Primary Faculty

Shannon Conley, Ph.D.

Shannon Conley, Ph.D.

Assistant Professor, Department of Cell Biology


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:

The role of vascular smooth muscle cells in age-related cognitive decline

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




University of Oklahoma Health Sciences Center
Department of Cell Biology
940 Stanton L. Young Blvd, BMSB 105
Oklahoma City, OK 73104

Research Interests:

The role of vascular smooth muscle cells in age-related cerebrovascular dysfunction and cognitive decline

Age-related vascular cognitive impairment and dementia (VCID), a subgroup of Alzheimer’s Disease and Related Dementias (ADRD) is a common cause of disability and reduced quality of life among the elderly.  Extensive recent data have demonstrated that microvascular pathologies in the brain play a central role in these processes.  These pathologies include cerebral microhemorrhages (CMH), blood-brain-barrier disruption, microvascular rarefaction, and impaired cerebral myogenic autoregulation.  While the role of these vascular complications in cognitive decline has been clearly established, the underlying cellular mechanisms for increased age-related vascular fragility are unknown.  Our lab is particularly interested in the role of vascular smooth muscle cells (VSMCs) in brain aging.  Blood vessel integrity requires plasticity of VSMCs, which exhibit an adaptive switch from a highly contractile to a protective, anti-fragility phenotype in response to stress. Aging fundamentally alters VSMC phenotypic switching, suppressing the adoption of these protective VSMC features, which are otherwise promoted by insulin-like growth factor (IGF)-1. Circulating IGF-1 levels are dramatically decreased with age. Low IGF-1 levels increase the risk for cerebromicrovascular disease and promote the development of CMH in our rodent models, supporting a role for IGF-1 deficiency in age-related vascular fragility. Our lab is exploring the hypothesis is that impaired VSMC plasticity and function due to IGF-1 deficiency has a fundamental role in increased cerebrovascular fragility and development of cerebrovascular pathologies and cognitive decline with age. We utilize a variety of animal models to evaluate changes in behavior and cognition, vascular physiology, vascular cell biology, and molecular regulation in VSMCs.  Our current projects focus on 1) the hypothesis that VSMCs contribute to the development of VCID/ADRD phenotypes in IGF-1 signaling-deficient models, 2) the dynamic balance between VSMCs with maladaptive phenotypes and VSMCs with protective phenotypes induced by age-dependent decrease of IGF1, and 3) the transcriptional mechanisms governing maladaptive and protective VSMC phenotypes in regions of vascular fragility/CMH and in surrounding intact vessels. This work will significantly enhance our understanding of the role of IGF-1 deficiency in the development of CMH and will provide insight into underlying cellular mechanisms which are critical for the development of effective therapies.


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:

Miller LR, Tarantini S, Nyúl-Tóth Á, Johnston MP, Martin T, Bullen EC, Bickel MA, Sonntag WE, Yabluchanskiy A, Csiszar A, Ungvari ZI, Elliott MH, Conley SMIncreased Susceptibility to Cerebral Microhemorrhages Is Associated With Imaging Signs of Microvascular Degeneration in the Retina in an Insulin-Like Growth Factor 1 Deficient Mouse Model of Accelerated Aging. Front Aging Neurosci. 2022;14:788296. doi: 10.3389/fnagi.2022.788296. eCollection 2022. PubMed PMID: 35356301; PubMed Central PMCID: PMC8959924.


Kiss T, Nyúl-Tóth Á, Gulej R, Tarantini S, Csipo T, Mukli P, Ungvari A, Balasubramanian P, Yabluchanskiy A, Benyo Z, Conley SM, Wren JD, Garman L, Huffman DM, Csiszar A, Ungvari Z. Old blood from heterochronic parabionts accelerates vascular aging in young mice: transcriptomic signature of pathologic smooth muscle remodeling. Geroscience. 2022 Feb 5;. doi: 10.1007/s11357-022-00519-1. [Epub ahead of print] PubMed PMID: 35124764.


Tebbe L, Sakthivel H, Makia MS, Kakakhel M, Conley SM, Al-Ubaidi MR, Naash MI. Prph2 disease mutations lead to structural and functional defects in the RPE. FASEB J. 2022 May;36(5):e22284. doi: 10.1096/fj.202101562RR. PubMed PMID: 35344225.


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


Radojevic B, Conley SM, Bennett LD. Adherent but Not Suspension-Cultured Embryoid Bodies Develop into Laminated Retinal Organoids. J Dev Biol. 2021 Sep 10;9(3). doi: 10.3390/jdb9030038. PubMed PMID: 34564087; PubMed Central PMCID: PMC8482155.


István L, Czakó C, Élő Á, Mihály Z, Sótonyi P, Varga A, Ungvári Z, Csiszár A, Yabluchanskiy A, Conley S, Csipő T, Lipecz Á, Kovács I, Nagy ZZ. Imaging retinal microvascular manifestations of carotid artery disease in older adults: from diagnosis of ocular complications to understanding microvascular contributions to cognitive impairment. Geroscience. 2021 Aug;43(4):1703-1723. doi: 10.1007/s11357-021-00392-4. Epub 2021 Jun 8. Review. PubMed PMID: 34100219; PubMed Central PMCID: PMC8492863.


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:


Profile Last Updated: May 12, 2022