nih.gov
            John Hamre, Ph.D., MSc
        

    Research Fellow

        john.hamre@nih.gov
            Kimberly Rivers, RN, MSN, FNP-BC
        

    Nurse Practitioner

        kimberly.rivers@nih.gov
                    Load more members Back To Top Link
  

        

        Back to top
  Web Policies & Notices
  

        

              Accessibility
                      No FEAR Act Data
                      Privacy Policy
                      Freedom of Information Act (FOIA)
                      HHS Vulnerability Disclosure
    
          Related Government Websites
  

        

              Health and Human Services
                      National Institutes of Health
                      Office of the Inspector General
                      USA.gov
    
          Stay Connected
    
      
            chat bubblesLive ChatLive Chat with us, Monday through Friday, 8:30 a.m. to 5:00 p.m. EST.envelopeGet Email AlertsReceive automatic alerts about NHLBI related news and highlights from across the Institute.
  Footer Bottom
  

        



Contact Us
                            Site Index
                            Jobs