Howard B. Gutstein, M.D.

1982, Johns Hopkins

UT M. D. Anderson Cancer Center
Anesthesiology and Pain Medicine
Genetics

Research Interests: Proteomic approaches to opioid tolerance, dependence, and drug addiction; interaction of pan and analgesic signal transduction mechanisms

The primary focus of our research is to understand the molecular mechanisms underlying the transition from drug use to drug addiction. Addiction is one of the major problems facing society today, exacting a great cost both in terms of societal damage and personal distress. We employ a multidisciplinary approach to understand these problems using cutting-edge techniques. After demonstrating clinical and physiological relevance in animal behavioral studies, we dissect mechanisms underlying addiction and the related phenomena of opioid tolerance and physical dependence. Since addiction is a very complex phenomenon, involving the interaction of genetic, environmental, and social factors, we have turned to the emerging field of proteomics in an effort to determine in the broadest possible fashion which changes in cellular signaling are responsible for the adaptations causing addiction. Combining the techniques of laser-capture microdissection to analyze neurons expressing specific markers, 2-dimensional gel electrophoresis to separate proteins, and high-throughput mass spectrometry for protein identification permits us to address this issue with a power never before imagined. We also employ these multidisciplinary approaches to better understand the related problems of opioid tolerance and chronic pain.

The overall goal of these projects is to develop more effective therapies for treating chronic pain without causing the devastating side effects of tolerance, dependence, and addiction. Trainees gain experience integrating molecular, genetic, neuroanatomic, biochemical, and behavioral techniques to explore important neurobiological questions from many perspectives. Close relations with clinical colleagues in the pain clinic provide opportunities to translate our basic findings into clinical practice and eventually see the direct application of our efforts.

A tutorial in our laboratory would introduce students to concepts in addiction, pain mechanisms and opioid pharmacology. Students would employ a wide range of integrative techniques to explore these important neurobiological questions from many perspectives. Experience can be gained with techniques such as in situ hybridization, immunocytochemistry, cell culture and transfection, 2-D gel electrophoresis, mass spectrometry, image analysis, and behavioral studies on rats and mice.
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Gutstein HB, Akil H (2006) "Opioid Analgesics", in Goodman and Gilman's The Pharmacological Basis of Therapeutics, eleventh edition, Brunton, L, Ed., McGraw-Hill, pp. 547-590.

Xu JJ, Walla BC, Diaz MF, Fuller GN, Gutstein HB (2006) Intermittent lumbar puncture in rats: a novel method for the experimental study of opioid tolerance, Anesthesia and Analgesia, 103:714.

Morris JS, Baggerly KA, Gutstein HB, Coombes, KR (2007) "Statistical Contributions to Proteomic Research", in The Urinary Proteome, Rai, A., Ed., series "Methods in Molecular Biology", Humana Press, in press.

Hamacher M, Stephan C, Eisenacher M, van Hall A, Marcus K, Martens L, Park YM, Gutstein HB, Herberg F, Meyer HE (2007) Proteomics for everyday use: Activities of the HUPO Brain Proteome Project during the 5th HUPO World Congress, Proteomics, 7:1012.

Morris JS, Gutstein HB (2007) Laser capture sampling and analytical issues in proteomics, Expert Review of Proteomics, 4 (5):627.

Clark BN, Gutstein HB: The myth of automated, high-throughput 2-dimensional gel analysis, Proteomics, in press.

Gibson F, Anderson L, Babingg G, Baker M, Berth M, Binz PA, Borthwick A, Cash P, Day BW, Friedman DB, Garland D, Gutstein HB, Hoogland C, Jones NA, Jones AR, Khan A, Klose J, Lamond AI, Lemkin PF, Lilley KS, Minden J, Morris NJ, Paton NW, Pisano MR, Prime JE, Rabilloud T, Stead DA, Taylor CF, Voshol H, Wipat A: MIAPE: Gel Electrophoresis, Nature Biotechnology, in press.

Moulédous L, Diaz M, Gutstein HB (2007) Systemic ERK inhibition by SL-327 does not inhibit the development or expression of opioid tolerance or dependence: implications for neural plasticity, Pharmacology, Biochemistry, and Behavior, 88:39.

Gutstein HB, Morris J, Palani S, Sweedler JV: Microproteomics: The analysis of protein expression in small cell groups, Mass Spectrometry Reviews, in press.

Morris JS, Clark BN, Gutstein HB: A fast, automatic and accurate method for detecting and quantifying protein spots in 2-dimensional gel electrophoresis data, Bioinformatics, in press.

Program Affiliation:
Program in Genes and Development
Program in Neuroscience