Frederick A Pereira, Ph.D.
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Positions
- Associate Professor
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Huffington Center On Aging
Baylor College of Medicine
Houston, TX US
- Associate Professor
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Molecular and Cellular Biology
Baylor College of Medicine
- Associate Professor
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Otolaryngology–Head and Neck Surgery
Baylor College of Medicine
- Member
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Dan L Duncan Comprehensive Cancer Center
Baylor College of Medicine
Houston, Texas United States
- Director, Graduate and Postbaccalaureate Development
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Graduate School of Biomedical Sciences
Graduate and Postbaccalaureate Development, Initiative for Maximizing Student Development (IMSD) and Post-baccalaureate Research Education Program (PREP)
- Faculty Senator
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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
- Montemayor C, Montemayor OA, Ridgeway A, Lin F, Wheeler DA, Pletcher SD, Pereira FA "Genome-Wide Analysis of Binding Sites and Direct Target Genes of the Orphan Nuclear Receptor NR2F1/COUP-TFI.." PLoS ONE. 2010;5(1):e8910. Pubmed PMID: 20111703
- Rajagopalan L, Organ-Darling LE, Liu H, Davidson AL, Raphael RM, Brownell WE, Pereira FA "Glycosylation regulates prestin cellular activity.." J. Assoc. Res. Otolaryngol.. 2010 Mar;11(1):39-51. Pubmed PMID: 19898896
- Somma G, Alger HM, McGuire RM, Kretlow JD, Ruiz FR, Yatsenko SA, Stankiewicz P, Harrison W, Funk E, Bergamaschi A, Oghalai JS, Mikos AG, Overbeek PA, Pereira FA "Head bobber: an insertional mutation causes inner ear defects, hyperactive circling, and deafness.." J. Assoc. Res. Otolaryngol.. 2012 Jun;13(3):335-49. Pubmed PMID: 22383091
- Sfondouris J, Rajagopalan L, Pereira FA, Brownell WE "Membrane composition modulates prestin-associated charge movement.." J. Biol. Chem.. 2008 Aug 15;283(33):22473-81. Pubmed PMID: 18567583
- Tang LS, Montemayor C, Pereira FA "Sensorineural hearing loss: potential therapies and gene targets for drug development.." IUBMB Life. 2006 Sep;58(9):525-30. Pubmed PMID: 17002980
- Rajagopalan L, Greeson JN, Xia A, Liu H, Sturm A, Raphael RM, Davidson AL, Oghalai JS, Pereira FA, Brownell WE "Tuning of the outer hair cell motor by membrane cholesterol.." J. Biol. Chem.. 2007 Dec 14;282(50):36659-70. Pubmed PMID: 17933870
- Rajagopalan L, Pereira FA, Lichtarge O, Brownell WE "Identification of functionally important residues/domains in membrane proteins using an evolutionary approach coupled with systematic mutational analysis.." Methods Mol. Biol.. 2009;493:287-97. Pubmed PMID: 18839354
- Chen CA, Wang W, Pedersen SE, Raman A, Seymour ML, Ruiz FR, Xia A, van der Heijden ME, Wang L, Yin J, Lopez J, Rech ME, Lewis RA, Wu SM, Liu Z, Pereira FA, Pautler RG, Zoghbi HY, Schaaf CP "Nr2f1 heterozygous knockout mice recapitulate neurological phenotypes of Bosch-Boonstra-Schaaf optic atrophy syndrome and show impaired hippocampal synaptic plasticity." Hum Mol Genet.. 2019;29(5):705-715. Pubmed PMID: 31600777
- M Palmieri, HR. Nelvagal, P Lotfi, GR. Stinnett, ML. Seymour, DY. Tse, R. Pal, L Bajaj, D Sanagasetti, GG. Rodney, SM. Wu, Fred A. Pereira, RG. Pautler, JD. Cooper and M. Sardiello. "mTORC1-independent TFEB activation via Akt inhibition promotes cellular clearance in neurodegenerative storage diseases.." Nat. Comm.. 2017;13(8):15793. Pubmed PMID: 28165011
- Jeanne M Manalo, Hong Liu, Dalian Ding, John Hicks, Hong Sun, Richard Salvi, Rodney E Kellems, Fred A Pereira, Yang Xia "Adenosine A2B receptor: A pathogenic factor and a therapeutic target for sensorineural hearing loss." 2020 Nov 1;34(12):15771-15787. Pubmed PMID: 33131093
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