Robert A. Mitchell, PhD


Associate Professor of Medicine, and Biochemistry & Molecular Biology; Scientist, James Graham Brown Cancer Center

Research Program
Molecular Targets

Education

B.S., University of Iowa, Iowa City, Immunology, 1989
Ph.D., Albany Medical College, Albany, NY, Pathology, 1998
Postdoctoral Fellow, Picower Institute for Medical Research, Manhasset, NY, 1998-1999

Research and Professional Experience
1989-1991
Principal Research Assistant, University of Minnesota, Minneapolis, MN

1991-1992
Senior Research Assistant, Rockefeller University, New York, NY

1992-1994
Senior Research Associate, Picower Institute for Medical Research, Manhasset, NY

1994-1998
Graduate Student, Albany Medical College, Albany, NY

1999-2001
Senior Scientist, Picower Institute for Medical Research, Manhasset, NY

2002-present
Assistant Professor of Medicine, Division of Medical Oncology/Hemotology, Department of Medicine, University of Louisville, Louisville, KY

2002-2008
Assistant Professor, Department of Biochemistry & Molecular Biology(secondary), University of Louisville, Louisville, KY

2002-present
Member, James Graham Brown Cancer Center, University of Louisville, Louisville, KY

2008-present
Associate Professor, Department of Medicine, University of Louisville, Louisville, KY

2008-present
Associate Professor, Department of Biochemistry & Molecular Biology (secondary), University of Louisville, Louisville, KY

Selected Awards and Profressional Honors
Member, American Association for the Advancement of Sciences

Member, Molecular Medicine Society

Ad hoc reviewer, Molecular Medicine, Oncology, Journal of Histochemistry and Cytochemistry, Clinical Cancer Research, Journal of Infectious Diseases, Journal of Pathology

Research Interest

Robert A. Mitchell Ph.D, joined the James Graham Brown Cancer Center as an Assistant Professor in the Departments of Medicine and Biochemistry & Molecular Biology and as a member of the Molecular Targets Program in May of 2002. He received his Ph.D. in Experimental Pathology from Albany Medical College and his B.S. from the University of Iowa School of Medicine. Prior to joining the staff at the Brown Cancer Center, Dr. Mitchell was a Senior Scientist at the Picower Institute for Medical Research in New York. His research focuses on the investigation and discovery of lipid mediators and polypeptides as soluble tumor-promoting molecules. A good deal of Dr. Mitchell’s current research focuses on the pro-inflammatory cytokine, migration inhibitory factor (MIF) as it relates to non-immune cell cycle regulation, oncogenic transformation and in vivo carcinogenesis. Biochemical and cell biology studies designed to identify cell surface, cytosolic and nuclear effectors of MIF action constitute about half of his lab efforts. A smaller portion of the laboratory’s research effort is aimed at the investigation and discovery of immunologic and small molecule inhibitors of MIF in hopes of identifying novel cancer chemotherapeutic compounds. The remainder of Dr. Mitchell’s lab effort focuses on establishing in vivo models of tumorigenesis and investigating novel anti-tumor vaccination strategies.

Publications

Mitchell RA, Bucala R.  Tumor growth-promoting properties of macrophage migration inhibitory factor (MIF).  Semin Cancer Biol 10:359-66, 2000

Sampey AV, Hall PH,
Mitchell RA, Metz CN, Morand EF.  Regulation of synoviocyte phospholipase A2 and cyclooxygenase 2 by macrophage migration inhibitory factor.  Arthritis Rheum 44:1273-80, 2001

Senter PD, Al-Abed Y, Metz CN, Benigni F,
Mitchell RA, Gartner CG, Nelson SD, Todaro GJ, Bucala R.  Inhibition of macrophage migration inhibitory factor (MIF) tautomerase and biological activities by acetaminophen metabolites.  Proc Natl Acad Sci USA 99:144-9, 2002

Mitchell RA, Liao H, Chesney J, Fingerle-Rowson G, Baugh J, David J, Bucala R.  MIF sustains macrophage pro-inflammatory function by inhibiting p53: Regulatory role in the innate immune response. Proc Natl Acad Sci USA 99:345-50, 2002

Dios A,
Mitchell RA, Aljabari B, Lubetsky J, O'Connor KA, Liao H, Senter PD, Manogue KR, Lolis E, Metz CN, Bucala R, Callaway DJ, Al-Abed Y.  Inhibition of MIF bioactivity by rational design of pharmacological inhibitors of MIF tautomerase activity.  J Med Chem 45:2410-6, 2002

Lubetsky JB, Dios A, Han J, Aljabari B, Ruzsicska B,
Mitchell RA, Lolis E, Al-Abed Y.  The tautomerase activity of MIF is a potential target for discovery of novel anti-inflammatory agents.  J Biol Chem  277:24976-82, 2002

Atsumi T, Chesney J, Metz C, Leng L, Donnelly S, Makita Z,
Mitchell RA, Bucala R.  High expression of inducible 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (iPFK-2; PFKFB3) in human cancers.  Cancer Res 62:5881-87, 2002

Liao H, Bucala R,
Mitchell RA.  Adhesion-dependent signaling by macrophage migration inhibitory factor (MIF).  J Biol Chem 278:76-81, 2003

Rendon-Mitchell B, Ochani M, Li J, Han J, Wang H, Yang H, Susarla S, Czura C,
Mitchell RA, Chen G, Sama AE, Tracey KJ, Wang H.  IFN-gamma induces high mobility group box 1 potein release partly through a TNF-dependent mechanism.  J Immunol 170:3890-7, 2003

Leng L, Metz CN, Fang Y, Xu J, Donnelly S, Baugh J, Delohery T, Chen Y, Mitchell RA, Bucala R.  MIF signal transduction initiated by binding to CD74.  J Exp Med 197:1467-76, 2003

Petrenko O, Fingerle-Rowson G, Peng T,
Mitchell RA, Metz CN.  Macrophage migration inhibitory factor deficiency is associated with altered cell growth and reduced susceptibility to Ras-mediated transformation.  J Biol Chem 278:11078-85, 2003

Mitchell RA.  Mechanisms and effectors of MIF-dependent promotion of tumourigenesis.  Cell Signall 16:13-9, 2004

Swant JD, Rendon BE, Symons M, Mitchell RA. Rho GTPase-dependent signaling is required for macrophage migration inhibitory factor-mediated expression of cyclin D1. J Biol Chem 280(24):23066-72, 2005

Atsumi T, Cho YR, Leng L, McDonald C, Yu T, Danton C, Hong EG, Mitchell RA, Metz C, Niwa H, Takeuchi J, Onodera S, Umino T, Yoshioka N, Koike T, Kim JK, Bucala R. The proinflammatory cytokine macrophage migration inhibitory factor regulates glucose metabolism during systemic inflammation. J Immunol 179(8):5399-406, 2007

Rendon BE, Roger T, Teneng I, Zhao M, Al-Abed Y, Calandra T, Mitchell RA. Regulation of human lung adenocarcinoma cell migration and invasion by macrophage migration inhibitory factor. J Biol Chem 282(41):29910-8, 2007

Winner M, Koong AC, Rendon BE, Zundel W, Mitchell RA. Amplification of tumor hypoxic responses by macrophage migration inhibitory factor-dependent hypoxia-inducible factor stabilization. Cancer Res 67(1):186-93, 2007

Winner M, Leng L, Zundel W, Mitchell RA.  Macrophage migration inhibitory factor manipulation and evaluation in tumoral hypoxic adaptation.  Methods Enzymol 435:355-69, 2007.  Review.

Kamir D, Zierow S, Leng L, Cho Y, Diaz Y, Griffith J, McDonald C, Merk M, Mitchell RA, Trent J, Chen Y, Kwong YK, Xiong H, Vermeire J, Cappello M, McMahon-Pratt D, Walker J, Bernhagen J, Lolis E, Bucala R.  A Leishmania ortholog of macrophage migration inhibitory factor modulates host macrophage responses.  J Immunol 180(12):8250-61, 2008.

Coleman AM, Rendon BE, Zhao M, Qian MW, Bucala R, Xin D, Mitchell RA.  Cooperative regulation of non-small cell lung carcinoma angiogenic potential by macrophage migration inhibitory factor and its homolog, D-dopachrome tautomerase.  J Immunol 181(4):2330-7, 2008

Winner M, Meier J, Zierow S, Rendon BE, Crichlow GV, Riggs R, Bucala R, Leng L, Smith N, Lolis E, Trent JO, Mitchell RA.  A novel, macrophage migration inhibitory factor suicide substrate inhibits motility and growth of lung cancer cells.  Cancer Res 68(18):7253-7, 2008

Brewer BG, Mitchell RA, Harandi A, Eaton JW.  Embryonic vaccines against cancer: An early history.  Exp Mol Pathol 86(3):192-197, 2009

Rendon BE, Willer SS, Zundel W, Mitchell RA.  Mechanisms of macrophage migration inhibitory factor (MIF)-dependent tumor microenvironmental adaptation.  Exp Mol Pathol 86(3):180-185, 2009

Xin D, Rendon BE, Zhao M, Winner M, McGhee Coleman A, Mitchell RA.  The MIF homologue D-dopachrome tautomerase promotes COX-2 expression through beta-catenin-dependent and -independent mechanisms.  Mol Cancer Res. 8(12):1601-9, 2010.  doi: 10.1158/1541-7786.MCR-10-0101

Yaddanapudi K, Mitchell RA, Putty K, Willer S, Sharma RK, Yan J, Bodduluri H, Eaton JW.  Vaccination with embryonic stem cells protects against lung cancer:  is a broad-spectrum prophylactic vaccine against cancer possible?  PLoS One 7(7):e42289, 2012.  doi: 10.1371/journal.pone.0042289

Brock SE, Rendon BE, Yaddanapudi K, Mitchell RA.  Negative regulation of AMP-activated protein kinase (AMPK) activity by macrophage migration inhibitory factor (MIF) family members in non-small cell lung carcinomas.  J Biol Chem. 287(45):37917-25, 2012.  doi: 10.1074/jbc.M112.378299

Yaddanapudi K, Putty K, Rendon BE, Lamont GJ, Faughn JD, Satosar A, Lasnik A, Eaton JW, Mitchell RA.  Control of tumor-associated macrophage alternative activation by macrophage migration inhibitory factor.  J Immunol. 190(6):2984-93, 2013.  doi: 10.4049/jimmunol.1201650

Yaddanapudi K, Mitchell RA, Eaton JW.  Cancer vaccines:  Looking to the future.  Oncoimmunology 2(3):e23403, 2013.

Contact Information

CTR Building
505 South Hancock Street
Louisville, KY 40202
(502) 852-7698


Fax: (502) 852-3799