Bethany Janowski, Ph.D.

Dr. Bethany Janowski received her BS from the University of Wisconsin in 1988 and a MS in Biological Sciences, with an emphasis in neuroendocrinology in 1990. Dr. Janowski moved to Dallas in 1993 to attend graduate school at UT Southwestern. She joined the lab of Dr. Mangelsdorf in the Department of Pharmacology. While in graduate school, Dr. Janowski discovered that oxidized cholesterol was the ligand for the "orphan" nuclear hormone receptor, LXR. This discovery correctly suggested that LXR was a key regulator of cholesterol homeostasis. Her identification and extensive study of these oxidized cholesterol ligands for the LXR receptor became the foundation for medicinal chemistry/drug development for LXR. In 1998 she was awarded the Alfred Gilman Award in Pharmacology and in 1999 received her PhD in Cell and Molecular Biology in 1999. Postdoctoral training included further study in cholesterol regulation in the Department of Molecular Genetics, and developing new strategies for silencing gene expression in the Center for Biomedical Inventions at UT Southwestern.

Dr. Janowski joined the faculty in the Department of Pharmacology in 2004. In 2005 she discovered that RNA silences endogenous genes at the level of the chromosome. In 2007 she discovered that RNA can specifically activate gene expression inside cells. Her current research focuses on studying how endogenous regulatory RNAs regulate nuclear hormone receptor gene expression inside cells.

Undergraduate	University of Wisconsin-milwaukee (1988), Zoology
Graduate School	University of Wisconsin-milwaukee (1990)
Graduate School	University of Texas Southwestern Med Ctr Dallas (1999)

• Developing novel technology to selectively activate or silence genes within chromosomal DNA
• Mechanisms controlling recognition of DNA and gene transcription
• Recognition of chromosomal DNA by synthetic molecules
• Using new technology to study nuclear hormone receptors

Featured Publications

The hypocholesterolemic agent LY295427 upregulates INSIG-1, identifying the INSIG-1 protein as a novel mediator of cholesterol homeostasis through SREBP.

Janowski, B. A. Proceedings of the National Academy of Sciences October 2002 99 12675-80

Structural requirements of ligands for the oxysterol receptors LXR alpha and beta

Janowski, B.A., Grogan, M.J., Jones, S., Wisely, G.B., Kliewer, S.A., Corey, E.J., Mangelsdorf, D.J. Proceedings of the National Academy of Sciences January 1999 96 266-271

Cholesterol and bile acid metabolism are impaired in mice lacking the nuclear receptor LXR alpha.

Peet, D.J., Turley, S.D., Ma, W., Janowski, B.A., Lobaccaro, J.A., Hammer, R.E., Mangelsdorf, D.J. Cell May 1998 93 693-704

Identification of a signaling pathway mediated by the nuclear receptor, LXR alpha.

Janowski, B.A., Willy, P.J., Rama Devi, T., Falck, J.R., Mangelsdorf, D.J. Nature October 1996 383 728-731

Antisense transcripts are targets for activating small RNAs.

Schwartz, J. C., Younger S. T., Nguyen N., Hardy D., Prakash T., Bhat B., Monia B., Corey D.R. and *Janowski B.A. Nature Structural & Molecular Biology January 2008 15 842-848

Activating gene expression in mammalian cells with promoter-targeted duplex RNAs

Janowski, B.A., Younger, S.T., Hardy, D.B., Ram, R., Huffman, K.E., Corey, D.R. Nature Chemical Biology March 2007 3 166

Involvement of AGO1 and AGO2 in mammalian transcriptional gene silencing

Janowski, B.A., Huffman, K.E., Schwartz, J.C., Ram, R., Shames, D.S., Minna, J.D., Corey, D.R. Nature Structural and Molecular Biology September 2006 13 787

Inhibiting transcription of chromosomal DNA with antigene peptide nucleic acids.

Janowski, B. A., Kaihatsu, K., Huffman, K. E., Schwartz, J., Ram, R., Hardy, D., Mendelson, C.R., and Corey, D. R. Nature Chemical Biology September 2005 1 210-215

Inhibiting gene expression at transcription start sites in chromosomal DNA with antigene RNAs.

Janowski, B. A., Huffman, K. E., Schwartz, J., Ram, R., Hardy, D., Shames, D. S., Minna, J. D., and Corey, D. R. Nature Chemical Biology September 2005 1 216-222

• Awarded High Impacrt/High Risk Grant, Dean’s Office, UTSW
  Mechanism of Promoter-Directed RNAs on Gene Transcription (2008)
• Awarded Research Grant, Harold Simmons Comprehensive Cancer Center, UTSW
  RNA Switches at Gene Promoters: Turning off Cancer Cell Proliferation (2008)
• Plenary lecture, 4th International Symposium on Nucleic Acids Chemistry, Kyushu University, Japan
  Using RNA to turn off genes within chromosomal DNA (2005)
• Alfred Gilman Award
  Best Ph.D. thesis in the Department of Pharmacology (1998)
• Invited speaker, Hormone Action Gordon Conference
  Presented Ph.D. thesis work: discovery of new cholesterol signaling pathway (1998)