The University of Toledo

Dr. Doug Leaman's Research

 

Douglas Leaman

Professor and Chair
Ph.D. University of Missouri, 1993

 

 

 

 

Research

A primary focus of Dr. Leaman’s lab is the study of host-virus interactions. His laboratory is primarily interested in learning how interferons help protect cells from viral cytopathicity. In particular, his work is focuses on several proteins (RNF114, ISG12a, Noxa and XAF-1), some interferon-regulated, that are involved in mediating cellular innate immune responses to virus infections. These studies should help uncover molecular details of the antiviral mechanisms conferred by interferons. In addition, he has been studying the roles of specific viral proteins in blocking cellular innate immune responses. Some of this work is focused on a fish pathogen, viral hemorrhagic septicemia virus, which is a significant emerging pathogen in the Great Lakes. 

Publications (out of 56 since 1990)

Rosebeck, S.R., Sudini, K., T. Chen, and D.W. Leaman. (2011) Involvement of Noxa in mediating cellular ER stress responses to lytic virus infection. Virology. 417:293-303.

Cheriyath, V., DW Leaman and EC Borden. (2011) Emerging Roles of FAM14 Family Members (G1P3/ISG 6-16 and ISG12/IFI27) in Innate Immunity and Cancer. J IFN Cytokine Res. 31:173-181.

D. Goubau, R. Romieu-Mourez,M. Solis,E. Hernandez, T. Mesplède, R. Lin,D. Leaman, J. Hiscott. (2009) Transcriptional re-programming of primary macrophages reveals distinct apoptotic and anti-tumoral functions of IRF-3 and IRF-7. Eur. J. Immunol. Feb;39(2):527-40.

K. Vyas, S. Chaudhuri, D.W. Leaman, A.A. Komar, A. Musiyenko, S. Barik and B. Mazumder. (2009) Genome-wide polysome profiling reveals an inflammation-responsive post-transcriptional operon in IFN-γ-activated monocytes. Mol. Cell. Biol. 29(2):458-70.

Taylor KL, Leaman D.W., Grane R, Borden EC, Lindner DJ. (2008) Identification of Interferon-beta-Stimulated Genes That Inhibit Angiogenesis In Vitro. J Interferon Cytokine Res. 28:733-740

Leaman, D.W. (2008) Recent advances in Oligonucleotide Therapeutics: antisense to aptamers. Expert Opinion Drug Discovery 3:997-1009. 

Rosebeck, S.R. and D.W. Leaman. (2008) Mitochondrial localization of the Interferon-inducible protein ISG12a  Apoptosis. 13:562-572.

Sairyo, K., A. Biyani, V. K. Goel, D.W. Leaman, R. Booth Jr., J. Thomas, N. A. Ebraheim, I.A. Cowgill and S.E. Mohan.  (2007) Lumbar ligamentum flavum hypertrophy is due to accumulation of inflammation related scar tissue.  SPINE 32:2805-2811.

J.M. Paranjape, D. Xu, D.M. Kushner, J. Okicki, D. Lindner, H. Cramer, R.H. Silverman, and D.W. Leaman.  (2006) Assessing human telomerase RNA degradation by 2-5A- antisense chimeras in a cell-free system, tumor cells and murine xenografts.  Oligonucleotides, 16:225-240.

Reu, F., Bae, S., Cherkassky, L., Leaman, D.W., Beauliieu, N., Macleod, R., and E. Borden. (2006). Overcoming resistance to interferon-induced apoptosis of renal cancer and melanoma cells by DNA demethylation. J. Clin. Oncol. (Epub Jun 2006).

Reu, F., D.W. Leaman, Ratan Maitra, Soo In Bae, Leonid Cherkassky, Mark W. Fox, Donald R. Repinski, Normand Beaulieu, Mamta Chawla-Sarkar, A. Robert MacLeod, Ernest C. Borden. (2006) Expression of RASSF1A, an epigenetically silenced tumor suppressor, overcomes resistance to apoptosis induction by interferons. Cancer Res. 66:2785-2793.

Mohammad, M.K., B. Slotterbeck, M. Morran, D.W. Leaman, H. von Grafenstein, S-C. Hong, M.F. McInerney. (2006) Dysregulated Toll Like Receptors in Bone Marrow Derived Macrophages at the Onset of Diabetes in the Nonobese Diabetic Mouse. Int. Immunol. 18:1101-1113.

Taylor KL, RK Oates, R Grane, D.W. Leaman, EC Borden, and DJ Lindner. (2006) IFN-alpha1,8 Inhibits Tumor-Induced Angiogenesis in Murine Angiosarcomas. J Interferon Cytokine Res. 26:353-361.

Leaman, D.W., S. Rosebeck and E.C. Borden. (2005) Biological and Clinical Properties of Type I Interferons. In “Immunotherapy of Cancer”, Humana Press. pp 365-396.

Leaman, D.W. (2005). 2-5A Antisense Treatment of Respiratory Syncytial Virus. Current Opinions in Pharmacology, 5:502-507.

Sun, Y. and D.W. Leaman. (2005) Involvement of Noxa in cellular apoptotic responses to interferon, double-stranded RNA and virus infection. J. Biol. Chem. 280:15561-15568.

Sairyo, K., Biyani, A., Goel, V., Leaman, D.W., Booth Jr., R., Thomas, J., Gehling, D., Vishnubhotla, S., Long, R. and N. Ebraheim. (2005). Pathomechanism of ligamentum flavum hypertrophy: A multidisciplinary investigation based on clinical, biochemical, histological and biological assessments. SPINE, 30:2649-2656.

Sun, Y and D.W. Leaman. (2004) Ectopic expression of Toll-like receptor 3 (TLR3) overcomes the double-stranded RNA (dsRNA) signaling defects of P2.1 cells. J. IFN Cytokine Res. 24:350-361.

Sarkar, S., D. W. Leaman, S. Gupta, P. Sil, D. Young, A. Morehead, D. Mukherjee, Y. Sun, N. Ratliff, M. Rayborn, J. Hollyfield, and S. Sen. (2004) Cardiac Over-expression of Myotrophin Triggers Myocardial Hypertrophy and Heart Failure in Transgenic Mice. J. Biol. Chem. 279:20422-20434.

P. Madasamy, R. V. Sairam, R. Myers, H. Weirich, B. Smith, D.W. Leaman, S.L. Goldman. (2004) Microarray Analysis of Nitric Oxide Responsive Transcripts in Arabidopsis. Plant Biotechnology J. 2:359-366.

Leaman, D.W., M. Chawla-Sarkar, B. Jacobs, K. Vyas, Y. Sun, A. Ozdemir, T. Yi, B. Williams and E.C. Borden. (2003) Novel Growth and Death Related Interferon Stimulated Genes (ISGs) in Melanoma: Greater Potency of IFN-beta compared with IFN-alpha. J. IFN and Cytokine Res. 23:745-756

Vyas, K, D. L. Brassard, M. M. Y. Sun, M. J. Grace, E. C. Borden and D.W. Leaman. (2003). Biologic activity of polyethylene glycol12000-IFN- alpha 2b (PEG-IFN- alpha 2b) compared to IFN-alpha2b: Gene modulatory and anti-growth effects in tumor cells. J. Immunother. 26:202-211.

Leaman, D.W., M. Chawla-Sarkar, K. Vyas, M. Reheman, S. Toji, K Tamai and E.C. Borden. (2002). Identification of X-linked Inhibitor of Apoptosis-Associated Factor-1 (XAF1) as an Interferon-stimulated gene that augments TRAIL/Apo2L-induced apoptosis. J. Biol. Chem. 277:28504-28511.

Chawla-Sarkar, M., D. W. Leaman, B. S. Jacobs and E.C. Borden. (2002) IFN-b pretreatment sensitizes human melanoma cells to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL/Apo2L) induced apoptosis. J. Immunol. 169:847-855.