Clifford Steer, MD
Professor of Medicine
University of Minnesota, Minneapolis
University of Minnesota, Minneapolis
Dr. Steer accepted a Hepatology Fellowship at the NIH in the Section on Diseases of the Liver and remained on staff at the NIH as an Expert in his field for an additional 10 years. In 1989, Dr. Steer joined the University of Minnesota as a Professor in the Department of Medicine, Genetics and Cell Development. During his time at the University, Dr. Steer has been active in mentorship of PhD students and post-doctoral fellows in his lab, is a member of multiple committees and has continued to be academically productive in his current area of research.
- The Sleeping Beauty (SB) transposon system
- Ursodeoxycholic acid (UDCA), a hydrophilic bile acid
- Role of microRNAs in gene regulation for a number of different target organs and stem cell populations
- Basic and translational applications to human disease.
Steer’s laboratory has been involved in three major areas of research during the last five years. The Sleeping Beauty (SB) transposon system functions via a cut-and-paste mechanism catalyzed by the binding of SB transposase to inverted repeats/direct repeats (IR/DRs) of the mariner transposon. It excises the relevant transgene from the transposon at the IR/DRs and inserts the element into random TA dinucleotide sites within the genome. They are applying SB as a gene therapy vector to a variety of different animal disease models, including liver, bone marrow and brain disorders. Steer's laboratory is also interested in characterizing the effects of SB transposition on genomic methylation and histone acetylation.
The second major area of research involves the use of ursodeoxycholic acid (UDCA), a hydrophilic bile acid, as a potent antiapoptotic agent. They have used UDCA as a therapeutic agent to treat transgenic models of Huntington’s disease and retinitis pigmentosa as well as acute stroke, spinal cord injury, myocardial infarction, and acute renal failure. Steer's laboratory continues to study basic mechanisms and translational applications of UDCA. Of note, the South Korean FDA has recently approved its use for the treatment of ALS.
Steer's lab is actively characterizing the role of microRNAs in gene regulation for a number of different target organs and stem cell populations. In particular, they have identified specific microRNAs that may be involved in the progression of colon from polyp to cancer; as well as their role in the regenerating liver. The studies are both basic and translational in nature. They are also identifying specific microRNAs as biomarkers of disease that can be assayed in blood. Most notably, they have recently discovered a unique nuclear profile of mature microRNAs; and a subset of microRNAs in mitochondria that may act as a rheostat for the control of apoptosis.
- Aravalli RN, Sahin MB, Cressman ENK, and Steer CJ: Establishment and characterization of a unique 1-µm diameter liver-derived progenitor cell line. Biochem Biophys Res Commun 391:56-62, 2010.
- Zhu J, Park CW, Sjeklocha L, Kren BT, and Steer CJ: High-level genomic integration, epigenetic changes, and expression of Sleeping Beauty transgene. Biochemistry 2010 Jan 22 [Epub ahead of print].
- Wang L, Tang H, Thayanithy V, Subramanian S, Oberg AL, Cunningham JM, Cerhan JR, Steer CJ, and Thibodeau SN: Gene networks and microRNAs implicated in aggressive prostate cancer. Cancer Res 69:9490-9497, 2009.
- Sarver AL, French AJ, Borralho PM, Thayanithy V, Oberg AL, Silverstein KAT, Morlan BW, Riska SM, Boardman LA, Cunningham JM, Subramanian S, Wang L, Smyrk TC, Rodrigues CMP, Thibodeau SN, and Steer CJ: Human colon cancer profiles show differential microRNA expression depending on mismatch repair status and are characteristic of undifferentiated proliferative states. BMC Cancer 9:401, 2009.
- Kren BT, Wong PY-P, Shiota A, Zhang X, Zeng Y, and Steer CJ: Polysome trafficking of transcripts and microRNAs in regenerating liver after partial hepatectomy. Am J Physiol Gastrointest Liver Physiol 297:G1181-G1192, 2009.
- Kren BT, Unger GM, Sjeklocha L, Trossen AA, Korman V, Diethelm-Okita BM, Reding MT, and Steer CJ: Nanocapsule-delivered Sleeping Beauty mediates therapeutic FVIII expression in liver sinusoidal endothelial cells of hemophilia A mice. J Clin Invest 119:2086-2099, 2009.
- Kren BT, Wong PY-P, Sarver A, Zhang X, Zeng Y, and Steer CJ: microRNAs identified in highly purified liver-derived mitochondria may play a role in apoptosis. RNA Biology 6:65-72, 2009.
- Amaral JD, Castro RE, Solá S, Steer CJ, and Rodrigues CMP: p53 is a key molecular target of ursodeoxycholic acid in regulating apoptosis. J Biol Chem 282:34250-34259, 2007.
- Zhu J, Kren BT, Park CW, Bilgim R, Wong PY-P, and Steer CJ: Erythroid-specific expression of -globin by the Sleeping Beauty transposon for sickle cell disease. Biochemistry 46:6844-6858, 2007.
- Kren BT, Yin W, Key NS, Hebbel RP, and Steer CJ: BOEC as a vehicle for transgene delivery of hepatocyte secreted proteins via Sleeping Beauty. Endothelium 14:97-104, 2007.