My research interests lie in the area of Biomedical Genomics, aiming to further our understanding of transcriptional regulation (the control of gene expression) at the genome-wide level, in order to better comprehend and treat human disease. Through the development and application of novel genomic technologies, such as DNA microarrays, we are able to interrogate the entire transcriptome. Furthermore, the analysis of gene promoter and regulatory regions enables us to address complex questions in relation to how genes and their products form regulatory networks, and how these networks might be regulated in a given disease.

Current array technologies have revolutionized the fields of human genetics, allowing characterization of over a million Single Nucleotide Polymorphisms (SNPs) in 10,000’s of subjects. This has led to the discovery of numerous markers of disease resistance and susceptibility, from Crohn’s disease to Prostate cancer to Diabetes. Moreover, array comparative genomic hybridization (aCGH) enables us to assess copy number variations (CNVs) in the DNA of a given subjects tumor sample at high resolution. Clearly our ability to discover these markers and subsequently screen individuals for these SNPs and CNVs will have a tremendous impact on human health and the prevention and treatment of disease.

The recent development of Next Generation Sequencing technologies is already taking the field in a new direction, with the production of unprecedented data sets. This massively-parallel sequencing technology allows for rapid sequencing of billions of bp of DNA at a fraction of the cost of the cost of traditional Sanger-based sequencing. The result of this has opened the genomics field to new possibilities, including digital gene expression profiling (the ability to count mRNA molecules in a given sample), genome resequencing, cDNA sequencing (novel transcript discovery), small RNA quantification and discovery, and numerous Epigenomic applications, such as identification of transcription factor binding sites (ChIP-Seq), detection of histone modifications, methylation, nucleosome mapping, and mapping of DNase-1 hypersensitivity sites. Ultimately the potential of Biomedical Genomics is in the development of personalized medical care, enabling physicians to use the information contained in a given patients genetic make-up to identify and fine-tune the most appropriate drug treatment.

Tuteja G, Jensen ST, White P, Kaestner KH (2008). Cis-regulatory modules in the mammalian liver: composition depends on strength of Foxa2 consensus site. Nucleic Acids Research; 36(12):4149-57.

Bochkis IM, Rubins NE, White P, Furth EE, Friedman JR, Kaestner KH. (2008) Hepatocyte-specific ablation of Foxa2 alters bile acid homeostasis and results in endoplasmic reticulum stress. Nature Medicine; 14(8):828-36.

Hardy OT, Hohmeier HE, Becker TC, Manduchi E, Doliba NM, Gupta RK, White P, Stoeckert CJ Jr, Matschinsky FM, Newgard CB, Kaestner KH (2007). Functional genomics of the ß-cell: SCHAD regulates insulin secretion independent of K+ currents. Molecular Endocrinology; 21(3):765-73.

Mazzarelli JM, Brestelli J, Gorski RK, Liu J, Manduchi E, Pinney DF, Schug J, White P, Kaestner KH, Stoeckert CJ Jr (2007). EPConDB: a web resource for gene expression related to pancreatic development, beta-cell function and diabetes. Nucleic Acids Research; 35(Database issue):D751-5.

Gao N, White P, Doliba N, Golson ML, Matschinsky FM, Kaestner KH. (2007). Foxa2 controls vesicle docking and insulin secretion in mature Beta cells. Cell Metabolism; 6(4):267-79.

Keller DM, McWeeney S, Arsenlis A, Drouin J, Wright CV, Wang H, Wollheim CB, White P, Kaestner KH, Goodman RH (2007). Characterization of pancreatic transcription factor Pdx-1 binding sites using promoter microarray and serial analysis of chromatin occupancy. Journal of Biological Chemistry; 282(44):32084-92.

Gupta RK, Gao N, Gorski RK, White P, Hardy OT, Rafiq K, Brestelli JE, Chen G, Stoeckert CJ Jr, Kaestner KH. (2007). Expansion of adult beta-cell mass in response to increased metabolic demand is dependent on HNF-4alpha. Genes and Development; 21(7):756-69.

Ku HT, Chai J, Kim YJ, White P, Purohit-Ghelani S, Kaestner KH, Bromberg JS (2007). Insulin-expressing colonies developed from murine embryonic stem cell-derived progenitors. Diabetes; 56(4):921-9.

Mazzarelli JM, White P, Gorski R, Brestelli J, Pinney DF, Arsenlis A, Katokhin A, Belova O, Bogdanova V, Elisafenko E, Gubina M, Nizolenko L, Perelman P, Puzakov M, Shilov A, Trifonoff V, Vorobjeva N, Kolchanov N, Kaestner KH, Stoeckert CJ Jr (2006). Novel genes identified by manual annotation and microarray expression analysis in the pancreas. Genomics 88(6):752-61.

Burkhardt BR, Greene SR, White P, Wong RK, Brestelli JE, Yang J, Robert CE, Brusko TM, Wasserfall CH, Wu J, Atkinson MA, Gao Z, Kaestner KH, Wolf BA (2006). PANDER-induced cell-death genetic networks in islets reveal central role for caspase-3 and cyclin-dependent kinase inhibitor 1A (p21). Gene 2006 369:134-141.

White P, Brestelli JE, Kaestner KH, Greenbaum LE (2005). Identification of transcriptional networks during liver regeneration. Journal of Biological Chemistry; 280(5): 3715-3722.