Biography

Dr. Sirianni earned her doctorate in Biomedical Engineering at Yale University in 2008, during which time she developed models of drug delivery from polymeric biomaterials. She completed a postdoctoral fellowship in Diagnostic Radiology at the Yale School of Medicine, developing novel imaging techniques to track the distribution of polymers in the central nervous system. Her doctoral and postdoctoral works were supported by interdisciplinary training grants from the National Institutes of Health and bridged topics including polymeric drug delivery, transport modeling, neurobiology, and imaging.

Dr. Sirianni took her first faculty position in 2011 at the Barrow Neurological Institute, where her laboratory focused on drug delivery and tissue engineering for the treatment of central nervous system disorders. She joined the Department of Neurosurgery at UT in 2018. Her research program here is focused on engineering drug loaded nanoparticles for intrathecal and intraventricular drug delivery in Pediatric Neuro-Oncology

Education

Doctorate
Biomedical Engineering, Yale University, New Haven, Connecticut
Postdoctoral Fellowship
Diagnostic Radiology, Yale School of Medicine, New Haven, Connecticut

Areas of Interests

Research Interests

My research is focused on the development and translation of novel therapeutics for the treatment of pediatric brain tumors. Our approach focuses on encapsulation of drugs within biocompatible and biodegradable nanoparticles, which serve as drug carriers to prolong drug action and target drug delivery to specific tissue sites. In the past, we have developed a number of novel approaches for engineering nanoparticle composition and surface properties to enable central nervous system drug delivery in adult brain cancer and neurodegeneration. More recently, we are focused on developing these systems for intrathecal and intraventricular drug delivery for treatment of brain tumors in children. These approaches are designed to target leptomeningeal metastasis, infiltrative disease, and residual tumor following surgical resection. We have also developed a number of tissue engineering models to study microenvironmental regulation of tumor growth, treatment resistance, and metastasis in the central nervous system. The long-term goal of my research program at UT is to bring novel nanomedicine approaches into the clinic to improve outcomes for children affected by malignant brain tumors.

Publications

Publication Information

Publications

 

1.       Householder KT, DiPerna D, Sirianni RW. (2018) “Manipulation of evaporation phase pH to improve quisinostat loading in PLA-PEG nanoparticles for treatment of intracranial glioblastoma” Colloids and Surfaces B: Biointerfaces 166:37-44

2.       Heffernan JM, Sirianni RW. (2018) “Biomaterials for modeling microenvironmental regulation of glioblastoma stem cells” Frontiers in Materials 143:149-158

3.       Prakapenka AV, Hiroi R, Quihuis AM, Carson C, Patel S, Berns-Leone C, Fox C, Sirianni RW, Bimonte-Nelson HA. (2018) “Contrasting effects of individual versus combined estrogen and progestogen regimens as working memory load increases in middle-aged ovariectomized rats: one plus one does not equal two.” Neurobiol Aging. 64:1-14

4.       Moutal A, Villa L, Yeon S, Householder KT, Park KD, Sirianni RW, Khanna R. (2017) “CRMP2 phosphorylation drives glioblastoma cell proliferation” Molecular Neurobiology 55(5):4403-4416

5.       Prakapenka AV, Bimonte-Nelson HA, Sirianni RW. “Engineering poly(lactic-co-glycolic acid) micro- and nano-carriers for controlled delivery of 17β-estradiol” Annals of Biomedical Engineering 45(7):1697-1709

6.       Heffernan JM, McNamara JB, Borwege S, Vernon BL, Sanai N, Mehta S, Sirianni RW. (2017) “PNIPAAm-co-Jeffamine (PNJ) scaffolds as in vitro models for niche enrichment of glioblastoma stem-like cells” Biomaterials 143:149-158

7.       Medina DX, Householder KT, Ceton R, Kovalik T, Heffernan J, Shankar RV, Bowser RP, Wechsler-Reya RJ, Sirianni RW. (2017) “Optical barcoding of PLGA for multispectral analysis of nanoparticle fate in vivo” Journal of Controlled Release 10;253:171-182 PMID: 28263836

8.       Addington CP, Dharmawaj J, Heffernan JM, Sirianni RW, Stabenfeldt SE. (2016) “Hyaluronic acid-laminin hydrogels increase neural stem cell transplant retention and migratory response to SDF-1alpha” Matrix Biology 60-61:206-216 PMID: 27645115

9.       Kobes JE, Daryaei I, Howison CM, Bontrager JG, Sirianni RW, Meuillet EJ, Pagel MD. (2016) “Improved treatment of pancreatic cancer with drug delivery nanoparticles loaded with a novel AKT/PDK1 inhibitor” Pancreas 45(8):1158-66 PMID: 26918875

10.   Navaeis A, Truong D, Heffernan JM, Cutts J, Brafman D, Sirianni RW, Vernon BL, Nikkhah M. (2016) “PNIPAAm-based biohybrid injectable hydrogel for cardiac tissue engineering” Acta Biomaterialia 1(32):10-23 PMID: 26689467

11.   Dutta D, Salifu M, Sirianni RW, Stabenfeldt SE. (2015) “Modulation of release profiles from protein-loaded nanoparticles using centrifugal fractioning” Journal of Biomaterials Research: Part A  [epub ahead of print] PMID: 26517011

12.   Cook RL, Householder KT, Chung EP, Prakapenka AV, DiPerna DM, Sirianni RW*. (2015) “A critical evaluation of drug delivery from ligand modified nanoparticles: confounding small molecule distribution and efficacy in the central nervous system” Journal of Controlled Release 220(Pt A):89-97. PMID: 26471392

13.   Addington CP, Heffernan JM, Millar-Haskell CS, Sirianni RW, Stabenfeldt SE. (2015) “Enhancing neural stem cell response to SDF-1a gradients through hyaluronic acid-laminin hydrogels” Biomaterials 72:11-9. PMID: 26340314

14.   Heffernan JM, Overstreet DJ, Srinivasan S, Le LD, Vernon BL, Sirianni RW. (2015) “Temperature responsive hydrogels enable transient three-dimensional tumor cultures via rapid cell recovery” Journal of Biomaterials Research: Part A 104(1):17-25.  PMID: 26123863

15.   Householder KT, DiPerna D, Chung EP, Wohlleb G, Dhruv H, Berens M, Sirianni RW. (2015) “Intravenous delivery of camptothecin-loaded PLGA nanoparticles for the treatment of intracranial glioma.” International Journal of Pharmaceutics. 479(2):374-380. PMID: 25562639

16.   Heffernan JM, Overstreet DJ, Le LD, Vernon BL, Sirianni RW. (2014) “Bioengineered hydrogels for 3D analysis of glioblastoma invasion and proliferation”. Annals of Biomedical Engineering 43(8):1965-77. PMID: 25515315

17.   McCall RL, Cacaccio J, Wrabel E, Schwartz ME, Coleman TP, Sirianni RW. (2014) Pathogen-inspired drug delivery to the central nervous system. Tissue Barriers. 2:4, e944449-14. PMID: 25610755

18.   McCall RL, Sirianni RW. (2013) PLGA nanoparticles formed by single- or double-emulsion with vitamin E-TPGS. Journal of Visualized Experiments. (82):51015. PMID: 24429733.

19.   Sirianni RW, Zheng MQ, Patel TR, Schafbauer T, Zhou JB, Saltzman WM, Carson RE, Huang YY. (2014) Radiolabeling of poly(lactic-co-glycolic acid)  (PLGA) nanoparticles with biotinylated F-18 prosthetic groups and imaging of their delivery to the brain with positron emission tomography. Bioconjugate Chemistry. 25(12):2157-65. PMID: 25322194

20.   Zhou JB, Patel TR, Sirianni RW, Strohbehn G, Zheng MQ, Duong N, Schafbauer T, Huttner AJ, Huang Y, Carson RE, Zhang Y, Sullivan DJ, Piepmeier J, Saltzman WM. (2013) Highly-penetrative, drug-loaded nanocarriers improve treatment of glioblastoma. Proceedings of the National Academy of Sciences. 110(29): 11751-6. PMID: 23818631

21.   Sirianni RW, Zheng MQ, Saltzman WM, Huang Y, Carson RE. (2013) Direct, quantitative, and noninvasive imaging of the transport of active agents through intact brain with positron emission tomography. Molecular Imaging and Biology. 15(5):596-605. PMID: 23624949

22.   Sirianni RW, Olausson P, Chiu A, Taylor JR, Saltzman WM. (2010) Engineering the rate of BDNF release from a polymer implant to influence animal behavior. Brain Research. 1321(C): 40-50. PMID: 20096671

23.   Sirianni RW, Jang EH, Miller KM, Saltzman WM. (2009) Parameter estimation methodology in a model of hydrophobic drug release from a polymer coating. Journal of Controlled Release. 142(3): 474-482. PMID: 19958804

24.   Sirianni RW, Kremer J, Guler I, Chen YL, Keeley F, Saltzman WM. (2008) The effect of extracellular matrix elements on the transport of paclitaxel through an arterial wall tissue mimic. Biomacromolecules. 9(10): 2792-2798. PMID: 18785771

25.   Solis FJ, Weiss-Malik RA, Vernon BL. (2005) Local monomer activation model for phase behavior and calorimetric properties of LCST gel-forming polymers. Macromolecules. 38(10): 4456-4464. DOI: 10.1021/ma047895a

26.   Weiss-Malik RA, Solis FP, Vernon BL. (2004) Independent control of lower critical solution temperature and swelling behavior with pH for poly (N-isopropylacrylamide-co-maleic acid). Journal of Applied Polymer Science. 94(5): 2110-2116. DOI: 10.1002/app.21000