Rajeev Aurora , Ph.D.
Rajeev Aurora , Ph.D.
Doisy Research Center
Rajeev Aurora , Ph.D.
Macrophages play an important and multifunctional role in health and disease. The best-known role is in innate immunity where they act as phagocytes and inflammatory cells. In addition, they also act as a lynch pin between innate and adaptive immunity as antigen presenting cells (APC). Macrophages also have a key function in the uptake and clearance of cholesterol interacting with low-density lipoproteins (LDL) as foam cells. Finally, macrophages can also be differentiated to become osteoclasts that function to absorb or degrade bone during remodeling. Our group is interested in using animal models to study the differentiation of monocytes into macrophages and the subsequent development of macrophages under various physiological conditions. We will utilize genomics, gene expression profiling, proteomics and the tools of systems biology to develop quantitative mathematical and statistical models of macrophage development. While this process is understood in detail at the cellular or phenotypic level, only a few key molecular players have been identified to date. Our goal is to use global measurements from microarrays and proteomics to infer the underlying molecular program that regulates homeostasis and drives the differentiation. One of the key players in all the processes mentioned above is NFkB; it is activated early in all the development pathways.
Therefore, a central question is: how is the specificity of the outcome determined? What set of signals and downstream events drive the macrophage towards any given differentiation program? How robust is this program and how many subsystems are there? How are these signals integrated (spatial compartmentalization and parallel processing), and how do they determine the fate? In order to generate quantitative models our group is also interested developing algorithms for network inference using graph theoretic approaches and Bayesian statistics. Mathematics to model complex circuits have been previously developed, however, many of these have not been applied to biological networks. Biological systems use feedback loops and other regulatory mechanisms; we will also develop methods to deal with these mathematically. The systems biology approach combines computational biology and bioinformatics, systems and control theory and modeling methods to develop a coherent and causal picture of this important biological phenomenon. More information is available http://macro.slu.edu
Rajeev Aurora, Ph.D.
R. Aurora, D. Chatterjee, J. Hentzleman, G. Prasad, R. Sindwani, T. Sanford
Contrasting the Microbiomes From Healthy Volunteers and Patients With Chronic Rhinosinusitis.
JAMA Otolaryngology 10.1001/jamaoto.2013.5465.
Pubmed Abstract Link: 24177790
Z. Buchwald, and R. Aurora.
Osteoclasts and CD8 T cells form a negative feedback loop that contributes to homeostasis of both the skeletal and immune systems.
Clin Dev Immunol 2013: 429373.
Pubmed Abstract Link: 23840242
Z. Buchwald, J. Kiesel, C. Yang, R. DiPaolo, D. Novack, R. Aurora
Osteoclast-induced Foxp3+ CD8 T-cells limit bone loss in mice.
Bone, 2013 56: 163-73.
Pubmed Abstract Link: 23756229
S.H. Dho, B. Deverman, C. Lapido, S. Manson, L. Gan, J. Riehm, R. Aurora, K.S. Kwon, S. Weintraub
Control of cellular Bcl-xL levels by deamidation-regulated degradation.
PLoS Biol, 2013 11: e1001588.
Pubmed Abstract Link: 23823868
J. Tavis, X. Cheng, Y. Hu, M. Totten, F. Cao, E. Michailidis, R. Aurora, M. Meyers, E. Jacobsen, M. Parniak, S. Sarafianos
The hepatitis B virus ribonuclease H is sensitive to inhibitors of the human immunodeficiency virus ribonuclease H and integrase enzymes.
PLoS Pathog, 2013 9: e1003125.
Pubmed Abstract Link: 23349632
R. Upadhya, L. Campbell, M. Donlin, R. Aurora, J, Lodge
Global transcriptome profile of Cryptococcus neoformans during exposure to hydrogen peroxide induced oxidative stress.
PLoS ONE, 2013 8: e55110.
Pubmed Abstract Link: 23383070
T. Zhu, J. Chappel, F. Hsu, J. Turk, R. Aurora, K. Hyrc, P. De Camilli, T. Broekelmann, R. Mecham, S. Teitelbaum, W. Zou
Type I phosphotidylinosotol 4-phosphate 5-kinase gamma regulates osteoclasts in a bifunctional manner.
J Biol Chem, 2013 288: 5268-77.
Pubmed Abstract Link: 23300084
M. Anderson*, Z. Buchwald*, J. Ko, R. Aurora1, T. Sanford1
Pediatric Obstructive Sleep Apnea Patients Show Altered T-Cell Populations With A Dominant TH17 Profile.
2013 Manuscript under review. * Equal contribution; 1Corresponding authors
Buchwald, Z. and Aurora, R
Osteoclasts and CD8 T-cells form a negative feedback loop that contributes to homeostasis of both the skeletal and immune system.
Clinical Developmental Immunology 2013:9.
Pubmed Abstract Link:23840242
Donlin MJ, Szeto B, Gohara DW, Aurora R, Tavis JE
Genome-wide networks of amino acid covariances are common among viruses.
J. Virol. 2012 Mar 86(6):3050-3063.
Pubmed Abstract Link:22238298
Buchwald ZA, Kiesel JR, DiPaolo R, Pagadama MS, Aurora R
Osteoclast activatd FoxP3+ CD8+ T-cells suppress bone resorption in vitro.
PLoS One 2012 Jun 6; 7(6):e38199.
Pubmed Abstract Link:22701612
Tavis JE, Donlin MJ, Aurora R, Fan X, Di Bisceglie AM.
Prospects for personalizing antiviral therapy for hepatitis C virus with pharmacogenetics.
Genome Med. 2011 Feb 8;3(2):8.
Pubmed Abstract Link:21345258
Donlin MJ, Cannon NA, Aurora R, Li J, Wahed AS, Di Bisceglie AM, Tavis JE; Virahep-C Study Group.
Contribution of genome-wide HCV genetic differences to outcome of interferon-based therapy in Caucasian American and African American patients.
PLoS One. 2010 Feb 3;5(2):e9032.
Pubmed Abstract Link:20140258
Singh AK, Bhattacharyya-Pakrasi M, Elvitigala T, Ghosh B, Aurora R, Pakrasi HB.
A systems-level analysis of the effects of light quality on the metabolism of a cyanobacterium.
Plant Physiol. 2009 Nov;151(3):1596-608. Epub 2009 Sep 16.
Kiesel JR, Buchwald ZS, Aurora R.
Cross-presentation by osteoclasts induces FoxP3 in CD8+ T cells.J Immunol. 2009 May 1;182(9):5477-87.
Aurora R, Donlin MJ, Cannon NA, Tavis JE.
Genome-wide hepatitis C virus amino acid covariance networks can predict response to antiviral therapy in humans.
J Clin Invest. 2009 Jan;119(1):225-36. doi: 10.1172/JCI37085. Epub 2008 Dec 22.
Pubmed Abstract Link:19104147
Welsh EA, Liberton M, Stöckel J, Loh T, Elvitigala T, Wang C, Wollam A, Fulton RS, Clifton SW, Jacobs JM, Aurora R, Ghosh BK, Sherman LA, Smith RD, Wilson RK, Pakrasi HB.
The genome of Cyanothece 51142, a unicellular diazotrophic cyanobacterium important in the marine nitrogen cycle.
Proc Natl Acad Sci U S A. 2008 Sep 30;105(39):15094-9. Epub 2008 Sep 23.
Pubmed Abstract Link:18812508
Dubec SJ, Aurora R, Zassenhaus HP.
Mitochondrial DNA mutations may contribute to aging via cell death caused by
peptides that induce cytochrome c release.
Rejuvenation Res. 2008 Jun;11(3):611-9.
Pubmed Abstract link: 18593279
Cannon NA, Donlin MJ, Fan X, Aurora R, Tavis JE; Virahep-C Study Group.
Hepatitis C virus diversity and evolution in the full open-reading frame during
PLoS ONE. 2008 May 7;3(5):e2123.
Pubmed Abstract link: 18463735
Stöckel J, Welsh EA, Liberton M, Kunnvakkam R, Aurora R, Pakrasi HB.
Global transcriptomic analysis of Cyanothece 51142 reveals robust diurnal
oscillation of central metabolic processes.
Proc Natl Acad Sci U S A. 2008 Apr 22;105(16):6156-61. Epub 2008 Apr 21.
Pubmed Abstract link: 18427117
Aurora R, Hihara Y, Singh AK, Pakrasi HB.
A network of genes regulated by light in cyanobacteria.
OMICS. 2007 Summer;11(2):166-85.
Pubmed Abstract link: 17594236
Kiesel J, Miller C, Abu-Amer Y, Aurora R.
Systems level analysis of osteoclastogenesis reveals intrinsic and extrinsic regulatory interactions.
Dev Dyn. 2007 Aug;236(8):2181-97.
Pubmed Abstract link: 17584858
Donlin MJ, Cannon NA, Yao E, Li J, Wahed A, Taylor MW, Belle SH, Di Bisceglie AM, Aurora R, Tavis JE; Virahep-C Study Group.
Pretreatment sequence diversity differences in the full-length hepatitis C virus open reading frame correlate with early response to therapy.
J Virol. 2007 Aug;81(15):8211-24.
Pubmed Abstract link: 17522222
U.S. Department of Energy's Biological and Environmental Research Program
Membrane Biology EMSL Scientific Grand Challenge Project
NSF Frontiers in Integrative Biological Research Program
A Systems Approach to Study Redox Regulation of Functions of Photosynthetic Organisms
Missouri Life Sciences Trust Fund 01/01/08-06/30/10
Discovery & Utilization of Enzymes for Renewable Biofuels Production