Huda Akil, Ph.D.
Co-Director and Research Professor, MBNI
Distinguished University Professor and Quarton Professor of Neurosciences,
Department of Psychiatry

2064 MBNI Building
205 Zina Pitcher Place
Ann Arbor, MI 48109-0720

akil@umich.edu

734-763-3770

Current Research Interests:

Research in the Akil laboratory is focused on understanding the neurobiology of emotions, including pain, anxiety, depression and substance abuse. Early on, our research focused on the role of the endorphins and their receptors in pain and stress responsiveness. We provided the first physiological evidence for a role of endogenous opioids in the brain; and showed that endorphins are activated by stress and cause pain inhibition, a phenomenon we termed Stress-Induced Analgesia. We defined how the postranslational processing of opioid precursors is modulated by stress, and demonstrated the coordinate actions of the neuropeptide products on behavior.

We collaborated with Dr. Stanley Watson in a series of studies characterizing the anatomy of the opioid peptides and their receptors. The Akil & Watson research groups collaboratively cloned two types of opioid receptors and conducted structure-function analyses defining the molecular basis of high affinity and selectivity towards the endogenous ligands.

Our laboratory investigated the molecular and neural mechanisms underlying stress reactivity and their relation to anxiety and depression. We demonstrated that social defeat in rodents activates unique neural pathways that resemble those altered in human depression. We focused on the role of the steroid stress hormone receptors in emotionality, demonstrating the involvement of the mineralocorticoid receptor in human depression. Most recently our research group has created a transgenic mouse that overexpresses the glucocorticoid receptor selectively in forebrain and exhibits increased emotional lability and responsiveness to antidepressants, two features of bipolar illness.

Our research group is one of four nodes in a major research consortium using genomic tools to uncover the neural phenotypes associated with major depression and bipolar illness in human postmortem brains. In a recent discovery this research consortium has implicated, for the first time, the FGF (Fribroblast Growth Factor) system in major depression. The Consortium is now undertaking a major collaborative effort to discover the genetic basis of bipolar disorder.

Research tools in our laboratory include the use of a range of molecular,genetic, anatomical, behavioral and clinical approaches in a highly interdisciplinary environment. The goal is to use a convergence of strategies to understand the biology of emotions.

"The Scientific Method is doing your damnedest, no holds barred!"
Percy Bridgeman, High Pressure Physicist.

Selected Publications:

Kabbaj, M., Devine, D.P., Savage, V. and Akil, H.: Neurobiological correlates of individual differences in novelty seeking behavior in the rat: Differential expression of stress-related molecules. J. Neuroscience, 20(18): 6983-6988, 2000

Young, E.A., Lopez, J.F., Murphy-Weinberg, V., Watson, S.J. and Akil, H.: Mineralocorticoid receptor function in major depression. Arch. Gen. Psychiatry, 60:24-28, 2003.

Wei, Q., Lu, X.-Y., Liu, L., Schafer, G., Shieh, K.-R., Burke, S., Robinson, T.E., Watson, S.J., Seasholtz, A.F. & Akil, H.:  Glucocorticoid receptor overexpression in forebrain: a mouse model of increased emotional lability. Proc. Natl. Acad. Sci. U.S.A., 101(32): 11851-11856, 2004

Evans SJ, Choudary PV, Neal CR, Li JZ, Vawter MP, Tomita H, Lopez JF, Thompson RC, Meng F, Stead JD, Walsh DM, Meyers RM, Bunney WE, Watson SJ, Jones EG and Akil H. Dysregulation of the Fibroblast Growth Factor (FGF) system in Major Depression. Proc. Natl. Acad. Sci. U.S.A., 101 (43) 15506-11, 2004.

Akil, H: Stressed and depressed. Nature Medicine, 11, 116-118, 2005

Choudary PV, Molnar M, Evans SJ, Tomita H, Li JZ, Vawter MP, Myers RM, Bunney WE Jr, Akil H, Watson SJ, Jones EG. Altered cortical glutamatergic and GABAergic signal transmission with glial involvement in depression.Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15653-8. Epub 2005 Oct 17.

Stead JD, Neal C, Meng F, Wang Y, Evans S, Vazquez DM, Watson SJ, Akil H. Transcriptional profiling of the developing rat brain reveals that the most dramatic regional differentiation in gene expression occurs postpartum. J Neurosci. 2006 Jan 4;26(1):345-53.

Rozeboom AM, Akil H, Seasholtz AF. Mineralocorticoid receptor overexpression in forebrain decreases anxiety-like behavior and alters the stress response in mice. Proc Natl Acad Sci U S A. 2007 Mar 13;104(11):4688-93. Epub 2007 Mar 5.