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Ruth W. Craig, Ph.D.

Title(s):
Professor of Pharmacology & Toxicology

Department(s):
Pharmacology & Toxicology

Education:
Pomona College, BA 1974
Boston University, MA 1980
SUNY - Buffalo, PHD 1984

Programs:
Immunology Program
Norris Cotton Cancer Center
Pharmacology and Toxicology Graduate Program
Program in Experimental and Molecular Medicine

Websites:
http://dms.dartmouth.edu/pharm-tox

Contact Information:

HB 7650, Remsen
Geisel School of Medicine
Dept. of Pharmacology and Toxicology
Hanover NH 03755

Office: Remsen 513B
Phone: 603-650-1657
Fax: 603-650-1129
Email: ruth.craig@dartmouth.edu

Asst. Phone: 603-650-1345


Professional Interests:

Molecular mechanisms of the induction of differentiation and inhibition of the cancer phenotype; genes affecting the control of differentiation and viability, MCL1 and other genes in the BCL2 family

Dr. Craig's research is centered on understanding the role of MCL1 in normal cell development and in cancer. MCL1 and pro-survival members of the BCL2 family maintain cell viability, while other family members promote cell death. The expression of the MCL1 mRNA and the stability of the MCL1 protein are modulated by environmental cues such as growth and differentiation factors. This serves to maintain and amplify cell types and lineages that are needed by the organism, while eliminating cells that are not needed or are damaged or senescent. However, loss of the normal regulated pattern of expression of MCL1 can allow for prolonged cell survival, further tumorigenic changes , and increased resistance of cancer cells to damaging stimuli and therapeutic drugs.

The work in Dr. Craig’s laboratory focuses on how MCL1 and other pro-survival genes contribute to the ongoing maintenance of homeostasis in hematopoietic and lymphoid cells, and on how alterations affecting the regulation of these genes can lead to the development of leukemia and lymphoma. The long-term goal is to utilize understanding of the role of genes that control survival, prominently MCL1, in order to regulate normal B-, T-, and hematopoietic cell development and to inhibit tumorigenesis. Major questions being addressed in the laboratory are listed below.

Rotations and Thesis Projects:

1. Can MCL1 expression be manipulated to enhance the function of normal lymphocytes and other immune cells, to enhance responsiveness to infection in young as well as aging animals?
2. How are the various pathways that normally regulate MCL1 coordinated, and what alterations promote survival and drug resistance in cancer?
3. Can MCL1 degradation be enhanced in tumor cells to promote death and enhance sensitivity to other chemotherapeutic agents ?

Grant Information:

NIH R01 CA57359: Modifications Matter in MCL1 Turnover and Tumorigenesis

Courses Taught:

Endocrinology and Reproduction Sections of Medical Pharmacology

Scientific Basis of Disease - PEMM 102

Biography:

Dr. Ruth Craig received her B.S. in Zoology from Pomona College. She completed M.A. and Ph.D. degrees in Pharmacology at, respectively, Boston University Medical School and the State University of New York. After postdoctoral training at Harvard Medical School, she became an Assistant Professor at Johns Hopkins University School of Medicine. She is currently a Professor of Pharmacology and Toxicology at the Dartmouth Medical School.


Selected Publications:

 

  • Vrana JA, Cleaveland ES, Eastman AE, Craig RW. Inducer-and cell type-specific regulation of antiapoptotic MCL1 in myeloid leukemia and multiple myeloma cells exposed to differentiation-inducing or microtubule-disrupting agents. Apoptosis 11:1275-1288, 2006 (view details on MedLine)

  • De Biasio A, Vrana JA, Zhou P, Qian L, Bieszczad CK, Braley KE, Domina AM, Neveu JM, Weintraub S J, Lane WS, Craig RW N-Terminal Truncation of MCL1 Yields a Viability-promoting Form that is Stabilized Upon ERK Activation and is Abundant in Tumor Cells. J Biological Chemistry 282:23919-23936, 2007 (view details on MedLine)

  • Kobayashi S, Lee SH, Meng XW, Mott JL, Bronk SF, Werneburg NW, Craig RW, Kaufmann SH, Gores GJ. Serine 64 phosphorylation enhances the antiapoptotic function of Mcl-1. J Biol Chem. 2007 Jun 22;282(25):18407-17. (view details on MedLine)

  • Kahraman A, Mott JL, Bronk SF, Werneburg NW, Barreyro FJ, Guicciardi ME, Akazawa Y, Braley K, Craig RW, Gores GJ. Overexpression of mcl-1 attenuates liver injury and fibrosis in the bile duct-ligated mouse. Dig Dis Sci. 2009 Sep;54(9):1908-17. (view details on MedLine)

  • Gui J, Mustachio LM, Su DM, Craig RW. Thymus Size and Age-related Thymic Involution: Early Programming, Sexual Dimorphism, Progenitors and Stroma. Aging Dis. 2012 Jun;3(3):280-90. (view details on MedLine)

  • Nifoussi, S. K., Vrana, J. A., Domina, A. M., De Biasio, A., Gui, J., Gregory, M. A., Hann, S. R., and Craig, R. W. Thr 163 Phosphorylation Causes Mcl-1 Stabilization When Degradation is Independent of the Adjacent GSK3-targeted Phosphodegron, Promoting Drug Resistance in Cancer. PLoS One. 2012;7(10):e47060. (view details on MedLine)