pete detloffAssociate Professor

Research Areas
molecular mechanisms of neurological disease


Biography

Peter J. Detloff (b. 1963) received his B.S. degree in Biochemistry from the University of Illinois at Champaign Urbana in 1985 and his Ph.D. degree from the University of Chicago in 1991. He was a postdoctoral fellow with Professor Oliver Smithies in the Department of Pathology in the School of Medicine at the University of North Carolina at Chapel Hill. In 1993 he joined UAB as an Assistant Professor in the Department of Biochemistry and Molecular Genetics.

Research Interests

The main goal of the Detlofflab is to understand the molecular mechanisms of neurological disease with the goal of finding molecular steps in the pathological processes that might be modulated to provide therapeutic benefit. Our focus has been on Huntington’s Disease, a late onsetneurological disease caused by the inheritance of an expanded CAG/polyglutamine repeat in a gene of unknown function called Huntingtin (HD). In order to provide an experimental system for the study of HD we engineered several HD knock-in mouse models. These mice exhibit HD-like features which are late onset and dependent on repeat length. Each line is available to the HD research community through the Jackson Laboratory.

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As in humans, mice with HD longer repeats tend to cause early onset of HD-like features. We developed an allelic series of knock-in HD mouse models that allows analyses of any potential molecular change across the series. Such analyses are useful in assessing the potential involvement of any altered molecular process in causing the HD-like features in these mouse lines. Our initial use of the allelic series revealed that of the thousands of mRNA levels that differ in the striatum (a brain area affected by HD) between normal and knock-in mice, only a handful correlated with the degree of phenotypic severity across the allelic series. Our current efforts are to deepen our initial analysis of the transcriptome, to extend this analysis to determine alterations in the proteome and metabolome while providing the field with bioinformatics coding resources allowing discorrelate analyses to be performed on this and other diseases.

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Our second major focus in the lab is to develop small molecules capable of downregulating expression of mutant HD alleles. We have found a process that when inhibited decreases the expression of expanded mutant HD mRNA levels in the brains of knock-in mice. The compounds we have currently do not cross the blood brain barrier, so we are performing a high throughput screen to find other inhibitors. The goal of this project is to develop a small molecule with good pharmacokinetic properties that could be used to delay or prevent the onset and progression of HD.

Education

Graduate School
Ph.D., University of Chicago

Postdoctoral Fellowship
University of North Carolina at Chapel Hill

Contact

Office
Kaul Human Genetics Building
Room 540B
720 20thStreet South
Birmingham, AL 35294-0024

Phone
(205) 975-8157

Email
detloff@uab.edu

Committed to exploring new frontiers in basic and translational research.

The Department of Biochemistry and Molecular Genetics at the University of Alabama at Birmingham (UAB) ranks among the top public institutions of higher education in terms of research and training awards. Our faculty currently receives $4 million per year in extramural, investigator-initiated grants.

Research

The Department of Biochemistry and Molecular Genetics carries out cutting-edge basic and translational research. Research strengths in the department includes cancer biology, chromatin and epigenetic signaling, metabolism and signaling, regulation of gene expression, structural biology, DNA synthesis and repair, and disease mechanisms.

Education

Graduate students and postdoctoral fellows in the Department of Biochemistry and Molecular Genetics are trained to carry out hypothesis-driven research using advanced research techniques. This training will prepare our graduates for a career in not just biomedical research, but also in other diverse fields that require critical thinking. Our faculty also proudly trains professional (MD, DDS, & DO) students, as well as undergraduate students at UAB.

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