Introduction:

This web page briefly describes the Southwestern Comprehensive Sickle Cell Center (subsequently referred to as “the Center”) based at the University of Texas Southwestern Medical Center at Dallas (UT Southwestern).  The Center conducts a broad array of state-of-the-art patient care, clinical research, basic laboratory research, education, and advocacy programs.  This web page aims to introduce the Center’s various activities to healthcare professionals, patients and their families, and the general public.  

History:

The Southwestern Comprehensive Sickle Cell Center had its genesis late in 2001 during the preparation for an application to the National Heart, Lung and Blood Institute to be designated as one of the 10 comprehensive sickle cell centers during the 2003-2008 grant cycle.  The application was deemed worthy of support, and funding through a U54 grant mechanism from the NHLBI began April 1, 2003.  The grantee for the Center’s activities is the University of Texas Southwestern Medical Center at Dallas (UT Southwestern). 

Its primary clinical site is Children's Medical Center Dallas, and other sites of Center activity include Parkland Health and Hospital System, UT Southwestern University Hospitals, the University of Texas at Dallas, the University of Oklahoma Health Sciences Center, the University of Texas Medical Branch at Galveston, and the Sickle Cell Disease Association of Dallas.   Long before receipt of the grant award and formal designation of the Center, Dallas was recognized as a city where novel and high quality patient care, clinical research, and education was being practiced.  In particular, the Pediatric Sickle Cell Disease Program based at Children's Medical Center Dallas, has been known for over 25 years as a Center of Excellence.  The description that follows in subsequent sections emphasizes the Pediatric Sickle Cell Program activities at Children’s but provides links to the other hospitals, universities, and organizations that are Center components and which conduct important work as well.

Center Components:

The Southwestern Comprehensive Sickle Cell Center is a virtual Center (“center without walls”).  Its administrative centerpiece is the Division of Hematology-Oncology in the Department of Pediatrics at UT Southwestern and the Center for Cancer and Blood Disorders  at Children's Medical Center Dallas.

UT Southwestern, one of the major academic medical centers in the United States, handles the financial and most of the administrative components of the Center grant.  Six full time faculty members at UT Southwestern are funded investigators in the Center.  They include Dr. George R. Buchanan (principal investigator and Center Director), Dr. Zora Rogers  (Clinical Core Director and intercenter research study principal investigator), Dr. Charles Quinn  (clinical research project and intercenter study principal investigator), and Dr. Cynthia Rutherford, Dr. Victor Garcia-Martinez (basic research principal investigator).  Dr. Michael Dowling was our first Sickle Cell Scholar from February 2004 - June 2006.  As of November 01, 2006 our scholar is Dr. Amy Becker. 

• Children's Medical Center Dallas, a 356 bed tertiary care academic children’s hospital, is adjacent to UT Southwestern.  It is the site of the Pediatric Sickle Cell Disease Program in Dallas.  Sickle Cell Program personnel and Center members at Children’s include UT Southwestern faculty physicians, advanced practice nurses, nurse clinicians, clinical research associates, research nurses, and other clinical support staff.  Over 600 active sickle cell patients from Dallas (see patient statistics) and surrounding communities receive their outpatient and hospital care at Children’s.
• UT Southwestern University Hospital  and Parkland Hospital and Health Care System  are the major clinical sites for the Adult sickle Cell Program in Dallas.  Center staff includes UT Southwestern faculty members and nursing and social work personnel which serve approximately 200 adult patients.
• The University of Texas at Dallas  in the adjacent suburb of Richardson is the site of a Center basic laboratory research project (Dr. Steven Goodman, principal investigator) and of the UTD Sickle Cell Disease Research Center, directed by Dr. Betty Pace.  The institution’s focus is on basic research and education.
• The University of Oklahoma Health Sciences Center  provides care and conducts Center research projects involving children with sickle cell disease. 
• The University of Texas Medical Branch at Galveston  provides education and clinical research focusing on adults with sickle cell disease. 
• The Sickle Cell Disease Association of Dallas  functions in the Center as a local site for screening, counseling, communication education, and advocacy.

Membership in the Center is open to any individual at a Center institution who expresses an interest in sickle cell disease and devotes his or her energy to patient care, education, research, or advocacy in the area.

Administration:

The Center is directed by Dr. George R. Buchanan.  Key administrative staff support is provided by Sandra Richardson and AnnMarie Fillmore at Children’s and UT Southwestern respectively.  An internal advisory committee consisting of principal investigators and senior faculty from all of the participating Center institutions meets regularly to provide direction, and a highly effective External Advisory Committee has visited Dallas annually to provide a careful and comprehensive review of the Center’s progress and future plans.  Funding of Center activities is derived from the NHLBI Comprehensive Sickle Cell Center U54 grant but also from other NIH research grants, hospital support, revenue derived from patient care, and support from the Texas Legislature.

Patients Served:

Sickle cell disease is one of the most common serious inherited disorders in the United States.  African Americans are most frequently affected.  It is estimated that over 70, 000 individuals in the United States and over 6,000 persons in Texas have sickle cell disease.  Since 1983 babies in Texas with sickle cell disease have been diagnosed by newborn screening performed by the Department of State Health Services.  The Center’s institutions in Dallas provide comprehensive specialty care for children and adults but not primary care, although close communication is maintained with primary care providers.  Since formal establishment of the Pediatric Sickle Cell Disease Program in 1977, over 1,700 children have been followed in the program.  At present, approximately 650 of them are “active” in that they are being seen regularly.  The adult program, which formally began with receipt of the Center grant in 2003, currently follows about 200 active patients.  An outreach initiative by the pediatric program, in place since the 1980’s, serves patients in rural east Texas.  Clinics are held four times annually in two small cities in that region.  Patient care in the pediatric program is provided by a multi-disciplinary team.  Education of patients and their parents and trainees at various levels and volunteer participation by patients in clinical trials are integral parts of the care program.  An online password-protected database catalogs key clinical and hematologic information on all pediatric patients.  It is accessible to the emergency department and other qualified hospital staff to facilitate patient care and is also an extremely valuable resource for clinical research studies. 

Clinical Research:

Clinical research is a major activity in the Center, building upon the long term track record of patient-oriented investigations carried out in Dallas since the late 1970’s.  The Bibliography provides references to publications by Center investigators. 

Clinical research involves both multi-center collaborative studies and investigator initiated research performed in Dallas.   The Center has been a major participant in the Comprehensive Sickle Cell Center Clinical Trials Consortium (CTC) established in 2003 to foster clinical trials.  Drs. Zora Rogers  and Charles Quinn  have been leaders in the design and execution of several CTC trials involving pain, priapism, chest syndrome, and development of a comprehensive database.  Other NIH-funded multi-center studies in which the Center is participating include the BABY HUG Trial determining the safety and efficacy of hydroxyurea in infants, the SITT Study assessing the value of chronic transfusions in children with sickle cell anemia and silent infarct, and the SWiTCH Study exploring the safety and effectiveness of switching patients following initial stroke from chronic transfusions to hydroxyurea.  The Center, through the work of Dr. Michael Dowling (former Sickle Cell Scholar and Pediatric Neurologist) is also participating in several multi-center collaborative studies involving stroke in which children with sickle cell disease are enrolled.  

Local investigator initiated research projects currently involve studying the relationship between acute chest syndrome and both chronic pulmonary disease and pulmonary hypertension, priapism, blood transfusion practices, etiopathogenesis of stroke (role of patent foremen ovale and causes of silent stroke), and identification of early risk predictors of later adverse outcomes.  All of these studies employ the Center’s sickle cell database and involve study of the Dallas Newborn Cohort, the world’s largest inception cohort of patients with sickle cell disease diagnosed by newborn screening.  A dedicated staff of clinical research associates and research nurses provide invaluable support to the physician investigators in the conduct of these and other studies. 

Basic Research:

Basic laboratory research conducted in the Center is carried out at UT Southwestern  and the University of Texas at Dallas (UTD).  Dr. Victor Garcia-Martinez at UT Southwestern (and his colleague Dr. James Ellis at the University of Toronto) and Dr. Steven Goodman  at UTD receive direct support from the Center grant for their research.  Drs. Garcia and Ellis are studying novel approaches to gene therapy in sickle cell disease by means of stem cell manipulation, and Dr. Goodman is investigating red blood cell membrane alterations and proteomic profiles in sickle cell disease.  Two other Center investigators, who arrived in Dallas after submission of the successful grant in September 2001, are also engaged in peer-reviewed laboratory research:  Dr. Matthew Porteus  of UT Southwestern is exploring gene therapy using the novel approach of homologous recombination – i.e., “excising” a small portion of the abnormal gene and replacing it with a normal DNA segment.  Dr. Betty Pace  at UTD is studying single nucleotide polymorphisms in the beta globin gene complex that might modulate clinical severity of SCD.  Each of these laboratory research groups has benefited from close collaboration with the clinical SCD program, including acquisition of blood specimens from willing patients as part of IRB-approved protocols.

Education:

Education is a major priority of the Center.  First year medical students receive during the initial weeks of class a clinical correlation of lecture on sickle cell disease that includes a presentation by a patient.  Opportunities for special electives in clinical research (including summer internship experiences) are available for high school, undergraduate, and medical students desiring exposure to sickle cell disease.  Education is also directed to pediatric residents and hematology-oncology fellows in a number of venues.  Sickle cell disease is regularly covered in noon conferences, morning report, daily rounds, and periodic special seminars and lectureships.  Education of the referring medical community is assured by means of regular contact with primary physicians following patient encounters, distribution of management guidelines, and presentations on sickle cell disease at the annual Pediatric Hematology-Oncology CME Course each October.  In addition, the Dr. George R. Buchanan, Center Director, and other Center staff, regularly give Grand Rounds and other presentations regarding sickle cell disease at other sites around the country during visiting professorships. 

Advocacy:

The Southwestern Comprehensive Sickle Cell Center takes seriously its role as a vehicle for community education and advocacy with the aim of achieving increased funding for patient care and research and promoting the visibility of sickle cell disease in the community at large.  Community Relations Manager, Shirley Miller, who has been a leader in the local and national Sickle Cell Disease Association of America organizations, plays a key role in this endeavor.  Ms. Miller, among other things, currently serves as a liaison with the Sickle Cell Disease Association’s Dallas chapter, spearheads efforts to maintain the Center’s high profile at UT Southwestern and its affiliated hospitals, and works tirelessly to see that Center activities and accomplishments are heralded in local media.  She has written numerous articles and has been interviewed on countless occasions explaining what sickle cell disease is, how it impacts patients, and the importance of our Center as a resource for patient care and education.  She also oversees the Center’s East Texas Outreach Project, spearheads publication of a regular center newsletter, and organizes support groups. 

Support and advocacy functions are also undertaken by many other Center personnel, including social workers, nurses, and research staff.  These activities include Camp Jubilee, a week long summer camp for children with sickle cell disease who are followed in our Center and in the nearby Fort Worth pediatric program.  Camp Jubilee is held each July at Camp John Marc, 90 miles southwest of Dallas.  It is funded through by foundations, corporations, and private donors.  Over 120 children attend each summer.  The Center also supports a fall teen weekend camping experience at Camp John Marc. Other Center activities related to advocacy include a liaison with Carter Blood Care, the regional blood center, aimed at increasing the number of African American donors.

Future Plans:

The Southwestern Comprehensive Sickle Cell Center intends to apply for and hopefully receive continued NHLBI funding to serve during 2008-2013 as a Center of Excellence in for patients and their health care provides throughout the mid-south and southwest.  The Center’s various programs will continue to expand in size and scope, with particular focus on further engagement in local and multi-center clinical trials, fundamental research discovery, and translation of research advances to document their effectiveness for patients and their families.

Sickle Cell-Related Publications from the Center's Funded Investigators
2000-Present:

Mantadakis E, Ewalt DH, Cavender JD, Rogers ZR, Buchanan, G:  Outpatient penile aspiration and epinephrine irrigation for young patients with sickle cell anemia and prolonged priapism.   Blood 2000; 95:78-82.

Walters MC, Storb R, Patience M, Leisenring W, Taylor T, Sanders JE, Buchanan GR, Rogers ZR, Dinndorf P, Davies SC, Roberts IAG, Dickerhoff R, Yeager AM, Hsu L, Kurtzberg J, Ohene-Frempong K, Bunin N, Bernaudin F, Wong W-Y, Scott JP, Margolis D, Vichinsky E, Wall DA, Wayne AS, Pegelow C, Redding-Lallinger R, Wiley J, Klemperer M, Mentzer WC, Smith FO, Sullivan KM for the Multicenter Investigation of Bone Marrow Transplantation for Sickle Cell Disease.  Impact of bone marrow transplantation for symptomatic sickle cell disease: an interim report.  Blood 2000; 95:1918-1924.

Walters MC, Patience M, Leisenring W, Rogers ZR, Aquino V, Buchanan GR, Roberts IAG, Yeager AM, Hsu L, Adamkiewicz T, Kurtzberg J, Vichinsky E, Storer B, Storb R, Sullivan Km for the Multicenter Investigation of Bone Marrow Transplantation for Sickle Cell Anemia.  Stable mixed hematopoietic chimerism  after bone marrow transplantation for sickle cell anemia. Biology of Blood and Marrow Transplantation 2001; 7:665-673.

Scothorn DJ, Price C, Schwartz D, Terrill C, Buchanan GR, Shurney W, Sarniak I, Fallon R, Chu J-Y, Pegelow CH, Wang W, Casella JF, Resa LS, Berman B, Adamkiewicz T, Hsu LL, Ohene-Frempong K, Smith-Whitley K, Mahoney D, Scott JP, Woods GM, Watanabe M, DeBaun MR:  Risk of recurrent stroke in children with sickle cell disease receiving blood transfusion therapy for at least five years after initial stroke.  J Pediatr 2002; 140:348-54.

Quinn CT, Buchanan GR:  Predictors of outcome in sickle cell disease.  J Pediatr Hematol Onc 2002; 24:244-245.

Lane PA, Buchanan GR, Desposito F, Pegelow CH, Vichinsky EP, Wethers DL, Woods GM:  Health supervision for children with sickle cell disease.  Pediatrics 2002; 109:526-535.

Adamkiewicz TV, Sarnaik S, Buchanan GR, Iyer RV, Miller ST, Pegelow CH, Rogers ZR, Vichinsky E, Elliott J, Facklam RR, O’Brien KL, Schwartz B, Van Beneden CA, Cannon MJ, Eckman JR, Keyserling H, Sullivan K, Wong WY, Wang WC.  Invasive pneumococcal infections in children with sickle cell disease in the era of penicillin prophylaxis, antibiotic resistance and 23-valent pneumococcal polysaccharide vaccination.  J Pediatr 2003; 143:438-44.

Assanasen C, Quinton RA, Buchanan GR.  Acute myocardial infarction in sickle cell anemia.  J Pediatr Hematol Oncol 2003; 25:9778-982.

Quinn CT, Rogers ZR, Buchanan GR: Survival of children with sickle cell disease.  Blood 2004; 13:4023-4027.

Rogers ZR and Buchanan GR.  Expanding the role of hydroxyurea in children with sickle cell disease. J Pediatr 2004; 145:287-288.

Buchanan GR, DeBaun MR, Quinn CT, Steinberg MH. Sickle cell disease. Hematology 2004; 35-47

Ghatpande, S.S, and Goodman, S.R. Effect of Spectrin Ubiquitination on the Dissociation of the Spectrin-Protein 4.1-Actin Ternary Complex in Erythrocytes. Cellular and Molecular Biology, 2004; 50:67-74.

Mishra, R. and Goodman, S.R. Ubiquitination of Spectrin Regulates the Dissociation of the Spectrin-Adducin-F-Actin Ternary Complex In Vitro.Cellular and Molecular Biology, 2004; 50:75-80.

Kakhniashvili, D.G., Bulla, L.E.and Goodman, S.R.The Human Erythrocyte Proteome: Analysis by Ion Trap Tandem Mass Spectrometry.  Molecular and Cellular Proteomics, 2004;  Volume Three; 501-509.

Quinn CT, Miller ST.  Risk Factors and Prediction of Outcomes in Children and Adolescents with Sickle Cell Anemia.  Hematol Oncol Clin N Am, 2004; 18: 1339-54.

Quinn CT, Rogers ZR, Buchanan GR.  Survival of Children with Sickle Cell Disease.  Blood, 2004; 103: 4023-4027.

Hankins JS, Ware RE, Rogers ZR, Wynn LW, Lane PA, Scott JP, Wang WC.  Long-term hydroxyurea therapy for infants with sickle cell anemia – the HUSOFT extension study.  Blood,  2005; 106: 2269-2275.

Buchanan GR.  Blood transfusions in children with cancer and hematologic disorders: Why, when, and how?  Pediatr Blood Cancer 2005;44:114-116.

Riahi, M.H., Kakhniashvili, D.G., and Goodman, S.R. Ubiquitination of Red Blood Cell α-Spectrin Does Not Effect Heterodimer Formation. Am. J. Hematol., 2005; 78: 281-287.

Chang, T.L., Kakhniashvili, D.G, and Goodman, S.R. Spectrin’s E2/E3 Ubiquitin Conjugating/Ligating Activity is Diminished in Sickle Cells. Am. J. Hematol, 2005; 79:89-96.

Kakhniashvili, D.G. Griko, N.B., Bulla Jr.,L.A. and S. R. Goodman.  The Proteomics of Sickle Cell Disease: Profiling of Erythrocyte Membrane Proteins by 2D-DIGE and Tandem Mass Spectrometry. Exper. Biol. Med. 2005; 230: 787-792.

Fu T, Corrigan NJ, Quinn CT, Roger ZR, Buchanan GR.  Minor Elective Surgical Procedures Using General Anesthesia in Children with Sickle Cell Anemia Without Pre-Operative Blood Transfusion.  Pediatr Blood Cancer, 2005; 45: 43-7.

Quinn CT, Ahmad N.  Clinical Correlates of Steady-State Oxhaemoglobin Desaturation in Children Who Have Sickle Cell Disease.  Br J Haematol, 2005; 131: 129-34.

Hulbert, ML, Scothorn DJ, Panepinto JA, Scott JP, Buchanan GR, Sarnaik S, Fallon R, Chu J, Wang W, Casella JF, Resar L, Berman B, Adamkiewicz T, Hsu LL, Smith-Whitley K, Mahoney D, Woods G, Watanabe M DeBaun MR. Exchange blood transfusion for first overt stroke is associated with a lower risk of subsequent stroke than simple transfusion: a retrospective cohort of 137 children with sickle cell disease. J Pediatr 2006; 149: 710-2.

Quinn CT, Shull EP, Ahmad N, Lee NJ, Rogers ZR, and Buchanan GR.  Prognostic significance of early vaso-occlusive complications in children with sickle cell anemia. Blood 2006; 109: 40-5.

Chou, J. Choudhary, P.K., and Goodman, S.R. Protein Profiling of Sickle Cell Versus Control RBC Core Membrane Skeletons by ICAT Technology and Tandem Mass Spectrometry. Cell Mol. Biol. Lett. 2006; 11: 326-337.