Lisa L. Sandell, PhD
Associate Professor,
Dept. Oral Immunology & Infectious Diseases
ORCID: 0000-0002-1735-8223

Vitamin A is an essential nutrient that is metabolized into the potent hormone-like molecule retinoic acid. Our studies focus on identifying how Vitamin A and retinoic acid regulate normal embryonic development, and how disturbances of these molecules may contribute to congenital abnormalities. We use mouse as a model system to investigate how Vitamin A metabolism and retinoic acid regulate development of craniofacial structures and salivary glands.  This knowledge will help in prevention of birth defects, and will contribute to bioengineering approaches for treatment of salivary gland dysfunction.

Contact:lisa.sandell@louisville.edu

Background:
Senior Research Associate (Birth defects research - mouse genetic models) Stowers Institute for Medical Research, Kansas City, MO
Postdoctoral Fellowship, (Genomic Imprinting – mouse molecular genetics) Department of Molecular Biology, Princeton University, Princeton, NJ
Doctor of Philosophy (Molecular Biology – Yeast telomere function) research at Fred Hutchinson Cancer Research Center, Department of Pathology, University of Washington, Seattle, WA
Bachelor of Science (Biology) University of Washington, Seattle, WA

Salivary gland researcher map

Publications (also available at NCBI-PubMed)

Guertin TM, Palaria A, Mager J, Sandell LL, Trainor PA, Tremblay KD. Deciphering the role of retinoic acid in hepatic patterning and induction in the mouse. Dev Biol. 2022;491:31-42. Epub 2022/08/27. doi: 10.1016/j.ydbio.2022.08.003. PubMed PMID: 36028102.

Wu Y, Kurosaka H, Wang Q, Inubushi T, Nakatsugawa K, Kikuchi M, Ohara H, Tsujimoto T, Natsuyama S, Shida Y, Sandell LL, Trainor PA, Yamashiro T. Retinoic Acid Deficiency Underlies the Etiology of Midfacial Defects. J Dent Res. 2022;0(0):00220345211062049. doi: 10.1177/00220345211062049. PubMed PMID: 35001679.

Engelbrecht E, Metzler MA, Sandell LL. Retinoid signaling regulates angiogenesis and blood-retinal barrier integrity in neonatal mouse retina. Microcirculation. 2022:e12752. Epub 2022/02/25. doi: 10.1111/micc.12752. PubMed PMID: 35203102.

Wang Q, Xu L, Miura J, Saha MK, Uemura Y, Sandell LL, Trainor PA, Yamashiro T, Kurosaka H. Branchiomeric Muscle Development Requires Proper Retinoic Acid Signaling. Front Cell Dev Biol. 2021;9:596838. Epub 2021/07/27. doi: 10.3389/fcell.2021.596838. PubMed PMID: 34307338; PMCID: PMC8299418.

Kurosaka H, Mushiake J, Mithun S, Wu Y, Wang Q, Kikuchi M, Nakaya A, Yamamoto S, Inubushi T, Koga S, Sandell LL, Trainor P, Yamashiro T. Synergistic role of retinoic acid signaling and Gata3 during primitive choanae formation. Hum Mol Genet. 2021. Epub 2021/07/18. doi: 10.1093/hmg/ddab205. PubMed PMID: 34272563.

Dash S, Bhatt S, Falcon KT, Sandell LL, Trainor PA. Med23 Regulates Sox9 Expression during Craniofacial Development. J Dent Res. 2021;100(4):406-14. Epub 2020/11/07. doi: 10.1177/0022034520969109. PubMed PMID: 33155500.

Dash S, Bhatt S, Sandell LL, Seidel CW, Ahn Y, Krumlauf RE, Trainor PA. The Mediator Subunit, Med23 Is Required for Embryonic Survival and Regulation of Canonical WNT Signaling During Cranial Ganglia Development. Front Physiol. 2020;11:531933. Epub 2020/11/17. doi: 10.3389/fphys.2020.531933. PubMed PMID: 33192541; PMCID: PMC7642510.

Ono K, Sandell LL, Trainor PA, Wu DK. Retinoic acid synthesis and autoregulation mediate zonal patterning of vestibular organs and inner ear morphogenesis. Development. 2020;147(15). Epub 2020/07/16. doi: 10.1242/dev.192070. PubMed PMID: 32665247; PMCID: PMC7420839.

Friedl RM, Raja S, Metzler MA, Patel ND, Brittian KR, Jones SP, Sandell LL. RDH10 function is necessary for spontaneous fetal mouth movement that facilitates palate shelf elevation. Disease Models and Mechanisms. 2019;12(7):dmm039073. doi: 10.1242/dmm.039073.

Inman KE, Caiaffa CD, Melton KR, Sandell LL, Achilleos A, Kume T, Trainor PA. Foxc2 is required for proper cardiac neural crest cell migration, outflow tract septation, and ventricle expansion. Dev Dyn. 2018. Epub 2018/10/31. doi: 10.1002/dvdy.24684. PubMed PMID: 30376688.

Sandell L, Inman K, Trainor P. DAPI Staining of Whole-Mount Mouse Embryos or Fetal Organs. Cold Spring Harb Protoc. 2018;2018(10):pdb.prot094029. Epub 2018/10/03. doi: 10.1101/pdb.prot094029. PubMed PMID: 30275072.

Metzler MA, Raja S, Elliott KH, Friedl RM, Tran NQH, Brugmann SA, Larsen M, Sandell LL. RDH10-mediated retinol metabolism and RARalpha-mediated retinoic acid signaling are required for submandibular salivary gland initiation. Development. 2018;145(15). Epub 2018/07/11. doi: 10.1242/dev.164822. PubMed PMID: 29986869; PMCID: PMC6110144.

Xue Y, Sato S, Razafsky D, Sahu B, Shen SQ, Potter C, Sandell LL, Corbo JC, Palczewski K, Maeda A, Hodzic D, Kefalov VJ. The role of retinol dehydrogenase 10 in the cone visual cycle. Sci Rep. 2017;7(1):2390. Epub 2017/05/26. doi: 10.1038/s41598-017-02549-8. PubMed PMID: 28539612.

Ogoh H, Yamagata K, Nakao T, Sandell LL, Yamamoto A, Yamashita A, Tanga N, Suzuki M, Abe T, Kitabayashi I, Watanabe T, Sakai D. Mllt10 knockout mouse model reveals critical role of Af10-dependent H3K79 methylation in midfacial development. Sci Rep. 2017;7(1):11922. Epub 2017/09/22. doi: 10.1038/s41598-017-11745-5. PubMed PMID: 28931923; PMCID: PMC5607342.

Kurosaka H, Wang Q, Sandell L, Yamashiro T, Trainor PA. Rdh10 loss-of-function and perturbed retinoid signaling underlies the etiology of choanal atresia. Hum Mol Genet. 2017. Epub 2017/02/09. doi: 10.1093/hmg/ddx031. PubMed PMID: 28169399.

Abashev TM, Metzler MA, Wright DM, Sandell LL. Retinoic acid signaling regulates Krt5 and Krt14 independently of stem cell markers in submandibular salivary gland epithelium. Dev Dyn. 2017;246(2):135-47. Epub 2016/11/25. doi: 10.1002/dvdy.24476. PubMed PMID: 27884045; PMCID: PMC5348080.

Metzler MA, Sandell LL. Enzymatic Metabolism of Vitamin A in Developing Vertebrate Embryos. Nutrients. 2016;8(12). Epub 2016/12/17. doi: 10.3390/nu8120812. PubMed PMID: 27983671; PMCID: PMC5188467.

Lenti E, Farinello D, Yokoyama KK, Penkov D, Castagnaro L, Lavorgna G, Wuputra K, Sandell LL, Tjaden NE, Bernassola F, Caridi N, De Antoni A, Wagner M, Kozinc K, Niederreither K, Blasi F, Pasini D, Majdic G, Tonon G, Trainor PA, Brendolan A. Transcription factor TLX1 controls retinoic acid signaling to ensure spleen development. J Clin Invest. 2016;126(7):2452-64. Epub 2016/05/24. doi: 10.1172/jci82956. PubMed PMID: 27214556; PMCID: PMC4922703.

Wu DK, Sandell LL. Development and Lineage relationships of the Mouse Inner Ear. In: Baldock R, Bard J, Davidson D, Morriss-Kay G, editors. Kaufman’s Atlas of Mouse Development Supplement. 1 ed. London: Academic Press; 2015. p. 267-74.

Wright DM, Buenger DE, Abashev TM, Lindeman RP, Ding J, Sandell LL. Retinoic acid regulates embryonic development of mammalian submandibular salivary glands. Dev Biol. 2015;407(1):57-67. doi: 10.1016/j.ydbio.2015.08.008. PubMed PMID: 26278034; PMCID: 4641807.

Warner DR, Sakai D, Sandell LL. Mammalian Cell Culture. In: Gallagher SR, Wiley EA, editors. Current Protocols Essential Laboratory Techniques: John Wiley & Sons, Inc.; 2015.

Cunningham TJ, Brade T, Sandell LL, Lewandoski M, Trainor PA, Colas A, Mercola M, Duester G. Retinoic Acid Activity in Undifferentiated Neural Progenitors Is Sufficient to Fulfill Its Role in Restricting Fgf8 Expression for Somitogenesis. PLoS One. 2015;10(9):e0137894. Epub 2015/09/15. doi: 10.1371/journal.pone.0137894. PubMed PMID: 26368825; PMCID: 4569375.

Aoto K, Sandell LL, Butler Tjaden NE, Yuen KC, Watt KEN, Black BL, Durnin M, Trainor PA. Mef2c-F10N enhancer driven beta-galactosidase (LacZ) and Cre recombinase mice facilitate analyses of gene function and lineage fate in neural crest cells. Dev Biol. 2015;402(1):3-16. doi: 10.1016/j.ydbio.2015.02.022. PubMed PMID: 25794678; PMCID: 4433593.

Sandell LL, Butler Tjaden NE, Barlow AJ, Trainor PA. Cochleovestibular nerve development is integrated with migratory neural crest cells. Dev Biol. 2014;385(2):200-10. Epub 2013/11/21. doi: 10.1016/j.ydbio.2013.11.009. PubMed PMID: 24252775; PMCID: 4556368.

Sandell LL. Neural Crest Cells in Ear Development. In: Trainor PA, editor. NEURAL CREST CELLS Evolution, Development and Disease. London: Academic Press; 2014. p. 167-88.

Hadel DM, Keller BB, Sandell LL. Confocal imaging of whole vertebrate embryos reveals novel insights into molecular and cellular mechanisms of organ development. In: Rollins AM, Lo CW, Fraser SE, editors. SPIE BiOS; 2014; San Francisco. San Francisco, CA, USA: International Society for Optics and Photonics; 2014. p. 895302--7.

Cunningham Thomas J, Zhao X, Sandell Lisa L, Evans Sylvia M, Trainor Paul A, Duester G. Antagonism between Retinoic Acid and Fibroblast Growth Factor Signaling during Limb Development. Cell Reports. 2013;3(5):1503-11. doi: 10.1016/j.celrep.2013.03.036. PubMed PMID: WOS:000321899300022; PMCID: 3745640.

Sandell LL, Lynn ML, Inman KE, McDowell W, Trainor PA. RDH10 oxidation of Vitamin A is a critical control step in synthesis of retinoic acid during mouse embryogenesis. PLoS One. 2012;7(2):e30698. doi: 10.1371/journal.pone.0030698. PubMed PMID: 22319578; PMCID: 3271098.

Sandell LL, Kurosaka H, Trainor PA. Whole mount nuclear fluorescent imaging: convenient documentation of embryo morphology. Genesis. 2012;50(11):844-50. doi: 10.1002/dvg.22344. PubMed PMID: 22930523; PMCID: 3504639.

Sandell LL. Regulated metabolism of Vitamin A by retinol dehydrogenase 10 is critical for embryonic development of the heart The FASEB Journal [Internet]. 2012; 26 339.3.

Kumar S, Sandell LL, Trainor PA, Koentgen F, Duester G. Alcohol and aldehyde dehydrogenases: Retinoid metabolic effects in mouse knockout models. Biochim Biophys Acta. 2012;1821(1):198-205. Epub 2011/04/26. doi: 10.1016/j.bbalip.2011.04.004. PubMed PMID: 21515404; PMCID: 3161159.

Sandell LL, Iulianella A, Melton KR, Lynn M, Walker M, Inman KE, Bhatt S, Leroux-Berger M, Crawford M, Jones NC, Dennis JF, Trainor PA. A phenotype-driven ENU mutagenesis screen identifies novel alleles with functional roles in early mouse craniofacial development. Genesis. 2011;49(4):342-59. Epub 2011/02/10. doi: 10.1002/dvg.20727. PubMed PMID: 21305688; PMCID: 3374396.

Sandell L, Sakai D. Mammalian Cell Culture.  Current Protocols Essential Laboratory Techniques: John Wiley & Sons, Inc.; 2011.

Farjo KM, Moiseyev G, Nikolaeva O, Sandell LL, Trainor PA, Ma JX. RDH10 is the primary enzyme responsible for the first step of embryonic Vitamin A metabolism and retinoic acid synthesis. Dev Biol. 2011;357(2):347-55. Epub 2011/07/26. doi: 10.1016/j.ydbio.2011.07.011. PubMed PMID: 21782811; PMCID: 3164597.

Cunningham TJ, Chatzi C, Sandell LL, Trainor PA, Duester G. Rdh10 mutants deficient in limb field retinoic acid signaling exhibit normal limb patterning but display interdigital webbing. Dev Dyn. 2011;240(5):1142-50. Epub 2011/03/02. doi: 10.1002/dvdy.22583. PubMed PMID: 21360789; PMCID: 3081420.

Cunningham TJ, Chatzi C, Sandell L, Trainor P, Duester G, editors. Total loss of limb bud retinoic acid signaling in Rdh10 mutants does not affect limb patterning but results in interdigital webbing. Dev Biol; 2011 8/1/.

Morgan SC, Relaix F, Sandell LL, Loeken MR. Oxidative stress during diabetic pregnancy disrupts cardiac neural crest migration and causes outflow tract defects. Birth Defects Research Part A - Clinical and Molecular Teratology. 2008;82(6):453-63. doi: 10.1002/bdra.20457. PubMed PMID: 18435457.

Morgan SC, Lee HY, Relaix F, Sandell LL, Levorse JM, Loeken MR. Cardiac outflow tract septation failure in Pax3-deficient embryos is due to p53-dependent regulation of migrating cardiac neural crest. Mech Dev. 2008;125(9-10):757-67. doi: 10.1016/j.mod.2008.07.003. PubMed PMID: WOS:000259927600001; PMCID: 2654333.

Sandell LL, Sanderson BW, Moiseyev G, Johnson T, Mushegian A, Young K, Rey JP, Ma JX, Staehling-Hampton K, Trainor PA. RDH10 is essential for synthesis of embryonic retinoic acid and is required for limb, craniofacial, and organ development. Genes Dev. 2007;21(9):1113-24. Epub 2007/05/03. doi: 10.1101/gad.1533407. PubMed PMID: 17473173; PMCID: 1855236.

Sandell LL, Trainor PA. Neural Crest Cell Plasticity. In: Saint-Jeannet J-P, editor. Neural Crest Induction and Differentiation: Springer US; 2006. p. 78-95.

Dixon J, Jones NC, Sandell LL, Jayasinghe SM, Crane J, Rey JP, Dixon MJ, Trainor PA. Tcof1/Treacle is required for neural crest cell formation and proliferation deficiencies that cause craniofacial abnormalities. Proc Natl Acad Sci U S A. 2006;103(36):13403-8. doi: 10.1073/pnas.0603730103. PubMed PMID: 16938878; PMCID: 1557391.

Sandell LL, Guan X-J, Ingram R, Tilghman SM. Gatm, a creatine synthesis enzyme, is imprinted in mouse placenta. Proceedings of the National Academy of Sciences. 2003;100(8):4622-7. doi: 10.1073/pnas.0230424100. PubMed PMID: 12671064; PMCID: 153605.

Mangahas JL, Alexander MK, Sandell LL, Zakian VA. Repair of chromosome ends after telomere loss in Saccharomyces. Mol Biol Cell. 2001;12(12):4078-89. doi: 10.1091/mbc.12.12.4078. PubMed PMID: 11739802; PMCID: 60777.

Sandell LL, Gottschling DE, Zakian VA. Transcription of a yeast telomere alleviates telomere position effect without affecting chromosome stability. Proceedings of the National Academy of Sciences. 1994;91(25):12061-5. doi: DOI 10.1073/pnas.91.25.12061. PubMed PMID: WOS:A1994PW70800061; PMCID: 45376.

Sandell LL, Zakian VA. Loss of a yeast telomere: arrest, recovery, and chromosome loss. Cell. 1993;75(4):729-39. Epub 1993/11/19. PubMed PMID: 8242745.

Sandell LL, Zakian VA. Telomeric position effect in yeast. Trends Cell Biol. 1992;2(1):10-4. doi: http://dx.doi.org/10.1016/0962-8924(92)90138-D. PubMed PMID: 14731632.

Perrino FW, Preston BD, Sandell LL, Loeb LA. Extension of mismatched 3' termini of DNA is a major determinant of the infidelity of human immunodeficiency virus type 1 reverse transcriptase. Proc Natl Acad Sci U S A. 1989;86(21):8343-7. doi: DOI 10.1073/pnas.86.21.8343. PubMed PMID: WOS:A1989AY57000037; PMCID: 298277.

Sandell L, Johnson G, Przepiorka D, Torok-Storb B. Phenotype and function of T-cells associated with marrow graft failure and rejection. In: Martelli MF, Grignani F, Reisner Y, editors. T-Cell Depletion in Allogeneic Bone-Marrow Transplantation Serono Symposia Review; 1988. New York: Raven Press; 1987. p. 49-56.