Photo of David A. Williams, MD

David A. Williams, MD

Boston Children's Hospital

Boston Children's Hospital
Phone: (617) 919-2697
Fax: (617) 730-0934


DAWilliams@childrens.harvard.edu

Photo of David A. Williams, MD

Boston Children's Hospital
Phone: (617) 919-2697
Fax: (617) 730-0934


DAWilliams@childrens.harvard.edu

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David A. Williams, MD

Boston Children's Hospital

EDUCATIONAL TITLES

  • Leland Fikes Professor of Pediatrics, Pediatrics, Harvard Medical School
  • Chief, Hematology/Oncology, Boston Children's Hospital
  • Senior Vice President, Chief Scientific Officer, Boston Children's Hospital

DF/HCC PROGRAM AFFILIATION

Research Abstract

Primary Research Interest

The major interest of our laboratory is focused on the biology of hematopoietic stem cells. The work has focused on understanding the interaction of hematopoietic stem cells with the bone marrow and abnormalities of these interactions which are associated with leukemia. These basic studies contribute to our translational research focus that utilizes hematopoietic stem cells as a target for gene therapy manipulations.

Projects

Rho GTPases in normal hematopoiesis

The Rho family of small GTPases are members of the Ras superfamily. The best studied members of this family are Rac1, RhoA and Cdc42. In fibroblasts, Rho activation induces the assembly of filamentous (F)-actin and myosin filaments (stress fibers), while Rac and Cdc42 promote the formation of surface protrusions and ruffling (lamellipodia) and finger-like membrane extensions (filopodia) respectively, both actin containing structures. Using gene-targeted mice, we have shown that Rac plays a critical role in blood cell development and function. Rac activity has been demonstrated to be important for such diverse functions as retention in the bone marrow, long-term engraftment of hematopoietic stem cells and hematopoietic stem cell mobilization. Furthermore, in more committed hematopoietic cells Rac activity is associated with B–lymphocyte development and signaling, granulocyte chemotaxis and superoxide production, migration and degranulation of mast cells, and maturation of TRAP–positive, pro-osteoclasts into multi-nucleated osteoclasts.

Rho GTPases in leukemia

Activation of Rac has previously been shown in Bcr-abl+ chronic myelogenous leukemia (CML). We have utilized gene-targeted mice lacking Rac GTPases to show that Rac is critical for the development and evolution of the myeloproliferative disease associated with expression of the p210 Bcr-abl oncogene. These studies have led to the testing of a small molecule inhibitor of Rac developed by our colleague, Dr. Yi Zheng, on primary CML samples and in the mouse model. These studies are being done in collaboration with Dr. Jose Cancelas, Dr. Brian Druker and Dr. John Byrd. We are also studying the potential role of other GTPases in acute myeloid leukemia and chronic. These studies examine primary samples and leukemia cell lines and are specifically examining the role of Rac and another GTPase, called RhoH, in the leukemia cell phenotype. This work is being done in collaboration with Drs. Yi Gu and John Byrd.

Publications from Harvard Catalyst Profiles

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  • Aziz-Bose R, Margossian R, Ames BL, Moss K, Ehrhardt MJ, Armenian SH, Yock TI, Nekhlyudov L, Williams D, Hudson M, Nohria A, Kenney LB. Delphi Panel Consensus Recommendations for Screening and Managing Childhood Cancer Survivors at Risk for Cardiomyopathy. JACC CardioOncol 2022; 4:354-367. PubMed
  • Canovas Nunes S, De Vita S, Anighoro A, Autelitano F, Beaumont E, Klingbeil P, McGuinness M, Duvert B, Harris C, Yang L, Pokharel SP, Chen CW, Ermann M, Williams DA, Xu H. Validation of a small molecule inhibitor of PDE6D-RAS interaction with favorable anti-leukemic effects. Blood Cancer J 2022; 12:64. PubMed
  • Horiguchi H, Xu H, Duvert B, Ciuculescu F, Yao Q, Sinha A, McGuinness M, Harris C, Brendel C, Troeger A, Chiarle R, Williams DA. Deletion of murine leads to de-repression of via decreased KAISO levels and accelerates a malignancy phenotype in a murine model of lymphoma. 2022; 13:267-281. PubMed
  • Liggett LA, Cato LD, Weinstock JS, Zhang Y, Nouraie SM, Gladwin MT, Garrett ME, Ashley-Koch A, Telen MJ, Custer B, Kelly S, Dinardo CL, Sabino EC, Loureiro P, Carneiro-Proietti AB, Maximo C, , Reiner AP, Abecasis GR, Williams DA, Natarajan P, Bick AG, Sankaran VG. Clonal hematopoiesis in sickle cell disease. J Clin Invest 2022. PubMed
  • Renella R, Gagne K, Beauchamp E, Fogel J, Perlov A, Sola M, Schlaeger T, Hofmann I, Shimamura A, Ebert BL, Schmitz-Abe K, Markianos K, Murphy K, Sun L, Rockowitz S, Sliz P, Campagna DR, Springer TA, Bahl C, Agarwal S, Fleming MD, Williams DA. Congenital X-linked neutropenia with myelodysplasia and somatic tetraploidy due to a germline mutation in SEPT6. Am J Hematol 2021. PubMed
  • Pulsipher MA, Lehmann LE, Bertuch AA, Sasa G, Olson T, Nakano T, Gilio A, Burroughs LM, Lipton JM, Huang JN, Dickerson K, Bertaina A, Zhuang C, Malsch M, Fleming M, Weller E, Shimamura A, Williams DA. A study assessing the feasibility of randomization of pediatric and young adult patients between matched unrelated donor bone marrow transplantation and immune-suppressive therapy for newly diagnosed severe aplastic anemia: A joint pilot trial of the Nort Pediatr Blood Cancer 2020. PubMed
  • Kogler M, Tortola L, Negri GL, Leopoldi A, El-Naggar AM, Mereiter S, Gomez Diaz C, Nitsch R, Tortora D, Kavirayani AM, Gapp BV, Rao S, Uribesalgo I, Hoffmann D, Cikes D, Novatchkova M, Williams DA, Trent JM, Ikeda F, Daugaard M, Hagelkruys A, Sorensen PH, Penninger JM. HACE1 prevents lung carcinogenesis via inhibition of RAC-family GTPases. Cancer Res 2020. PubMed
  • Verboon JM, Mahmut D, Kim AR, Nakamura M, Abdulhay NJ, Nandakumar SK, Gupta N, Akie TE, Geddis AE, Manes B, Kapp ME, Hofmann I, Gabriel SB, Klein DE, Williams DA, Frangoul HA, Parkhurst SM, Crane GM, Cantor AB, Sankaran VG. Infantile Myelofibrosis and Myeloproliferation with CDC42 Dysfunction. J Clin Immunol 2020; 40:554-566. PubMed
  • Curran KJ, Margossian SP, Kernan NA, Silverman LB, Williams DA, Shukla N, Kobos R, Forlenza CJ, Steinherz P, Prockop S, Boulad F, Spitzer B, Cancio MI, Boelens JJ, Kung AL, Szenes V, Park JH, Sauter CS, Heller G, Wang X, Senechal B, O'Reilly RJ, Riviere I, Sadelain M, Brentjens RJ. Toxicity and response after CD19-specific CAR T-cell therapy in pediatric/young adult relapsed/refractory B-ALL. Blood 2019; 134:2361-2368. PubMed
  • Hu T, Chong Y, Lu S, McGuinness M, Williams DA, Cowell JK. RAC1/2 activation promotes FGFR1 driven leukemogenesis in stem cell leukemia/lymphoma syndrome. Haematologica 2019. PubMed
  • Rogers ZR, Nakano TA, Olson TS, Bertuch AA, Wang W, Gillio A, Coates TD, Chawla A, Castillo P, Kurre P, Gamper C, Bennett CM, Joshi S, Geddis AE, Boklan J, Nalepa G, Rothman JA, Huang JN, Kupfer GM, Cada M, Glader B, Walkovich KJ, Thompson AA, Hanna R, Vlachos A, Malsch M, Weller EA, Williams DA, Shimamura A. Immunosuppressive therapy for pediatric aplastic anemia: a North American Pediatric Aplastic Anemia Consortium study. Haematologica 2019. PubMed
  • Wu Y, Zeng J, Roscoe BP, Liu P, Yao Q, Lazzarotto CR, Clement K, Cole MA, Luk K, Baricordi C, Shen AH, Ren C, Esrick EB, Manis JP, Dorfman DM, Williams DA, Biffi A, Brugnara C, Biasco L, Brendel C, Pinello L, Tsai SQ, Wolfe SA, Bauer DE. Highly efficient therapeutic gene editing of human hematopoietic stem cells. Nat Med 2019. PubMed
  • Esrick EB, Manis JP, Daley H, Baricordi C, Trébéden-Negre H, Pierciey FJ, Armant M, Nikiforow S, Heeney MM, London WB, Biasco L, Asmal M, Williams DA, Biffi A. Successful hematopoietic stem cell mobilization and apheresis collection using plerixafor alone in sickle cell patients. Blood Adv 2018; 2:2505-2512. PubMed
  • Clarke EL, Connell AJ, Six E, Kadry NA, Abbas AA, Hwang Y, Everett JK, Hofstaedter CE, Marsh R, Armant M, Kelsen J, Notarangelo LD, Collman RG, Hacein-Bey-Abina S, Kohn DB, Cavazzana M, Fischer A, Williams DA, Pai SY, Bushman FD. T cell dynamics and response of the microbiota after gene therapy to treat X-linked severe combined immunodeficiency. Genome Med 2018; 10:70. PubMed
  • Park HH, Triboulet R, Bentler M, Guda S, Du P, Xu H, Gregory RI, Brendel C, Williams DA. DROSHA Knockout Leads to Enhancement of Viral Titers for Vectors Encoding miRNA-Adapted shRNAs. Mol Ther Nucleic Acids 2018; 12:591-599. PubMed
  • D'Cruz AA, Speir M, Bliss-Moreau M, Dietrich S, Wang S, Chen AA, Gavillet M, Al-Obeidi A, Lawlor KE, Vince JE, Kelliher MA, Hakem R, Pasparakis M, Williams DA, Ericsson M, Croker BA. The pseudokinase MLKL activates PAD4-dependent NET formation in necroptotic neutrophils. Sci Signal 2018. PubMed
  • Gavillet M, Martinod K, Renella R, Wagner DD, Williams DA. A key role for Rac and Pak signaling in neutrophil extracellular traps (NETs) formation defines a new potential therapeutic target. Am J Hematol 2018; 93:269-276. PubMed
  • De Vita S, Li Y, Harris CE, McGuinness MK, Ma C, Williams DA. The gp130 Cytokine IL-11 Regulates Engraftment of Vav1-/- Hematopoietic Stem and Progenitor Cells in Lethally Irradiated Recipients. Stem Cells 2017. PubMed
  • Alonso-Ferrero ME, van Til NP, Bartolovic K, Mata MF, Wagemaker G, Moulding D, Williams DA, Kinnon C, Waddington SN, Milsom MD, Howe SJ. Enhancement of mouse hematopoietic stem/progenitor cell function via transient gene delivery using integration-deficient lentiviral vectors. Exp Hematol 2017. PubMed
  • Mehta PA, Davies SM, Leemhuis T, Myers K, Kernan NA, Prockop SE, Scaradavou A, O'Reilly RJ, Williams DA, Lehmann L, Guinan E, Margolis D, Baker KS, Lane A, Boulad F. Radiation-free, alternative donor HCT for Fanconi anemia patients: results from a prospective multi-institutional study. Blood 2017. PubMed
  • Brendel C, Guda S, Renella R, Bauer DE, Canver MC, Kim YJ, Heeney MM, Klatt D, Fogel J, Milsom MD, Orkin SH, Gregory RI, Williams DA. Lineage-specific BCL11A knockdown circumvents toxicities and reverses sickle phenotype. J Clin Invest 2016; 126:3868-3878. PubMed
  • Mino A, Troeger A, Brendel C, Cantor A, Harris C, Ciuculescu MF, Williams DA. RhoH participates in a multi-protein complex with the zinc finger protein kaiso that regulates both cytoskeletal structures and chemokine-induced T cells. 2016. PubMed
  • Labenski V, Suerth JD, Barczak E, Heckl D, Levy C, Bernadin O, Charpentier E, Williams DA, Fehse B, Verhoeyen E, Schambach A. Alpharetroviral self-inactivating vectors produced by a superinfection-resistant stable packaging cell line allow genetic modification of primary human T lymphocytes. Biomaterials 2016; 97:97-109. PubMed
  • Altrock PM, Brendel C, Renella R, Orkin SH, Williams DA, Michor F. Mathematical modeling of erythrocyte chimerism informs genetic intervention strategies for sickle cell disease. Am J Hematol 2016. PubMed
  • Reddy PN, Radu M, Xu K, Wood J, Harris CE, Chernoff J, Williams DA. p21-activated kinase 2 regulates HSPC cytoskeleton, migration, and homing via CDC42 activation and interaction with β-Pix. Blood 2016; 127:1967-75. PubMed
  • Townsend EC, Murakami MA, Christodoulou A, Christie AL, Köster J, DeSouza TA, Morgan EA, Kallgren SP, Liu H, Wu SC, Plana O, Montero J, Stevenson KE, Rao P, Vadhi R, Andreeff M, Armand P, Ballen KK, Barzaghi-Rinaudo P, Cahill S, Clark RA, Cooke VG, Davids MS, DeAngelo DJ, Dorfman DM, Eaton H, Ebert BL, Etchin J, Firestone B, Fisher DC, Freedman AS, Galinsky IA, Gao H, Garcia JS, Garnache-Ottou F, Graubert TA, Gutierrez A, Halilovic E, Harris MH, Herbert ZT, Horwitz SM, Inghirami G, Intlekoffer AM, Ito M, Izraeli S, Jacobsen ED, Jacobson CA, Jeay S, Jeremias I, Kelliher MA, Koch R, Konopleva M, Kopp N, Kornblau SM, Kung AL, Kupper TS, LaBoeuf N, LaCasce AS, Lees E, Li LS, Look AT, Murakami M, Muschen M, Neuberg D, Ng SY, Odejide OO, Orkin SH, Paquette RR, Place AE, Roderick JE, Ryan JA, Sallan SE, Shoji B, Silverman LB, Soiffer RJ, Steensma DP, Stegmaier K, Stone RM, Tamburini J, Thorner AR, van Hummelen P, Wadleigh M, Wiesmann M, Weng AP, Wuerthner JU, Williams DA, Wollison BM, Lane AA, Letai A, Bertagnolli MM, Ritz J, Brown M, Long H, Aster JC, Shipp MA, Griffin JD, Weinstock DM. The Public Repository of Xenografts Enables Discovery and Randomized Phase II-like Trials in Mice. Cancer Cell 2016; 29:574-86. PubMed
  • Gavillet M, Martinod K, Renella R, Harris C, Shapiro NI, Wagner DD, Williams DA. Flow cytometric assay for direct quantification of neutrophil extracellular traps in blood samples. Am J Hematol 2015. PubMed
  • Guda S, Brendel C, Renella R, Du P, Bauer DE, Canver MC, Grenier JK, Grimson AW, Kamran SC, Thornton J, de Boer H, Root DE, Milsom MD, Orkin SH, Gregory RI, Williams DA. miRNA-embedded shRNAs for Lineage-specific BCL11A Knockdown and Hemoglobin F Induction. Mol Ther 2015. PubMed
  • Ciuculescu MF, Park SY, Canty K, Mathieu R, Silberstein LE, Williams DA. Perivascular deletion of murine Rac reverses the ratio of marrow arterioles and sinusoid vessels and alters hematopoiesis in vivo. Blood 2015. PubMed
  • Alkhairy OK, Rezaei N, Graham RR, Abolhassani H, Borte S, Hultenby K, Wu C, Aghamohammadi A, Williams DA, Behrens TW, Hammarström L, Pan-Hammarström Q. RAC2 loss-of-function mutation in 2 siblings with characteristics of common variable immunodeficiency. J Allergy Clin Immunol 2015. PubMed
  • Walter D, Lier A, Geiselhart A, Thalheimer FB, Huntscha S, Sobotta MC, Moehrle B, Brocks D, Bayindir I, Kaschutnig P, Muedder K, Klein C, Jauch A, Schroeder T, Geiger H, Dick TP, Holland-Letz T, Schmezer P, Lane SW, Rieger MA, Essers MA, Williams DA, Trumpp A, Milsom MD. Exit from dormancy provokes DNA-damage-induced attrition in haematopoietic stem cells. Nature 2015. PubMed
  • Forester CM, Sartain SE, Guo D, Harris MH, Weinberg OK, Fleming MD, London WB, Williams DA, Hofmann I. Pediatric aplastic anemia and refractory cytopenia: A retrospective analysis assessing outcomes and histomorphologic predictors. Am J Hematol 2015; 90:320-6. PubMed
  • Zhang MY, Churpek JE, Keel SB, Walsh T, Lee MK, Loeb KR, Gulsuner S, Pritchard CC, Sanchez-Bonilla M, Delrow JJ, Basom RS, Forouhar M, Gyurkocza B, Schwartz BS, Neistadt B, Marquez R, Mariani CJ, Coats SA, Hofmann I, Lindsley RC, Williams DA, Abkowitz JL, Horwitz MS, King MC, Godley LA, Shimamura A. Germline ETV6 mutations in familial thrombocytopenia and hematologic malignancy. Nat Genet 2015; 47:180-5. PubMed
  • Zhang MY, Keel SB, Walsh T, Lee MK, Gulsuner S, Watts AC, Pritchard CC, Salipante SJ, Jeng MR, Hofmann I, Williams DA, Fleming MD, Abkowitz JL, King MC, Shimamura A. Genomic analysis of bone marrow failure and myelodysplastic syndromes reveals phenotypic and diagnostic complexity. Haematologica 2015. PubMed
  • Bruedigam C, Bagger FO, Heidel FH, Paine Kuhn C, Guignes S, Song A, Austin R, Vu T, Lee E, Riyat S, Moore AS, Lock RB, Bullinger L, Hill GR, Armstrong SA, Williams DA, Lane SW. Telomerase inhibition effectively targets mouse and human AML stem cells and delays relapse following chemotherapy. Cell Stem Cell 2014; 15:775-90. PubMed
  • Hacein-Bey-Abina S, Pai SY, Gaspar HB, Armant M, Berry CC, Blanche S, Bleesing J, Blondeau J, de Boer H, Buckland KF, Caccavelli L, Cros G, De Oliveira S, Fernández KS, Guo D, Harris CE, Hopkins G, Lehmann LE, Lim A, London WB, van der Loo JC, Malani N, Male F, Malik P, Marinovic MA, McNicol AM, Moshous D, Neven B, Oleastro M, Picard C, Ritz J, Rivat C, Schambach A, Shaw KL, Sherman EA, Silberstein LE, Six E, Touzot F, Tsytsykova A, Xu-Bayford J, Baum C, Bushman FD, Fischer A, Kohn DB, Filipovich AH, Notarangelo LD, Cavazzana M, Williams DA, Thrasher AJ. A modified γ-retrovirus vector for X-linked severe combined immunodeficiency. N Engl J Med 2014; 371:1407-17. PubMed
  • Brendel C, Williams DA. Unexpected help: mTOR meets lentiviral vectors. Blood 2014; 124:832-3. PubMed
  • Lane SW, Williams DA, Watt FM. Modulating the stem cell niche for tissue regeneration. Nat Biotechnol 2014; 32:795-803. PubMed
  • Keerthivasan G, Mei Y, Zhao B, Zhang L, Harris CE, Gao J, Basiorka AA, Schipma MJ, McElherne J, Yang J, Verma AK, Pellagatti A, Boultwood J, List AF, Williams DA, Ji P. Aberrant overexpression of CD14 on granulocytes sensitizes the innate immune response in mDia1 heterozygous del(5q) MDS. Blood 2014. PubMed
  • Kiem HP, Baum C, Bushman FD, Byrne BJ, Carter BJ, Cavagnaro J, Malech HL, Mendell JR, Naldini LM, Sorrentino BP, Williams DA, Flotte TR. Charting a clear path: the ASGCT Standardized Pathways Conference. Mol Ther 2014; 22:1235-8. PubMed
  • Williams DA, Bennett C, Bertuch A, Bessler M, Coates T, Corey S, Dror Y, Huang J, Lipton J, Olson TS, Reiss UM, Rogers ZR, Sieff C, Vlachos A, Walkovich K, Wang W, Shimamura A. Diagnosis and treatment of pediatric acquired aplastic anemia (AAA): an initial survey of the North American Pediatric Aplastic Anemia Consortium (NAPAAC). Pediatr Blood Cancer 2014; 61:869-74. PubMed
  • Williams DA, Thrasher AJ. Concise review: lessons learned from clinical trials of gene therapy in monogenic immunodeficiency diseases. Stem Cells Transl Med 2014. PubMed
  • De Vita S, Schneider RK, Garcia M, Wood J, Gavillet M, Ebert BL, Gerbaulet A, Roers A, Levine RL, Mullally A, Williams DA. Loss of function of TET2 cooperates with constitutively active KIT in murine and human models of mastocytosis. PLoS ONE 2014; 9:e96209. PubMed
  • Rose SR, Kim MO, Korbee L, Wilson KA, Ris MD, Eyal O, Sherafat-Kazemzadeh R, Bollepalli S, Harris R, Jeng MR, Williams DA, Smith FO. Oxandrolone for the treatment of bone marrow failure in Fanconi anemia. Pediatr Blood Cancer 2014; 61:11-9. PubMed
  • Troeger A, Chae HD, Senturk M, Wood J, Williams DA. A unique carboxyl-terminal insert domain in the hematopoietic-specific, GTPase-deficient Rho GTPase RhoH regulates post-translational processing. J Biol Chem 2013; 288:36451-62. PubMed
  • Williams DA. Broadening the indications for hematopoietic stem cell genetic therapies. Cell Stem Cell 2013; 13:263-4. PubMed
  • Mullally A, Bruedigam C, Poveromo L, Heidel FH, Purdon A, Vu T, Austin R, Heckl D, Breyfogle LJ, Kuhn CP, Kalaitzidis D, Armstrong SA, Williams DA, Hill GR, Ebert BL, Lane SW. Depletion of Jak2V617F myeloproliferative neoplasm-propagating stem cells by interferon-α in a murine model of polycythemia vera. Blood 2013; 121:3692-702. PubMed
  • Dorrance AM, De Vita S, Radu M, Reddy PN, McGuinness MK, Harris CE, Mathieu R, Lane SW, Kosoff R, Milsom MD, Chernoff J, Williams DA. The Rac GTPase effector p21-activated kinase is essential for hematopoietic stem/progenitor cell migration and engraftment. Blood 2013; 121:2474-82. PubMed
  • Williams DA, Mack J. Enough is indeed enough: ACGME required changes in pediatric training. Pediatr Blood Cancer 2012; 59:1158-9. PubMed
  • Hassett AL, Epel E, Clauw DJ, Harris RE, Harte SE, Kairys A, Buyske S, Williams DA. Pain is associated with short leukocyte telomere length in women with fibromyalgia. J Pain 2012; 13:959-69. PubMed
  • Crequer A, Troeger A, Patin E, Ma CS, Picard C, Pedergnana V, Fieschi C, Lim A, Abhyankar A, Gineau L, Mueller-Fleckenstein I, Schmidt M, Taieb A, Krueger J, Abel L, Tangye SG, Orth G, Williams DA, Casanova JL, Jouanguy E. Human RHOH deficiency causes T cell defects and susceptibility to EV-HPV infections. J Clin Invest 2012; 122:3239-47. PubMed
  • Müller LU, Schlaeger TM, DeVine AL, Williams DA. Induced pluripotent stem cells as a tool for gaining new insights into Fanconi anemia. Cell Cycle 2012; 11:2985-90. PubMed
  • Keller RB, Gagne KE, Usmani GN, Asdourian GK, Williams DA, Hofmann I, Agarwal S. CTC1 Mutations in a patient with dyskeratosis congenita. Pediatr Blood Cancer 2012; 59:311-4. PubMed
  • Chang KH, Sanchez-Aguilera A, Shen S, Sengupta A, Madhu MN, Ficker AM, Dunn SK, Kuenzi AM, Arnett JL, Santho RA, Agirre X, Perentesis JP, Deininger MW, Zheng Y, Bustelo XR, Williams DA, Cancelas JA. Vav3 collaborates with p190-BCR-ABL in lymphoid progenitor leukemogenesis, proliferation, and survival. Blood 2012; 120:800-11. PubMed
  • Williams DA, Thrasher AJ. Out of harm's way. Nat Biotechnol 2011; 29:41-2. PubMed
  • Williams DA, Thrasher AJ, Baum C. Transatlantic consortium spotlights need for changes in gene therapy trials. Mol Ther 2010; 18:1892. PubMed
  • Williams DA, Porter ES, Lux SE, Grier HE, Mack JW, Orkin SH. Training program in cancer and blood diseases: Pediatric Hematology/Oncology Fellowship Program, Children's Hospital Boston/Dana-Farber Cancer Institute. Am J Hematol 2010; 85:793-4. PubMed
  • Williams DA, Keating A. Enhancing research in regenerative medicine. Blood 2010; 116:866-7. PubMed
  • Milsom MD, Williams DA. Gaining the hard yard: pre-clinical evaluation of lentiviral-mediated gene therapy for the treatment of beta-thalassemia. EMBO Mol Med 2010; 2:291-3. PubMed
  • Sengupta A, Arnett J, Dunn S, Williams DA, Cancelas JA. Rac2 GTPase deficiency depletes BCR-ABL+ leukemic stem cells and progenitors in vivo. Blood 2010; 116:81-4. PubMed
  • Lane SW, Sykes SM, Al-Shahrour F, Shterental S, Paktinat M, Lo Celso C, Jesneck JL, Ebert BL, Williams DA, Gilliland DG. The Apcmin mouse has altered hematopoietic stem cell function and provides a model for MPD/MDS. Blood 2010; 115:3489-97. PubMed
  • Williams DA. The American Society of Pediatric Hematology/Oncology (ASPHO) 2010 Distinguished Career Award Goes to Dr. Sam Lux. Pediatr Blood Cancer 2010; 54:785-786. PubMed
  • Chen M, LeDuc B, Kerr S, Howe D, Williams DA. Identification of human UGT2B7 as the major isoform involved in the O-glucuronidation of chloramphenicol. Drug Metab Dispos 2010; 38:368-75. PubMed
  • Chae HD, Siefring JE, Hildeman DA, Gu Y, Williams DA. RhoH regulates subcellular localization of ZAP-70 and Lck in T cell receptor signaling. PLoS ONE 2010; 5:e13970. PubMed
  • 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; 95:27-35. PubMed
  • Xu H, Eleswarapu S, Geiger H, Szczur K, Daria D, Zheng Y, Settleman J, Srour EF, Williams DA, Filippi MD. Loss of the Rho GTPase activating protein p190-B enhances hematopoietic stem cell engraftment potential. Blood 2009; 114:3557-66. PubMed
  • Choy EH, Arnold LM, Clauw DJ, Crofford LJ, Glass JM, Simon LS, Martin SA, Strand CV, Williams DA, Mease PJ. Content and criterion validity of the preliminary core dataset for clinical trials in fibromyalgia syndrome. J Rheumatol 2009; 36:2330-4. PubMed
  • Mease P, Arnold LM, Choy EH, Clauw DJ, Crofford LJ, Glass JM, Martin SA, Morea J, Simon L, Strand CV, Williams DA, . Fibromyalgia syndrome module at OMERACT 9: domain construct. J Rheumatol 2009; 36:2318-29. PubMed
  • Williams DA. National Institutes of Health releases new guidelines on human stem cell research. Mol Ther 2009; 17:1485-6. PubMed
  • Adams BE, Reid CA, Myers D, Ng C, Powell K, Phillips AM, Zheng T, O'Brien TJ, Williams DA. Excitotoxic-mediated transcriptional decreases in HCN2 channel function increase network excitability in CA1. Exp Neurol 2009; 219:249-57. PubMed
  • Liu DS, O'Brien TJ, Williams DA, Hicks RJ, Myers DE. Lamina-specific changes in hippocampal GABA(A)/cBZR and mossy fibre sprouting during and following amygdala kindling in the rat. Neurobiol Dis 2009; 35:337-47. PubMed
  • Williams DA. Gene therapy continues to mature and to face challenges. Mol Ther 2009; 17:1305-6. PubMed
  • Müller LU, Williams DA. Finding the needle in the hay stack: Hematopoietic stem cells in Fanconi anemia. Mutat Res 2009; 668:141-149. PubMed
  • Singh TR,Bakker ST,Agarwal S,Jansen M,Grassman E,Godthelp BC,Ali AM,Du CH,Rooimans MA,Fan Q,Wahengbam K,Steltenpool J,Andreassen PR,Williams DA,Joenje H,de Winter JP,Meetei AR. Impaired FANCD2 monoubiquitination and hypersensitivity to camptothecin uniquely characterize Fanconi anemia complementation group M. Blood 2009; 114:174-80. PubMed
  • Cancelas JA,Williams DA. Rho GTPases in hematopoietic stem cell functions. Curr Opin Hematol 2009; 16:249-54. PubMed
  • Ali AM,Kirby M,Jansen M,Lach FP,Schulte J,Singh TR,Batish SD,Auerbach AD,Williams DA,Meetei AR. Identification and characterization of mutations in FANCL gene: A second case of Fanconi anemia belonging to FA-L complementation group. Hum Mutat 2009; 30:E761-70. PubMed
  • Muller LU,Daley GQ,Williams DA. Upping the ante: recent advances in direct reprogramming. Mol Ther 2009; 17:947-53. PubMed
  • Williams DA. Rapid development of pluripotent stem cells as a potential therapeutic modality. Mol Ther 2009; 17:929-30. PubMed
  • Milsom MD,Schiedlmeier B,Bailey J,Kim MO,Li D,Jansen M,Ali AM,Kirby M,Baum C,Fairbairn LJ,Williams DA. Ectopic HOXB4 overcomes the inhibitory effect of tumor necrosis factor-{alpha} on Fanconi anemia hematopoietic stem and progenitor cells. Blood 2009; 113:5111-20. PubMed
  • Williams DA. Recombinant DNA advisory committee updates recommendations on gene transfer for x-linked severe combined immunodeficiency. Mol Ther 2009; 17:751-2. PubMed
  • Williams DA. Progress in genetic therapy for severe combined immunodeficiency associated with adenosine deaminase deficiency. Mol Ther 2009; 17:577-8. PubMed
  • Monif M,Reid CA,Powell KL,Smart ML,Williams DA. The P2X7 receptor drives microglial activation and proliferation: a trophic role for P2X7R pore. J Neurosci 2009; 29:3781-91. PubMed
  • Williams DA. New approaches in the potential treatment of HIV-acquired immunodeficiency disease. Mol Ther 2009; 17:209-10. PubMed
  • Williams DA. ESCGT 2008: progress in clinical gene therapy. Mol Ther 2009; 17:1-2. PubMed
  • Gan B,Sahin E,Jiang S,Sanchez-Aguilera A,Scott KL,Chin L,Williams DA,Kwiatkowski DJ,DePinho RA. mTORC1-dependent and -independent regulation of stem cell renewal, differentiation, and mobilization. Proc Natl Acad Sci U S A 2008; 105:19384-9. PubMed
  • Powell KL,Ng C,O'Brien TJ,Xu SH,Williams DA,Foote SJ,Reid CA. Decreases in HCN mRNA expression in the hippocampus after kindling and status epilepticus in adult rats. Epilepsia 2008; 49:1686-95. PubMed
  • Yamada Y,Sanchez-Aguilera A,Brandt EB,McBride M,Al-Moamen NJ,Finkelman FD,Williams DA,Cancelas JA,Rothenberg ME. FIP1L1/PDGFRalpha synergizes with SCF to induce systemic mastocytosis in a murine model of chronic eosinophilic leukemia/hypereosinophilic syndrome. Blood 2008; 112:2500-7. PubMed
  • Guo F,Cancelas JA,Hildeman D,Williams DA,Zheng Y. Rac GTPase isoforms Rac1 and Rac2 play a redundant and crucial role in T-cell development. Blood 2008; 112:1767-75. PubMed
  • Zhang X,Shang X,Guo F,Murphy K,Kirby M,Kelly P,Reeves L,Smith FO,Williams DA,Zheng Y,Pang Q. Defective homing is associated with altered Cdc42 activity in cells from patients with Fanconi anemia group A. Blood 2008; 112:1683-6. PubMed
  • Williams DA. Sleeping beauty vector system moves toward human trials in the United States. Mol Ther 2008; 16:1515-6. PubMed
  • Milsom MD,Jerabek-Willemsen M,Harris CE,Schambach A,Broun E,Bailey J,Jansen M,Schleimer D,Nattamai K,Wilhelm J,Watson A,Geiger H,Margison GP,Moritz T,Baum C,Thomale J,Williams DA. Reciprocal relationship between O6-methylguanine-DNA methyltransferase P140K expression level and chemoprotection of hematopoietic stem cells. Cancer Res 2008; 68:6171-80. PubMed
  • Williams DA. Progress reported in two studies of clinical gene transfer into the retina. Mol Ther 2008; 16:1181. PubMed
  • Müller LU, Milsom MD, Kim MO, Schambach A, Schuesler T, Williams DA. Rapid Lentiviral Transduction Preserves the Engraftment Potential of Fanca(-/-) Hematopoietic Stem Cells. Mol Ther 2008; 16:1154-1160. PubMed
  • Muller LU,Milsom MD,Kim MO,Schambach A,Schuesler T,Williams DA. Rapid lentiviral transduction preserves the engraftment potential of Fanca(-/-) hematopoietic stem cells. Mol Ther 2008; 16:1154-60. PubMed
  • Wu X, Tu X, Joeng KS, Hilton MJ, Williams DA, Long F. Rac1 activation controls nuclear localization of beta-catenin during canonical Wnt signaling. Cell 2008; 133:340-53. PubMed
  • Ghiaur G, Ferkowicz MJ, Milsom MD, Bailey J, Witte D, Cancelas JA, Yoder MC, Williams DA. Rac1 is essential for intraembryonic hematopoiesis and for the initial seeding of fetal liver with definitive hematopoietic progenitor cells. Blood 2008; 111:3313-21. PubMed
  • Chae HD, Lee KE, Williams DA, Gu Y. Cross-talk between RhoH and Rac1 in regulation of actin cytoskeleton and chemotaxis of hematopoietic progenitor cells. Blood 2008; 111:2597-605. PubMed
  • Yang L, Wang L, Kalfa TA, Cancelas JA, Shang X, Pushkaran S, Mo J, Williams DA, Zheng Y. Cdc42 critically regulates the balance between myelopoiesis and erythropoiesis. Blood 2007; 110:3853-61. PubMed
  • Thomas EK, Cancelas JA, Chae HD, Cox AD, Keller PJ, Perrotti D, Neviani P, Druker BJ, Setchell KD, Zheng Y, Harris CE, Williams DA. Rac guanosine triphosphatases represent integrating molecular therapeutic targets for BCR-ABL-induced myeloproliferative disease. Cancer Cell 2007; 12:467-78. PubMed
  • Williams DA. AAV and Insertional Mutagenesis. Mol Ther 2007; 15:1737. PubMed
  • Milsom MD, Williams DA. Live and let die: in vivo selection of gene-modified hematopoietic stem cells via MGMT-mediated chemoprotection. DNA Repair (Amst) 2007; 6:1210-21. PubMed
  • Kelly PF, Radtke S, Kalle CV, Balcik B, Bohn K, Mueller R, Schuesler T, Haren M, Reeves L, Cancelas JA, Leemhuis T, Harris R, Auerbach AD, Smith FO, Davies SM, Williams DA. Stem Cell Collection and Gene Transfer in Fanconi Anemia. Mol Ther 2007; 15:211-219. PubMed
  • Kelly PF, Radtke S, Kalle C, Balcik B, Bohn K, Mueller R, Schuesler T, Haren M, Reeves L, Cancelas JA, Leemhuis T, Harris R, Auerbach AD, Smith FO, Davies SM, Williams DA. Stem cell collection and gene transfer in fanconi anemia. Mol Ther 2007; 15:211-9. PubMed
  • Debidda M, Williams DA, Zheng Y. Rac1 GTPase regulates cell genomic stability and senescence. J Biol Chem 2006; 281:38519-28. PubMed
  • Williams DA, Cancelas JA. Leukaemia: niche retreats for stem cells. Nature 2006; 444:827-8. PubMed
  • 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; 108:3637-45. PubMed
  • Gu Y, Chae HD, Siefring JE, Jasti AC, Hildeman DA, Williams DA. RhoH GTPase recruits and activates Zap70 required for T cell receptor signaling and thymocyte development. Nat Immunol 2006; 7:1182-90. PubMed
  • Ghiaur G, Lee A, Bailey J, Cancelas JA, Zheng Y, Williams DA. Inhibition of RhoA GTPase activity enhances hematopoietic stem and progenitor cell proliferation and engraftment. Blood 2006; 108:2087-94. PubMed
  • Cornetta K, Croop J, Dropcho E, Abonour R, Kieran MW, Kreissman S, Reeves L, Erickson LC, Williams DA. A pilot study of dose-intensified procarbazine, CCNU, vincristine for poor prognosis brain tumors utilizing fibronectin-assisted, retroviral-mediated modification of CD34+ peripheral blood cells with O6-methylguanine DNA methyltransferase. Cancer Gene Ther 2006; 13:886-95. PubMed
  • Guo F, Debidda M, Yang L, Williams DA, Zheng Y. Genetic deletion of Rac1 GTPase reveals its critical role in actin stress fiber formation and focal adhesion complex assembly. J Biol Chem 2006; 281:18652-9. PubMed
  • Yamada Y, Rothenberg ME, Lee AW, Akei HS, Brandt EB, Williams DA, Cancelas JA. The FIP1L1-PDGFRA fusion gene cooperates with IL-5 to induce murine hypereosinophilic syndrome (HES)/chronic eosinophilic leukemia (CEL)-like disease. Blood 2006; 107:4071-9. PubMed
  • Cancelas JA, Williams DA. Stem cell mobilization by beta2-agonists. Nat Med 2006; 12:278-9. PubMed
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DF/HCC members that share similar concepts* with David A. Williams, MD but have yet to coauthor a publication with this researcher.

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