Edward V. Maytin,  M.D., Ph.D.

Edward V. Maytin, M.D., Ph.D.

Staff

Lerner Research Institute, 9500 Euclid Avenue, Cleveland, Ohio 44195
Phone: (216) 445-6676

 

Our research program involves two thematic areas: (1) wound healing, and (2) skin cancer. For wound healing, we are interested in the role of the extracellular matrix in wound repair. A large carbohydrate molecule called hyaluronan is an abundant component of the matrix and also of the pericellular coats of fibroblasts, epithelial cells, and blood vessels; the addition of certain proteins to hyaluronan after injury appears to be critical for regulating inflammation and fibrosis in healing wounds. Understanding this regulation may provide new ideas for therapy of poorly healing wounds in diabetes.

For skin cancer, we are working to improve a skin cancer treatment called photodynamic therapy (PDT). PDT has two components: a porphyrin precursor that is selectively taken up into malignant cells and converted to porphyrin, and a strong light source that activates the porphyrin inside the cancer cells, producing oxygen free radicals and causing cell death. Under the proper conditions, PDT can also stimulate anti-tumor immunity. We have found that pretreatment with certain drugs and hormones (including methotrexate and Vitamin D) can lead to more porphyrin accumulation, more efficient cell killing upon exposure to light, and improved stimulation of anti-tumor immune mechanisms.

Lay Summary

Our lab studies wound healing and skin cancer. In the case of wound healing, we are interested in how the extracellular matrix, a sort of scaffold in the body, can regulate inflammation and scarring in healing wounds. We aim to develop new treatments for poorly healing skin wounds such as leg ulcers.  For skin cancer, we are trying to improve a technique called photodynamic therapy (PDT), in which a sensitizing drug (usually a cream) is applied on the skin, and then a laser or other strong light source is used to activate the drug to kill cancer cells. Our laboratory has discovered that when a skin cancer is pre-treated with certain drugs, it becomes much more sensitive to PDT. We hope to make PDT work for thicker and more serious skin cancers.


View publications for Edward V. Maytin, M.D., Ph.D.

Hanada Y, Pereira SP, Pogue B, Maytin EV, Hasan T, Linn B, Mangels-Dick T, Wang KK. EUS-guided verteporfin photodynamic therapy for pancreatic cancer. Gastrointest Endosc. 2021 Jul;94(1):179-186. doi: 10.1016/j.gie.2021.02.027. Epub 2021 Feb 26. PMID: 33647286.

Anand S, Chan TA, Hasan T, Maytin EV. Current Prospects for Treatment of Solid Tumors via Photodynamic, Photothermal, or Ionizing Radiation Therapies Combined with Immune Checkpoint Inhibition (A Review). Pharmaceuticals (Basel). 2021 May 10;14(5):447. doi: 10.3390/ph14050447. PMID: 34068491; PMCID: PMC8151935.

Anand S, Govande M, Yasinchak A, Heusinkveld L, Shakya S, Fairchild RL, Maytin EV. Painless Photodynamic Therapy Triggers Innate and Adaptive Immune Responses in a Murine Model of UV-induced Squamous Skin Pre-cancer. Photochem Photobiol. 2020 Oct 28. doi: 10.1111/php.13350. Online ahead of print. PMID: 33113217 

Nun N, Cruz M, Jain T, Tseng YM, Menefee J, Jatana S, Patil PS, Leipzig ND, McDonald C, Maytin E, Joy A. Thread Size and Polymer Composition of 3D Printed and Electrospun Wound Dressings Affect Wound Healing Outcomes in an Excisional Wound Rat Model. Biomacromolecules. 2020 Oct 12;21(10):4030-4042. doi: 10.1021/acs.biomac.0c00801. Epub 2020 Sep 23. PMID: 32902971 

Shakya S, Asosingh K, Mack JA, Maytin EV. Optimized protocol for the preparation of single cells from cutaneous wounds for flow cytometric cell sorting and analysis of macrophages. MethodsX. 2020 Aug 8;7:101027. doi: 10.1016/j.mex.2020.101027. eCollection 2020.PMID: 32939347 Free PMC article. 

Shakya S, Mack JA, Alipour M, Maytin EV. Cutaneous Wounds in Mice Lacking TSG-6 Exhibit Delayed Closure and an Abnormal Inflammatory Response. J Invest Dermatol. 2020 Dec;140(12):2505-2514. doi: 10.1016/j.jid.2020.04.015. Epub 2020 May 15. PMID: 32422216 

Anbil S, Pigula M, Huang HC, Mallidi S, Broekgaarden M, Baglo Y, De Silva P, Simeone DM, Mino-Kenudson M, Maytin EV, Rizvi I, Hasan T. Vitamin D Receptor Activation and Photodynamic Priming Enables Durable Low-dose Chemotherapy. Mol Cancer Ther. 2020 Jun;19(6):1308-1319. doi: 10.1158/1535-7163.MCT-19-0791. Epub 2020 Mar 27. PMID: 32220968 Free PMC article. 

Abbadi A, Loftis J, Wang A, Yu M, Wang Y, Shakya S, Li X, Maytin E, Hascall V. Heparin inhibits proinflammatory and promotes anti-inflammatory macrophage polarization under hyperglycemic stress. J Biol Chem. 2020 Apr 10;295(15):4849-4857. doi: 10.1074/jbc.RA119.012419. Epub 2020 Feb 27. PMID: 32107314 Free PMC article. 

Maytin EV, Hasan T. Vitamin D and Other Differentiation-promoting Agents as Neoadjuvants for Photodynamic Therapy of Cancer. Photochem Photobiol. 2020 May;96(3):529-538. doi: 10.1111/php.13230. Epub 2020 Apr 15. PMID: 32077114 Free PMC article. 

LaRochelle EPM, Chapman MS, Maytin EV, Hasan T, Pogue BW. Weather-informed Light-tissue Model-Based Dose Planning for Indoor Daylight Photodynamic Therapy. Photochem Photobiol. 2020 Mar;96(2):320-326. doi: 10.1111/php.13170. Epub 2019 Oct 21. PMID: 31581341 Free PMC article. 

Wang Y, Mack JA, Maytin EV. CD44 inhibits α-SMA gene expression via a novel G-actin/MRTF-mediated pathway that intersects with TGFβR/p38MAPK signaling in murine skin fibroblasts. J Biol Chem. 2019 Aug 23;294(34):12779-12794. doi: 10.1074/jbc.RA119.007834. Epub 2019 Jul 8. PMID: 31285260 Free PMC article. 

Anand S, Yasinchak A, Bullock T, Govande M, Maytin EV. A non-toxic approach for treatment of breast cancer and its metastases: capecitabine enhanced photodynamic therapy in a murine breast tumor model. J Cancer Metastasis Treat. 2019;5:6. doi: 10.20517/2394-4722.2018.98. Epub 2019 Jan 24. PMID: 30740528 Free PMC article. 

Anand S, Yasinchak A, Govande M, Shakya S, Maytin EV. Painless versus conventional photodynamic therapy for treatment of actinic keratosis: Comparison of cell death and immune response in a murine model. Proc SPIE Int Soc Opt Eng. 2019 Feb;10860:108600K. doi: 10.1117/12.2511646. Epub 2019 Feb 28. PMID: 33790491 Free PMC article. 

LaRochelle EPM, Marra K, LeBlanc RE, Chapman MS, Maytin EV, Pogue BW. Modeling PpIX effective light fluence at depths into the skin for PDT dose comparison. Photodiagnosis Photodyn Ther. 2019 Mar;25:425-435. doi: 10.1016/j.pdpdt.2019.01.022. Epub 2019 Jan 25. PMID: 30685548 

Marra K, LaRochelle EP, Chapman MS, Hoopes PJ, Lukovits K, Maytin EV, Hasan T, Pogue BW. Comparison of Blue and White Lamp Light with Sunlight for Daylight-Mediated, 5-ALA Photodynamic Therapy, in vivo. Photochem Photobiol. 2018 Sep;94(5):1049-1057. doi: 10.1111/php.12923. Epub 2018 May 16. PMID: 29663426 Free PMC article. 

Maytin EV, Anand S, Riha M, Lohser S, Tellez A, Ishak R, Karpinski L, Sot J, Hu B, Denisyuk A, Davis SC, Kyei A, Vidimos A. 5-Fluorouracil Enhances Protoporphyrin IX Accumulation and Lesion Clearance during Photodynamic Therapy of Actinic Keratoses: A Mechanism-Based Clinical Trial. Clin Cancer Res. 2018 Jul 1;24(13):3026-3035. doi: 10.1158/1078-0432.CCR-17-2020. Epub 2018 Mar 28. PMID: 29593028 Free article. 

Maytin EV, Kaw U, Ilyas M, Mack JA, Hu B. Blue light versus red light for photodynamic therapy of basal cell carcinoma in patients with Gorlin syndrome: A bilaterally controlled comparison study. Photodiagnosis Photodyn Ther. 2018 Jun;22:7-13. doi: 10.1016/j.pdpdt.2018.02.009. Epub 2018 Feb 19. PMID: 29471147 Free PMC article. 

de Souza ALR, LaRochelle E, Marra K, Gunn J, Davis SC, Samkoe KS, Chapman MS, Maytin EV, Hasan T, Pogue BW. Assessing daylight & low-dose rate photodynamic therapy efficacy, using biomarkers of photophysical, biochemical and biological damage metrics in situ. Photodiagnosis Photodyn Ther. 2017 Dec;20:227-233. doi: 10.1016/j.pdpdt.2017.10.005. Epub 2017 Oct 14. PMID: 29037911 Free PMC article. 

Anand S, Rollakanti KR, Brankov N, Brash DE, Hasan T, Maytin EV. Fluorouracil Enhances Photodynamic Therapy of Squamous Cell Carcinoma via a p53-Independent Mechanism that Increases Protoporphyrin IX levels and Tumor Cell Death. Mol Cancer Ther. 2017 Jun;16(6):1092-1101. doi: 10.1158/1535-7163.MCT-16-0608. Epub 2017 Mar 23. PMID: 28336806 Free PMC article. 

de Souza AL, Marra K, Gunn J, Samkoe KS, Kanick SC, Davis SC, Chapman MS, Maytin EV, Hasan T, Pogue BW. Comparing desferrioxamine and light fractionation enhancement of ALA-PpIX photodynamic therapy in skin cancer. Br J Cancer. 2016 Sep 27;115(7):805-13. doi: 10.1038/bjc.2016.267. Epub 2016 Aug 30. PMID: 27575852 Free PMC article. 

Maytin EV. Hyaluronan: More than just a wrinkle filler. Glycobiology. 2016 Jun;26(6):553-9. doi: 10.1093/glycob/cww033. Epub 2016 Mar 9.PMID: 26964566 Free PMC article. 

Ghatak S, Maytin EV, Mack JA, Hascall VC, Atanelishvili I, Moreno Rodriguez R, Markwald RR, Misra S.Roles of Proteoglycans and Glycosaminoglycans in Wound Healing and Fibrosis. Int J Cell Biol. 2015;2015:834893. doi: 10.1155/2015/834893. Epub 2015 Sep 10. PMID: 26448760 Free PMC article. 

Shakya S, Wang Y, Mack JA, Maytin EV. Hyperglycemia-Induced Changes in Hyaluronan Contribute to Impaired Skin Wound Healing in Diabetes: Review and Perspective. Int J Cell Biol. 2015;2015:701738. doi: 10.1155/2015/701738. Epub 2015 Sep 10. PMID: 26448756 Free PMC article. 

Rollakanti KR, Anand S, Davis SC, Pogue BW, Maytin EV. Noninvasive Optical Imaging of UV-Induced Squamous Cell Carcinoma in Murine Skin: Studies of Early Tumor Development and Vitamin D Enhancement of Protoporphyrin IX Production. Photochem Photobiol. 2015 Nov;91(6):1469-78. doi: 10.1111/php.12503. Epub 2015 Sep 25. PMID: 26223149 Free PMC article. 

Rollakanti K, Anand S, Maytin EV. Topical calcitriol prior to photodynamic therapy enhances treatment efficacy in non-melanoma skin cancer mouse models. Proc SPIE Int Soc Opt Eng. 2015 Mar 2;9308:93080Q. doi: 10.1117/12.2077296. PMID: 25983370 Free PMC article. 

Rollakanti KR, Anand S, Maytin EV. Vitamin D enhances the efficacy of photodynamic therapy in a murine model of breast cancer. Cancer Med. 2015 May;4(5):633-42. doi: 10.1002/cam4.361. Epub 2015 Feb 25. PMID: 25712788 Free PMC article. 

Anand S, Ebner J, Warren CB, Raam MS, Piliang M, Billings SD, Maytin EV. C/EBP transcription factors in human squamous cell carcinoma: selective changes in expression of isoforms correlate with the neoplastic state. PLoS One. 2014 Nov 17;9(11):e112073. doi: 10.1371/journal.pone.0112073. eCollection 2014. PMID: 25402211 Free PMC article. 

Wang Y, Lauer ME, Anand S, Mack JA, Maytin EV. Hyaluronan synthase 2 protects skin fibroblasts against apoptosis induced by environmental stress. J Biol Chem. 2014 Nov 14;289(46):32253-32265. doi: 10.1074/jbc.M114.578377. Epub 2014 Sep 29. PMID: 25266724 Free PMC article. 

Kanick SC, Davis SC, Zhao Y, Hasan T, Maytin EV, Pogue BW, Chapman MS. Dual-channel red/blue fluorescence dosimetry with broadband reflectance spectroscopic correction measures protoporphyrin IX production during photodynamic therapy of actinic keratosis. J Biomed Opt. 2014;19(7):75002. doi: 10.1117/1.JBO.19.7.075002. PMID: 24996661 Free PMC article. 

Anand S, Rollakanti KR, Horst RL, Hasan T, Maytin EV. Combination of oral vitamin D3 with photodynamic therapy enhances tumor cell death in a murine model of cutaneous squamous cell carcinoma. Photochem Photobiol. 2014 Sep-Oct;90(5):1126-35. doi: 10.1111/php.12286. Epub 2014 May 26.PMID: 24807677 Free PMC article. 

Techniques for fluorescence detection of protoporphyrin IX in skin cancers associated with photodynamic therapy. Rollakanti KR, Kanick SC, Davis SC, Pogue BW, Maytin EV. Photonics Lasers Med. 2013 Nov 1;2(4):287-303. doi: 10.1515/plm-2013-0030. PMID: 25599015 Free PMC article. 

Anand S, Hasan T, Maytin EV. Mechanism of differentiation-enhanced photodynamic therapy for cancer: upregulation of coproporphyrinogen oxidase by C/EBP transcription factors. Mol Cancer Ther. 2013 Aug;12(8):1638-50. doi: 10.1158/1535-7163.MCT-13-0047. Epub 2013 May 16. PMID: 23686770 Free PMC article. 

Maytin EV, Honari G, Khachemoune A, Taylor CR, Ortel B, Pogue BW, Sznycer-Taub N, Hasan T. Vitamin D Combined with Aminolevulinate (ALA)-Mediated Photodynamic Therapy (PDT) for Human Psoriasis: A Proof-of-Principle Study. Isr J Chem. 2012 Sep;52(8-9):767-775. doi: 10.1002/ijch.201200005. Epub 2012 Aug 21. PMID: 23264699 Free PMC article.

Anand S, Wilson C, Hasan T, Maytin EV. Vitamin D3 enhances the apoptotic response of epithelial tumors to aminolevulinate-based photodynamic therapy. Cancer Res. 2011; 71(18): 6040-50.

Mack JA, Feldman RJ, Itano N, Kimata K, Lauer M, Hascall VC, Maytin EV. Enhanced Inflammation and Accelerated Wound Closure Following Tetraphorbol Ester Application or Full-Thickness Wounding in Mice Lacking Hyaluronan Synthases Has1 and Has3. J Invest Dermatol. 2011 Aug 18 [Epub ahead of print].

Warren CB, Lohser S, Wene LC, Pogue BW, Bailin PL, Maytin EV. Noninvasive fluorescence dosimetry to define protoporphyrin IX production rates in actinic keratoses following short-contact application of 5-aminolaevulinate. J Biomedical Optics 2010; 15(2) Sept/October, Issue 051607, pages 1-8.

Mack JA, Maytin EV. Persistent Inflammation and Angiogenesis during Wound Healing in K14-Directed Hoxb13 Transgenic Mice. J Invest Dermatol 2010; 130:856-65.

Monslow J, Sato N, Mack JA, Maytin EV. Wounding-induced synthesis of hyaluronic acid in organotypic epidermal cultures requires the release of heparin-binding egf and activation of the EGFR. J Invest Dermatol. 2009 Aug;129(8):2046-58. doi: 10.1038/jid.2009.9. Epub 2009 Feb 19. PMID: 19225541 Free PMC article. 

Ajani G, Sato N, Mack JA, Maytin EV. Cellular responses to disruption of the permeability barrier in a three-dimensional organotypic epidermal model. Exp Cell Res. 2007 Aug 15;313(14):3005-15. doi: 10.1016/j.yexcr.2007.04.021. Epub 2007 Apr 24.PMID: 17512930 Free PMC article. 

Sato N, Moore BW, Keevey S, Drazba JA, Hasan T, Maytin EV. Vitamin D enhances ALA-induced protoporphyrin IX production and photodynamic cell death in 3-D organotypic cultures of keratinocytes. J Invest Dermatol. 2007 Apr;127(4):925-34. doi: 10.1038/sj.jid.5700595. Epub 2006 Oct 19.PMID: 17068479 Free article. 

Mack JA, Anand S, Maytin EV. Proliferation and cornification during development of the mammalian epidermis. Birth Defects Res C Embryo Today. 2005 Dec;75(4):314-29. doi: 10.1002/bdrc.20055. PMID: 164252526 

Anand S, Chakrabarti E, Kawamura H, Taylor CR, Maytin EV. Ultraviolet light (UVB and UVA) induces the damage-responsive transcription factor CHOP/gadd153 in murine and human epidermis: evidence for a mechanism specific to intact skin. J Invest Dermatol. 2005 Aug;125(2):323-33. doi: 10.1111/j.0022-202X.2005.23784.x. PMID: 16098044 Free article. 

Mack JA, Li L, Sato N, Hascall VC, Maytin EV. Hoxb13 up-regulates transglutaminase activity and drives terminal differentiation in an epidermal organotypic model. J Biol Chem. 2005 Aug 19;280(33):29904-11. doi: 10.1074/jbc.M505262200. Epub 2005 Jun 17. PMID: 15964834 Free article. 

Maytin EV, Chung HH, Seetharaman VM. Hyaluronan participates in the epidermal response to disruption of the permeability barrier in vivo. Am J Pathol. 2004 Oct;165(4):1331-41. doi: 10.1016/S0002-9440(10)63391-3.PMID: 15466397 Free PMC article.


12/16/2020 |  

Study Reveals How Improved Type of Light Therapy Kills Pre-Cancerous Cells

Dr. Maytin and colleagues developed a less painful but equally effective form of photodynamic therapy to treat pre-cancerous actinic keratosis, demonstrating that it works through a completely different signaling pathway than the conventional therapy.