WARREN HEIDEMAN, PHD

Research

Cell Cycle Regulation. We are working to understand how yeast regulate the cell cycle in response to internal and external signals. Cell cycle regulation is an important process: improper cell cycle regulation can lead to cancer, and organized regulation of proliferative growth is a fundamental requirement for an organism. More specifically, we are studying regulatory mechanisms that govern the conserved cyclin/cyclin dependent kinase (CDK) pathway that controls progress through the G1 phase of the cell cycle. We are interested in how signals that control proliferation in yeast are coupled to transcription factors that control the expression of CLN3 and CDC28. Yeast cells regulate G1 progression to match the ability of nutrients in the medium to support growth, and we are identifying the components necessary for this process. We are also studying the differential regulation of G1 length in mother and daughter cells. We have recently discovered that this is the result of asymmetric distribution of the Ace2 transcription factor to daughter cells.

Developmental Toxicology. We are interested in studying the molecular mechanisms by which TCDD (dioxin) disrupts the normal developmental programming of fish. TCDD is a widespread environmental toxicant that accumulates in the food chain. TCDD activates a transcription factor, the arylhydrocarbon receptor (AhR) that in turn alters the pattern of gene expression. While it is assumed that alterations in gene expression lead to the toxic effects, it is not known what genes are critical in this response. Early life stage fish are more sensitive to TCDD than any other known organism. Because of their well-known utility in genetic and developmental studies, we have established the zebrafish as a model system for studying this toxicity. In an attempt to identify genes that play a role in TCDD toxicity, we have initiated a selection for zebrafish mutants that are resistant to TCDD lethality. We are also characterizing the role that the receptor for TCDD plays in normal heart formation and development. This work provides basic understanding of an important environmental problem as well as insight into developmental mechanisms.

Publications

• Chen, J., Carney, S.A., Peterson, R.E., and Heideman, W.: Comparative genomics identifies genes mediating cardiotoxicity in the embryonic zebrafish heart. Physiol. Genomics 33: 148-158, 2008
• King Heiden TC, Dengler E, Kao WJ, Heideman W, Peterson RE. Developmental toxicity of low generation PAMAM dendrimers in zebrafish. Toxicol Appl Pharmacol. 2007 Jul 31;
• Kim KH, Antkiewicz DS, Yan L, Eliceiri KW, Heideman W, Peterson RE, Lee Y. Lrrc10 is required for early heart development and function in zebrafish. Dev Biol. 2007 308(2):494-506
• Antkiewicz DS, Peterson RE, Heideman W. Blocking expression of AHR2 and ARNT1 in zebrafish larvae protects against cardiac toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin. Toxicol Sci. 2006 Nov;94(1):175-82.
• Liko D, Slattery MG, Phillips CL, Heideman W. Using the yeast gene deletion collection to customize gene expression. Biotechniques. 2006 Jun;40(6):728, 730, 732

Mentor to METC Graduate Students:

• Felipe Burns (2015), Shaina Johnson (2012),
• Vatsal Mehta (2009), Dagmara Antkiewicz (2007

Mentor to METC Post-Doc:

• Tracie Baker (2014)