CE SEMINAR by John B. Hogenesch/Leveraging time: drug action, health, and dark matter

Author: College of Engineering
Time: 11:00
Location: STDB335







Speaker: Prof.Dr. John Hogenesch


Title: Leveraging time: drug action, health, and dark matter

Date: Novemberc 11,  2014,  Tuesday

Time: 11:00-12:00

Place: STDB335





The mammalian circadian clock regulates much of our physiology and behavior. Here I will introduce the clock and its mechanisms, discuss our efforts at defining genome wide transcriptional output, new clock mechanisms, and big data approaches to finding clock genes. I will focus on our efforts to generate and analyze high-resolution multi-organ data showing that nearly half of all genes in the mouse genome oscillate with circadian rhythm somewhere in the body. Moreover, a majority of best-selling drugs in the United States target circadian gene products. Many blockbuster drugs that target these genes have relatively short half-lives, and our data predict which drugs may benefit most from careful temporal dosing. I will also talk about how we are leveraging big data such as this to find new clock genes and our ongoing efforts to better define clock mechanisms.

Bio: John Hogenesch did his graduate work with Chris Bradfield at Northwestern University working on signal transduction pathways mediated by bHLH-PAS transcription factors. In his thesis work, he used sequence analysis to discover new members of the bHLH-PAS family, including Hif1a, Hif2a, Hif3a, Bmal1, Bmal2, and Npas2  (Hogenesch et al., JBC, 1997; Hogenesch et al, J. Neuroscience, 2000).  Characterization of Bmal1 showed that it partnered with Clock, a master regulator of circadian rhythms, (Hogenesch, et. al, PNAS, 1998), to form the positive arm of the circadian clock. Later work showed that Bmal1 is the only required clock component (Bunger et al., Cell, 2000).

In 1999, he joined Steve Kay and Peter Schultz at Novartis La Jolla as a postdoc, then scientist (2000), then Director of Genomics (2002). At Novartis, building on interests in informatics and genome biology, he worked on the assembly of the complete human transcriptome (Hogenesch et al., Cell, 2001), as well as on the mRNA characterization of the transcriptomes of human, mouse, and rat (The Gene Atlas, Su et al, PNAS 2002; Su et al., PNAS, 2004). Collectively, these papers have more than 3700 citations times and stand as important landmarks in genome biology. These interests evolved into high throughput hypothesis testing and the development of genome wide methodologies for the study of cellular pathways using cDNAs and siRNAs (Conkright et al., Molecular Cell, 2003; Sato et al, Neuron, 2004 ; Willingham et al., Science, 2005; Sato et al., Nature Genetics, 2006).

In 2006, Dr. Hogenesch joined the Department of Pharmacology at the University of Pennsylvania School of Medicine and is now Professor of Pharmacology, Associate Director of the Penn Genomics Institute, and Interim Director of the Institute for Biomedical Informatics. His interests continue to include genome biology and its application to understanding circadian behavior. Currently, Dr. Hogenesch is a Penn Fellow, sits on the Scientific Advisory Boards of Qiagen, Bio-Rad, the Ryan Light Sang Foundation Medical Committee, and the Gene Ontology (GO) consortium, and is an advisor to several National Institutes of Health, NIDDK, NCI, NHLBI.