Clifford Steer, MD

Professor of Medicine, Division of Gastroenterology, Hepatology, and Nutrition

Clifford Steer

Contact Info

steer001@umn.edu

Office Phone 612-625-6648

Mailing Address:
420 Delaware ST SE
MMC 36
Minneapolis, MN 55455

Administrative Phone
612-624-9684

Administrative Email
gidivision@umn.edu

Professor of Medicine, Division of Gastroenterology, Hepatology, and Nutrition

Faculty, Graduate School Program in Integrative Biology and Physiology

Faculty, Graduate School in Molecular, Cellular, Developmental Biology and Genetics

Faculty, Graduate Degree Program in Stem Cell Biology

Faculty, Graduate Program, College of Veterinary Medicine

Preceptor, Medical Scientist Training Program (Combined MD/PhD Training Program)

Director, Physician-Scientist Training Program

Member, Stem Cell Institute


Medical School, University of Minnesota, Minneapolis, MN

Medicine Residency, University of Minnesota, Minneapolis, MN

Fellowship, National Institute of Health, Bethesda, MD

Bachelor's Degree, University of Minnesota, Minneapolis, MN

Summary

Dr. Steer accepted a Hepatology Fellowship at the NIH in the Section on Diseases of the Liver in 1976 and remained on staff at the NIH as an Expert in his field for an additional 10 years. In 1989, Dr. Steer returned to the University of Minnesota as a Professor in the Departments of Medicine, and Genetics, Cell Biology and 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, which is regenerative medicine.

Awards & Recognition

  • Phi Beta Kappa, Magna Cum Laude, University of Minnesota (1970)
  • Holloman Award in Biotechnology (1998)
  • American Society for Clinical Investigation (1991)
  • Associate Editor, Hepatology (2001-06)
  • Thorne Stroke Award (2004)
  • Department of Medicine Faculty Award for Outstanding Research (2004)
  • Member, NIH Gene and Drug Delivery Systems Study Section (2004-08)
  • Member, Gastrointestinal Cell and Molecular Biology Study Section (2008-09)
  • Member, Hepatobiliary Pathophysiology Study Section (2009-2012)
  • Honorary Editorial Board member, Hepatic Medicine: Evidence and Research, (2009–pres)
  • Senior Investigator Award, University of Minnesota Medical School (2012)
  • Fellow, American Association for the Study of Liver Diseases (2014)

Research

Research Summary/Interests

  • The Sleeping Beauty (SB) transposon system in non-viral gene therapy
  • Ursodeoxycholic acid (UDCA), a hydrophilic bile acid, as an anti-apoptotic agent
  • Role of microRNAs in gene regulation for different target organs and stem cell populations
  • Basic and translational applications to human disease
  • Regenerative medicine using gene editing (CRISPR) and blastocyst complementation

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.

Over the past seven years, Steer’s lab has also focused on regenerative medicine, and research to create human livers in pigs for transplantation. The approach utilizes a combination of gene editing and a technology referred to as blastocyst complementation. This involves the knockout (KO) of specific developmental genes in the blastocyst of the pig; and the intra-blastocyst injection of pluripotent stem cells from the human donor to generate offspring that carry organs/cell types derived from that donor. The ultimate goal is to create human livers in pigs that are immunology identical to the recipient, thereby not requiring the use of immunosuppression…a paradigm shift in organ transplantation.

Publications

  • Aravalli RN, Shiao M, Lu W-C, Xie H, Pearce C, Toman NG, Danczyk G, Sipe C, Miller ZD, Crane A, Voth J, Low WC, and Steer CJ. The bioengineering of exogenic organs and/or cells for use in regenerative medicine. In Iaizzo P (Ed): Engineering in Medicine, lst ed., Academic Press, 2019, pp. 381-415.
  • Moscoso CG, Potz KR, Tan S, Jacobson PA, Berger KM, and Steer CJ: Precision medicine, agriculture and genome editing: science and ethics. Ann NY Acad Sci 1465:59-75, 2020.
  • Collins DP, Hapke JH, Aravalli RN, and Steer CJ. Development of immortalized human hepatocyte-like hybrid cells by fusion of multi-lineage progenitor cells with primary hepatocytes. PLoS ONE 15(6):e0234002, 2020.
  • Collins DP and Steer CJ. Binding of the SARS-CoV-2 spike protein to the asialoglycoprotein receptor on human primary hepatocytes and immortalized hepatocyte-like cells by confocal analysis. Hepatic Med 13:37-44, 2021.
  • Ruiz-Estevez M, Crane AT, Rodriguez-Villamil P, Ongaratto FL, You Y, Steevens AR, Hill C, Goldsmith T, Webster DA, Sherry L,Lim S,Denman N,Low WC, Carlson DF, Dutton JR, Steer CJ, and Gafni O. Liver development is restored by blastocyst complementation of HHEX knockout in mice and pigs. Stem Cell Res Ther 12(1):292, 2021.