ANNE KASUS-JACOBI, Ph.D.
Assistant Professor of Research
Department of Ophthalmology

Telephone: (405) 271-8244
Fax: (405) 271-8128
Email: anne-kasus-jacobi@ouhsc.edu

 

Research Interests: We are investigating the physiological roles of photoreceptor retinol dehydrogenases (RDHs). We are particularly interested in the role of RDH12 and why its inactivation leads to a severe and early onset retinal dystrophy.


Present Research

            Our goal is to understand the physiological roles of the retinol dehydrogenases RDH11 and RDH12 in photoreceptor cells. The first characterization of the RDH11 deficient mice, demonstrated the importance of this gene for maintaining normal visual adaptation to the dark. More importantly in terms of clinical relevance, RDH12, an enzyme resembling RDH11 in its sequence, localization, and catalytic activity has been found to be mutated in a subset of patients having the most early onset blinding disease called Leber Congenital Amaurosis. Such retinal degenerative disease is irreversible because once the photoreceptor cells are lost, they can not be replaced.

            The pathogenesis, or molecular events, that link the cause (mutation of RDH12) to the effect (retinal degeneration, blindness) is unknown. We are proposing that RDH12 is in fact acting as a protective agent against toxic molecules that are released in photoreceptor cells during light stimulation. Very recent and unpublished results in cell culture confirm a protective role of various RDHs against light-induced oxidative stress and lipid peroxidation.

            If this finding is confirmed in vivo, it will have an important clinical impact because these enzymes can then be used as pharmacological targets in order to enhance the detoxification processes in photoreceptor cells and maintain the integrity and function of these cells throughout life. We are using the Rdh11 and Rdh12 knockout mice as models to investigate the functions of these genes.

Curriculum Vitae

Full CV can be accessed here.

B.S.

1990

University of Paris XII, France

Ph.D.

1998

University of Paris XI, France, Endocrinology

Post-Doctoral 

2004 

University of Texas Southwestern Medical Center, Dallas, TX, Molecular Genetics 

Assistant Professor

2004-present 

University of Oklahoma Health Sciences Center, Oklahoma City, OK, Ophthalmology 


Research Support

P20 RR017703-04 Anderson (PI)                                         09/15/02-06/30/12                                          

NIH/NCRR/COBRE                                                                   

Mentoring Vision Research in Oklahoma   

Sub-project: Photoreceptor Retinol Dehydrogenases and Vision

Anne Kasus-Jacobi (PI of sub-project)                                   07/01/04-06/30/09

Goal: To understand the role of RDH11 and RDH12 in visual functions and photoreceptor survival.  

Selected Publications

Yogita Kanan, Anne Kasus Jacobi, Kjell Sawyer, David S. Mannel, Joyce Tombran Tink and Muayyad R. Al-Ubaidi. An In-Vivo Assay to Identify Compounds Protective Against Light Induced Apoptosis. To be published in Retinal Degenerative Diseases edited by Joe G. Hollyfield, Robert E. Anderson, and Matthew M. LaVail. Springer, New York, NY, 2008.

 

Yogita Kanan, Anne Kasus-Jacobi, Gennadiy Moiseyev, Kjell Sawyer, Jian-Xing Ma and Muayyad R. Al-Ubaidi. Retinoid Recycling in Murine Cone Photoreceptors: an In Vitro Study. Manuscript submitted in October 2007.

 

Yogita Kanan, Lea D. Wicker, Muayyad R. Al-Ubaidi, Nawajes A. Mandal and Anne Kasus-Jacobi. Retinol Dehydrogenases RDH11 and RDH12 in the Mouse Retina: Expression Levels During Development and Regulation by Oxidative Stress. Manuscript submitted in October 2007.

 

Anne Kasus-Jacobi, David G. Birch, and Robert E. Anderson. Photoreceptor Retinol Dehydrogenases. An attempt to characterize the function of Rdh11. Retinal Degenerative Diseases edited by Joe G. Hollyfield, Robert E. Anderson, and Matthew M. LaVail. Springer, New York, NY, 2006.

 

Kasus-Jacobi A., Ou J., Birch D. G., Locke K. G., Shelton J. M., Richardson J. A., Murphy A. J., Valenzuela D. M., Yancopoulos G. D., and Edwards A. O. Functional Characterization of mRDH11 as a Retinol Dehydrogenase Involved in Dark Adaptation in vivo. J Biol Chem. 2005 May 27;280(21):20413-20.

 

Kasus-Jacobi A., Ou J., Bashmakov Y., Shelton J.M., Richardson J.A., Brown M.S., Goldstein J.L. Characterization of Mouse Short-chain Aldehyde Reductase (SCALD), an Enzyme Regulated by Sterol Regulatory Element-binding Proteins. J Biol Chem. 2003 Aug 22;278(34):32380-9.