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Ruth W. Craig, Ph.D.

Contact Information:

Professional Interests:

Molecular mechanisms of induction of differentiation and reversal of the leukemic phenotype; oncogenes, tumor suppressor genes, and genes affecting the programming of differentiation and viability, such as MCL1.

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.

Dr. Craig's research is centered on understanding the events involved in hematopoietic cell commitment to differentiation with the prevention of apoptosis. Initial studies demonstrated that the expression of c-myb and other oncogenes is decreased early in differentiation, while expression of the p53 tumor suppressor gene is increased. MCL1 was identified as a key member of the BCL2 family of viability-promoting genes. MCL1 is rapidly upregulated in response to differentiation-inducing agents as well as specific growth factors and stress signals, where MCL1 serves to promote short-term cell survival. Studies of MCL1 have led to an overall model suggesting that genes that control cell viability can also regulate the flow of cells along various pathways of proliferation and differentiation. These genes thus contribute to the maintenance of homeostasis in tissues, organs, and the organism as a whole. However, alterations affecting viability-regulating genes can subvert this homeostatic control mechanism, predisposing cells to immortalization and tumorigenesis.

Dr. Craig's ongoing work is aimed at understanding how MCL1 is regulated and how alterations in its regulation contribute to the development of cancer. In accord with its critical role in regulating cell viability, MCL1 appears to be highly regulated through transcriptional, alternate splicing, and post-translational mechanisms. Thus, Dr. Craig's studies aim to identify means of inhibiting MCL1 in overexpressing tumor cells, as means of inducing these cells to undergo apoptosis.

In a complementary line of research, Dr. Craig's laboratory is using a microarray approach to identify the entire panoply of genes involved in differentiation-induction. This should provide further insight into the mechanism involved in this process, as well additional potential therapeutic targets.

Courses Taught:

Endocrinology and Reproduction Sections of Medical Pharmacology

Graduate Student Seminar course on Regulation of Eukaryotic Cell Growth and Development, laboratory for Medical Student Developmental Biology course

Grant Information:

NIH R01 CA57359: Modifications Matter in MCL1 Turnover and Tumorigenesis”