- Neural-vascular development, epigenetic regulation of vascular-microenvironmental interactions in development and disease
My current teaching includes a combination of upper and lower division courses that are designed to encourage interactive learning paradigms. In the Fall, I teach Developmental Biology (BIO378) that provides an overview of general developmental biology principles, including the general stages of development associated with a variety of species, experimental approaches used to study developmental processes, and the genetic and environmental influences that govern development. Over the years, I have taught a variety of courses, including General Biology I (BIOL150), General Biology II (BIOL151), Special Topics Seminars (BIOL491/503) on the Brain, Cell and Molecular Biology, and Integrative Biology, the Biology Senior Capstone (BIOL480), Orientation to the Major (BIOL120), and Scientific Writing (BIOL509). In all my teaching, I incorporate team-based learning approaches and discussion as part of student-centered learning.
The overarching theme of my research addresses how changes in gene expression patterns regulate cell fate choices during central nervous system (CNS) development. In addition to the regulatory processes that occur during normal development, I am interested in the cell, molecular, and epigenetic changes that occur in response to environmental toxins. I am a member of the Society for Neuroscience, the North American Vascular Biology Organization (UND Campus Representative), and the Society for Developmental Biology.
My current research addresses the influence of heterotypic cell-cell interactions during central nervous system development. My work is designed to test the hypothesis that neurovascular interactions stabilize the vasculature during development and under pathologic conditions. I am also investigating the role of a traditionally vascular factor, vascular endothelial growth factor (VEGF) on the regulation of neurogenesis. I am currently conducting these studies using in vitro cell culture approaches and an in vivo system using transgenic mice. I also collaborate with Dr. Tristan Darland to investigate the impact of environmental toxins (i.e. cadmium) on the development of the nervous system using the zebrafish as a model organism. The rationale behind these latter investigations is to determine the impact that early, low levels of toxin exposure can have on not only the neural stem cells of the developing system, but also on the ability of the adult system to respond to stress.
In addition, I am a member of the UND Epigenetics and Epigenomics group and am investigating the epigenetic mechanisms that control neural stem cell fate choice and neural-vascular interactions in early mouse cortical development. This work is funded by the COBRE grant on "Epigenetics and Epigenomics of Development and Disease".
Current Lab Members: Diane Darland (P.I.), Elvira Tkach (Research Technician), Jeremy Martin (M.Sc. Graduate Student), Yingfen Wu (Ph.D. graduate student, co-advised with Dr. Julia Zhao through Chemistry Department), Di (Sandy) Sun (Ph.D. graduate student, co-advised with Dr. Julia Zhao through Chemistry Department), Chloe Kaelberer (Research Assistant), Uchechukwu (Mike) Monday (Research Assistant), Elisabeth Kolb (Biology undergraduate), Delton Gabel (Biology undergraduate, Honor's Thesis), and Kirati Tayutivutikul (Biology undergraduate). Despite COVID 19 restrictions, research progress continues due to the awesome teamwork!
Kaur, H., Golovko, S., Golovko, M.Y., Singh, S., Darland, D.C., Combs, C.K. Effects of probiotic supplementation on short chain fatty acids in the AppN-L-GF mouse. Journal of Alzheimer’s Disease, 2020; 76(3):1083-1102. DOI: 10.3233/JAD-200436.
Yin, J., Suo, Y., Zou, Z., Sun, J., Zhang, S., Wang, B., Xu, Y., *Darland, D., *Zhao, J.X., and *Mu, Y. Integrated microfluidic systems with sample preparation and nucleic acid amplification. Lab on a Chip, 2019; 19:2769-2785 DOI: 10.1039/c9lc00389d. *senior co-corresponding authors
Vomhof-DeKrey, E.E., Lee, J., Lansing, J., Brown, C., Darland, D., Basson, M.D. Schlafen 3 knockout mice display gender-specific differences in weight gain, food efficiency, and expression of markers of intestinal epithelial differentiation, metabolism, and immune cell function. 2019 PLoS ONE, 14(7):e0219267; [PMID: 31260507; DOI: 10.1371/journal.pone.0219267]
Zhang, Y., Liu, X., GMichelson, K., Schepp, E., Trivedi, R., Xing, Y., *Darland, D., and *Zhao, J.X. Graphene oxide-based biocompatible 3D Mesh with a tunable porosity and tensility for use in cell culture. ACS Biomaterials Science and Engineering, 2018 March 26; 4(5):1505-1517. [DOI:10.1021/acsbiomaterials.8b00190]; *senior co-corresponding authors
*Zhang, Y., *Darland, D., He, Y., Yang, L., Dong, X., and Chang, Y. Reduction of PM2.5 toxicity on human alveolar epithelial cells A549 by tea polyphenols. Journal of Food Biochemistry, 2017 Dec 19; [DOI:10.1111/jfbc.12496]; *co-first authors
Wold, M., Beckmann, M., Poitra, S., Espinoza, A., Longie, R., Mersereau, E., Darland, D.C., and Darland, T. The Longitudinal Effects of Early Developmental Cadmiu Exposure on Conditioned Place Preference and Cardiovascular Physiology in Zebrafish. Aquatic Toxicology, 2017 Aug 3; 191:73-84; [PMID: 28804037; doi:10.1016]
Mersereau, E., Boyle, C.A., Poitra, S., Espinosa, A., Seiler, J., Longie, R., Delvo, L., Szarkowski, M. Maliske, J., Chalmers, S., Darland, D.C., Darland, T. Longitudinal Effects of Embryonic Exposure to Cocaine on Morphology, Cardiovascular Physiology, and Behavior in Zebrafish. International Journal of Molecular Sciences, 2016 May 17:847-865; [PMID: 2725824; doi:10.3390/ijms17060847] Special Note: This is an issue dedicated to zebrafish toxicology models.
Cain, JT, Berosik, MA, Snyder, SD, Crawford, NF, Nour, SI, Schaubhut, GJ, and Darland, DC Shifts in the Vascular endothelial growth factor (Vegf) isoforms result in transcriptome changes correlated with early neural stem cell proliferation and differentiation in mouse forebrain. Developmental Neurobiology, 2014; 74(1):63-81. PMID: 24124161
Darland, T, Mauch, JT, Meier, EM, Hagan, SJ, Dowling, JE, and Darland, DC Sulpiride, but not SCH23390, modifies cocaine-induced conditioned place preference and expression of Tyrosine hydroxylase and Elongation factor 1α in zebrafish. Pharmacology, Biochemistry, and Behavior 2012; 103(2):157-167. PMID: 22910534
Darland, DC and Carmichael, JS Long-term retention of knowledge and critical thinking skills in Developmental Biology. J of Microbiology and Biology Education 2012; 13(2):125-132. PMID: 23653799
Darland, DC, Cain, JT, Berosik, MA, Saint-Geniez, M, Odens, PW, Schaubhut, GJ, Frisch, S, Stemmer-Rachamimov, A, Darland, T, and D'Amore, PA Vascular endothelial growth factor (VEGF) isoform regulation of early forebrain development. Developmental Biology 358(1):9-22, 2011. PMID: 21803034
Sharma, S, Darland, DC, Lei, S, Rakoczy, S, Brown-Borg, HM NMDA and kainate receptor expression, long-term potentiation and neurogenesis in the hippocampus of long-lived Ames dwarf mice. AGE May 5. [Epub ahead of print]) PMID: 21544578, 2011. PMID: 21544578
Saint-Geniez, M, Maharaj, ASR, Walshe, TE, Tucker, BA, Sekiyama, E, Kurihara, T, Darland, DC, Young, MJ and D'Amore, PA Endogenous VEGF Is Required for Visual Function: Evidence for a Survival Role on Müller Cells and Photoreceptors. J Experimental Medicine 3(11):e3554, 2008. PMID: 18978936
Ergorul, C, Ray, A, Huang, W, Darland, D, Zhonghui, K, and Grosskreutz, C Levels of Vascular endothelial growth factor-A 165-b (VEGF165b) are elevated in experimental glaucoma. Molecular Vision 14:1517-1524, 2008. PMID: 18728749
Levenberg, S, Rouwkema, J, MacDonald, M, Garfein, ES, Kohane, D, Darland, DC, Marini, R, vanBlitterswijk, CA, Muligan, RC, D'Amore, PA, Langer, R. Engineering vascularized skeletal muscle tissue. Nature Biotechnology, 23(7):879-84, 2005. PMID: 15965465
Arboleda-Velasquez, JF, Rampal, R, Fung, E, Darland, DC, Liu, M, Martinez, MC, Donahue, CP, Navarro-Gonzalez, MF, Libby, P, D'Amore, PA, Aikawa, M, Haltiwanger, RS, Kosik, KS. Cadasil mutations impair Notch3 glycosylation by fringe. Human Molecular Genetics, 14(12): 1631-1639, 2005. PMID: 15857853
Garcia, CM, Darland, DC, Massingham, LJ, D'Amore, PA. Endothelial cell-astrocyte interactions and TGFB are required for induction of blood-neural barrier properties, Developmental Brain Research, 152:25-38, 2004. PMID: 15283992
Morris PN, Dunmore BJ, Tadros A, Marchuk DA, Darland DC, D'Amore PA & Brindle NPJ. Functional analysis of a mutant form of the receptor tyrosine kinase Tie2 causing venous malformations. Journal of Molecular Medicine, 83:58-63, 2004. PMID: 15526080
Ding, R, Darland, DC, Parmacek, MS, and D'Amore, PA. Endothelial-mesenchymal interactions in vitro reveal molecular mechanisms of smooth muscle/pericyte differentiation. Stem Cells and Development, 13:509-520, 2004. PMID: 15588508
Darland, DC, Massingham, LJ, Smith, SR, Piek, E, Saint-Geniez, M. and D'Amore, PA. Pericyte production of cell-associated VEGF is differentiation-dependent and is associated with endothelial survival. Developmental Biology, 264:275-288, 2003. PMID: 14623248
Darland, DC and D'Amore, PA. TGFβ is required for the formation of capillary-like structures in three-dimensional cocultures of 10T1/2 and endothelial cells. Angiogenesis, 4:11-20, 2001 PMID: 11824373
UND SMHS Epigenetics COBRE Project Vaughan, R. (PI)
Role: Project Director 07/11/19-07/10/22
Project: The role of class IIa Hdac in regulating cell fate choice in early development. The goal of the proposed studies is to understand how microenvironment-induced, acetylation-based modifications to chromatin influence cortical gliogenesis during development and in glioma tumor progression. The proposed work targets the intersection of development and disease at two levels: neural stem cells as they alter cell fate in response to vascular cell cues and glioma cells as they progress in tumor stages in response to vascular cell cues.
1988 B.A. University of California, San Diego, Biology; Revelle College
1998 Ph.D. Oregon Health Sciences University, Cell & Developmental Biology
1998 Research Fellow Vascular Development Children’s Hospital, Boston, MA
1998- Research Fellow Vascular Development The Schepens Eye Research Institute
Hospital or Affiliated Institution Appointments:
1998 Research Fellow, Department of Pathology, Children’s Hospital
1998 - 2001 Research Fellow, Department of Ophthalmology, Schepens Eye Research Institute
2001 - 2005 Mentored-Investigator, Schepens Eye Research Institute, non-tenured
2001 - 2005 Instructor, Harvard Medical School, non-tenured
2005 - 2012 Assistant Professor of Biology, University of North Dakota, tenure-track
2012 - Associate Professor Biology, University of North Dakota, tenured