Research Summary

The Knox Lab research program investigates the role of peripheral nerves in controlling epithelial organ development, regeneration, and chronic disease (autoimmune disease, aging, cancer). To explore these areas, we utilize a multiorgan approach that includes the salivary glands and cornea. Our experimental approach employs a bevy of tools that define cell identity, cell-cell relationships and cell/tissue behavior during development and response to injury and regenerative cues including mouse genetics, single cell/bulk RNA sequencing, organoids, atomic force microscopy, ex vivo organ culture, hydrogel synthesis (mechanical, physical and biological testing etc.) and high-resolution imaging. Using this strategy, we have discovered essential functions of peripheral nerves in regulating stem cell maintenance, differentiation and maturation, tissue morphogenesis and regeneration, and cell lineage outcomes. We have also uncovered multiple aspects of nerve-epithelial cell interactions and factors that drive reinnervation. Importantly, our basic research has led to the initiation of translational projects. For example, based on our recent discovery of a nerve-derived factor that promotes glandular repair after radiation-induced damage, we designed a drug-hydrogel system that provides local penetration of irradiated tissue for achieving long-term functional and structural regeneration. This therapeutic product has the potential to regenerate the salivary glands of patients who have received radiotherapy for head and neck cancer, an off target injury for which there are no regenerative therapies, and poor palliative therapies. These studies are funded by the CDOCTOR/NIDCR program and the California Institute for Regenerative Medicine translational award (TRAN1). We have conducted a pre-IND and are currently performing a pre-clinical trial in 2 large animal models (dog and rabbit) to meet the needs of the FDA for clinical translation.

Research Funding

  • September 1, 2021 - July 31, 2026 - Lacritin Regulation of Homeostasis and Ocular Surface Health , Co-Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01EY032956
  • August 1, 2021 - July 31, 2026 - Defining mechanisms driving dry eye disease progression , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01EY033040
  • September 18, 2018 - June 30, 2026 - Defining mechanisms driving salivary gland regeneration , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R35DE028255
  • September 30, 2017 - June 30, 2021 - Autonomic regulation of lacrimal stem cells , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01EY027392
  • August 1, 2015 - June 30, 2021 - Defining the role of the nervous system in aqueous-deficient dry eye , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01EY025980
  • September 30, 2016 - July 31, 2020 - Defining the role of immune-neuronal crosstalk in dry eye disease , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01EY026492
  • February 1, 2019 - January 31, 2020 - 2018 Salivary Glands and Exocrine Biology Gordon Research Conference and Seminar , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R13DE028494
  • April 1, 2014 - December 31, 2018 - Neuronal regulation of salivary stem cells , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01DE024188
  • April 1, 2016 - March 31, 2018 - Impact of aging on salivary stem cells and organ regeneration , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R21DE025736
  • May 1, 2016 - April 30, 2017 - 2016 Proteoglycans Gordon Research Conference & Gordon Research Seminar , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R13AR069957
  • January 24, 2012 - December 31, 2015 - Neuronal-epithelial interactions that regulate mouse salivary gland development , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R00DE018969
  • July 20, 2012 - June 30, 2015 - Salivary gland repair and regeneration via Schwann cell-nerve interactions , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R21DE022951

Education

University of New South Wales, Sydney, Australia, Ph.D., 4/2002, Biomedical Engineering
University of New South Wales, Sydney, Australia, B.S (Hon), 4/1998, Biochemistry

Honors & Awards

  • 1998
    Pacific Dunlop Postgraduate Scholarship
  • 1998
    Australian Postgraduate Award (APA)
  • 2005
    Australian Post-Doctoral Industrial Fellowship (APDI)
  • 2005
    UNSW Faculty of Engineering Research Grant
  • 2008
    NIH Pathway to Independence Award (K99/R00)
  • 2008
    Pathway to Independence Award (K99/R00)

Selected Publications

  1. Musicant AM, Billington JMR, Damrauer JS, Modliszewski JL, Landau LJB, Tsai YH, Mehta JH, Powers J, Betancourt R, Sekhri R, Padilla RJ, Hernandez-Prera JC, Hayes DN, Hackman TG, Gokcumen O, Knox SM, Amelio AL Correction: An FGFR-p53 developmental signaling axis drives salivary cancer progression.  View on PubMed
  2. Musicant AM, Billington JMR, Damrauer JS, Modliszewski JL, Landuau LJB, Tsai YH, Mehta JH, Powers J, Betancourt R, Sekhri R, Padilla RJ, Hernandez-Prera JC, Hayes DN, Hackman TG, Gokcumen O, Knox SM, Amelio AL An FGFR-p53 developmental signaling axis drives salivary cancer progression.  View on PubMed
  3. Li J, Sun B, Tan LX, Griffin N, Niknezhad SV, Yu C, Berthoin L, Cruz-Pacheco N, Mohabbat S, Sinada H, Efraim Y, Chen FYT, An L, Gaylord EA, Bahney CS, Lombaert IMA, Knox SM. Rescue of non-healing, degenerative salivary glands by cholinergic-calcium signaling. bioRxiv. 2025 Feb 28.  View on PubMed
  4. Efraim Y, Chen FYT, Niknezhad SV, Pham D, Cheong KN, An L, Sinada H, McNamara NA, Knox SM. Rebuilding the autoimmune-damaged corneal stroma through topical lubrication. bioRxiv. 2024 Dec 03.  View on PubMed
  5. Arias-Ortiz A, Wolfe J, Bridgham SD, Knox S, McNicol G, Needelman BA, Shahan J, Stuart-Haëntjens EJ, Windham-Myers L, Oikawa PY, Baldocchi DD, Caplan JS, Capooci M, Czapla KM, Derby RK, Diefenderfer HL, Forbrich I, Groseclose G, Keller JK, Kelley C, Keshta AE, Kleiner HS, Krauss KW, Lane RR, Mack S, Moseman-Valtierra S, Mozdzer TJ, Mueller P, Neubauer SC, Noyce G, Schäfer KVR, Sanders-DeMott R, Schutte CA, Vargas R, Weston NB, Wilson B, Megonigal JP, Holmquist JR Methane fluxes in tidal marshes of the conterminous United States.  View on PubMed
  6. Bansal S, Creed IF, Tangen BA, Bridgham SD, Desai AR, Krauss KW, Neubauer SC, Noe GB, Rosenberry DO, Trettin C, Wickland KP, Allen ST, Arias-Ortiz A, Armitage AR, Baldocchi D, Banerjee K, Bastviken D, Berg P, Bogard MJ, Chow AT, Conner WH, Craft C, Creamer C, DelSontro T, Duberstein JA, Eagle M, Fennessy MS, Finkelstein SA, Göckede M, Grunwald S, Halabisky M, Herbert E, Jahangir MMR, Johnson OF, Jones MC, Kelleway JJ, Knox S, Kroeger KD, Kuehn KA, Lobb D, Loder AL, Ma S, Maher DT, McNicol G, Meier J, Middleton BA, Mills C, Mistry P, Mitra A, Mobilian C, Nahlik AM, Newman S, O'Connell JL, Oikawa P, van der Burg MP, Schutte CA, Song C, Stagg CL, Turner J, Vargas R, Waldrop MP, Wallin MB, Wang ZA, Ward EJ, Willard DA, Yarwood S, Zhu X Practical Guide to Measuring Wetland Carbon Pools and Fluxes.  View on PubMed
  7. Delcroix V, Mauduit O, Lee HS, Ivanova A, Umazume T, Knox SM, de Paiva CS, Dartt DA, Makarenkova HP. The First Transcriptomic Atlas of the Adult Lacrimal Gland Reveals Epithelial Complexity and Identifies Novel Progenitor Cells in Mice. Cells. 2023 05 21; 12(10).  View on PubMed
  8. Li J, Sudiwala S, Berthoin L, Mohabbat S, Gaylord EA, Sinada H, Cruz Pacheco N, Chang JC, Jeon O, Lombaert IMA, May AJ, Alsberg E, Bahney CS, Knox SM. Long-term functional regeneration of radiation-damaged salivary glands through delivery of a neurogenic hydrogel. Sci Adv. 2022 Dec 21; 8(51):eadc8753.  View on PubMed
  9. May AJ, Mattingly AJ, Gaylord EA, Griffin N, Sudiwala S, Cruz-Pacheco N, Emmerson E, Mohabbat S, Nathan S, Sinada H, Lombaert IMA, Knox SM. Neuronal-epithelial cross-talk drives acinar specification via NRG1-ERBB3-mTORC2 signaling. Dev Cell. 2022 11 21; 57(22):2550-2565.e5.  View on PubMed
  10. Efraim Y, Chen FYT, Cheong KN, Gaylord EA, McNamara NA, Knox SM. A synthetic tear protein resolves dry eye through promoting corneal nerve regeneration. Cell Rep. 2022 08 30; 40(9):111307.  View on PubMed
  11. Pajic P, Shen S, Qu J, May AJ, Knox S, Ruhl S, Gokcumen O. A mechanism of gene evolution generating mucin function. Sci Adv. 2022 08 26; 8(34):eabm8757.  View on PubMed
  12. Viswanathan V, Cao H, Saiki J, Jiang D, Mattingly A, Nambiar D, Bloomstein J, Li Y, Jiang S, Chamoli M, Sirjani D, Kaplan M, Holsinger FC, Liang R, Von Eyben R, Jiang H, Guan L, Lagory E, Feng Z, Nolan G, Ye J, Denko N, Knox S, Rosen DM, Le QT. Aldehyde dehydrogenase 3A1 deficiency leads to mitochondrial dysfunction and impacts salivary gland stem cell phenotype. PNAS Nexus. 2022 May; 1(2):pgac056.  View on PubMed
  13. Khan S, Fitch S, Knox S, Arora R. Exocrine gland structure-function relationships. Development. 2022 01 01; 149(1).  View on PubMed
  14. Zhang Z, Poulter B, Knox S, Stavert A, McNicol G, Fluet-Chouinard E, Feinberg A, Zhao Y, Bousquet P, Canadell JG, Ganesan A, Hugelius G, Hurtt G, Jackson RB, Patra PK, Saunois M, Höglund-Isaksson L, Huang C, Chatterjee A, Li X Anthropogenic emission is the main contributor to the rise of atmospheric methane during 1993-2017.  View on PubMed
  15. Nnabue OE, Pletcher SD, Gurrola JG, Goldberg AN, Jordan KM, Knox SM, May AJ. Septum submucosal glands exhibit aberrant morphology and reduced mucin production in chronic rhinosinusitis. Int Forum Allergy Rhinol. 2021 10; 11(10):1443-1451.  View on PubMed
  16. Pastorello G, Trotta C, Canfora E, Chu H, Christianson D, Cheah YW, Poindexter C, Chen J, Elbashandy A, Humphrey M, Isaac P, Polidori D, Reichstein M, Ribeca A, van Ingen C, Vuichard N, Zhang L, Amiro B, Ammann C, Arain MA, Ardö J, Arkebauer T, Arndt SK, Arriga N, Aubinet M, Aurela M, Baldocchi D, Barr A, Beamesderfer E, Marchesini LB, Bergeron O, Beringer J, Bernhofer C, Berveiller D, Billesbach D, Black TA, Blanken PD, Bohrer G, Boike J, Bolstad PV, Bonal D, Bonnefond JM, Bowling DR, Bracho R, Brodeur J, Brümmer C, Buchmann N, Burban B, Burns SP, Buysse P, Cale P, Cavagna M, Cellier P, Chen S, Chini I, Christensen TR, Cleverly J, Collalti A, Consalvo C, Cook BD, Cook D, Coursolle C, Cremonese E, Curtis PS, D'Andrea E, da Rocha H, Dai X, Davis KJ, De Cinti B, de Grandcourt A, De Ligne A, De Oliveira RC, Delpierre N, Desai AR, Di Bella CM, di Tommasi P, Dolman H, Domingo F, Dong G, Dore S, Duce P, Dufrêne E, Dunn A, Dušek J, Eamus D, Eichelmann U, ElKhidir HAM, Eugster W, Ewenz CM, Ewers B, Famulari D, Fares S, Feigenwinter I, Feitz A, Fensholt R, Filippa G, Fischer M, Frank J, Galvagno M, Gharun M, Gianelle D, Gielen B, Gioli B, Gitelson A, Goded I, Goeckede M, Goldstein AH, Gough CM, Goulden ML, Graf A, Griebel A, Gruening C, Grünwald T, Hammerle A, Han S, Han X, Hansen BU, Hanson C, Hatakka J, He Y, Hehn M, Heinesch B, Hinko-Najera N, Hörtnagl L, Hutley L, Ibrom A, Ikawa H, Jackowicz-Korczynski M, Janouš D, Jans W, Jassal R, Jiang S, Kato T, Khomik M, Klatt J, Knohl A, Knox S, Kobayashi H, Koerber G, Kolle O, Kosugi Y, Kotani A, Kowalski A, Kruijt B, Kurbatova J, Kutsch WL, Kwon H, Launiainen S, Laurila T, Law B, Leuning R, Li Y, Liddell M, Limousin JM, Lion M, Liska AJ, Lohila A, López-Ballesteros A, López-Blanco E, Loubet B, Loustau D, Lucas-Moffat A, Lüers J, Ma S, Macfarlane C, Magliulo V, Maier R, Mammarella I, Manca G, Marcolla B, Margolis HA, Marras S, Massman W, Mastepanov M, Matamala R, Matthes JH, Mazzenga F, McCaughey H, McHugh I, McMillan AMS, Merbold L, Meyer W, Meyers T, Miller SD, Minerbi S, Moderow U, Monson RK, Montagnani L, Moore CE, Moors E, Moreaux V, Moureaux C, Munger JW, Nakai T, Neirynck J, Nesic Z, Nicolini G, Noormets A, Northwood M, Nosetto M, Nouvellon Y, Novick K, Oechel W, Olesen JE, Ourcival JM, Papuga SA, Parmentier FJ, Paul-Limoges E, Pavelka M, Peichl M, Pendall E, Phillips RP, Pilegaard K, Pirk N, Posse G, Powell T, Prasse H, Prober SM, Rambal S, Rannik Ü, Raz-Yaseef N, Rebmann C, Reed D, de Dios VR, Restrepo-Coupe N, Reverter BR, Roland M, Sabbatini S, Sachs T, Saleska SR, Sánchez-Cañete EP, Sanchez-Mejia ZM, Schmid HP, Schmidt M, Schneider K, Schrader F, Schroder I, Scott RL, Sedlák P, Serrano-Ortíz P, Shao C, Shi P, Shironya I, Siebicke L, Šigut L, Silberstein R, Sirca C, Spano D, Steinbrecher R, Stevens RM, Sturtevant C, Suyker A, Tagesson T, Takanashi S, Tang Y, Tapper N, Thom J, Tomassucci M, Tuovinen JP, Urbanski S, Valentini R, van der Molen M, van Gorsel E, van Huissteden K, Varlagin A, Verfaillie J, Vesala T, Vincke C, Vitale D, Vygodskaya N, Walker JP, Walter-Shea E, Wang H, Weber R, Westermann S, Wille C, Wofsy S, Wohlfahrt G, Wolf S, Woodgate W, Li Y, Zampedri R, Zhang J, Zhou G, Zona D, Agarwal D, Biraud S, Torn M, Papale D Author Correction: The FLUXNET2015 dataset and the ONEFlux processing pipeline for eddy covariance data.  View on PubMed
  17. Saitou M, Gaylord EA, Xu E, May AJ, Neznanova L, Nathan S, Grawe A, Chang J, Ryan W, Ruhl S, Knox SM, Gokcumen O. Functional Specialization of Human Salivary Glands and Origins of Proteins Intrinsic to Human Saliva. Cell Rep. 2020 11 17; 33(7):108402.  View on PubMed
  18. Pastorello G, Trotta C, Canfora E, Chu H, Christianson D, Cheah YW, Poindexter C, Chen J, Elbashandy A, Humphrey M, Isaac P, Polidori D, Reichstein M, Ribeca A, van Ingen C, Vuichard N, Zhang L, Amiro B, Ammann C, Arain MA, Ardö J, Arkebauer T, Arndt SK, Arriga N, Aubinet M, Aurela M, Baldocchi D, Barr A, Beamesderfer E, Marchesini LB, Bergeron O, Beringer J, Bernhofer C, Berveiller D, Billesbach D, Black TA, Blanken PD, Bohrer G, Boike J, Bolstad PV, Bonal D, Bonnefond JM, Bowling DR, Bracho R, Brodeur J, Brümmer C, Buchmann N, Burban B, Burns SP, Buysse P, Cale P, Cavagna M, Cellier P, Chen S, Chini I, Christensen TR, Cleverly J, Collalti A, Consalvo C, Cook BD, Cook D, Coursolle C, Cremonese E, Curtis PS, D'Andrea E, da Rocha H, Dai X, Davis KJ, Cinti B, Grandcourt A, Ligne A, De Oliveira RC, Delpierre N, Desai AR, Di Bella CM, Tommasi PD, Dolman H, Domingo F, Dong G, Dore S, Duce P, Dufrêne E, Dunn A, Dušek J, Eamus D, Eichelmann U, ElKhidir HAM, Eugster W, Ewenz CM, Ewers B, Famulari D, Fares S, Feigenwinter I, Feitz A, Fensholt R, Filippa G, Fischer M, Frank J, Galvagno M, Gharun M, Gianelle D, Gielen B, Gioli B, Gitelson A, Goded I, Goeckede M, Goldstein AH, Gough CM, Goulden ML, Graf A, Griebel A, Gruening C, Grünwald T, Hammerle A, Han S, Han X, Hansen BU, Hanson C, Hatakka J, He Y, Hehn M, Heinesch B, Hinko-Najera N, Hörtnagl L, Hutley L, Ibrom A, Ikawa H, Jackowicz-Korczynski M, Janouš D, Jans W, Jassal R, Jiang S, Kato T, Khomik M, Klatt J, Knohl A, Knox S, Kobayashi H, Koerber G, Kolle O, Kosugi Y, Kotani A, Kowalski A, Kruijt B, Kurbatova J, Kutsch WL, Kwon H, Launiainen S, Laurila T, Law B, Leuning R, Li Y, Liddell M, Limousin JM, Lion M, Liska AJ, Lohila A, López-Ballesteros A, López-Blanco E, Loubet B, Loustau D, Lucas-Moffat A, Lüers J, Ma S, Macfarlane C, Magliulo V, Maier R, Mammarella I, Manca G, Marcolla B, Margolis HA, Marras S, Massman W, Mastepanov M, Matamala R, Matthes JH, Mazzenga F, McCaughey H, McHugh I, McMillan AMS, Merbold L, Meyer W, Meyers T, Miller SD, Minerbi S, Moderow U, Monson RK, Montagnani L, Moore CE, Moors E, Moreaux V, Moureaux C, Munger JW, Nakai T, Neirynck J, Nesic Z, Nicolini G, Noormets A, Northwood M, Nosetto M, Nouvellon Y, Novick K, Oechel W, Olesen JE, Ourcival JM, Papuga SA, Parmentier FJ, Paul-Limoges E, Pavelka M, Peichl M, Pendall E, Phillips RP, Pilegaard K, Pirk N, Posse G, Powell T, Prasse H, Prober SM, Rambal S, Rannik Ü, Raz-Yaseef N, Rebmann C, Reed D, Dios VR, Restrepo-Coupe N, Reverter BR, Roland M, Sabbatini S, Sachs T, Saleska SR, Sánchez-Cañete EP, Sanchez-Mejia ZM, Schmid HP, Schmidt M, Schneider K, Schrader F, Schroder I, Scott RL, Sedlák P, Serrano-Ortíz P, Shao C, Shi P, Shironya I, Siebicke L, Šigut L, Silberstein R, Sirca C, Spano D, Steinbrecher R, Stevens RM, Sturtevant C, Suyker A, Tagesson T, Takanashi S, Tang Y, Tapper N, Thom J, Tomassucci M, Tuovinen JP, Urbanski S, Valentini R, van der Molen M, van Gorsel E, van Huissteden K, Varlagin A, Verfaillie J, Vesala T, Vincke C, Vitale D, Vygodskaya N, Walker JP, Walter-Shea E, Wang H, Weber R, Westermann S, Wille C, Wofsy S, Wohlfahrt G, Wolf S, Woodgate W, Li Y, Zampedri R, Zhang J, Zhou G, Zona D, Agarwal D, Biraud S, Torn M, Papale D The FLUXNET2015 dataset and the ONEFlux processing pipeline for eddy covariance data.  View on PubMed
  19. Efraim Y, Chen FYT, Stashko C, Cheong KN, Gaylord E, McNamara N, Knox SM. Alterations in corneal biomechanics underlie early stages of autoimmune-mediated dry eye disease. J Autoimmun. 2020 11; 114:102500.  View on PubMed
  20. Fekedulegn D, Andrew ME, Shi M, Violanti JM, Knox S, Innes KE Actigraphy-Based Assessment of Sleep Parameters.  View on PubMed

Go to UCSF Profiles, powered by CTSI