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David Williams

UC Department of Pediatrics

Adjunct Professor, Experimental Hematology and Cancer Biology

Phone: 513-636-0364

Email: david.williams@cchmc.org

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Specialties

Genetic manipulation of mammalian cells; hematopoietic stem cell biology

Biography

Dr. Williams’ major research interests are in the study of blood stem cell biology, blood formation, leukemia and the treatment of genetic blood diseases using gene therapy. He has published over 200 peer-reviewed manuscripts and textbook chapters. He was an investigator of the HHMI for 16 years. He has been continuously funded by the NIH since 1986. His laboratory co-discovered and cloned Interleukin-11 (Neumega™) and carried out developmental studies that assisted in obtaining FDA approval of this drug. His laboratory also described the use of fibronectin in retrovirus-mediated gene transfer, now nearly universally used (as Retronectin®) in clinical gene therapy trials and basic research utilizing gene transfer.

Dr. Williams basic research has focused on hematopoietic stem cell biology and specifically molecular and biochemical analysis of the interaction between hematopoietic stem cells and the bone marrow supporting environment. This work has recently focused on the roles of Rho GTPases in stem cell engraftment, retention and mobilization from the bone marrow. His laboratory has defined Rac GTPases (Rac1, Rac2 in particular) as key regulatory switches that control stem cell adhesion, migration and survival/proliferation in the adult bone marrow cavity and during fetal development in yolk sac, fetal liver and other embryonic sites. His laboratory has also recently demonstrated that Rac GTPases are essential signaling molecules in BCR-ABL oncogene transformation of hematopoietic stem cells. He and Dr. Yi Zheng (Cincinnati Children’s Hospital) have developed a new small molecule inhibitor of Rac GTPases that is being investigated as a molecular target in cancer therapies. His laboratory is investigating the role of several other Rho GTPases in normal and abnormal hematopoiesis.

Dr. Williams is currently the Chief, Division of Hematology/Oncology and Director of Clinical and Translational Research, Children’s Hospital Boston and the Leland Fikes Professor of Pediatrics, Harvard Medical School. Dr. Williams is also an adjunct faculty member at Cincinnati Children's.

Education and Training

BA: Indiana State University, Terre Haute, IN, 1975.

MD: Indiana University School of Medicine, Indianapolis, IN, 1979.

Residency: Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 1979-1982.

Fellowships: Harvard Medical School, Boston, MA, 1982-1985; The Children's Hospital Boston, Boston, MA, 1982-1985.

Publications

View PubMed Publications

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 Nov 12;5(11):e13970.

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 Jul 8;116(1):81-4.

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.

Sanchez-Aguilera A, Rattmann I, Drew DZ, Müller LU, Summey V, Lucas DM, Byrd JC, Croce CM, Gu Y, Cancelas JA, Johnston P, Moritz T, Williams DA. Involvement of RhoH GTPase in the development of B-cell chronic lymphocytic leukemia. Leukemia. 2010 Jan;24(1):97-104.

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 Oct 22;114(17):3557-66.

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 Jul 2;114(1):174-80.

Cancelas JA, Williams DA. Rho GTPases in hematopoietic stem cell functions. Curr Opin Hematol. 2009 Jul;16(4):249-54.

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 Jul;30(7):E761-70.

Hoskins EE, Morris TA, Higginbotham JM, Spardy N, Cha E, Kelly P, Williams DA, Wikenheiser-Brokamp KA, Duensing S, Wells SI. Fanconi anemia deficiency stimulates HPV-associated hyperplastic growth in organotypic epithelial raft culture. Oncogene. 2009 Feb 5;28(5):674-85.

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 Aug 1;68(15):6171-80.

Grants

Cell Type and Stimulus-Specific Signaling Role of CDC42. National Institutes of Health. Jul 2006 - May 2011.

Training Program in Cancer Therapeutics. National Cancer Institute. Sep 2006 - Aug 2011.

Rac GTPases as Targets in Lymphomagenesis. National Institutes of Health. Feb 2007 - Jan 2012.

Rac proteins in hematoppietic cell survival and function. Prinical Investigator. National Institute of Diabetes and Digestive and Kidney Diseases. Feb 2002 - Jun 2012.

Rac1 and Rac2 Guanosine Triphosphotase in Erythroid Function and Differentiation. National Heart, Lung and Blood Institute. Feb 2008 - Nov 2012.

Role of tumor necrosis factor in leukemogenesis. Leukemia & Lymphoma Society. Jul 2008 - Jun 2013.

Regulation of Systemis RNA Interface in the Nematode C elegans. National Institutes of Health. Jan 2009 - Dec 2013.