Richard I Morimoto, PhD

Dean of Graduate School
John Evans Professor of Biology
Director, Rice Institute for Biomedical Research
Department of Biochemistry, Molecular Biology, and Cell Biology
Weinberg College of Arts and Sciences

Research Interests:
The current research in Richard Morimoto’s laboratory is to understand how eukaryotes sense and respond to physiologic and environmental stress by the activation of stress signaling pathways that integrate stress responses with cell growth and cell death. At the biochemical level, they are investigating how molecular chaperones recognize and capture folded intermediates and the processes by which proteins are refolded, degraded or undergo aggregation. Through the combination of molecular, cellular, and genetic approaches, they hope to understand how misfolded proteins and protein aggregates cause diseases such as Huntington's, Parkinson's, ALS, Scrapie/Prion, Cystic Fibrosis, and Alzheimers.

The laboratory research program addresses the following areas of research:

1. Transcriptional regulation of the heat shock response-Central to the stress-induced transcriptional regulation of heat shock genes is the regulation of a family of heat shock transcription factors (HSFs). Molecular characterization of heat shock transcription factors and the role of positive and negative regulatory co-factors in sensing the stress signal, activation, and attenuation. The focus of Dr. Morimoto’s lab is to establish the nature of the stress signal and the sequence of events involved in activation and attenuation of the heat shock transcriptional response.

2. Function of molecular chaperones in cell stress and cell death-Biochemical studies on the regulation of the Hsp70 chaperones by positive (Hdj and Hip) and negative (Bag1) co-chaperones. As Bag1 is a positive regulator of proteins that prevent apoptosis (Bcl2 and Raf1) and a negative regulator of Hsp70 his lab is focusing in vitro on the mechanisms underlying this crosstalk and in vivo on the events which direct the chaperone machinery to determine when stressed cells repair molecular damage or initiate apoptosis.

3. Protein misfolding, protein aggregation diseases, and biochemical stress in living animals-Expression of polyglutamine expansions as occurs in Huntington's Diseases causes the formation of protein aggregates in tissues of C. elegans which causes cellular toxicity and developmental delay; this in turn activates the heat shock transcriptional response and expression of chaperones and proteases. Richard Morimoto’s lab is interested in cell-specific toxicity to understand why neuronal cells exhibit unusual sensitivity to misfolded proteins and protein aggregation. To address this, they have employed a genetic approach to the identification of new genes that influence protein aggregation and protection from environmental stress and a candidate gene and bioinformatic/microarray approach to establish a global understanding of how the environment influences tissue-specific responses to biochemical events.