Sickle cell disease and other hemoglobinopathies; red blood cell physiology; cation transport and volume regulation; hematological problems of the newborn

Hammill AM, Risinger MA, Joiner CH, Keddache M, Kalfa TA. Compound heterozygosity for two novel mutations in the erythrocyte protein 4.2 gene causing spherocytosis in a Caucasian patient. Br J Haematol. 2011 Jan 31.

Yang MQ, Laflamme K, Gotea V, Joiner CH, Seidel NE, Wong C, Petrykowska HM, Lichtenberg J, Lee S, Welch L, Gallagher PG, Bodine DM, Elnitski L. Genome-wide detection of a TFIID localization element from an initial human disease mutation.Nucleic Acids Res. 2010 Nov 11.

George A, Pushkaran S, Li L, An X, Zheng Y, Mohandas N, Joiner CH, Kalfa TA. Altered phosphorylation of cytoskeleton proteins in sickle red blood cells: the role of protein kinase C, Rac GTPases, and reactive oxygen species. Blood Cells Mol Dis. 2010 Jun 15;45(1):41-5.

Rayburg M, Kalinyak KA, Towbin AJ, Baker PB, Joiner CH. Fatal bone marrow embolism in a child with hemoglobin SE disease.Am J Hematol. 2010 Mar;85(3):182-4.

Barber LA, Palascak MB, Joiner CH, Franco RS. Aminophospholipid translocase and phospholipid scramblase activities in sickle erythrocyte subpopulations. Br J Haematol. 2009 Aug;146(4):447-55.

Cohen RM, Franco RS, Khera PK, Smith EP, Lindsell CJ, Ciraolo PJ, Palascak MB, Joiner CH. Red cell life span heterogeneity in hematologically normal people is sufficient to alter HbA1c. Blood. 2008 Nov 15;112(10):4284-91.

Khera PK, Joiner CH, Carruthers A, Lindsell CJ, Smith EP, Franco RS, Holmes YR, Cohen RM. Evidence for interindividual heterogeneity in the glucose gradient across the human red blood cell membrane and its relationship to hemoglobin glycation.Diabetes. 2008 Sep;57(9):2445-52.

Joiner CH. Gardos pathway to sickle cell therapies? Blood. 2008 Apr 15;111(8):3918-9.

Lindsell CJ, Franco RS, Smith EP, Joiner CH, Cohen RM. A method for the continuous calculation of the age of labeled red blood cells.Am J Hematol. 2008 Jun;83(6):454-7. Erratum in: Am J Hematol. 2008 Jul;83(7):608.

Roszell NJ, Danton MJ, Jiang M, Witte D, Daugherty C, Grimes T, Girdler B, Anderson KP, Franco RS, Degen JL, Joiner CH. Fibrinogen deficiency, but not plasminogen deficiency, increases mortality synergistically in combination with sickle hemoglobin SAD in transgenic mice.Am J Hematol. 2007 Dec;82(12):1044-8.

Coagulation; hemophilia; thrombosis

Gruppo RA. Treatment of hemophilia in developing countries: a journey of a thousand miles. Pediatr Blood Cancer. 2010 Mar;54(3):348-9. No abstract available

Gelfand MJ, Gruppo RA, Nasser MP. Ventilation-perfusion scintigraphy in children and adolescents is associated with a low rate of indeterminate studies. Clin Nucl Med. 2008 Sep;33(9):606-9.

Wu SW, Graham B, Gelfand MJ, Gruppo RE, Dinopolous A, Gilbert DL. Clinical and positron emission tomography findings of chorea associated with primary antiphospholipid antibody syndrome. Mov Disord. 2007 Sep 15;22(12):1813-5.

Balasa VV, Gruppo RA, Glueck CJ, Wang P, Roy DR, Wall EJ, Mehlman CT, Crawford AH. Legg-Calve-Perthes disease and thrombophilia. J Bone Joint Surg Am. 2004 Dec;86-A(12):2642-7.

Gruppo RA, Brown D, Wilkes MM, Navickis RJ. Increased breakthrough bleeding during prophylaxis with B-domain deleted factor VIII--a robust meta-analytic finding. Haemophilia. 2004 Sep;10(5):449-51.

Morrison JA, Gruppo R, Glueck CJ, Stroop D, Fontaine RN, Wang P, Smith KL. Population-specific alleles: the polymorphism (K121Q) of the human glycoprotein PC-1 gene is strongly associated with race but not with insulin resistance in black and white children. Metabolism. 2004 Apr;53(4):465-8.

Gruppo RA, Brown D, Wilkes MM, Navickis RJ. Comparative effectiveness of full-length and B-domain deleted factor VIII for prophylaxis--a meta-analysis. Haemophilia. 2003 May;9(3):251-60. Review.

Balasa VV, Kalinyak KA, Bean JA, Stroop D, Gruppo RA. Hyperhomocysteinemia is associated with low plasma pyridoxine levels in children with sickle cell disease. J Pediatr Hematol Oncol. 2002 Jun-Jul;24(5):374-9.

McNamara JL, Lombardi JP, Ferguson R, Manning PB, Gruppo RA. Alternative methods for anticoagulation monitoring in pediatric patients with applicability to a patient with severe hemophilia A and circulating inhibitor. J Extra Corpor Technol. 2001 Dec;33(4):239-42.

Gruppo R, Degrauw A, Fogelson H, Glauser T, Balasa V, Gartside P. Protein C deficiency related to valproic acid therapy: a possible association with childhood stroke. J Pediatr. 2000 Nov;137(5):714-8.

Signaling in erythrocytes; erythropoiesis; Sickle Cell disease; endothelial cell biology

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Hammill AM, Risinger MA, Joiner CH, Keddache M, Kalfa TA. Compound heterozygosity for two novel mutations in the erythrocyte protein 4.2 gene causing spherocytosis in a Caucasian patient. Br J Haematol. 2011 Jan 31.

Kalfa TA. Anchoring at an island to relieve stress. Blood. 2011 Jan 20;117(3):748-9.

Mizukawa B, George A, Pushkaran S, Weckbach L, Kalinyak K, Heubi JE, Kalfa TA. Cooperating G6PD mutations associated with severe neonatal hyperbilirubinemia and cholestasis.Pediatr Blood Cancer. 2010 Oct 14.

Konstantinidis DG, George A, Kalfa TA. Rac GTPases in erythroid biology. Transfus Clin Biol. 2010 Sep;17(3):126-30.

George A, Pushkaran S, Li L, An X, Zheng Y, Mohandas N, Joiner CH, Kalfa TA. Altered phosphorylation of cytoskeleton proteins in sickle red blood cells: the role of protein kinase C, Rac GTPases, and reactive oxygen species. Blood Cells Mol Dis. 2010 Jun 15;45(1):41-5.

Kalfa TA, Pushkaran S, Zhang X, Johnson JF, Pan D, Daria D, Geiger H, Cancelas JA, Williams DA, Zheng Y. Rac1 and Rac2 GTPases are necessary for early erythropoietic expansion in the bone marrow but not in the spleen.Haematologica. 2010 Jan;95(1):27-35.

Mulloy JC, Cancelas JA, Filippi MD, Kalfa TA, Guo F, Zheng Y. Rho GTPases in hematopoiesis and hemopathies. Blood. 2010 Feb 4;115(5):936-47.

Wang D, Zhang W, Kalfa TA, Grabowski G, Davies S, Malik P, Pan D. Reprogramming erythroid cells for lysosomal enzyme production leads to visceral and CNS cross-correction in mice with Hurler syndrome.Proc Natl Acad Sci U S A. 2009 Nov 24;106(47):19958-63.

Diwan A, Koesters AG, Capella D, Geiger H, Kalfa TA, Dorn GW 2nd. Targeting erythroblast-specific apoptosis in experimental anemia. Apoptosis. 2008 Aug;13(8):1022-30.

Daria D, Filippi MD, Knudsen ES, Faccio R, Li Z, Kalfa T, Geiger H. The retinoblastoma tumor suppressor is a critical intrinsic regulator for hematopoietic stem and progenitor cells under stress. Blood. 2008 Feb 15;111(4):1894-902.

Diwan A, Koesters AG, Odley AM, Pushkaran S, Baines CP, Spike BT, Daria D, Jegga AG, Geiger H, Aronow BJ, Molkentin JD, Macleod KF, Kalfa TA, Dorn GW. Unrestrained erythroblast development in Nix-/- mice reveals a mechanism for apoptotic modulation of erythropoiesis. Proc Natl Acad Sci U S A. 2007 Apr 17;104(16):6794-9.

Kalfa TA, Pushkaran S, Mohandas N, Hartwig JH, Fowler VM, Johnson JF, Joiner CH, Williams DA, Zheng Y. Rac GTPases regulate the morphology and deformability of the erythrocyte cytoskeleton. Blood. 2006 Dec 1;108(12):3637-45.

Hematology; bone marrow failure; sickle cell anemia; hemoglobinopathy

Wang W, Brugnara C, Snyder C, Wynn L, Rogers Z, Kalinyak K, Brown C, Qureshi A, Bigelow C, Neumayr L, Smith-Whitley K, Chui DH, Delahunty M, Woolson R, Steinberg M, Telen M, Kesler K. The effects of hydroxycarbamide and magnesium on haemoglobin SC disease: results of the multi-centre CHAMPS trial.Br J Haematol. 2011 Jan 31.

Mizukawa B, George A, Pushkaran S, Weckbach L, Kalinyak K, Heubi JE, Kalfa TA. Cooperating G6PD mutations associated with severe neonatal hyperbilirubinemia and cholestasis.Pediatr Blood Cancer. 2010 Oct 14.

Rayburg M, Kalinyak KA, Towbin AJ, Baker PB, Joiner CH. Fatal bone marrow embolism in a child with hemoglobin SE disease.Am J Hematol. 2010 Mar;85(3):182-4.

Crosby LE, Modi AC, Lemanek KL, Guilfoyle SM, Kalinyak KA, Mitchell MJ. Perceived barriers to clinic appointments for adolescents with sickle cell disease. J Pediatr Hematol Oncol. 2009 Aug;31(8):571-6.

Grueneich R, Ris MD, Ball W, Kalinyak KA, Noll R, Vannatta K, Wells R. Relationship of structural magnetic resonance imaging, magnetic resonance perfusion, and other disease factors to neuropsychological outcome in sickle cell disease.J Pediatr Psychol. 2004 Mar;29(2):83-92.

Koontz K, Short AD, Kalinyak K, Noll RB. A randomized, controlled pilot trial of a school intervention for children with sickle cell anemia.J Pediatr Psychol. 2004 Jan-Feb;29(1):7-17.

Balasa VV, Kalinyak KA, Bean JA, Stroop D, Gruppo RA. Hyperhomocysteinemia is associated with low plasma pyridoxine levels in children with sickle cell disease.J Pediatr Hematol Oncol. 2002 Jun-Jul;24(5):374-9.

Graumlich SE, Powers SW, Byars KC, Schwarber LA, Mitchell MJ, Kalinyak KA. Multidimensional assessment of pain in pediatric sickle cell disease. J Pediatr Psychol. 2001 Jun;26(4):203-14.

Noll RB, Stith L, Gartstein MA, Ris MD, Grueneich R, Vannatta K, Kalinyak K. Neuropsychological functioning of youths with sickle cell disease: comparison with non-chronically ill peers.J Pediatr Psychol. 2001 Mar;26(2):69-78.

Balasa VV, Gruppo RA, Gartside PS, Kalinyak KA. Correlation of the C677T MTHFR genotype with homocysteine levels in children with sickle cell disease.J Pediatr Hematol Oncol. 1999 Sep-Oct;21(5):397-400.

Interactions between the hemostatic system and innate immunity effecting tumor progression; Langerhans' cell hystiocytosis

Horowitz NA, Blevins EA, Miller WM, Perry AR, Talmage KE, Mullins ES, Flick MJ, Queiroz KC, Shi K, Spek CA, Conway EM, Monia BP, Weiler H, Degen JL, Palumbo JS. Thrombomodulin is a determinant of metastasis through a mechanism linked to the thrombin binding domain but not the lectin-like domain. Blood. 2011 Jul 25.

Flick MJ, Chauhan AK, Frederick M, Talmage KE, Kombrinck KW, Miller W, Mullins ES, Palumbo JS, Zheng X, Esmon NL, Esmon CT, Thornton S, Becker A, Pelc LA, Di Cera E, Wagner DD, Degen JL. The development of inflammatory joint disease is attenuated in mice expressing the anticoagulant prothrombin mutant W215A/E217A. Blood. 2011 Jun 9;117(23):6326-37.

Akunuru S, Palumbo J, Zhai QJ, Zheng Y. Rac1 targeting suppresses human non-small cell lung adenocarcinoma cancer stem cell activity. PLoS One. 2011 Feb 9;6(2):e16951.

Palumbo JS, Degen JL. Mechanisms coupling the hemostatic system to colitis-associated cancer. Thromb Res. 2010 Apr;125 Suppl 2:S39-43. Review.

Steinbrecher KA, Horowitz NA, Blevins EA, Barney KA, Shaw MA, Harmel-Laws E, Finkelman FD, Flick MJ, Pinkerton MD, Talmage KE, Kombrinck KW, Witte DP, Palumbo JS. Colitis-associated cancer is dependent on the interplay between the hemostatic and inflammatory systems and supported by integrin alpha(M)beta(2) engagement of fibrinogen.Cancer Res. 2010 Apr 1;70(7):2634-43.

Palumbo JS. Mechanisms linking tumor cell-associated procoagulant function to tumor dissemination.Semin Thromb Hemost. 2008 Mar;34(2):154-60. Review.

Palumbo JS, Barney KA, Blevins EA, Shaw MA, Mishra A, Flick MJ, Kombrinck KW, Talmage KE, Souri M, Ichinose A, Degen JL. Factor XIII transglutaminase supports hematogenous tumor cell metastasis through a mechanism dependent on natural killer cell function.J Thromb Haemost. 2008 May;6(5):812-9.

Palumbo JS, Degen JL. Mechanisms linking tumor cell-associated procoagulant function to tumor metastasis.Thromb Res. 2007;120 Suppl 2:S22-8.

Flick MJ, LaJeunesse CM, Talmage KE, Witte DP, Palumbo JS, Pinkerton MD, Thornton S, Degen JL. Fibrin(ogen) exacerbates inflammatory joint disease through a mechanism linked to the integrin alphaMbeta2 binding motif.J Clin Invest. 2007 Nov;117(11):3224-35.

Palumbo JS, Talmage KE, Massari JV, La Jeunesse CM, Flick MJ, Kombrinck KW, Hu Z, Barney KA, Degen JL. Tumor cell-associated tissue factor and circulating hemostatic factors cooperate to increase metastatic potential through natural killer cell-dependent and-independent mechanisms.Blood. 2007 Jul 1;110(1):133-41.

Clinical Interests

Sickle cell disease; thalassemia; hemoglobinopathies; disorders of red blood cells; iron overload and iron chelation; chronic transfusion therapy

Research Interests

Novel causes of sickle cell pain; Role of hemoglobin desaturation in the pathogenesis of sickle cell disease; Survival and long-term follow-up of sickle cell disease; Causes and treatment of stroke in sickle cell disease

MD:  University of Texas Southwestern Medical Center, Dallas, TX, 1994.

MS:  University of Texas Southwestern Medical Center, Dallas, TX, 2008.

Residency & Chief Residency:  Children's Medical Center Dallas, Dallas, TX; University of Texas Southwestern Medical Center, Dallas, TX, 1998.

Fellowship:  Children's Medical Center Dallas, Dallas, TX; University of Texas Southwestern Medical Center, Dallas, TX, 2001.

Certifications:  Pediatrics, 1998; Pediatric Hematology-Oncology, 2002.

Quinn CT, Johnson VL, Kim HY, Trachtenberg F, Vogiatzi MG, Kwiatkowski JL, Neufeld EJ, Fung E, Oliveri N, Kirby M, Giardina PJ; for the Thalassemia Clinical Research Network. Renal dysfunction in patients with thalassaemia. Br J Haematol. 2011 Feb 21. doi: 10.1111/j.1365-2141.2010.08477.x.

McCavit TL, Quinn CT, Techasaensiri C, Rogers ZR. Increase in Invasive Streptococcus Pneumoniae Infections in Children with Sickle Cell Disease since Pneumococcal Conjugate Vaccine Licensure. J Pediatr. 2011 Mar;158(3):505-7.

Sobota A, Yamashita R, Xu Y, Trachtenberg F, Kohlbry P, Kleinert DA, Giardina PJ, Kwiatkowski JL, Foote D, Thayalasuthan V, Porter JB, Thompson AA, Schilling L, Quinn CT, Neufeld EJ; Thalassemia Clinical Research Network. Quality of life in thalassemia: a comparison of SF-36 results from the thalassemia longitudinal cohort to reported literature and the US norms. Am J Hematol. 2011 Jan;86(1):92-5.

Mednick L, Yu S, Trachtenberg F, Xu Y, Kleinert DA, Giardina PJ, Kwiatkowski JL, Foote D, Thayalasuthan V, Porter JB, Thompson AA, Schilling L, Quinn CT, Neufeld EJ, Yamashita R; Thalassemia Clinical Research Network. Symptoms of depression and anxiety in patients with thalassemia: prevalence and correlates in the thalassemia longitudinal cohort. Am J Hematol. 2010 Oct;85(10):802-5.

Jordan LC, McKinstry RC 3rd, Kraut MA, Ball WS, Vendt BA, Casella JF, DeBaun MR, Strouse JJ; Silent Infarct Transfusion Trial Investigators. Incidental findings on brain magnetic resonance imaging of children with sickle cell disease. Pediatrics. 2010 Jul;126(1):53-61.

Fung EB, Xu Y, Kwiatkowski JL, Vogiatzi MG, Neufeld E, Olivieri N, Vichinsky EP, Giardina PJ; Thalassemia Clinical Research Network. Relationship between chronic transfusion therapy and body composition in subjects with thalassemia. J Pediatr. 2010 Oct;157(4):641-7, 647.e1-2.

Quinn CT, Rogers ZR, McCavit TL, Buchanan GR. Improved survival of children and adolescents with sickle cell disease. Blood. 2010 Apr 29;115(17):3447-52.

Dowling MM, Lee N, Quinn CT, Rogers ZR, Boger D, Ahmad N, Ramaciotti C, Buchanan GR. Prevalence of intracardiac shunting in children with sickle cell disease and stroke. J Pediatr. 2010 Apr;156(4):645-50.

Ghatpande SS, Choudhary PK, Quinn CT, Goodman SR. In vivo pharmaco-proteomic analysis of hydroxyurea induced changes in the sickle red blood cell membrane proteome. J Proteomics. 2010 Jan 3;73(3):619-26.

Dowling MM, Quinn CT, Rogers ZR, Buchanan GR. Acute silent cerebral infarction in children with sickle cell anemia. Pediatr Blood Cancer. 2010 Mar;54(3):461-4.

MD: Stanford University School of Medicine, Stanford, CA, 2003.

Residency: Yale-New Haven Hospital, New Haven, CT, 2006.

Fellowship: University of Texas Southwestern Medical Center Dallas, Dallas, TX, 2009.

Certification: Pediatrics, 2006.