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Clifford J. Steer, M.D.

Professor


Mailing Address:
University of Minnesota
Department of Genetics, Cell Biology, and Development
6-160 Jackson
321 Church St. SE
Minneapolis, MN 55455
USA


Education:
M.D. University of Minnesota, 1974

Honors:
Office:
A536 Mayo
P: 612-625-8999 or
612-624-6648
F: 612-625-5620

Email:
steer001@umn.edu

Lab:
6-207 PWB
P: 612-625-0979

Areas of Research Strength:

Membranes and receptors
Cell interactions
Gene expression
Gene Therapy
Apoptosis


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Research Techniques:

Light, confocal and electron microscopy
Immunostaining and morphometric analysis
FACS analysis
Northern, western and Southern blotting
Isolation of nuclei, polysomes and mitochondria
Run-on transcription, in vitro RNA decay and RNase protection
Electrophoretic mobility gel shifts
Microarrrays
Tissue culture both primary and cell lines
Reporter gene assays - luciferase and CAT
PCR, RT-PCR, quantitative PCR and RT-PCR, real-time PCR
Apoptosis detection: TUNEL, annexin, mitochondrial and caspase assays
Plasmid and transgene construction using the Sleeping Beauty transposon system
Nonviral transgene and oligonucleotide delivery for gene augmentation and repair
Biochemical assays for gene activity - specific to model system being studied
Protein production and purification


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Research Interests:

The Steer laboratory is involved in two major areas of research. In the first,
the lab has over the last six years developed a novel gene therapy that involves
the precise repair of genetic defects in cells. The lab has concentrated on the
genetic repair of a variety of diseases, including hemophilia, sickle cell disease,
Crigler-Najjar syndrome type I, ornithine transcarbamylase deficiency,
ß-thalassemia, von Willebrand’s disease and certain neurodegenerative
disorders like Huntington’s disease. In fact, Steer has successfully treated
several accurate animal models for these human disorders. The technology
of gene repair is remarkable for its broad application. The ability to now correct
a genetic sequence in combination with the knowledge from the human genome
project creates a remarkable vista of potential therapeutic clinical studies. The
correction of a precise genetic defect allows the gene to be endogenously
regulated without the potential problems associated with viral vectors. It may
provide us with the first cures to diseases such as sickle cell and hemophilia.
The Steer lab has successfully elucidated the basic science and will now apply
the technology as therapy for human disease. In addition, the lab has also
developed a more traditional type of gene therapy for diseases that are
not candidates for genetic repair. However, while it is just as powerful
as any traditional approach, it does not require potentially harmful viral
vectors. The future of gene therapy is non-viral and that is the focus
of our research as it applies to human therapy.

In the second area research, Steer has discovered that ursodeoxycholic
acid, an endogenous hydrophilic bile acid in humans, is a potent antiapoptotic
agent. Several animal models have been for diseases that are relatively
accurate to their human counterparts. Specifically, ursodeoxycholic
acid as a therapeutic agent to treat models of Huntington’s disease,
head trauma, acute stroke, as well as Parkinson’s disease. One common
characteristic shared by these disorders as well as others is the role that
apoptosis plays in disease progression. Bile acid has been determined as
a potent antiapoptotic agent, significantly improves neurologic status in
these models. In the basic science studies, the lab has delineated the
molecular mechanism by which ursodeoxycholic acid acts to preserve
cell survival and cell function. As a therapeutic agent, ursodeoxycholic
acid is unique in that it is a natural bile acid with no toxicity, crosses the
blood-brain barrier, and can be delivered easily to patients. There are,
in fact, many disease states that could potentially benefit, including
myocardial infarction, autoimmune diseases, and the many acute
and chronic neurodegenerative disorders for which there is little
available treatment.

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Selected Publications:

Amaral JD, Viana RJS, Ramalho RM, Steer CJ, and Rodrigues CMP:  Bile acids: regulation of apoptosis by ursodeoxycholic acid.  J Lipid Res, in press.

Wang X, Sarkar DP, Mani P, Steer CJ, Chen Y, Guha C, Chandrasekhar V, Chaudhuri A, Roy-Chowdhury N, Kren BT, and Roy-Chowdhury J:  Long-term reduction of jaundice in Gunn rats by non-viral liver-targeted delivery of Sleeping Beauty transposon.  Hepatology, in press.

Aravalli RN, Steer CJ, Sahin B, and Cressman ENK: Stem cell origins and animal models of hepatocellular carcinoma. Dig Dis Sci, in press

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, in press.

Aranha MM, Solá S, Low WC, Steer CJ, and Rodrigues CMP: Caspases and p53 modulate FOXO3A/Id1 signaling during mouse neural stem cell differentiation. J Cell Biochem 107:748-758, 2009.

Wang L, Oberg AL, Asmann YW, Sicotte H, McDonnell SK, Riska SM, Liu W, Steer CJ, Subramanian S, Cunningham JM, Cerhan JR, and Thibodeau SN: Genome-wide transcriptional profiling reveals microRNA-correlated genes and biological processes in human lymphoblastoid cell lines. PLoS ONE 4(6):e5878, 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 Biol 6:65-72, 2009

Bruzzone CM, Belcher JD, Schuld NJ, Newman KA, Vineyard J, Nguyen J, Chen C, Beckman JD, Steer CJ, and Vercellotti GM: Quantitative real-time polymerase chain reaction (qRT-PCR) restriction fragment length polymorphism (RFLP) method for monitoring highly conserved transgene expression during gene therapy. Transl Res 152:290-297, 2008.

Aravalli RN, Steer CJ, and Cressman ENK: Molecular mechanisms of hepatocellular carcinoma. Hepatology 48:2047-2063, 2008.

Ramalho RM, Viana RS, Castro RE, Steer CJ, Low WC, and Rodrigues CMP: Apoptosis in transgenic mice expressing the P301L mutated form of human tau. Mol Med 14:309-317, 2008

Wangensteen KJ, Wilber A, Keng VW, He Z, Matise I, Wangensteen L, Carson CM, Chen Y, Steer CJ, McIvor RS, Largaespada DA, Wang X, and Ekker SC: A facile method for somatic, lifelong manipulation of multiple genes in the mouse liver. Hepatology 47:1714-1724, 2008

Ramalho RM, Viana RJS, Low WC, Steer CJ, and Rodrigues CMP: Bile acids and apoptosis modulation: an emerging role in experimental Alzheimer's disease. Trends Mol Med 14:54-62, 2008.

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.

Castro RE, Solá S, Steer CJ, and Rodrigues CMP: Bile acids as modulators of apoptosis. In Sahu SC (Ed): Hepatotoxicity: From Genomics to in vitro and in vivo Models, Wiley & Sons, Ltd, 2007, pp. 391-419

Castro RE, Amaral JD, Solá S, Kren BT, Steer CJ, and Rodrigues CMP: Differential regulation of cyclin D1 and cell death by bile acids in primary rat hepatocytes. Am J Physiol Gastrointest Liver Physiol 293:G327-G334, 2007

Amaral JD, Solá S, Steer CJ, and Rodrigues CMP: Function of nuclear steroid receptors in apoptosis: role of ursodeoxycholic acid. Expert Rev Endocrinol Metab 2:487-501, 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


To view these and other publications visit http://www.ncbi.nlm.nih.gov/PubMed
search menu should say PubMed
type Steer CJ in the avaliable line

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