Medical Student Research Fellowship for Summer 2006

Mentor: Osamu Nakagawa
Department: Internal Medicine, Cardiology
Room number: NB10.224
Mail Code: 8573
Phone number: 8-4001
E-mail: osamu.nakagawa@utsouthwestern.edu
Project title: Transcription factor complexes in cardiac and muscle development and disease

Human subjects IRB approved project number (where applicable): N/A
Animal subjects IRB approved project number (where applicable): N/A

Project Type (patient-based research, animal-based research, or basic research; this characterization is only to permit a general classification for grouping similar types of projects)

Basic research

Brief Description of Project:

Transcription factors play essential roles in regulating tissue-specific gene expression for proper embryonic development and mature organ function. In addition, the expression profiles of distinct sets of genes are altered in various diseases, indicating the involvement of transcriptional regulation in response to disease stimuli.
Transcription factors form multi-protein complexes, and such complexes, not individual transcription factors, dictate the specificity of downstream gene expression. Despite recent progress of transcription factor research, little is known about combinatorial actions of DNA-binding transcription factors, co-factors and histone modifying enzymes. It is therefore important to elucidate and characterize novel transcriptional factor complexes that are important for development and disease. In addition, since transcription factors act as "molecular switches" for downstream target genes, it is critical to analyze the functions of target genes that directly regulate cellular functions downstream of transcriptional control. Characterization of those genes may provide a link from basic studies of transcriptional mechanisms to the etiologies of human diseases.
Using biochemical approaches and mouse model analyses, my group is pursuing these two general paradigms, characterization of novel transcriptional factor complexes and downstream target genes, mainly focusing on the cardiovascular system and skeletal muscle.

Previous Research Activities or Publications with Medical Students:

Nakagawa O, McFadden DG, Nakagawa M, Yanagisawa H, Hu T, Srivastava D, Olson EN.
Members of the HRT family of bHLH proteins act as transcriptional repressors downstream of Notch signaling.
Proc. Nat. Acad. Sci. USA 97(25): 13655-13660, 2000.

Kathiriya IS, King IN, Murakami M, Nakagawa M, Astle JA, Gardner KA, Gerard RD, Olson EN, Srivastava D, Nakagawa O.
Hairy-related transcription factors inhibit GATA-dependent cardiac gene expression through a signal-responsive mechanism.
J. Biol. Chem. 279(52): 54937-54943, 2004.

Nakagawa O, Arnold M, Nakagawa M, Hamada H, Shelton JM, Kusano H, Harris TM, Childs G, Campbell KP, Richardson JA, Nishino I, Olson EN.
Centronuclear myopathy in mice lacking a novel muscle-specific protein kinase transcriptionally regulated by MEF2.
Genes Dev. 19(17): 2066-2077, 2005.

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