University of Cincinnati Department of Pediatrics

Bruce Aronow, PhD

Title

Professor; Co-director, Computational Medicine Center

Appointment

Professor of Pediatrics, University of Cincinnati College of Medicine

Email

bruce.aronow@cchmc.org

Phone

513-636-0263

Fax

513-636-2056

Bio

Dr. Aronow's research lab is devoted to unraveling both the role and mechanism by which the functional capabilities of the human genome shape human health and our ability to adapt to stressful challenges. His lab is using a wide variety of available structural and functional genomic and biological systems descriptive data to form models of how biological systems assemble, adapt and become impaired in disease. The lab's overall hypothesis is that by interconnecting as much experimental and observational information as possible, we can gain new insights into the mechanisms by which different biological systems can achieve health or healthy adaptation, or undergo disease processes.

More specific, with the co-leadership of Anil Jegga, DVM, the lab is identifying genetic features that control gene expression including cis-elements, trans factors and microRNAs, which normally work together in extended cell, tissue, organ and systems networks to enable development and homeostasis. Alterations of these features can alter phenotypes and increase or decrease disease. Some of the lab's work includes the identification of conserved, diverged and evolved cis-element clusters that are acted on by transcription and chromatin proteins. The lab has developed a web-based tool called GenomeTraFaC that at present allows discovery of shared cis-elements in conserved non-coding sequences of mice and humans. GenomeTraFaC identifies the cis-elements in phylogenetic footprints, or non-coding DNA regions of six or more base pairs having almost 100 percent similarity and conserved across several species separated by several million years of evolution.

Extending the scope of GenomeTraFaC, the lab has developed CisMols, a tool that identifies compositionally similar cis-regulatory element clusters that occur in groups of co-regulated genes. These computationally predicted cis-clusters could serve as valuable probes for genome-wide identification of regulatory regions.

Another area of the lab's research is the integration of SNP information with the protein structure and protein functional domains. The lab is using all available gene-to-disease and gene-to-pathway association data to study the effects of non-synonymous SNPs and other important polymorphisms that occur in functional domains of proteins in specific diseases and biological processes. The lab has developed another web-based tool, PolyDoms, to aid in this effort.

Credentials

BS: Chemistry, Stanford University, Stanford, CA, 1976
PhD: Biochemistry, University of Kentucky, Lexington, KY, 1986
Research Fellowship: Division of Basic Science Research, Cincinnati Children's Research Foundation, Cincinnati, OH, 1986-1989

Awards and Honors

Work "Central role of c-myb in a thymic locus control region" (senior author, B. Aronow) awarded "Theodore Woodward Award" by the Society for Clinical and Climatologic Studies from the Mayo Foundation, 1997.
Leo Prize for "A repressor-switch mechanism regulates tissue specific and injury inducible gene expression in transgenic mice." 3rd International Workshop on Clusterin, Villars-sur-Ollon, Switzerland, January 1997.
Publication "Coordinate developmental regulation" in J. Cell Biol. (1991, senior author, B. Aronow) awarded 1992 Lotte Strauss Prize for Outstanding Basic Research Paper, Pediatric Pathology Society, 1992.
National Research Service Award GM119828, 1987-1989.
University Fellow: University of Kentucky, 1983-1985.
Annual Sigma Xi Graduate Research Award, University of Kentucky, 1984.

Research Grants and Contracts

Title: CTSA - Enabling Tehnologies: Ctr for Translational & Molecular Disease
Sponsor: National Institutes of Health (University of Cincinnati)
Dates: 04/03/09 - 03/31/14

Title: Murine Atlas of Genitourinary Smooth Muscle Development
Sponsor: National Institutes of Health
Dates: 04/01/09 - 03/31/10

Title: Digestive Health Center: Bench to Bedside Research in Pediatric Digestive Disease
Sponsor: National Institutes of Health
Dates: 06/01/09 - 05/31/10

Publications, Most Recent

Barnes MG, Grom AA, Thompson SD, Griffin TA, Pavlidis P, Itert L, et al. Subtype-specific peripheral blood gene expression profiles in recent-onset juvenile idiopathic arthritis. Arthritis and rheumatism. 2009 Jul;60(7):2102-12.

Qu XA, Gudivada RC, Jegga AG, Neumann EK, Aronow BJ. Inferring novel disease indications for known drugs by semantically linking drug action and disease mechanism relationships. BMC Bioinformatics. 2009 May;10 Suppl 5:S4.

Gu Y, Harley IT, Henderson LB, Aronow BJ, Vietor I, Huber LA, et al. Identification of IFRD1 as a modifier gene for cystic fibrosis lung disease. Nature. 2009 Apr 23;458(7241):1039-42.

Nishijo K, Chen QR, Zhang L, McCleish AT, Rodriguez A, Cho MJ, et al. Credentialing a preclinical mouse model of alveolar rhabdomyosarcoma. Cancer Res. 2009 Apr 1;69(7):2902-11.

Chen J, Aronow BJ, Jegga AG. Disease candidate gene identification and prioritization using protein interaction networks. BMC Bioinformatics. 2009 Feb;10:73.

Shen H, Powers N, Saini N, Comstock CE, Sharma A, Weaver K, et al. The SWI/SNF ATPase Brm is a gatekeeper of proliferative control in prostate cancer. Cancer Res. 2008 Dec 15;68(24):10154-62.

Brunskill EW, Aronow BJ, Georgas K, Rumballe B, Valerius MT, Aronow J, et al. Atlas of gene expression in the developing kidney at microanatomic resolution. Developmental cell. 2008 Nov;15(5):781-91.

Mahller YY, Sakthivel B, Baird WH, Aronow BJ, Hsu YH, Cripe TP, et al. Molecular analysis of human cancer cells infected by an oncolytic HSV-1 reveals multiple upregulated cellular genes and a role for SOCS1 in virus replication. Cancer Gene Ther. 2008 Nov;15(11):733-41.

Kucherlapati MH, Yang K, Fan K, Kuraguchi M, Sonkin D, Rosulek A, et al. Loss of Rb1 in the gastrointestinal tract of Apc1638N mice promotes tumors of the cecum and proximal colon. Proc Natl Acad Sci U S A. 2008 Oct 7;105(40):15493-8.

Gudivada RC, Qu XA, Chen J, Jegga AG, Neumann EK, Aronow BJ. Identifying disease-causal genes using Semantic Web-based representation of integrated genomic and phenomic knowledge. J Biomed Inform. 2008 Oct;41(5):717-29.

Kardia SL, Kelly RJ, Keddache MA, Aronow BJ, Grabowski GA, Hahn HS, et al. Multiple interactions between the alpha 2C- and beta1-adrenergic receptors influence heart failure survival. BMC medical genetics. 2008 Oct;9:93.

Swift SM, Gaume BR, Small KM, Aronow BJ, Liggett SB. Differential coupling of Arg- and Gly389 polymorphic forms of the beta1-adrenergic receptor leads to pathogenic cardiac gene regulatory programs. Physiol Genomics. 2008 Sep 17;35(1):123-31.

Chakraborty S, Cheek J, Sakthivel B, Aronow BJ, Yutzey KE. Shared gene expression profiles in developing heart valves and osteoblast progenitor cells. Physiol Genomics. 2008 Sep 17;35(1):75-85.

Sun Y, Jia L, Williams MT, Zamzow M, Ran H, Quinn B, et al. Temporal gene expression profiling reveals CEBPD as a candidate regulator of brain disease in prosaposin deficient mice. BMC Neurosci. 2008;9:76.

Chen X, Ehrhardt WM, Halberg RB, Aronow BJ, Dove WF. Cellular expression patterns of genes upregulated in murine and human colonic neoplasms. J Histochem Cytochem. 2008 May;56(5):433-41.

Ouyang X, Jessen WJ, Al-Ahmadie H, Serio AM, Lin Y, Shih WJ, et al. Activator protein-1 transcription factors are associated with progression and recurrence of prostate cancer. Cancer Res. 2008 Apr 1;68(7):2132-44.

Aronow BJ. Dysfunctional genomics: toward an integrative biology of disease and health--application to IBDs. J Pediatr Gastroenterol Nutr. 2008 Apr;46 Suppl 1:E3-4.

McMahon AP, Aronow BJ, Davidson DR, Davies JA, Gaido KW, Grimmond S, et al. GUDMAP: the genitourinary developmental molecular anatomy project. J Am Soc Nephrol. 2008 Apr;19(4):667-71.

Jegga AG, Inga A, Menendez D, Aronow BJ, Resnick MA. Functional evolution of the p53 regulatory network through its target response elements. Proc Natl Acad Sci U S A. 2008 Jan 22;105(3):944-9.

Heineke J, Auger-Messier M, Xu J, Oka T, Sargent MA, York A, et al. Cardiomyocyte GATA4 functions as a stress-responsive regulator of angiogenesis in the murine heart. J Clin Invest. 2007 Nov;117(11):3198-210.

Chen J, Xu H, Aronow BJ, Jegga AG. Improved human disease candidate gene prioritization using mouse phenotype. BMC Bioinformatics. 2007;8:392.

Banach-Petrosky W, Jessen WJ, Ouyang X, Gao H, Rao J, Quinn J, et al. Prolonged exposure to reduced levels of androgen accelerates prostate cancer progression in Nkx3.1; Pten mutant mice. Cancer Res. 2007 Oct 1;67(19):9089-96.

Shanley TP, Cvijanovich N, Lin R, Allen GL, Thomas NJ, Doctor A, et al. Genome-level longitudinal expression of signaling pathways and gene networks in pediatric septic shock. Mol Med. 2007 Sep-Oct;13(9-10):495-508.

Jeong JW, Lee KY, Han SJ, Aronow BJ, Lydon JP, O'Malley BW, et al. The p160 steroid receptor coactivator 2, SRC-2, regulates murine endometrial function and regulates progesterone-independent and -dependent gene expression. Endocrinology. 2007 Sep;148(9):4238-50.

Mayhew CN, Carter SL, Fox SR, Sexton CR, Reed CA, Srinivasan SV, et al. RB loss abrogates cell cycle control and genome integrity to promote liver tumorigenesis. Gastroenterology. 2007 Sep;133(3):976-84.

Oka T, Xu J, Kaiser RA, Melendez J, Hambleton M, Sargent MA, et al. Genetic manipulation of periostin expression reveals a role in cardiac hypertrophy and ventricular remodeling. Circ Res. 2007 Aug 3;101(3):313-21.

Deichmann A, Hacein-Bey-Abina S, Schmidt M, Garrigue A, Brugman MH, Hu J, et al. Vector integration is nonrandom and clustered and influences the fate of lymphopoiesis in SCID-X1 gene therapy. J Clin Invest. 2007 Aug;117(8):2225-32.

Wong HR, Shanley TP, Sakthivel B, Cvijanovich N, Lin R, Allen GL, et al. Genome-level expression profiles in pediatric septic shock indicate a role for altered zinc homeostasis in poor outcome. Physiol Genomics. 2007 Jul 18;30(2):146-55.

Markey MP, Bergseid J, Bosco EE, Stengel K, Xu H, Mayhew CN, et al. Loss of the retinoblastoma tumor suppressor: differential action on transcriptional programs related to cell cycle control and immune function. Oncogene. 2007 Apr 23.

Diwan A, Koesters AG, Odley AM, Pushkaran S, Baines CP, Spike BT, et al. Unrestrained erythroblast development in Nix-/- mice reveals a mechanism for apoptotic modulation of erythropoiesis. Proc Natl Acad Sci U S A. 2007 Apr 17;104(16):6794-9.

Deane NG, Manning HC, Foutch AC, Washington MK, Aronow BJ, Bornhop DJ, et al. Targeted imaging of colonic tumors in smad3-/- mice discriminates cancer and inflammation. Mol Cancer Res. 2007 Apr;5(4):341-9.

Wong HR, Shanley TP, Sakthivel B, Cvijanovich N, Lin R, Allen GL, et al. Genome level expression profiles in pediatric septic shock indicate a role for altered zinc homeostasis in poor outcome. Physiol Genomics. 2007 Mar 20.

Schleiss MR, Aronow BJ, Handwerger S. Cytomegalovirus Infection of Human Syncytiotrophoblast Cells Strongly Interferes with Expression of Genes Involved in Placental Differentiation and Tissue Integrity. Pediatr Res. 2007 Mar 15.

Liang Y, Jansen M, Aronow B, Geiger H, Van Zant G. The quantitative trait gene latexin influences the size of the hematopoietic stem cell population in mice. Nature genetics. 2007 Feb;39(2):178-88.

Jegga AG, Chen J, Gowrisankar S, Deshmukh MA, Gudivada R, Kong S, et al. GenomeTrafac: a whole genome resource for the detection of transcription factor binding site clusters associated with conventional and microRNA encoding genes conserved between mouse and human gene orthologs. Nucleic Acids Res. 2007 Jan;35(Database issue):D116-21.

Liu C, Aronow BJ, Jegga AG, Wang N, Miethke A, Mourya R, et al. Novel resequencing chip customized to diagnose mutations in patients with inherited syndromes of intrahepatic cholestasis. Gastroenterology. 2007 Jan;132(1):119-26.

Jegga AG, Gowrisankar S, Chen J, Aronow BJ. PolyDoms: a whole genome database for the identification of non-synonymous coding SNPs with the potential to impact disease. Nucleic Acids Res. 2007 Jan;35(Database issue):D700-6.

Bosco EE, Wang Y, Xu H, Zilfou JT, Knudsen KE, Aronow BJ, et al. The retinoblastoma tumor suppressor modifies the therapeutic response of breast cancer. J Clin Invest. 2007 Jan;117(1):218-28.

Liu X, Jessen WJ, Sivaganesan S, Aronow BJ, Medvedovic M. Bayesian hierarchical model for transcriptional module discovery by jointly modeling gene expression and ChIP-chip data. BMC Bioinformatics. 2007;8:283.

Kaiser S, Park YK, Franklin JL, Halberg RB, Yu M, Jessen WJ, et al. Transcriptional recapitulation and subversion of embryonic colon development by mouse colon tumor models and human colon cancer. Genome Biol. 2007;8(7):R131.

Wells JM, Esni F, Boivin GP, Aronow BJ, Stuart W, Combs C, et al. Wnt/beta-catenin signaling is required for development of the exocrine pancreas. BMC developmental biology. 2007;7:4.

Professional Organization Memberships

Board of Scientific Advisors, "Critical Assessment of Micrarray Data Analysis" (CAMDA) at Duke University, 2000-present.
Member, NIH Physiological Chemistry Study Section, 1998-2002.
Scientific Advisory Board, Silicon Genetics, Inc., 2000.
Editorial Advisory Board, Biotechnology and Internet Report, 1999.
Ad Hoc Member and Chair, Mammalian Genome SBIR Biotechnology Study Section, 1998-1999.