• Agarwal, Rajesh, Ph.D.
• Anchordoquy, Thomas J., Ph.D.
• Anderson, Peter, Pharm.D.
• Aquilante, Christina, Pharm.D.
• Bain, David L., Ph.D.
• Carpenter, John, Ph.D.
• Franklin, Christopher, Ph.D.
• Hail, Jr., Numsen, Ph.D.
• Irons, Richard D., Ph.D.
• Jones Braun, LaToya, Ph.D.
• Ju, Cynthia, Ph.D.
• Kiser, Jennifer, Pharm.D.
• Kompella Uday B., PhD
• Malkinson, Alvin M., Ph.D.
• Mallela, Krishna M. G., Ph.D.
• Maluf, N. Karl, Ph.D.
• Patel, Manisha, Ph.D.
• Petersen, Dennis R., Ph.D.
• Radcliffe, Richard, Ph.D.
• Ross, David, Ph.D.
• Ruth, James. A., Ph.D.
• Scheinman, Robert I., Ph.D.
• Thompson, John A., Ph.D.
• Vasiliou, Vasilis, Ph.D.

Robert I. Scheinman, Ph.D.

Assistant Professor of Biochemistry , Department of Pharmaceutical Sciences

Mailing address:
4200 E. 9th Ave, C238
Denver, CO 80262

Telephone:
Voice:     303-315-6194
Lab:        303-315-8049
Fax:        303-315-0274
E-Mail:   Robert.Scheinman@uchsc.edu

Affiliations:
Member, University of Colorado Cancer Center
Member, Pharmacology Gradute Program
Member, Biomedical Sciences Graduate Program

Training and Education:
B.S., Massachusetts Institute of Technology (Biology)
Ph.D., University of Washington, Seattle (Pharmacology)

Clinical/Research Interests:
                My work has focused on the biology of NF-κB for some time. NF-κB is a transcription factor that plays a role in numerous physiological processes including inflammation and the immune response. More recently, we have moved upstream to study the inflammatory cytokine TNF, which functions as a major activator of NF-κB. TNF plays a very interesting role in inflammation in that it is involved in both the initiation of the process as well as its resolution. This becomes of particular interest when one considers chronic inflammatory disease where both initiation and resolution signals are randomly intermixed. We are involved in studying these signaling interactions using rheumatoid arthritis and diabetes as disease models.
                Our work in rheumatoid arthritis (RA) has been particularly interesting. TNF clearly plays an important role in RA as evidenced by the use of TNF blockers such as Embrel and Remicade to treat this disease. We are in the process of dissecting TNF signaling circuitry in a mouse model of RA. We have both TNF receptor 1 and TNF receptor 2 knockout mice and have established a bone marrow transplant model in which we can limit receptor expression to specific tissue compartments. Using these manipulations we have uncovered an anti-inflammation (resolution) circuit for TNF involving cells of hematopoietic origin. We are currently mapping these circuits to better understand the nature of anti-inflammatory signaling mediated by TNF. The complexity of these circuits requires developing a model in which we can control TNF signaling in specific tissues in an inducible tissue specific fashion. We are currently generating the vectors to create these mice.
                Finally, an emerging area of research in my laboratory is the newly discovered protein: autoimmune regulator (AIRE). In the absence of AIRE function, humans develop antibodies against P450 and steroidogenic enzymes, resulting in the multiorgan autoimmune disease: APECED. This indicates that AIRE is required for the immune system to develop tolerance to this important class of enzymes. Our data indicates that AIRE functions to modify gene transcription by an as-of-yet unknown mechanism. We are currently studying AIRE biochemistry to better understand AIRE function.

Teaching:
Professional Program: Biochemistry, Pharmacology

Representative Publications:
Wheat, W., Kupfer, R., Gutches, D.G., Rayat, G.R., Beilke, J., Scheinman, R.I., and Wegmann, D.R. (2004) Increased NF-kB activity in B cells and bone marrow derived DC from Non-obese Diabetic (NOD) Mice. European J. Immunol. 34(5):1395-404.
Lang, J.A., Kominski, D., Bellgrau, D., and Scheinman, R.I. (2004) Partial Activation Precedes Apoptotic Death in T Cells Harboring an IAN Gene Mutation. European J. Immunol. 34:2396-2406.
Tao, Y., Kupfer, R., Stewart, B., Williams-Skipp, C., Crowell, C., Patel, D.D. Sain, S. and Scheinman, R.I. (2006) AIRE Recruits Multiple Transcriptional Components to Specific Genomic Regions Through Tethering to Nuclear Matrix. Molecular Immunology 43:335-45
Kupfer, R. Lang, J., Williams-Skipp, C., Nelson, M., Bellgrau D., and Scheinman, R.I. (2006) Loss of an gimap/ian Gene leads to Activation of NF-κB Through a MAPK Dependent Pathway. Molecular Immunol. In press
Crowell, CK, Grampp, GE, Rogers, GN, Miller, J, and Scheinman, RI. (2006) Amino Acid and Manganese Supplementation Modulates the Glycosylation state of Erythropoietin in a CHO culture system. Biotechnology and Bioengineering. In press.

Key Words: NF-κB, Arthritis, Diabetes, Inflammation, TNF, Signal transduction, Autoimmunity, Negative selection, Thymic selection, AIRE, Autoimmune Regulator

Curriculum Vitae
Recent Publications