Positions

Associate Professor

Huffington Center On Aging
Baylor College of Medicine
Houston, TX US

Associate Professor

Molecular and Cellular Biology
Baylor College of Medicine

Associate Professor

Otolaryngology–Head and Neck Surgery
Baylor College of Medicine

Member

Dan L Duncan Comprehensive Cancer Center
Baylor College of Medicine
Houston, Texas United States

Director, Graduate and Postbaccalaureate Development

Graduate School of Biomedical Sciences

Graduate and Postbaccalaureate Development, Initiative for Maximizing Student Development (IMSD) and Post-baccalaureate Research Education Program (PREP)

Faculty Senator

Baylor College of Medicine

Education

Advanced Training from Baylor College Of Medicine

01/1993 - Houston, TX United States

Ph.D. from University Of Manitoba

01/1993 - Winnipeg, Canada

B.Sc. from University Of Manitoba

01/1983 - Winnipeg, Canada

Professional Interests

• Signaling pathways in auditory development, aging and cancer prevention
• Circadian Rhythms
• Hearing and Balance disorders
• Auditory neuropathy
• Orphan Nuclear Receptors
• Tinnitus
• Lipidemia

Professional Statement

Our long-term goal is to enhance, protect, repair or regenerate hair cells, supporting cells and associated nerves in the mammalian hearing organ and neurons in the auditory cortex that are loss with age (development or aging) or due to noise, trauma and chemotherapeutic insults. We aim to identify molecules and their signaling pathways that modulate inner ear and brain cell function.

Deafness is a relatively common disorder, with approximately 1 in 1000 children born with a serious permanent hearing impairment, single gene defects account for over half of the cases of childhood deafness. The World Health Organization (WHO) estimated hearing loss and deafness affected at least 250 million people worldwide in 2002 and is an increasing challenge to public health as lifespan increases and the general population ages.

We have identified gene-signaling pathways important for development, aging and regeneration of hair cells and auditory neurons. We discovered that loss of the orphan nuclear receptor NR2F1 results in the production of extra hair cells and supporting cells (a stem cell pool) and changes in cortical neurogenesis. We are characterizing the signaling pathways NR2F1 regulates by performing biochemical, molecular, bioinformatic and computational, and transcriptome (chromatin boundaries and structure, epigenetic and transcriptional regulation of gene expression) analyses. One pathway involves circadian rhythms; a diurnal (24h) molecular clock that controls the synchronization of gene functions in response to environmental and cellular cues. We are characterizing how circadian rhythms regulate the development, aging and regeneration of hair cells and neurons at the molecular and organ level. Findings from these studies will help us to develop therapies to regenerate and/or protect aging hair cells and neurons.

We also investigate the structure and function of a novel membrane motor protein, SLC26A5 prestin (quick tempo protein) in outer hair cells (OHC). Prestin is responsible for the active feedback mechanism required for amplifying and selecting high frequency hearing, which is preferentially reduced with age. We discovered that prestin is localized in membrane microdomains or rafts and that changes in membrane cholesterol disrupts OHC functions. Indeed, humans that are dyslipidemic have reduced hearing abilities and we found that cholesterol is able to modulate and tune prestin activity and the hair cell motor for hearing. Studies are directed to understanding the mechanisms of prestin and OHC function with increasing age and in altered cholesterol environments.

Our studies hope to provide insights into understanding human disorders of auditory and neuronal function and to develop pharmacologic, gene or cell-based therapy to improve the quality of life during aging and cancer.

Websites

Selected Publications

• Cai T, Seymour ML, Zhang H, Pereira FA, Groves AK "Conditional deletion of atoh1 reveals distinct critical periods for survival and function of hair cells in the organ of corti.." J. Neurosci.. 2013 Jun 12;33(24):10110-22. Pubmed PMID: 23761906
• Tang LS, Alger HM, Pereira FA "COUP-TFI controls Notch regulation of hair cell and support cell differentiation.." Development. 2006 Sep;133(18):3683-93. Pubmed PMID: 16914494
• Rajagopalan L, Patel N, Madabushi S, Goddard JA, Anjan V, Lin F, Shope C, Farrell B, Lichtarge O, Davidson AL, Brownell WE, Pereira FA "Essential helix interactions in the anion transporter domain of prestin revealed by evolutionary trace analysis.." J. Neurosci.. 2006 Dec 6;26(49):12727-34. Pubmed PMID: 17151276
• Sturm AK, Rajagopalan L, Yoo D, Brownell WE, Pereira FA "Functional expression and microdomain localization of prestin in cultured cells.." Otolaryngol Head Neck Surg. 2007 Mar;136(3):434-9. Pubmed PMID: 17321873