Biomedical Engineering

Alyssa Panitch

panitchEdward Teller Professor
Department Chair

Phone: 530-754-3222

Office: 2311 GBSF

Email: apanitch@ucdavis.edu

Lab: Laboratory for Engineered Therapeutics

Personal Education

B.S.; Chemical Engineering, University of Massachusetts at Amherst

PhD; Polymer Science and Engineering, University of Massachusetts, Amherst

 

Research Interests

Engineering at the extracellular level

The extracellular matrix (ECM) provides a spectrum of biophysical and biochemical clues that influence cell and tissue response. Biophysical and biochemical clues come from the molecular composition of the ECM and come in the form of chemical, morphological, and mechanical cues. Our laboratory has focused largely on the glycosaminoglycan (GAG), or long chain sugar biopolymers, and the instructive role they play in the ECM. The GAGs themselves can be chemically modified and used to form hydrogels for tissue engineering. The modified GAGs can also be used to engineer mimetics of the proteoglycans found within the ECM. Synthesis and evaluation of proteoglycan mimetics composes a large portion of the more recent effort in the Panitch laboratory. These molecules can be designed to mimic many of the functional properties of native proteoglycans, and we have used them in vasculardermal and cartilage applications. Our published work has shown that these mimics can inhibit dermal scarring, improve vessel healing after balloon angioplasty and suppress osteoarthritis following traumatic joint injury. Ongoing efforts include partnering to translate these therapeutics into the market place in addition to developing new ECM therapeutics.

Engineering at the intracellular level

Inflammation plays a critical role in tissue healing. Thus, fine-tuning the inflammatory process to promote normal tissue repair, while preventing scar formation is an on going effort in many labs throughout the world. Our laboratory has focused on the design of cell-penetrating peptide therapeutics that help regulate the inflammatory response by controlling key pathways in both inflammation and fibrosis. Our main effort has been focused on optimization and delivery of peptide inhibitors of the kinase Mitogen-Activated Protein Kinase-Activated Protein Kinase II, or MK2. Past efforts involving optimization of the peptide showed that both the cell-penetrating peptide and the kinase inhibitor sequence contribute to the specificity and activity of the peptide. With key collaborators we have shown that the peptide is effective at inhibiting surgical adhesionsintimal hyperplasia following vein-graft bypass, and the progression of idiopathic pulmonary fibrosis. Current efforts include developing methodologies to study key cellular delivery mechanisms, developing nanoparticle delivery technologies to improve efficacy, and expanding into the bioinformatics area, through collaborations with the Rundell and Kinzer-Ursem laboratories to elucidate how the MK2 signaling pathway interfaces with the AKT and TGF-β1 pathways to regulate tissue healing.

Selected Publications

2. A. Panitch, K. Matsuki, E. Cantor, S. J. Cooper, E. D. T. Atkins, M. J. Fournier, T. L. Mason and D. A. Tirrell. Poly(L-alanylglycine): ‘Multigram-Scale Biosynthesis, Chrystallization, and Structural Analysis of Chain-Folded Lamella’. Macromolecules. 30, 1997: 42-49.

3. A. Panitch, T. Yamaoka, M. J. Fournier, T. L. Mason, D. A. Tirrell. Design and Biosynthesis of Elastin-Like Artificial Extracellular Matrix Proteins Containing Periodically Spaced Fibronectin CS5 Domains. Macromolecules. 32, 1999: 1701-1704.

4. T. Tamura, T. Yamaoka, S. Kunki, A. Panitch and D. A. Tirrell. Effects of Temperature and Pressure on the Aggregational Properties of an Engineered Elastin Model Peptide in Aqueous Solution. Biomacromolecules. 1(4) 2000: 552-5.

5. S. Sakiyama-Elbert, A. Panitch and J. A. Hubbell. Development of Growth Factor Fusion Proteins for Cell-Triggered Drug Delivery. FASEB J. 15(7), 2001: 1300-1302.

6. B.L. Seal*, T. Otero*, and A. Panitch. Polymeric Biomaterials for Tissue and Organ Regeneration. Materials Science and Engineering R: Reports. 43(4-5), 2001: 147-230.

7. S. Halstenberg, A. Panitch, S. Rizzi, H. Hall, and J.A. Hubbell. Biologically Engineered Protein-graft-Poly(Ethylene Glycol) Hydrogels: A Cell-Adhesive and Plasmin-Degradable Biosynthetic Material for Tissue Repair, Biomacromolecules, 3(4), 2002: 710-723.

8. Flynn CR, Komalavilas P, Tessier D, Thresher J, Niederkofler E, Nelson RW, Panitch A, Joshi L, Brophy CM. Transduction of biologically active motifs of the small heat shock related protein, HSP20, leads to relaxation of vascular smooth muscle. Faseb J, 17(10), 2003: 1358-60.

9. Tessier D, Komalavilas P, Panitch A, Joshi L, Brophy CM. The small heat shock protein, HSP20, is dynamically associated with the actin cross-linking protein, actinin. J Surg Res, 111(1), 2003: 152-157.

10. B Seal* and A. Panitch. Physical Polymer Matrices Based on Affinity Interactions Between Peptides and Polysaccharides. Biomacromolecules, 4(6), 2003: 1572-1582

11. BA Koeneman*, K Lee, A Singh, J He, GB Raupp, A Panitch, David G. Capco. An Ex Vivo Method for Evaluating the Biocompatibility of Neural Electrodes in Rat Brain Slice Cultures. Journal of Neuroscience Methods, 137(2) 2004: 257-263.

12. Tessier DJ, Komalavilas P, Liu B, Kent CK, Thresher, JS, Dreiza*, CM, Panitch A, Joshi L, Furnish, E, Stone W, Fowl R, Brophy CM. Transduction of peptide analogs of the small heat shock-related protein HSP20 inhibits intimal hyperplasia. Journal of Vascular Surgery, 40(1), 2004: 206-214.

13. C Dreiza*, C Brophy, P Komalavilas, M Pallero, J Murphy-Ullrich, E Furnish, L Joshi, M von Rechenberg, J Ho, B Richardson, N Xu, Y Zhen, J M Peltier, A Panitch. Transducible Heat Shock Protein 20 (HSP20) Phosphopeptide Alters Cytoskeletal Dynamics. FASEB J 19(2) 2005: 261-3.

14. L. B. Lopes, C. M. Brophy, E. Furnish, C. R. Flynn, O. Sparks, P. Komalavilas, L. Joshi, A. Panitch, V. L. B. Bentley, Comparative Study of the Skin Penetration of Protein Transduction Domains and a Conjugated Protein. Pharmaceutical Research, 22(5) 2005: 750-7.

15. B. Seal* and A. Panitch, Physical Matrices Stabilized by Enzymatically Sensitive Covalent Crosslinks, Acta Biomaterialia, 2(3) 2006: 241-251.

16. B. Seal* and A. Panitch, Viscoelastic Behavior of Environmentally Sensitive Biomimetic Polymer Matrices, Macromolecules, 39(6), 2006: 2268-2274.

17. E Horn, M Beaumont*, A Harvey*, M Preul and A Panitch, 2007, Influence of Cross-Linked Hyaluronan Hydrogels on Neurite Outgrowth and Recovery from Spinal Cord Injury. Journal of Neurosurgery-Spine, 6(2), 2007: 133-40

18. P. Stice, A. Gilletti, A. Panitch, J. Muthuswamy, Thin microelectrodes reduce GFAp expression in the implant site in rodent somatosensory cortex. Journal of Neuroscience Methods, Journal of Neurological Engineering, 4, 2007: 42-53.

19. S. Padalkar, Y. Zhao, K. Stuart*, A. Panitch, J. Rickus, L. Stanciu Preparation of Biomolecule Gel Matrices for Electron Microscopy Ultramicroscopy, 108(4), 2007: 309-313.

20. L. B. Lopes, E. Furnish, P. Komalavilas, B. L. Seal*, A. Panitch, M. V. L. B. Bentley, C. M. Brophy, Enhanced skin penetration of P20 phosphopeptide using protein transduction domains. European Journal of Pharmaceutics and Biopharmaceutics, 68 (2), 2008: 441-445.

21. K. Stuart* and A. Panitch, Influence of Chondroitin Sulfate on Collagen Gel Structure and Mechanical Properties at Physiologically Relevant Levels, Biopolymers 89(10), 2008: 841-851.

22. K.J. Jeong*, K. Butterfield* and A. Panitch, A novel assay to probe heparin-peptide interactions using peptide stabilized gold nanoparticles, Langmuir, 24(16), 2008: 8794-8800.

23. J.E. Paderi* and A. Panitch, Design of a Synthetic Collagen-Binding Peptidoglycan that Modulates Collagen Fibrillogenesis, Biomacromolecules, 9(9), 2008: 2562-2566.

24. L.B. Lopes, E.J. Furnish, P. Komalavilas, C. R. Flynn, P. Ashby, A. Hansen, D.P. Ly, G. P. Yang, M. T. Longaker, A. Panitch, C. M. Brophy, Cell Permeant Peptide Analogues of the Small Heat Shock Protein, HSP20, Reduce TGF-β1-Induced CTGF Expression in Keloid Fibroblasts. Investigative Dermatology, 129(3), 2009: 590-598. doi: 10.1038/jid.2008.264

25. R. Sistiabudi, J. Paderi*, A. Panitch and A. Ivanisevic, Modification of Native Collagen with Cell-Adhesive Peptide to Promote RPE Cell Attachment on Bruch’s Membrane. Biotechnology and Bioengineering, 102(6), 2008: 1723-1729.

26. K. Stuart* and A. Panitch, Characterization of Gels Composed of Blends of Collagen I, Collagen III, and Chondroitin Sulfate, Biomacromolecules, 10(1), 2009: 25-31.

27. K.J. Jeong* and A. Panitch, The Interplay between Covalent and Physical Interactions within Environment Sensitive Hydrogel, Biomacromolecules, 10(5), 2009: 1090-1099.

28. L. Lopes, C. Flynn, P. Komalavilas, A. Panitch, C.M. Brophy and B.L. Seal*, Inhibition of HSP27 Phosphorylation by a Novel Cell-permeant MAPKAP Kinase 2 Inhibitor, Biochemical and Biophysical Research Communications, 382(3), 2009: 535-539

29. A. Ishwar*, K.J. Jeong*, A. Panitch, and O. Akkus, Raman Spectroscopic Investigation of GAG-Peptide Interactions, Applied Spectroscopy, 63(6), 2009: 636-641.

30. J. Paderi*, R. Sistiabudi, A. Ivanisevic, and A. Panitch, Collagen-Binding Peptidoglycans: A Biomimetic Approach to Modulate Collagen Fibrillogenesis for Tissue Engineering Applications, Tissue Engineering, 15(10), 2009: 2991-2999.

31. B.C. Ward*, B.L. Seal, C.M. Brophy and A. Panitch, Design of a Bioactive Cell-Penetrating, Peptide: When a Transduction Domain Does More Than Transduce, J. Peptide Sci. 15(10), 2009: 668-674 (NIHMSID 212825).

32. A. Conovaloff*, H-W. Wang, J. Cheng, and A. Panitch, Imaging Growth of Neurites in Conditioned Hydrogel by Coherent Anti-Stokes Raman Scattering Microscopy, 5(4) 2009: 149-155.

33. B.C. Ward* and A. Panitch, Abdominal Adhesions: Current and Novel Therapies, Journal of Surgical Research, 165(1), 2011: 91-111. DOI: 10.1016/j.jss.2009.09.015

34. D.H. Eng*, M. Caplan, M. Preul, and A. Panitch, Hyaluronan Scaffolds – A Balance between Backbone Functionalization and Bioactivity, Acta Biomaterialia, 6(7), 2010: 2407-2414.

35. K.C. Butterfield*, M. Caplan and A. Panitch, Identification and Sequence Composition Characterization of Chondroitin Sulfate-Binding Peptides through Peptide Array Screening, Biochemistry, 49(7), 2010 1549-1555

36. S. Chaterji*, K. Park and A. Panitch, Scaffold-free in vitro arterial mimetics: the importance of smooth muscle-endothelium contact, Tissue Engineering, 16(6), 2010: 1901-1912.

37. K.C. Butterfield*, A. Conovaloff*, and A. Panitch, Chondroitin sulfate-binding peptides block chondroitin 6-sulfate inhibition of cortical neurite growth, Neuroscience Letters, 478(2), 2010: 82-87.

38. J. Brugnano*, B.C. Ward* and A. Panitch, “Cell Penetrating Peptides Can Exert Biological Activity: A Review” BioMolecular Concepts, 1(2), 2010: 109-116.

39. L.B. Lopes, C. M. Brophy, C.R. Flynn, Z. Yi, B.P. Bowen, C. Smoke, B. Seal*, A. Panitch and P. Komalavilas, A novel cell permeant peptide inhibitor of MAPKAP kinase II inhibits intimal hyperplasia in a human saphenous vein organ culture model, Journal of Vascular Surgery, 52(6), 2010: 1596-1607.

40. B. Beier, K. Musick, A. Matsumoto, A. Panitch, E. Nauman, and P. Irazoqui, Toward a continuous intravascular glucose monitoring system, Sensors, 11(1), 2011: 409-424.

41. J.E. Paderi*, K. Stuart*, K. Park, M. Sturek and A. Panitch, The inhibition of platelet adhesion and activation on collagen during balloon angioplasty by collagen-binding peptidoglycans, Biomaterials, 32(10), 2011: 2516-2523.

42. B.C. Ward*, S. Kavalukas, J. Brugnano*, A. Barbul, A. Panitch, Peptide inhibitors of MK2 show promise for inhibition of abdominal adhesions, J. Surg. Res. 169(1), 2011: e27-e36.

43. V. Kishore, J.E. Paderi*, S. Beaudoin, A. Panitch, O. Akkus, Incorporation of a decorin biomimetic enhances the mechanical properties of electrochemically aligned collagen threads, Acta Biomterialia, 7(6), 2011: 2428-2436.

44. J. Brugnano*, B.L. Seal, A. Panitch, Cell-penetrating peptides can confer biological function regulation of inflammatory cytokines in human monocytes by MK2 inhibitor peptides. Journal of Controlled Release, 155(2), 2011: 128-133 doi:10.1016/j.jconrel.2011.05.007 .

45. K. O’Shaughnessey*, A. Panitch and J. Woodell-May, Blood-derived anti-inflammatory protein solution blocks the effect of IL-1β on human macrophages in vitro, Inflammation Research, 60(10), 2011: 929-936. doi:10.1007/s00011-011-0353-2

46. K. Stuart*, J.E. Paderi*, P. Snyder, L. Freeman, A. Panitch, Collagen-Binding Peptidoglycans Inhibit MMP Mediated Collagen Degradation and Reduce Dermal Scarring, PLoS ONE, 6(7), 2011: 10.1371/journal.pone.0022139.

47. A. Conovaloff* and A. Panitch, Characterization of a chondroitin sulfate hydrogel for nerve root regeneration, Journal of Neural Engineering, 2011, 8 056003 doi:10.1088/1741-2560/8/5/056003

48. C.M. Rupert Perez*, A. Panitch, and J. Chmielewski, A collagen peptide-based physical hydrogel for cell encapsulation, Macromolecular Biosciences, 11(10), 2011: 1426-1431 DOI: 10.1002/mabi.201100230.

49. A. Conovaloff* and A. Panitch, Effects of a synthetic bioactive peptide on neurite growth and nerve growth factor release in chondroitin sulfate hydrogels, Biomatter, 1(2), 2011: 165-173.

50. A. Muto, A. Panitch, N. Kim*, K. Park, P. Komalavilas, C.M. Brophy, A. Dardik, Inhibition of Mitogen Activated Protein Kinase Activated Protein Kinase II with MMI-0100 reduces intimal hyperplasia ex vivo and in vivo, Vascular Pharmacology, 56(1-2), 2011: 47-55, http://dx.doi.org/10.1016/j.vph.2011.07.008,

51. K. Butterfield*, A. Conovaloff*, and A. Panitch, Development of affinity-based delivery of NGF from a chondroitin sulfate biomaterial, Biomatter, 1(2), 2011: 174-181.

52. J.C. Bernhard* and A. Panitch, Synthesis and Characterization of an Aggrecan Mimic, Acta Biomaterialia, 8(4), 2012:1543-1550, http://dx.doi.org/10.1016/j.actbio.2011.12.029

53. R.L. Bartlett II*, M.R. Medow*, A. Panitch, and B. Seal, Hemocompatible poly(NIPam-MBA-AMPS) colloidal nanoparticles as carriers of anti-inflammatory cell penetrating peptides. Biomacromolecules, 13(4), 2012:1204-1211.

54. A. Hicks*, M Caplan, A Panitch, and J Sweeney, An Incubatable Direct Current Stimulation System for In Vitro Studies of Mammalian Cells, Bioresearch Open Access, 1(4), 2012:199-203.

55. R. Bartlett* and A. Panitch, Thermosensitive nanoparticles with pH triggered degradation and release of anti-inflammatory cell penetrating-peptides, Biomacromolecules, 13(8), 2012: 2578-2584.

56. S. Sharma*, A. Panitch and CP Neu, Incorporation of an Aggrecan Mimic Prevents Proteolytic Degradation of Anisotropic Cartilage Analogs. Acta Biomaterialia, 9(1), 2013: 4618-4625.

57. R. Bartlett*, S. Sharma*, and A. Panitch, Cell penetrating peptides released from thermosensitive nanoparticles suppress pro-inflammatory cytokine response by specifically targeting inflamed cartilage explants, Nanomedicine: Nanotechnology, Biology, and Medicine, 9(3), 2012: 419-427.

58. A. Kosinski*, J. Brugnano*, F. Knight*, and B. Seal, A. Panitch, Synthesis and Characterization of a Poly(lactic-co-glycolic acid) Core + Poly(N-isopropylacrylamide) Shell Nanoparticle System, Biomatter, 2(4), 2012: 195-201

59. R.A. Scott, K. Park, and A. Panitch, Water Soluble Polymer Films for Intravascular Drug Delivery of Antithrombotic Biomolecules, European Journal of Pharmaceutics and Biopharmaceutics, 2013, http://dx.doi.org/10.1016/j.ejpb.2012.12.002

60. R. Vittal, A. Fisher, H. Gu, E.A. Mickler, A. Panitch, C. Lander, O.W. Cummings, D.S. Wilkes, MAPKAPK2 inhibition with MMI-0100 protects against established bleomycin-induced pulmonary fibrosis in mice, American Journal of Respiratory Cell and Molecular Biology, 49(1), 2013: 47-57.

61. R.A. Scott and A. Panitch, Glycosaminoglycans in Biomedicine, WIREs Nanomedince & Nanobiotechnology, 5(4), 2013: 388-398.

62. S. Sharma, A. Lee, K. Choi, K. Kim, I. Youn, and A. Panitch, Biomimetic aggrecan reduces cartilage extracellular matrix from degradation and lowers catabolic activity in ex vivo and in vivo models Macromolecular Bioscience, 13(9), 2013: 1228-1237. DOI: 10.1002/mabi.201300112

63. J.L. Brugnano, J. McMasters, and A. Panitch, Characterization of Endocytic uptake of MK2-Inhibitor Peptides, Journal of Peptide Science, 19(10), 2013:629-638.

64. R.A. Scott*, J.E. Paderi*, M. Sturek, and A. Panitch, Decorin mimic inhibits vascular smooth muscle proliferation and migration, PLoS One, 8(11), 2013:e82456.

65. J. Brugnano* and A. Panitch, Matrix Stiffness affects endocytic uptake of MK2-inhibitor peptides, PLoS One, 9(1), 2014:e84821.

66. M. Mohamed, M Hamed, A Panitch, and M Seleem, Targeting methicillin-resistant Staphylococcus aureus with short salt-resistant synthetic peptides, Antimicrobial Agents & Chemotherapy, In Press

67. R. Scott and A. Panitch Decorin Mimic Regulates Platelet-Derived Growth Factor and Interferon-γ Stimulation of Vascular Smooth Muscle Cells, Biomacromolecules, 15(6), 2014:2090-2103.

68. R. Scott and A. Panitch, Macromolecular Approaches to Prevent Thrombosis and Intimal Hyperplasia Following Percutaneous Coronary Intervention, Biomacromolecules, 2014 (DOI: 10.1021/bm5007757) In Press.

69. Q. Zhang, B. Filas, R. Roth, J. Heuser, N. Ma, S. Sharma, A. Panitch, D.C. Beebe, Y. Shui, Preservation of the structure of enzymatically-degraded bovine vitreous using synthetic proteoglycan mimics, Investigative Ophthalmology & visual science, 55(12), 2014:8153-8162.

70. A. Kosinski, J. Pothen, A. Panitch and P. Sivsankar, Dexamethasone Controlled Release on TGF-β1 Treated Vocal Fold Fibroblasts, Annals of Otology, Rhinology & Laryngology, In Press

71. S. Poh, J.B. Lin, and A. Panitch, Release of Anti-inflammatory peptides from thermosensitive nanoparticles with degradable cross-links suppresses pro-inflammatory cytokine production, Biomacromolecules, 16(4), 2015:1191-1200.

72. A.M. Kosinski, M.P. Sivasankar, and A. Panitch, Varying RGD concentration and cell phenotype alters the expression of extracellular matrix genes in vocal fold fibrosis, Journal of Biomedical Materials Research part A, DOI: 10.1002/jbm.a.35456, 2015

73. N. Vazquez-Portalatin, GJ Breur, A Panitch and CJ Goergen, Accuracy of ultrasound-guided intra-articular injections in guinea pig knees, Bone and Joint Research, 4(1), 2015:1-5.

74. R.S. Scott, A. Ramaswamy, K. Park and A. Panitch, Decorin mimic promotes endothelial cell health in endothelial monolayers and endothelial-smooth muscle co-cultures, Journal of Tissue Engineering and Regenerative Medicine, DOI: 10.1002/term.2035, 2015

75. J.R. Wodicka, N.I. Onunkwo, A.J. Wooley, A. Panitch and K.J. Otto, A cell penetrating peptide for inhibition of MAPKAP kinase 2-mediated inflammatory cytokine release following glial cell activation. World Journal of Neuroscience, DOI: 10.4236/wjns.2015.52012, 2015

76. J. McMasters and A. Panitch, Prevention of collagen induced platelet binding and activation by thermosensitive nanoparticles. The American Association of Pharmaceutical Scientists Journal, 2015 In Press.

77. A. Lawrence, X. Xu, M.D. Bible, S. Calve, C.P. Neu, and A. Panitch, Synthesis and characterization of a lubricin mimic 9mLub) to reduce friction and adhesion on the articular cartilage surface, Biomaterials, 2015, In Press

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