Miles A. Pufall, PhD, a research fellow with Professor Keith Yamamoto at University of California, San Francisco, has been recruited to the Carver College of Medicine as a new assistant professor of biochemistry. Dr. Pufall’s regular appointment will become effective July 1, 2011. He remains at UCSF during this academic year and is associated with the Department of Biochemistry as an adjunct assistant professor, effective immediately.
Miles received his PhD in 2004 from the University of Utah, where he worked at the Huntsman Cancer Institute with Professor Barbara Graves. In six publications, which include a first author Science paper and a first author Annual Review of Cell and Developmental Biology article. Dr. Pufall showed that multiple phosphorylation events within an unstructured domain of the Ets-1 transcription factor act as a rheostat, shifting the protein from a state competent for DNA-binding to an autoinhibited form. In the course of this work, Dr. Pufall received training in NMR spectroscopy from Professor Lawrence McIntosh and also collaborated with the noted X-ray crystallographer, Professor Cynthia Wolberger.
In the Yamamoto laboratory, Dr. Pufall continued working in the area of transcriptional regulation by DNA binding proteins but changed his focus to the glucocorticoid receptor. Whereas the dogma in DNA-binding proteins suggests that as an operator site accumulates differences from an ideal sequence, protein affinity is simply decreased, Dr. Pufall and co-workers tested the hypothesis that different DNA sequences bind the same protein differently, influencing its activity, and producing different transcriptional outcomes. This work resulted in a 2009 Science paper of which Dr. Pufall is co-first author. He further developed this work into a Howard Temin Award from the National Cancer Institute to investigate the genomics of glucocorticoid-resistant and glucocorticoid-sensitive acute lympoblastic leukemia.
Dr. Pufall’s work suggests that DNA is an unanticipated allosteric regulator of protein function in transcriptional regulation. As an independent investigator, he plans to push this work to dissect fundamental mechanisms by which DNA-protein complexes create specific scaffolds for complex regulation and to translate these discoveries in order to improve human health.