Nancy A. Speck, Ph.D.
Professor of Biochemistry and James J. Carroll Professor in Oncology
| Contact Information |
| Phone: 603-650-1159 |
| Fax: 603-650-1128 |
| Labphone: 603-650-1235 |
| Email Address: Nancy.Speck@Dartmouth.edu |
| Website: http://www.dartmouth.edu/~immuno/faculty/speck.html |
| Laboratory Website : http://dms.dartmouth.edu/speck/ |
Postal Address |
| Dr. Nancy A. Speck |
| Vail 315A |
| Dartmouth Medical School |
| Hanover NH 03755 |
Education |
| Northwestern University, PHD 1983 |
In the News |
| 8/4/04: Nancy Speck Appointed Carroll Chair in Oncology at Norris Cotton Cancer Center |
Program Membership |
| Cancer Mechanisms Research Program |
Department Membership |
| Biochemistry |
Graduate Training Program Affiliation |
| Molecular and Cellular Biology |
Biography |
| Professor Speck received her B.A. degree from Western Maryland College (now McDaniel College) in 1977, and her Ph.D. in immunology from Northwestern University in 1982. She trained as a postdoctoral fellow at the Center for Cancer Research and the Whitehead Institute at the Massachusetts Institute of Technology. Dr. Speck moved to Dartmouth Medical School in 1989 as an Assistant Professor. She is currently a Professor of Biochemistry and the Associate Director for Basic Science at the Norris Cotton Cancer Center at Dartmouth. |
Selected Recent Publications |
| Li, Z., J. Yan, C.J. Matheny, T. Corpora, J. Bravo, A.J. Warren, J.H. Bushweller, and N.A. Speck. Energetic contribution of residues in the Runx1 Runt domain to DNA binding. J Biol Chem. 278, 33088-33096, 2003 |
| Zhang, L., Z. Li, J. Yan, P. Pradhan, T. Corpora, M.D. Cheney, J. Bravo, A.J. Warren, J.H. Bushweller, and N.A. Speck. Mutagenesis of the Runt domain defines two energetic hotspots for heterodimerization with the core binding factor ß subunit. J. Biol Chem. 278, 33097-33104, 2003 |
| Yan, J. Y. Liu, N.A. Speck, and J.H. Bushweller. CBFß allosterically regulates the Runx1 Runt domain by shifting conformational exchange in the Runt domain and DNA. Nat Struct Mol Biol. 11, 901-906, 2004 |
| Liu, Y., M. D. Cheney, J.J. Gaudet, M. Chruszcz, S.M. Lukasik, D. Sugiyama, J. Lary, J. Cole, Z. Dauter, W. Minor, N.A. Speck*, J.H. Bushweller*. The tetramer structure of the Nervy homology two domain, NHR2, is critical for AML1/ETO’s activity. Cancer Cell, 9, 249-260, 2006 (*corresponding authors) (Comment by Sitwalar and Hess in Cancer Cell 9, 241-242) |
| Zeigler, B.M., D. Sugiyama, M. Chen, Y. Guo, K.M. Downs*, and N.A. Speck*. The allantois and chorion, isolated before circulation or chorio-allantoic fusion, have hematopoietic potential. Development 133, 4183-4192, 2006. (*corresponding authors) (Featured in “In This Issue”) |
| Matheny, C., M.E. Speck, P. Cushing, Y. Zhou, T. Corpora, M. Regan, M. Newman, L. Roudaia, C.L. Speck, T.-L. Gu, S.M. Griffey, J.H. Bushweller*, and N.A. Speck*. Mutations in the Runt domain found in hematopoietic disorders and cleidocranial dysplasia create nonfunctional, dominant negative, and hypomorphic alleles. EMBO J. 26, 1163-1175, 2007 (*corresponding authors) |
| Liu, Y., W. Chen, J. Gaudet, M.D. Cheney, L. Roudaia, T. Cierpicki, R.C. Klet, K. Hartman, T.M. Laue, N.A. Speck*, and J.H. Bushweller*. Structural basis for recognition of SMRT/N-CoR by the MYND domain and its contribution to AML1/ETO’s activity. Cancer Cell 11, 483-497, 2007 (*corresponding authors). |
| Gorczynski, M.J., Y. Grembecka, Y. Zhou, Y. Kong, L. Roudaiya, M.G. Douvas, M.Newman, G. Baber, IZ. Bielnicka, T. Corpora, J. Shi, M. Sridharan, R. Lilien, B.R. Donald, N.A. Speck, M.L. Brown, J.H. Bushweller. Development of an allosteric inhibitor of the protein-protein interaction between the leukemia-associated proteins RUNX1 and CBFß. Chem Biol. in press, 2007 |
Research / Lab Interests |
| The laboratory investigates the functions of RUNX1 and CBFß in normal
hematopoiesis and in acute myeloid and lymphocytic leukemias that originate
in chromosomal translocations involving RUNX1 and CBFß. The laboratory
makes extensive use of the Flow Cytometry, Irradiation, Microarray,
Bioinformatics, and Transgenic Mouse Cores. In collaboration with former NCCC member, John Bushweller, now at the University of Virginia, structures of all five conserved domains in AML1/ETO, the protein produced as a result of the t(8;21) in AML, have been solved. With the support of a Leukemia and Lymphoma Society Specialized Center of Excellence Award, they now aim to use the structures to develop small molecule inhibitors for AML1/ETO. Lead compounds have been identified and a small library of compounds were subsequently generated to explore structure-activity relationships. Several low micromolar inhibitors are currently being tested in mice. Speck and Bushweller characterize the pharmacokinetics of these compounds in collaboration with Lionel Lewis in the NCCC Clinical and Molecular Pharmacology Shared Resource. To further dissect the roles of Runx1 and CBFß in hematopoiesis, a new project has been initiated with Scott Gerber in which a set of Runx1-CBFß interacting proteins was identified by tandem mass spectrometry. |
Honors |
| American Cancer Society Junior Faculty Research Award |
| Leukemia Society of America Scholar |
| Fogarty International Center Senior Fellow |
| Chair, Hematopoiesis Study Section (NIH) (2005-2007) |
| Chair, Leukemia and Lymphoma Society Career Development Awards Study Section (2007-2012) |
Grants: |
| 8/1/93 - 11/30/07 "Biochemistry of Leukemia Virus Core-Binding Factor" National Institutes of Health R01 CA58343 |
| 7/1/97 - 6/30/08 "Structure/Function of CBFß" National Institutes of Health R01 CA75611 |
| 12/01/00 - 11/30/05 "Mouse Models for Familial Platelet Disorder with Predisposition to Acute Myelogenous Leukemia (FPD/AML)" National Institutes of Health R01 CA89419 |
| 9/1/03 - 12/31/07 "Runx1 as a Marker for Stem Cells" National Institutes of Health R01 AI051427 |
| 4/1/04 - 3/31/09 "Structural Biology of AML1 (CBFA2) and AML1-ETO National Institutes of Health R01 CA108056 (J.H. Bushweller, P.I.) |
| 7/1/98 - 6/30/08 "Biochemistry and Molecular Biology of Protein Complexes" National Institutes of Health T32 GM08704 |
| 10/1/04 - 9/30/09 "Targeted Inhibition of Oligomeric Translocation Products in AML and CML (SCOR) 7006-05 (J.H. Bushweller, P.I.) |
Invited lectures (recent): |
| Mar 2007 US-Japan Workshop on "Animal Models for Hematological Malignancies and Hematopoiesis", Kauai, Hawaii, Co-Organizer |
| July 2007 FASEB Conference on Hematological Malignancies (Session Chair) |
| Aug 2007 Conference on Runt Domain Proteins, Singapore |
| Sep 2007 University of New Mexico |
| Sep 2007 University of Chicago |
| Sept 2007 Johns Hopkins School of Public Health |
| Nov 2007 Colloquium des Treilles on "Stem Cells of the Blood/Vascular System" Co-Organizer |
| May 2008 Cornell University |
