Cell Biology - all faculty and staff

Shannon Conley, Ph.D.

Shannon Conley, Ph.D.

Assistant Professor, Department of Cell Biology


Education:

Ph.D., Pharmacology and Toxicology, University of Arizona, Tucson, AZ
M.P.H., University of Arizona, Tucson, AZ
B.A., University of the South, Sewanee, TN


Research Interests:

Mechanisms underlying vascular smooth muscle cell phenotypic plasticity

Understanding mechanisms associated with phenotypic heterogeneity in inherited retinal degenerations


Contact Information:

Office Phone: 405-271-8001  ext. 12493

Fax Number: 405-271-3548

 

Email: shannon-conley@ouhsc.edu 

 

University of Oklahoma Health Sciences Center
Department of Cell Biology
940 Stanton L. Young Blvd, BMSB 783
Oklahoma City, OK 73104
 


Research Interests:

 

Mechanisms underlying vascular smooth muscle cell phenotypic plasticity

Vascular smooth muscle cells (VSMCs) are an essential component of vascular homeostasis and vascular function.  VSMCs retain a high degree of plasticity and can transition from a contractile to a migratory/synthetic state in response to signaling from a variety of stimuli, including growth factors, mechanical stretch, cholesterol, and oxidative stress.  The phenotypic switch to a migratory state is an important part of vascular development, but can lead to pathological changes in various disease states including the vessel remodeling associated with diabetic retinopathy, atherosclerosis, vascularization of tumors, and cerebromicrovascular disease.  Much remains unknown about the mechanisms which regulate this phenotypic switch and about the variety of synthetic phenotypes VSMCs can adopt.  Our lab is interested in mechanisms underlying regulation of this plasticity, and have identified a variety of factors including transcription factors, guidance proteins, and small GTPases that play a role in this process.  We are also interested in understanding what signaling leads to the adoption of some aspects of the synthetic phenotype and not others. These studies are essential to our understanding of VSMC phenotypic switching and provide insight into the regulation of a process that is critical to multiple debilitating diseases.

 

 Understanding mechanisms associated with phenotypic heterogeneity in inherited retinal degenerations

 

Peripherin 2 (PRPH2), is a photoreceptor-specific tetraspanin protein necessary for the formation and function of rod and cone outer segments (OSs).  Mutations in PRPH2 lead to severe autosomal dominant retinal degenerations.  Critically, these mutations lead to widely varying blinding phenotypes ranging from severe retinitis pigmentosa to milder forms of macular and pattern dystrophy.  PRPH2-associated disease can display a high degree of variability in phenotype and severity both among distinct mutations and between patients carrying the same mutation.  Our past research utilized mouse models to understand how different PRPH2 mutations led to different disease phenotypes on a biochemical, cellular, and physiological level.  However, very little is known about what contributes to the vast variability seen among patients carrying the same mutation.  Understanding contributors to this intrafamilial phenotypic heterogeneity has been the focus of our more recent work.  Using in vitro and in vivo models, we and others have shown that Prph2-associated disease can arise due to loss-of-function (haploinsufficiency) or complex gain-of-function mechanisms, often associated with defects in oligomerization between PRPH2 and its homologue rod outer segment membrane protein 1 (ROM1).  In contrast to PRPH2, no pathogenic mutations in ROM1 have been confirmed in patients.  Eliminating Rom1 (Rom1-/-) in mice leads to minor defects, so it has been assumed that ROM1 plays an ancillary role.  However, recently we showed that in a mouse model carrying a Prph2 mutation associated with phenotypic variability in patients (Y141C), removing Rom1 results in the conversion of cone-rod dystrophy to a rod-cone RP phenotype, suggesting ROM1 may play a role in PRPH2-associated disease.  Our current research is focused on understanding how non-pathogenic ROM1 variants as well as non-pathogenic PRPH2 variants found on the opposing allele (i.e. not the allele with the primary pathogenic mutation, also known as haplotypes in trans) affect PRPH2-associated phenotypes.  This work involves both basic science experiments to evaluate the molecular and biochemical defects associated with PRPH2/ROM1 variants as well as collaborations with clinical scientists and clinical geneticists to understand the extent to which novel PRPH2/ROM1 variants exist in patient populations.


Selected Publications:

Czakó C, Kovács T, Ungvari Z, Csiszar A, Yabluchanskiy A, Conley SM, Csipo T, Lipecz A, Logan T, Zsolt Nagy Z, Kovács I. (2020) Retinal biomarkers for Alzheimer’s disease and vascular cognitive impairment and dementia (VCID): implication for early diagnosis and prognosis. Geroscience, doi: 10.1007/s11357-020-00252-7. Online ahead of print.

 

Kakakhel M, Tebbe L, Makia MS, Conley SM, Sherry DM, Al-Ubaidi MR, Naash MI. (2020) Syntaxin 3 is essential for photoreceptor outer segment trafficking and survival.  Proceedings of the National Academy of Sciences (USA).  Aug 10:202010751. doi: 10.1073/pnas.2010751117. 117(34):20615-20624. PMCID: PMC7456102

 

Lipecz A, Miller L, Kovacs I, Czakó C, Csipo T, Baffi J, Csiszar A, Tarantini S, Ungvari Z, Yabluchanskiy A, Conley SM. (2019) Microvascular contributions to age-related macular degeneration (AMD): from mechanisms of choriocapillaris aging to novel interventions. Geroscience, 41:813-845.  PMCID: PMC6925092

 

Lipecz A, Csipo T, Tarantini S, Hand RA, Ngo B-TN, Conley SM, Nemeth G, Tsorbatzoglou A, Courtney DL, Yabluchanska V, Csiszar A, Ungvari Z, Yabluchanskiy A. (2019) Age-related impairment of neurovascular coupling responses: a dynamic vessel analysis (DVA)-based approach to measure decreased flicker light stimulus-induced retinal arteriolar dilation in healthy older adults. Geroscience. 2019 Jun 17. PMID 31209739

 

Conley SM, Stuck MW, Watson JN, Zulliger R, Burnett JL, Naash MI. (2019) Prph2 initiates outer segment morphogenesis but maturation requires Prph2/Rom1 oligomerization.  Human Molecular Genetics, 28:459-475.  PMCID: PMC6337695

 

Fulop GA, Ramirez-Perez FI, Kiss T, Tarantini S, Valcarcel Ares MN, Toth P, Yabluchanskiy A, Conley SM, Ballabh P, Martinez-Lemus LA, Ungvari Z, Csiszar A. (2019) IGF-1 deficiency promotes pathological remodeling of cerebral arteries: a potential mechanism contributing to the pathogenesis of intracerebral hemorrhages in aging.  J Gerontol A Biol Sci Med Sci 74:446-454 PMCID: 6417448

 

Zulliger R*, Conley SM*, Mwoyosvi ML, Al-Ubaidi MR, Naash MI. (Joint first authors) (2018) Oligomerization of Prph2 and Rom1 is essential for photoreceptor outer segment formation. Human Molecular Genetics, 27:3507-3518. PMCID: PMC6168975

 

Kelley RA, Conley SM, Makkia R, Watson JN, Han Z, Cooper MJ, Naash MI. (2018) DNA Nanoparticles are safe and nontoxic in non-human primate eyes.  International Journal of Nanomedicine. 13:1361-1379, PMCID: PMC5849385

 

Conley SM, Stuck MW, Watson JN, Naash MI. (2017) Rom1 converts Y141C-Prph2-associated pattern dystrophy to retinitis pigmentosa. Human Molecular Genetics, 26:509-518. PMC Journal In Process.

 

Zulliger R, Conley SM, Mwoyosvi ML, Stuck MW, Azadi S, Naash MI. (2015) SNAREs interact with RDS/ROM-1 during conventional and unconventional outer segment targeting. PLOS ONE, 10(9):e0138508. PMCID: PMC4583372.

 

Conley SM, Al-Ubaidi MR, Han Z, Naash MI. (2014) Rim formation is not a prerequisite for distribution of cone photoreceptor outer segment proteins. FASEB Journal. 28:3468-79.  PMCID: PMC4101662

 

Conley SM, Stuck MW, Burnett JL, Chakraborty D, Azadi S, Fliesler SJ, Naash MI. (2014) Insights into the mechanisms of macular degeneration associated with the R172W mutation in RDS. Human Molecular Genetics, 23:3102-14. PMCID: PMC4030767

 

Han Z, Guo J, Conley SM, Naash MI. (2013) Retinal angiogenesis in the Ins2Akita mouse model of diabetic retinopathy. Invest Ophthalmol. Vis. Sci. 54:574-584.  PMCID: PMC3558298.

 

Koirala A, Conley SM, Makkia R, Liu Z, Cooper MJ, Sparrow JR, Naash MI. (2013) Persistence of Non-viral vector mediated RPE65 expression: case for viability as a gene transfer therapy for RPE-based diseases. Journal of Controlled Release. 172:745-52. PMCID: PMC3858392

 

Han Z, Conley SM, Makkia RS, Cooper MJ, Naash MI. (2012) DNA Nanoparticle-Mediated ABCA4 Delivery Rescues Stargardt Dystrophy in Mice.  J Clinical Investigation.  122:3221-3226.  PMCID: PMC3428101.

 

Conley SM,* Cai X,* Makkia R, Wu Y, Sparrow JR, Naash MI. (2012) (Joint first authors) Increased Cone Sensitivity to ABCA4 deficiency provides insight into macular vision loss in Stargardt’s Dystrophy. Biochemica Biophysica Acta. 1822:1169-1179.  PMCID: PMC3351560.

 

Conley SM, Naash MI. (2010) Nanoparticles for retinal gene therapy.  Progress in Retinal and Eye Research.  29(5):376-97. PMCID: PMC2907107.

 

Conley SM, Stricker HM, Ding XQ, Naash MI. (2010) Biochemical analysis of phenotypic diversity associated with mutations in codon 244 of the retinal degeneration slow gene.  Biochemistry.  49:905-11.  PMCID: PMC2937569.

 

 

 

Complete list of publications:
https://www.ncbi.nlm.nih.gov/myncbi/1P_S5xwUY52/bibliography/public/

 

Profile Last Updated: Oct 15, 2020