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Experimental Hematology and Cancer Biology

David A. Williams, MD, is director of Experimental Hematology at Cincinnati Children's Hospital Medical Center.

David A. Williams, MD

Title

Adjunct Professor of Pediatrics

Appointment

Professor of Pediatrics

Email

david.williams@cchmc.org

Phone

513-636-0364

Fax

513-636-3768

Bio

David A. Williams, MD, is director, Division of Experimental Hematology and attending physician in Hematology / Oncology in the Department of Pediatrics at Cincinnati Children's Hospital Medical Center (CCHMC). He is the Director of the Hematology/Oncology Fellowship Training Program.

Dr. Williams also serves as Associate Chairman for Translational Research, CCHMC.

Dr. Williams is currently the Beatrice Lampkin Endowed Chair of Hematology/ Oncology and Professor of Pediatrics at the University of Cincinnati College of Medicine. He serves on the Executive Committe of the Ohio State university Comprehensive Cancer Center.

Dr. Williams' major research interests are in the study of blood stem cell biology and blood formation and the treatment of genetic blood diseases using gene therapy.

Dr. Williams has published over 200 peer-reviewed manuscripts and chapters and holds multiple patents, several of which have been licensed for development.

After training in Pediatrics at Cincinnati Children's, Dr. Williams completed fellowship training in Pediatric Hematology / Oncology at Children's Hospital / Dana-Farber Cancer Institute / Boston, research training at the Whitehead Institute, Massachusetts Institute of Technology and then became a faculty member at Harvard Medical School and of the Howard Hughes Medical Institute (HHMI). He has had continuous NIH funding since 1986 and was an investigator of the HHMI for 16 years.

He served as the inaugural director of the Herman B Wells Center for Pediatric Research at Indiana University School of Medicine from 1991-2001, where he was the Kipp Professor of Pediatrics and Professor of Medical & Molecular Genetics.

Dr. Williams is past president of the International Society of Experimental Hematology, past member of the Council of the American Society of Clinical Investigation (ASCI), a past member of the board of the Federation of American Societies for Experimental Biology (FASEB). He is currently Editor-in-Chief of Molecular Therapy and was elected to the Institute of Medicine of the National Academy of Sciences in 2002.

Credentials

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

Residency: Children's Hospital Medical Center, Cincinnati, Ohio

Certification: American Board of Pediatrics, 1984

Research Fellow in Pediatrics, July 1982 - June 1985, Harvard Medical School, Boston, Mass.

Fellow in Medicine (Hematology / Oncology), July 1982 - June 1985, The Children's Hospital, Boston, Mass.

Clinical Fellow, July 1982 - June 1985, Dana-Farber Cancer Institute, Boston, Massachusetts

Awards and Honors


  • 2006 Donald Metcalf Award, Internatioal Society of Experimental Hematology
  • 2006 Frank Oski Award and Memorial Lecture, American Society of Pediatric Hematology/Oncology
  • Awarded "2005 Best Doctors"
  • 2003 American Pediatric Society
  • 2003 28th Annual Alan Cooper Smith Professor, The Johns Hopkins University
  • 2002 Institute of Medicine, National Academy of Sciences
  • 2002 Samuel Rosenthal Prize for Excellence in Pediatrics
  • 2000 William Dameshek Award, American Society of Hematology
  • 1999 Association of American Physicians
  • 1998 Indiana Health Forum, World of Difference Award
  • 1998-01 Secretary-Treasurer, American Society of Clinical Investigation
  • 1998-99 International Society for Experimental Hematology, President
  • 1996-97 International Society for Experimental Hematology, Vice President and President Elect
  • 1996 Distinguished Alumni of 1996, Indiana State University
  • 1994 Otis Bowen, M.D. Distinguished Leadership Award, IU School of Medicine Dean's Council
  • 1994 E. Mead Johnson Award for Excellence in Pediatric Research
  • 1985-89 NIH Young Investigator Award
  • 1985-87 Basil O'Connor Starter Research Award of the Natl. Foundation March of Dimes
  • 1982 Sam Dalinsky Resident Award, Children's Hospital Medical Center
  • 1979 M.D. with Distinction, Indiana University School of Medicine
  • 1979 Alpha Omega Alpha, National Honorary in Medicine
  • 1975 Sigma Zeta, National Honorary in Science
  • 1975 Magna Cum Laude, Indiana State University

Research

Visit the Williams Lab Site

Research Grants and Contracts

R01 DK62757 (Williams) 2/1/02-12/31/06 NIDDK
Rac proteins in hematopoietic cell survival and function

R01 DK074310 (Williams) 1/1/06-12/31/10 NIH
Chemoresistance and Stem Cell Selection

R01 HL081499 (Williams) 04/01/06-03/31/10 NIH
Novel Molecular and Cellualar Therapies in Fanconi Anemia

R01 CA113969 (Williams) 005/20/05-04/30/10 NIH
RhoH and GTPase in Hematopoiesis and Cancer

6152-06 (Williams) 10/01/05-09/3008 Leukemia & Lymphoma Society
Targeting Rac GTPases in Bcr-abl-induced Chronic Myelogenous Leukemia

K01 CA107110 (Gu) 02/01/05-12/31/10 NIH/NCI
RhoH GTPase in Blood Cell and Cancer Development

R03 CA125830 (Zheng) 12/01/06-11/30/08
NIH
Targeting RhoA in Lymphomagenesis

T32 CA117846 (Knudsen) 09/01/06-08/31/11
NCI
Role on Project: Mentor
Training Program in Cancer Therapeutics

R21 CA121578 (Wagner) 06/06/06-05/31/08
NIH
Gene Transfer to Facilitate Dose-Intensification in the Treatment of Pediatric Brain Tumors

No Number assigned (Meetei) 07/01/06-06/30/08
American Society of Hematology
Role of FAAP250/FANCM Enzymatic Activities in the FA-DNA Repair Function

NIH R01 HL069428, (Cook-Mills) 04/01/05-03/31/09
NIH.NHLBI
gp91 phox Function in VCAM-1-dependent Lung Eosinophilia

No Number assigned (Grimes) 07/01/05-06/30/10
Leukemia & Lymphoma Society
The Molecular Basis of Acute Myeloid Leukemia

K30 HL078581 (Tsevat) 12/01/04-11/30/09 Co-Investigator, Translational Research Curriculum
NIH
University of Cincinnati Clinical Research Curriculum Award

FD-R-002612 (Smith) 09/30/05-09/29/08
Co-Investigator, Clinical Trial
FDA
Oxandrolone for the Treatment of Marrow Aplasia in Fanconi Anemia

HL085362 (Yheng) 07/01/06-05/31/11
NIH
Cell Type and Stimulas-specific Signaling Role of CDC42

P01 HL69974 (Skalnik) 04/01/02-03/31/07 NHLBI
Role of Rac2 in Hematopoiesis

R01 HL076712 (Pang) 07/01/05-06/30/10 NIH
Role of FA Protein Complexes in Hematopoiesis

T32 HD043005 (Boat) 07/01/02-04/30/07 NICHD
NICHD Research Training Grant for Pediatric Subspecialties

R01GM53943 (Zheng) 04/01/05 - 03/31/10 NIH/NIGMS
Dbl-like regulators of small GTP-binding proteins

No number assigned (Filippi) 07/01/05-06/30/07 American Society of Hematology
The role of CDC42 in Neutrophil Functions

Publications, Most Recent

Connect to David Williams' publications on PubMed

Will E, Bailey J, Schuesler T, Balcik B, Burzynski B,Witte, Layh-Schmitt G, von Kalle C, Baum C, Sorrentino BP, Wagner LM, Kelly P, Reeves L, Williams DA: Importance of murine study design for testing toxicity of retroviral vectors in support of Phase I trials. Mol Ther. 15(4): 782-91, 2007.

Kelly P, Radtke S, von Kalle C, Balcik B, Bohn K, Mueller R, Schuesler T, Haren M, Reeves L, Cancelas J, Leemhuis T, Harris R, Auerbach A, Smith F, Davies S, Williams D: Stem cell collection and gene transfer in fanconi anemia. Mol Ther. 15(1): 211-9, 2007.

Gu Y, Chae H, Siefring JE, Jasti AC, Hildeman DA, Williams DA: RhoH GTPase recruits and activates Zap70 required for T cell receptor signaling and thymocyte development. Nature Immunology 7(11):11182-90, 2006.

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

Mehta PA, Ileri T, Harris RE, Williams DA, Mo J, Smolarek T, Auerbach AD, Kelly P, Davies SM: Chemotherapy for myeloid malignancy in children with Fanconi Anemia. Pediatric Blood and Cancer, 2006 Apr 11; [Epub ahead of print]

Ghiaur, G, Lee A, Bailey J, Cancelas J, Zheng Y, Williams DA: Inhibition of RhoA GTPase activity enhances hematopoietic stem and progenitor cell proliferation and engraftment In Vivo. Blood, 2006 May 18; [Epub ahead of print]

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. Journal of Biological Chemistry, 2006 May 11; [Epub ahead of print]

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 (PCV) for poor prognosis brain tumors utilizing Fibronectin-assisted, retroviral-mediated modification of CD34+ peripheral blood cells with 06-methylguanine DNA methyltransferase. Cancer Gene Therapy, 2006 Apr 28; [Epub ahead of print]

Cancelas JA, Jansen M, Williams DA: The role of chemokine activation of rac GTPases in hematopoietic stem cell marrow homing, retention and peripheral mobilization. Experimental Hematology, 34(8):976-85, 2006.

Schambach A, Will E, Modlich U, Galla M, Chandra S, Reeves L, Colbert M, Williams DA, von Kalle C, and Baum C. Lentiviral vectors pseudotyped with murine ecotropic envelope: increased biosafety and convenience in preclinical research. Experimental Hematology, 34(5):588-592, 2006.

Yamada Y, Rothenberg ME, Lee AW, Akei HS, Brandt EB, Williams DA, Cancelas JA: The FIP1L1-PDGFRα Fusion Gene Cooperates with IL-5 to Induce Murine Hypereosinophilic Syndrome (HES)/Chronic Eosinophilic Leukemia (CEL)-like Disease. Blood, 107(10):4071-4079, 2006.

Schambach A, Bohne J, Chandra S, Will E, Margison G, Williams DA, Baum C: Equal potency of gammaretroviral and lentiviral SIN vectors for expression of O6–methylguanine-DNA-methyltransferase in bone marrow cells. Molecular Therapy, 13(2):391-400, 2006.

Wang L, Yang L, Filippi MD, Williams DA, Zheng Y. Genetic deletion of Cdc42GAP reveals a role of Cdc42 in erythropoiesis and hematopoietic stem/progenitor cell survival, adhesion, and engraftment.Blood. 2006 Jan 1;107(1):98-105.

Will E, Speidel D, Wang Z, Ghiaur G, Rimek A, Schiedlmeier B, Williams DA, Baum C, Ostertag W, Klump H. HOXB4 Inhibits Cell Growth in a Dose-Dependent Manner and Sensitizes Cells Towards Extrinsic Cues.Cell Cycle. 2006 Jan;5(1):14-22.

Chandra S, Levran O, Jurickova I, Maas C, Kapur R, Schindler D, Henry R, Milton K, Batish SD, Cancelas JA, Hanenberg H, Auerbach AD, Williams DA. A rapid method for retrovirus-mediated identification of complementation groups in Fanconi anemia patients. Mol Ther. 2005 Nov;12(5):976-84.

Cripe TP, Thomson B, Boat TF, Williams DA. Promoting translational research in academic health centers: navigating the "roadmap".Acad Med. 2005 Nov;80(11):1012-8.

Fulkerson PC, Zhu H, Williams DA, Zimmermann N, Rothenberg ME. CXCL9 inhibits eosinophil responses by a CCR3- and Rac2-dependent mechanism. Blood. 2005 Jul 15;106(2):436-43.

Jansen M, Yang FC, Cancelas JA, Bailey JR, Williams DA. Rac2-deficient hematopoietic stem cells show defective interaction with the hematopoietic microenvironment and long-term engraftment failure.Stem Cells. 2005 Mar;23(3):335-46.

Cancelas JA, Lee AW, Prabhakar R, Stringer KF, Zheng Y, Williams DA. Rac GTPases differentially integrate signals regulating hematopoietic stem cell localization.Nat Med. 2005 Aug;11(8):886-91.

Carstanjen D, Yamauchi A, Koornneef A, Zang H, Filippi MD, Harris C, Towe J, Atkinson S, Zheng Y, Dinauer MC, Williams DA. Rac2 regulates neutrophil chemotaxis, superoxide production, and myeloid colony formation through multiple distinct effector pathways.J Immunol. 2005 Apr 15;174(8):4613-20.

Villella AD, Yao J, Getty RR, Juliar BE, Yiannoutsos C, Hartwell JR, Cai S, Sadat MA, Cornetta K, Williams DA and Pollok KE. Real-Time PCR: an Effective Tool for Measuring Transduction Efficiency in Human Hematopoietic Progenitor Cells.Molecular Therapy. 2005 Mar;11(3):483-91.

Symposium Proceedings/Invited Reviews, Most Recent


Williams DA, Xu H, Cancelas JA. "Children are not little adults: just ask their hematopoietic stem cells." Journal of Clinical Investigation, In press, 2006.

Williams DA. Editorial: A Pox on Your Tumor.Molecular Therapy, In press, 2006.

Williams DA. Editorial: Vector Insertion, Mutagenesis and Transgene Toxicity.Molecular Therapy, Volume 14 (4), 2006.

Williams, DA: Congenital Preleukemic Syndromes: "Fanconi's Anemia: Genomic instability leading to aplastic anemia and cancer."European Hematology Association Annual Meeting Educational Program, Volume 2 (1), 2006.

Nassar N, Cancelas J, Zheng J, Williams DA, Zheng Y: "Structure-function based design on small molecule inhibitors targeting Rho family GTPases."Current Topics of Medicinal Chemistry, Vol 6 (11): 1109-1116, 2006.

Williams DA and Cripe T. Editorial: Adventitious mutations in clinical grade vectors: An issue to consider?Molecular Therapy, Vol. 13 (5), 831-832, 2006.

Cancelas JA and Williams DA: "Stem Cell Mobilization by β2-Agonists."Nature Medicine, 12 (3), 278-279, 2006.

Editor-in-Chief Comment on Flotte et al., Editorial: "New AAV serotypes may broaden the therapeutic pipeline to human gene therapy."Molecular Therapy, Volume 13 (1), January, 2006.

Williams, DA: Editorial: FDA Guidance Document on Monitoring Delayed Adverse Events a Good First Start. Molecular Therapy, Vol. 12 (6), 991, 2005.

Nassar N, Cancelas J, Zheng J, Williams DA, Zheng Y: "Structure-function based design on small molecule inhibitors targeting Rho family GTPases."Current Topics of Medical Chemistry, In Press, 2005.

Williams DA, Croop J, Kelly P: Gene Therapy in the Treatment of Fanconi Anemia, a Progressive Bone Marrow Failure Syndrome.Current Opinion in Molecular Therapeutics, Volume 7 (5),461-466, 2005.

Editor-in-Chief Comment on High et al, Editorial: Stakeholders' Conference Sharpens Focus on Regulatory Challenges on Clinical Gene Transfer.Molecular Therapy. Volume 12 (4), 581, 2005.

Editor-in-Chief Comment on Friedman et al, Editorial: Clinical Application of Gene Transfer Technology: Overcoming the Obstacles.Molecular Therapy. Volume 12 (1), 2, 2005.

Editor-in-Chief Comment on Baum et al., Editorial: A Balanced Decision? Regulatory Reaction to the "Third Case."Molecular Therapy. Volume 11 (6), 819, 2005.

Williams, DA: Editorial: The NIH Roadmap: timing is everything.Molecular Therapy, Vol. 11 (2), 173, 2005.

Gu, Y, Zheng Y, Williams DA: RhoH GTPase: a key regulator of hematopoietic cell proliferation and apoptosis?Cell Cycle, Vol. 4 (2), 201-202, 2005.

Wiliams: DA: Editorial: A New Year and a Renewed Mission.Molecular Therapy, Vol. 11 (1), 1, 2005.

Editing


  • Molecular Therapy, Editor-in-Chief
  • Bone Marrow Transplantation
  • The Journal of Clinical Investigation, Board of Consulting Editors

Presentations, Most Recent:

  • Invited Speaker, FASEB Summer Research Conference, Regulation & Function of Small GTPases: "RhoH GTPase: Key Molecular Switch Regulating Thymocyte Development" Saxton Rivers, Vermont, July, 2006.
  • Invited Speaker, European Hematology Association,Congenital Preleukemic Syndromes: "Fanconi Anemia: Genomic Instability Leading to Aplastic Anemia and Cancer Predisposition," Amsterdam, The Netherlands, June, 2006.
  • Invited Speaker, "Rho GTPases in Normal and Abnormal Blood Development," Hannover Medical School, Hannover, Germany, June, 2006.
  • Invited Speaker, Transfusion Grand Rounds, "Rho GTPases as Regulators of Normal and Abnormal Hematopoiesis," Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, May, 2006.
  • Invited Speaker, Viral Vector Course Lecture, "Retrovirus Clinical Applications," John Hopkins Medical School, Baltimore, MD, May, 2006.
  • Invited Speaker, Frank Oski Memorial Lecture, "Cell Interactions in the Bone Marrow: How Basic Studies in Stem Cell Biology Informed New Therapeutics in Cancer and Gene Therapy," ASPHO and PAS Annual Meeting, San Francisco, CA, April, 2006.
  • Invited Speaker, Joint APS/SPR Council Meeting, "Pediatric Centers of Research Excellence," ASPHO and PAS Annual Meeting, San Francisco, CA, April, 2006.
  • Invited Speaker, Stu Orkin 60th Birthday Scientific Symposium, "Rac and Rho-How Blood Cells Dance," The Children's Hospital and Harvard Medical School, Boston, Massachusetts, April, 2006
  • Invited Speaker, British Society of Gene Therapy, "Early Results of the Clinical Collection and Genetic Correction of Fanconi Complement Type A Hematopoietic Stem Cells," London, March, 2006.
  • Invited Speaker, "Perspectives of Gene Therapy for the Treatment of Fanconi Anemia," Spanish Fanconi Anemia Network and CIEMAT, Madrid, Spain, March, 2006.
  • Invited Speaker, "The Role of RHO GTPases in Normal and Abnormal Blood Development," CIEMAT, Madrid, Spain, March, 2006.
  • Invited Speaker, "Gene Therapy for Pediatric Diseases-Present and Future" Dusseldorf Children's Hospital, Dusseldorf, Germany, March, 2006.
  • Invited Speaker, "Role of Rho GTPases in Normal and Malignant Hematopoiesis," University Clinic of Medicine, West German Cancer Center, Essen, Germany, March, 2006.
  • Invited Participant, Roundtable Meeting of the Translational Research Working Group, National Cancer Institute, Phoenix, AZ, February, 2006.
  • Invited Speaker, Stanford University Frontiers in Gene and Cellular Therapy Series, "Rac GTPases Regulate Hematopoietic Stem Cell Engraftment and Mobilization" Stanford, CA, February, 2006.
  • Invited Speaker and Discussion Leader, National Cancer Institute-Epidemiology of Birth Defects and Cancer, "Fanconi Anemia: Multiple Congenital Anomalies and Leukemia/Cancer Predisposition Associated with Genomic Instability." Bethesda, MD, February, 2006.
  • Invited Speaker, European School of Hematology and American Association of Cancer Research, Molecular Basis for Targeted Therapy for Leukemia Meeting: "Rho GTPases as Molecular Targets in Chronic Leukemias," Cascais, Portugal, February, 2006.
  • Invited Speaker, Moffitt Cancer Center Grand Rounds, "Rho GTPases in Normal and Abnormal Blood Development", Tampa, FL, January, 2006.
  • Invited Speaker, Red Cell Subcommittee, American Society of Hematology, "Rac GTPases: Critical Roles in Blood Cell Development and Erythroid Membrane Integrity," Atlanta, Georgia, December, 2005.
  • Invited Speaker, Cooley's Anemia Foundation, Vectors & Visions: Curative Approaches to Thalassemia. "Update on Human Gene Therapy Trials for Fanconi Anemia and Hematopoietic Stem Cell Selection in Cancer Therapy" Atlanta, Georgia, December, 2005.
  • Invited Speaker, red Cell Subcommittee, American Society of Hematology, "Rac GTPases: Critical Roles in Blood Cell Development and Erythroid Membrane Integrity", Atlanta, Georgia, December, 2005.
  • Invited Speaker, Robarts Research Institute, Cancer and Stem Cells Symposium, "RAC GTPases-Central Regulators of Stem Cell Engraftment and Mobilization," London, Ontario, September, 2005.
  • Invited Speaker, Oregon Health & Sciences University, "Aberrant Activity of Rho GTPases in Leukemia and Lymphoma," Portland, Oregon, August, 2005.
  • Invited Speaker, MGMT 2005, "Chemoresistance and Stem Cell Selection in Monogenic Diseases", Manchester, England, August, 2005
  • Invited Speaker, Cryo 2005 Stem Cell Workshop Scientific Program, "Rac GTPases Regulate Hematopoietic Stem Cell Engraftment and Trafficking by Regulating Interactions with the Hematopoietic Microenvironment", Minneapolis, Minnesota, July, 2005
  • Invited Speaker, Modern Trends in Human Leukemia XVI Wilsede meeting, "Rac and Rho: Antagonistic GTPases regulating hematopoietic engraftment, lymphopoiesis and possibly lymphomagenesis", Wilsede, Germany, June, 2005
  • Invited Plenary Speaker, European Hematology Association Annual Meeting, "Role of Rho GTPases in Hematopoietic Stem Cell Trafficking", Stockholm, Sweden, June, 2005
  • Invited Speaker, Capstone Lecturer Miami University of Ohio, "Gene Therapy in the Treatment of Severe Genetic Diseases of the Blood System", Oxford, Ohio, April, 2005
  • Invited Speaker, Pediatric Pharmacology Research Unit Network Steering Committee Quarterly Meeting, "Development of Rho GTPase Inhibitors for Cancer Therapy", Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, April, 2005.
  • John Hercules Lecture (Keynote address), 28th Annual Meeting of the Sickle Cell Disease Program, "Promise and Challenges of Gene Therapy for Hemoglobinopathies", Cincinnati, Ohio, April, 2005.
  • Keynote address, 3rd Annual Midwest Blood Club, "Rho GTPase Regulate Engraftment and Mobilization of Hematopoietic Stem Cells", University of Louisville, Louisville, Kentucky, April, 2005.
  • Invited Speaker, American Society of Gene Therapy Stakeholder Meeting (Challenges in Advancing the Field of Gene Therapy), "Stem Cell Gene Therapy in Fanconi Anemia", Washington, D.C. April, 2005
  • Keynote address, Georg-Speyer-Haus Symposium, "Chemoresistance and Stem Cell Selection", Frankfurt, Germany, March, 2005.
  • Invited Speaker, 6th International Symposium on Leukemia and Lymphoma, "RhoGTPase Rac2 is Required for In Vivo Transformation Activity by p210 Bcr-Abl Fusion", Vrije University Medical Center, Amsterdam, The Netherlands, March, 2005.
  • Invited Speaker, Ohio State University Comprehensive Cancer Center Annual Scientific Meeting, "Clinical Trials Using Gene Therapy", Columbus, OH, March, 2005.

 

Memberships


  • Cincinnati Pediatric Society
  • Reticuloendothelial Society
  • American Society of Human Genetics
  • American Society of Hematology
  • International Society for Experimental Hematology
  • American Society of Pediatric Hematology/Oncology
  • Midwest Society for Pediatric Research
  • American Association for Cancer Research
  • The Midwest Blood Club
  • American Association for the Advancement of Science
  • American Society for Blood and Marrow Transplantation
  • American Society of Gene Therapy
  • American Society for Clinical Investigation
  • Association of American Physicians
  • Federation of American Societies for Experimental Biology (FASEB)
  • American Pediatric Society
  • Institute of Medicine, National Academy of Sciences